diffusion mri is sensitive to brain tumor cell density clinical adc and cell density are negatively...
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Diffusion MRI is sensitive to brain tumor cell density
Clinical ADC and cell density are negatively correlated
(Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008)
ADC (or mean diffusion) = cell density (“hypercellularity”)ADC = cell density (“hypocellularity”)
Viable Tumor (Dark)
Necrotic Core
Edema
ADC Map
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Diffusion MRI is sensitive to brain tumor cell density
Tests at our laboratory have confirmed this relationship
- 17 glioma patients (WHO II-IV) underwent diagnostic stereotactic biopsy- Biopsy sites were spatially matched to pre-operative ADC maps
R2 = 0.7933; P < 0.001
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009From: Ellingson, et al. JMRI 2009, In Press
The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 From: Ellingson, JMRI, 2009, In Press
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 SNO/CNS 2009B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 SNO/CNS 2009B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 From: Ellingson et al. J Neurooncol, 2009, In Press
Early Detection of Brain Tumor Growth
T1+C
FLAIR
fDMs
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
HypercellularRegions (Blue)
Contrast-Enhancement(white)
fDMs in Brain Tumor Progression
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
T1+C
FLAIR
fDM
3 mo. 6 mo. 9 mo. (Onset of symptoms)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
fDMs in Progressive Disease (PD)
Hypercellularity
Hypercellularity
Hypercellularity
fDM Results in Stable Disease (SD)
Treatment: Radiation + Temozolomide
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
Treatment: Radiation + Temozolomide
fDM Results in Responding Disease (RD)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
fDM Results in Stable/Responding Disease (SD/RD)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
Hypocellularity Hypocellularity
Hypocellularity
fDMs are an early biomarker for cytotoxic and new anti-angiogenic treatments
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Ellingson BM, J Neurooncol, Under Prep
Results
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
• “fDM Responders” have significantly longer TTP after standard Tx– fDMs are a better predictor than tumor grade
Results
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009
• “fDM Responders” have significantly longer survival on bevacizumab– fDMs are better predictors than grade, age, or mono/combined therapy
Graded fDMs Allow Visualization of Growing Tumor
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
+ Hypercellular+ Hypocellular
1 Mo. 2 Mo. 3 Mo. 4 Mo.
Graded fDMs Allow Visualization of Growing Tumor
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
+ Hypercellular+ Hypocellular
7 Mo.5 Mo.3 Mo.
Graded fDMs Allow Visualization of Growing Tumor
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
+ Hypercellular+ Hypocellular
5 Mo.4 Mo.2 Mo.
Hyp
erc
ellu
lar
Hyp
oce
llula
r
Macrophages& Inflammatory Cells
Demyelination
Graded fDMs in Demyelination
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Biopsy Diagnosis = Demyelination (Multiple Sclerosis)
3 Mo. 5 Mo. 7 Mo. 9 Mo.
Graded fDMs: Radiation Necrosis vs. Tumor
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Hyp
erc
ellu
lar
Hyp
oce
llula
r
T1+
CF
LAIR
Gra
ded
fDM
Graded fDMs: Radiation Induced Changes
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Hyp
erc
ellu
lar
Hyp
oce
llula
r
2 Mo. 3 Mo. 5 Mo. 8 Mo.
14 Mo. 18 Mo. 21 Mo. 23 Mo.
Graded fDMs: Radiation Induced Changes
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Hyp
erc
ellu
lar
Hyp
oce
llula
r
2 Mo. 4 Mo. 6 Mo.
10 Mo. 14 Mo.18 Mo.
Graded fDMs Improve Tumor Localization/Grading in Stereotactic Needle Biopsy
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Graded fDMs Improve Tumor Localizationand Grading in Stereotactic Needle Biopsy
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
2 LesionsBiopsy (WHO II)
Hyp
erc
ellu
lar
Hyp
oce
llula
r
Graded fDMs Improve Tumor Localization for Resection
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Hyp
erc
ellu
lar
Hyp
oce
llula
r
ResectionCavity
Only 10% of Hypercellularregions were removed!
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