Multimodality imaging: prostate cancer diagnosis and follow up by TOF-PET &

MRI/MRSF. Garibaldi – INFN Roma and ISS Why do we need a dedicated multimodality system dedicated to prostate

imaging?

Potential design concept for prostate-specific PET Imaging

Background issue: the role of TOF-PET

PET – TOF design concept

The role of MRI and MRS

Multimodality challenge(s)

Silicon Photomultipliers (SiPm)

Summary and outlook

F. Garibaldi1, E. Cisbani, S. Colilli, F. Cusanno, R. Fratoni, F. Giuliani, M. Gricia, M. Lucentini, M.L. Magliozzi, F. Santavenere, S. Torrioli

Italian National Institute of Health and INFN Rome, ItalyItalian National Institute of Health – Rome

R. De Leo, E. NappiUniversity of Bari and INFN Bari

F. Giove, B. Maraviglia, F. Meddi,

Physics Department, University la Sapienza, Rome

S. Majewski, J ProffitJefferson Lab, Newport News, USA

Advanced molecular imaging techniques in the detection, diagnosis, therapy, and follow-up of prostate cancer

Rome - December 2005

Advanced molecular imaging techniques in the detection, diagnosis, therapy, and follow-up of prostate cancer

F. Garibaldi, Italian National Insitute of Health and INFN Rome1, gr. Sanita’

Workshop on Compton Camera Applications to Bio-medical

Imaging

Mattinata 5-7 September 2002

Frontiers in Imaging science: high performance detectors for vascular disease (brain and heart) imaging based on the latest developments in scintillators, photodetectors, and solid state materials

Rome - ISS - 12,13,14 November 2006

55/100,000 55/100,000 per year in Europe per year in Europe

90009000 new cases/year in Italynew cases/year in Italy

Prostate cancer is the Prostate cancer is the most common cancermost common cancer and andthe the second leading causesecond leading cause of cancer death in of cancer death in

Italian menItalian men

INCIDENCEProstate Cancer Diagnosis: Prostate Cancer Diagnosis: MRIMRI

PSA levelSensitivit

ySpecificit

y

1,1 ng/ml 83,4 38,9

1.6 ng/ml 67 58,7

2.1 ng/ml 52,6 72,5

2.6 ng/ml 40,5 81,1

3.1 ng/ml 32,2 86,7

4.1 ng/ml 20,5 93.8

6.1 ng/ml 4,6 98,5

8.1 ng/ml 1,7 99,4

10.1 ng/ml

0,9 99,7

Any Cancer (n.: 1225) VSAny Cancer (n.: 1225) VSNo Cancer (n: 4362 pts)No Cancer (n: 4362 pts)

Thompson IM, JAMA 2005

PSA: Sensitivity and Specificity

0

50

100

150

200

<4 4 e 10 10 e 20 >20

Distribuzione casi per range di PSA

No K

K

PSA remains an important prognostic markers of the biological potential of newly diagnosed prostatic cancer and the best marker to evaluate treatment outcome.

It will be a challenge to the medical community to change the long- held notion that there is a “normal” PSA value at which to recommended biopsy.

PSA proxy as Age, PSA Density, PSA velocity, Free PSA, ACT-PSA, BPSA can help the physician in the decision making process.

Future markers or tools for the early detection of clinically significant prostate cancer and to avoid unnecessary biopsy are strongly needed.

Cutoff?

Recent INDICATIONS for BIOPSY

• Abnormal PSA level

• DRE + false negative

false positive

BIOPSY

• TRUS (hypoechoic lesion)

• normal DRE and PSA

Not necessarily

BIOPSY

PROSTATE CANCER

PSA

DRE TRUS

CONCLUSION

I level

II level

BIOPSY

MRI and Spectroscopy

State of Art

*Catalona WJ, Smith DS ,Ornstein DK et al. JAMA 277: 1452-1455, 2004**Langer JE et al. Semin Roentgenol 34: 284-294,,2004

DRE

PSASensibility

PSA level ≤ 4.0 ng/ml 67.5 - 80% PSA level > 4.0 ng/ml 60 - 70%

TRUS

Normal DRE and PSA

< 4.0 ng/ml

Do not exclude prostate cancer*

DIAGNOSTIC PITFALLS• 30% palpable lesions at DRE

False Positive high rate• 20% hypoechoic lesions

are truly malignant**

EARLY DIAGNOSIS PITFALLS EARLY DIAGNOSIS PITFALLS

Prostate Cancer Diagnosis: MRI

Prostate Cancer

MRS: the role of CHOl

CHOl PET can differentiate aggressiveness (G<7 vs G>7)

Single Photon:111In-ProstaScint

Prostate

Rectum

Collimator

GammaImager

Source

Image Plane

1st Detector

2nd DetectorScatteredγ - Rays

N. Clinthorne. MichiganSingle photon Compton camera

Radinuclides Single photon

Internal PET prostate probe proposed by Levin and presented also by Moses that works in coincidence with an external PET detector. This figure is from presentation by Moses.

Device proposed by Clinthorne. and Majewski. Full ring external PET detector provides more complete sampling and can be used with more conventional PET protocols

Radionuclide imaging (PET)

potential of a multimodality dedicated device - Screening ?

- Reducing rate of false negative?

- Reducing rate of false positives?

- Staging?

- Detecting recurrence?

- Monitoring therapy?

requirements for radionuclide imaging

- radiotracer (high specificity)- high sensitivity- practical consideration, cost

high SNR

-

drawback of the standard PET

- detectors far away from prostate- poor spatial resolution (6 – 12 mm)- poor photon detection efficiency (<1%)- activity ouside the organ -> poor contrast resolution- relative high cost per study

design concept: a small rectal prostate probe (+ external panel detectors) compatible with MRI scanners

- close proximity imaging- improved spatial resolution and photon detection imaging- mobile- lower cost device - > lower cost study

TOF - PET

W. Moses NSS-MIC 2008

TOF issues

W. Moses NSS-MIC 2008

Proposed Side-Coupled Design

Proposed Geometry(Side-Coupled Crystal)

ScintillatorCrystal

PMT

PMT

Shorter Optical Path Length & Fewer ReflectionsShorter Optical Path Length & Fewer Reflections

Conventional Geometry(End-Coupled Crystal)

384 ps(543 ps coinc.)

218 ps

W. Moses NSS-MIC 2008

W. Moses NSS-MIC 2008

convTOF SNRx

DSNR

c

tx

2

Time Resolution

(ns)

x

(cm)

SNRimprovement(20 cm object)

SNRimprovement(40 cm object)

0.1 1.5 3.7 5.2

0.3 4.5 2.1 3.0

0.5 7.5 1.6 2.3

1.2 18.0 1.1 1.5

Time-of-Flight and SNR

DOI mandatory

25

30

35

40

45

50

0.95 1 1.05 1.1 1.15 1.2 1.25 1.3

Decay Time (ns)

Relative Light Output

Optimization: LSO CompositionOptimization: LSO Composition

Ca-Doping Gives High Light Output & Short Ca-Doping Gives High Light Output & Short

Normal LSO High Light Out

Short The Good Stuff!

= Ca-doped

0.1%0.2%0.4%

0.3%

• Ca-Doping Gives Good Timing Resolution• ~15% Improvement Over Normal LSO

• Ca-Doping Gives Good Timing Resolution• ~15% Improvement Over Normal LSO

150

160

170

180

190

200

210

220

230

80 100 120 140 160 180 200Time Resolution (ps fwhm)Initial Intensity (I

0)

Normal LSO

Scaled by1/sqrt(I0)

Measured Results: LSO Composition

Measured Results: LSO Composition

= Ca-doped

0.1%

0.2%

0.4%0.3%

W. Moses NSS-MIC 2008

• Intrinsic Timing Resolution is 63 ps fwhm• With Detectors, Same Timing as NIM Electronics

• Intrinsic Timing Resolution is 63 ps fwhm• With Detectors, Same Timing as NIM Electronics

Shaper

Shaper

4 ADCs

4 ADCsCFD

Sum

Sum

CFD

CERNTDC

FPGA

Out…

Based on Siemens “Cardinal” electronics.

CFD triggers if any of 4 adjacent modules fire.

CERN HPTDC digitizes arrival time w/ 24 ps LSB.

Pulse height from all 8 modules read out on every trigger.

FPGA uses pulse heights to identify interaction crystal.

FPGA also does calibration, event formatting, etc.

Electronics (W. Moses (IEEE 2008))

Our approach

- Using Silicon Photo ultipliers (compatibility with MRI/MRS)

- develop fast dedicated ASIC timing reolution ~ 100 ps

- using different faster scintillator (LaBr3)

-Starting with:- few channel lab. Electronics -> proving TOF capability- building a prostate probe with SiPm (dedicated readout (Jlab)) phatom tests on MRI scanner

J. Va’Vra IEEE 2008

Test card (48 channels using SPIROC ASIC)

It wil be used to test arrays of SiPm coupled to scintillators (continuous and pixellated (LSO, LYSO, LaBr3)

S. Majewski

Summary and outlook

- prostate cancer detection, diagnosis and staging very difficult

- standard PET systems are not sufficiently sensitive and “precise”

- Compact high resolution high sensititivity PET system is needed (prostate probe + external detector)

- 3D postioning capability- ~ 1 mm spatial resolution, high coincidence detection effciency- ~m12% energy resolution- to get rid of background TOF capability 150-250 ps timing resolution

- better radiotracers + multimodality (TOF – PET & MRI (and MRS) can be the solution

- Modern sensor technology allows to build a PET prostate probe insensitive to magntic fields PET MRI possible

- research program started in Rome (coll. with Majewski) for TOF-PET prototype to be tested in clinical scanner starting with phantoms