molecular imaging of prostate cancer for diagnosis and therapy · imaging of prostate cancer •...
TRANSCRIPT
Molecular Imaging of Prostate Cancer for Diagnosis
and TherapyPeter Choyke MD
Molecular Imaging ProgramNational Cancer Institute
Molecular Imaging ProgramNCAB December 7 2010
UltrasoundMicrobubbleColor doppler
MRIDCE-MRIMR SpectroscopyIron OxidesDWI
RadionuclideProstascintPSMA antibodiesAptamers
PET11C Choline11C Acetate18F Choline18F ACBC18F AR analog
What Modalities Will Guide Future Therapies
Molecular Imaging Program
Molecular Imaging Program
T2WDWI
DCE MRS
Multi-parametric Prostate MRI
bull 510 patients3 yearsbull 10 patientsweek
Molecular Imaging Program
Endorectal coil 16-channel cardiac coil3 Tesla MRI
T2W ADC MRSI DCE
Molecular Imaging Program
Turkbey B et al Radiology 2010
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
UltrasoundMicrobubbleColor doppler
MRIDCE-MRIMR SpectroscopyIron OxidesDWI
RadionuclideProstascintPSMA antibodiesAptamers
PET11C Choline11C Acetate18F Choline18F ACBC18F AR analog
What Modalities Will Guide Future Therapies
Molecular Imaging Program
Molecular Imaging Program
T2WDWI
DCE MRS
Multi-parametric Prostate MRI
bull 510 patients3 yearsbull 10 patientsweek
Molecular Imaging Program
Endorectal coil 16-channel cardiac coil3 Tesla MRI
T2W ADC MRSI DCE
Molecular Imaging Program
Turkbey B et al Radiology 2010
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
T2WDWI
DCE MRS
Multi-parametric Prostate MRI
bull 510 patients3 yearsbull 10 patientsweek
Molecular Imaging Program
Endorectal coil 16-channel cardiac coil3 Tesla MRI
T2W ADC MRSI DCE
Molecular Imaging Program
Turkbey B et al Radiology 2010
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Multi-parametric Prostate MRI
bull 510 patients3 yearsbull 10 patientsweek
Molecular Imaging Program
Endorectal coil 16-channel cardiac coil3 Tesla MRI
T2W ADC MRSI DCE
Molecular Imaging Program
Turkbey B et al Radiology 2010
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Turkbey B et al Radiology 2010
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
10 2172011
Improving Quantitation of T2 MRIConventional T2-weighted Imagingbull Qualitative
Depends on pulse sequence and acquisition parameters Subjects to inter-scanner and intra-scanner variations
T2 Mapping12
bull Quantitative Generates reproducible results for longitudinal studies and inter- and
intra-scanner comparisons Provides information for multi-parametric analysis (together with
diffusion DCE and MRS)bull Prior iterations=long scan durations
1 Storas TH et al 2008281166-1172 J Magn Reson Imag2 Roebuck JR et al 200927497-502 Magn Reson Imag
Molecular Imaging Program
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Fast T2 Mapping Protocol
bull An accelerated TSE sequenceo Resolution = 109 mm times 109 mm times 3 mm o Acquisition matrix = 256 times 256 o Sixteen echoes with TE = 30 45 60 hellip 255 mso Undersampling factor = 4 with 24 calibration lineso Scan time = 5 min 48 sec for 10 slices
measuredskippedcalibration
TE0 TE1 TE2 TE3 TE4 TE5 t
Ky
Wei Liu PhD
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
13
Representative Images
TE = 50 ms TE = 80 ms T2 map
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
T2 of Normal and Tumor Tissues
N = 7 for patients with tumorN = 11 for patients with lesions suspicious for cancer
0
50
100
150
200
250
T 2(m
s)Control+ control -Tumor + suspicious -
plt001 plt001p = NS
plt005
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Quantifying Apparent Diffusion Coefficient
Turkbey B et al Radiology (in press)
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
ADC map confirms presence of the lesion and ECE
PSA 48 Gleason 3+3 5 PSA 124 Neg Bxs
Apparent Diffusion Coefficient
Molecular Imaging Program
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
bull Two Parameter Fit
bull Three Parameter Fit
bull Estimation of Pharmacokinetics parameter ktrans and kep depends on accurate estimation ofconcentration of agent in plasma Cp
Ce
vevp
Cp
ktrans
Blood EES
int minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()(
Molecular Imaging Program
t tCp )(vpint minusminussdot=t utkepmiddot
pt dueuCtransktC0
)()()( +
kep
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Dce 4 ndash t2w 11
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Arterial Input Function Across Different Slices
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Inflow Suppressed Population Averaged Arterial Input Function
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Automated Region of Interest Measurement
Molecular Imaging Program
ROI-1 drawn on Slice 5
ROI-2 drawn on Slice 3Avg-AIF obtained using our semi-automated algorithm is operator independent
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Raw DCE image early enhancement
Ktrans map kep map
Gd-concentration curve of the lesion with the AIF overlay
Permeability Maps usingQuantitative arterial input function with population averaging and automatedregion of interest detection
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
MR Spectroscopy at 3T
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
MRS shows highly positive lesion
Interpolated MRS map
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Generation of the ldquoGold Standardrdquo
Design of Multi-parametric Analysis System
T2W DWI DCE
T1 Ktrans kepNormalize ADC
Feature Combining
SegmentationHistology
Region Classification
Training
Cancer Probability Map
Yes No
Training Classifier
Molecular Imaging Program Vijay Shah PhD
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
MR-Histology Correlation Solution
(b) Cluster Map (c) Region Map(a) T2W Image
Molecular Imaging Program
bull Clustering is performed on MP-MRIbull Region map based on 3D-connectivity of voxelsbull Correlate region map to histology to identify
cancer and non-cancer regions
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
Note p lt 00001 for all modalityMolecular Imaging Program
From 24 patients ndashbull 225 cancer region identified bull Observed GS 6 to GS 9 tumorsbull 264 non-cancerous region identified
Patient Population consisted of 31 patientsbull 7 patients excluded due to motion
artifacts dce analysis problems andor specimen processing error
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Optimized ResultsPathology
CancerPathology
Not CancerPrecision
Predicted Cancer
203 27 88
Predicted Not Cancer
22 237 92
Class Recall 90[Sensitivity]
90[Specificity]
After Optimization 5 increment in sensitivity and F-measure while 20 increase in the Kappa coefficient
F-measure = 89 (also known as Positive agreement)Kappa Coefficient = 80 (Raterrsquos agreement)
Molecular Imaging Program
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Comparison with Single Modality
00
100
200
300
400
500
600
700
800
900
1000
F-measure Sensitivity Specificity Kappa
T2W ADC T1map DCE T2W+ADC T2W+ADC+T1map Overall
Molecular Imaging Program
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Cancer Probability Map
Molecular Imaging Program
10
00
Designated as ldquotrade secretrdquo
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging of Prostate Cancer PET and SPECT
Molecular Imaging Program
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Metabolic Hallmarks
Fatty AcidSynthesis
Amino Acid Metabolism
Warburg
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
11C-Acetate PETCT Imaging of Prostate Cancer
bull Acetate a fatty acid precursorbull Uptake may correlate with fatty acid
synthetasebull A phase 2 trial of 40 patientsbull 11C-Acetate PET-CT synthesized in the
PET Department NIH
Molecular Imaging Program
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
58 M
PSA=82
Gleason 3+4 tumor
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
18F-FACBC PET-CT Imaging of Prostate Cancer
bull F-ACBC A synthetic L-leucine analoguebull Increased amino acid transport within tumorsbull A phase 2 trial of 30 patientsbull 18F-FACBC PET-CT vs MP-MRI vs histopathologybull Recently open to accrual (730 patients)bull In collaboration with GE Healthcare produced in
Greenbelt MD at Cardinal Health
Molecular Imaging Program
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
18F-FACBC PET-CT Imaging of Prostate Cancer
Molecular Imaging Program
57 M PSA=541
Gleason 3+3 tumor
5-7min post-injection PET-CT
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
bull Small molecule targeting the extracellular domain of prostate specific membrane antigen (PSMA) for SPECT imaging
bull A phase 2 trial of 20 patients in collaboration with Molecular Insight Pharmaceuticals
bull 3- 6 hours post injectionndash Optional 1 day post injectionndash Optional compact endorectal gamma camera imaging
Molecular Imaging Program
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Molecular Imaging Program
Courtesy of Dr J Babich Molecular Insight Pharmaceuticals
Anterior Posterior
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
18F-Sodium Fluoride PET-CT
bull 18F-Sodium Fluoride A calcium analoguebull Incorporated into hydroxyapatitebull A phase 2 trial of 60 patients
ndash First 30 patients have reproducibility studies
bull Recently opened to accrual (560 patients)bull Produced by Cardinal Health
Molecular Imaging Program
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
82-y-old patient with numerous bone metastases 2006 104
Tc-99m MDP Planar
Tc-99m MDP SPECT MIP
F-18 NaF PET MIP
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
18F-NaF PETCT scan 64 yo male with prostate cancer with elevated PSA level
99mTc-MDP Bone scan
Molecular Imaging Program
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Automated Bone Lesion Detection Motion compensation
2172011 43
ProblemsbullThe patient often moves involuntarily due to pain or pressure related to the needle insertionbullThe transrectal ultrasound probe can move and distort the prostatebullRespiratory motion of the patient may shift the prostateSolutionImage-based registration between pre-op and intra-op ultrasound
ResultThe overlap of the prostate between MRI and TRUS without and with motion compensation was 75 plusmn 19 and 94 plusmn 5 respectively
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Summarybull Improving anatomical and functional prostate MRI
ndash Improving HP correlationndash Quantitative MRIndash Decision Support Systems
bull Exploring PET and SPECT tracers for more accurate localization of prostate cancerndash Metabolomic Imaging Fatty Acid and Amino Acidndash Molecular Imaging Prostate Specific Membrane Antigen
Sodium Fluoride
bull Unique featuresndash Resource intense multidisciplinary integratedMolecular Imaging Program
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
Future Directions
bull Continue to improve quantitation of MRI parameters
bull Increase sophistication of Decision Support System to incorporate tumor aggressiveness
bull Develop and compare additional molecular imaging probes (EpCAM ferumoxytal)
bull Translate diagnostic information into image guided biopsy and therapy (Dr Pinto)
Molecular Imaging Program
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-
AcknowledgementsNIHndash Peter A PintoUOBndash Marston Linehan UOBndash Maria MerinoLab of Pathologyndash William DahutMOBndash Bradford WoodDRD NCIndash Paula JacobsNCIndash Aradhana KaushalROBndash James GulleyMOBndash Joanna ShihNCIndash Thomas PohidaNIH
Molecular Imaging Program
MIPndash Baris Turkbeyndash Esther Menandash Marcelino Bernardondash Karen Kurdzielndash Vijay Shahndash Steve Adlerndash Yolanda McKinneyndash Revia Wadendash Dagane Daarndash Gideon Kwarteng ndash Philip Eclarinalndash Liza Lindenbergndash Mirna Martinez
Outside collaborators Philips Medical Systems GE Healthcare Molecular Insight Pharmaceuticals
- Molecular Imaging of Prostate Cancer for Diagnosis and Therapy
- Slide Number 3
- Slide Number 4
- Multi-parametric Prostate MRI
- Slide Number 7
- Slide Number 8
- Design of Multi-parametric Analysis System
- Slide Number 10
- Slide Number 11
- Slide Number 12
- Slide Number 13
- Slide Number 14
- Quantifying Apparent Diffusion Coefficient
- Slide Number 16
- Quantitative pharmacokinetics maps from Dynamic Contrast Enhanced MRI
- Dce 4 ndash t2w 11
- Arterial Input Function Across Different Slices
- Inflow Suppressed Population Averaged Arterial Input Function
- Automated Region of Interest Measurement
- Slide Number 22
- MR Spectroscopy at 3T
- Slide Number 24
- Design of Multi-parametric Analysis System
- MR-Histology Correlation Solution
- Quantitative values of Multiparametric-MRI for Cancer and Non-cancer Region
- Optimized Results
- Comparison with Single Modality
- Cancer Probability Map
- Molecular Imaging of Prostate Cancer PET and SPECT
- Metabolic Hallmarks
- 11C-Acetate PETCT Imaging of Prostate Cancer
- Slide Number 35
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 18F-FACBC PET-CT Imaging of Prostate Cancer
- 123I-MIP-1072 (Trofex) SPECT Imaging of Prostate Cancer
- Slide Number 39
- 18F-Sodium Fluoride PET-CT
- 82-y-old patient with numerous bone metastases 2006 104
- Slide Number 42
- Automated Bone Lesion Detection Motion compensation
- Summary
- Future Directions
- Acknowledgements
-