1. F. Garibaldi – INFN Roma and ISS
Multimodality imaging: prostate cancer diagnosis and follow up by TOF-PET & MRI/MRS
F. 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

2. Italian National Institute of Health and INFN Rome, Italy
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, Italy
Italian National Institute of Health – Rome
R. De Leo, E. Nappi
University of Bari and INFN Bari
F. Giove, B. Maraviglia, F. Meddi,
Physics Department, University la Sapienza, Rome
S. Majewski, J Proffit
Jefferson Lab, Newport News, USA

3. Advanced molecular imaging techniques in the detection, diagnosis, therapy, and follow-up of prostate cancer
Rome - December 2005

4. Frontiers in Imaging science:
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

5. INCIDENCE 55/100,000 per year in Europe 9000 new cases/year in Italy
Prostate Cancer Diagnosis: MRI
INCIDENCE
55/100,000 per year in Europe
9000 new cases/year in Italy
Prostate cancer is the most common cancer and
the second leading cause of cancer death in
Italian men

6. PSA: Sensitivity and Specificity
Any Cancer (n.: 1225) VS
No Cancer (n: 4362 pts)
PSA level
Sensitivity
Specificity
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
Cutoff?
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.
Thompson IM, JAMA 2005

7. Recent INDICATIONS for BIOPSY
PROSTATE CANCER
Recent INDICATIONS for BIOPSY
Abnormal PSA level
DRE +
false negative
false positive
BIOPSY
Not necessarily
BIOPSY
TRUS (hypoechoic lesion)
normal DRE and PSA

8. CONCLUSION diagnosis I level PSA DRE II level TRUS BIOPSY
MRI and Spectroscopy

9. TRUS State of Art DRE PSA EARLY DIAGNOSIS PITFALLS
Prostate Cancer Diagnosis: MRI
State of Art
DRE
Normal DRE and PSA
< 4.0 ng/ml
Do not exclude prostate cancer*
PSA
Sensibility
PSA level ≤ 4.0 ng/ml %
PSA level > 4.0 ng/ml %
DIAGNOSTIC PITFALLS
30% palpable lesions at DRE
False Positive high rate
20% hypoechoic lesions
are truly malignant**
TRUS
EARLY DIAGNOSIS PITFALLS
*Catalona WJ, Smith DS ,Ornstein DK et al. JAMA 277: , 2004
**Langer JE et al. Semin Roentgenol 34: ,,2004

10. Prostate Cancer

11. MRS: the role of CHOl
CHOl PET can differentiate aggressiveness (G<7 vs G>7)

12. Radinuclides Single photon
111In-ProstaScint
Prostate
Rectum
Collimator
Gamma Imager
Single photon Compton camera
N. Clinthorne. Michigan

13. Radionuclide imaging (PET)
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

14. 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

15. 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

18. TOF - PET

24. TOF issues
W. Moses NSS-MIC 2008

25. W. Moses NSS-MIC 2008

26. Proposed Side-Coupled Design
PMT
384 ps
(543 ps coinc.)
Scintillator Crystal
Conventional Geometry
(End-Coupled Crystal)
218 ps
Proposed Geometry (Side-Coupled Crystal)
PMT
Shorter Optical Path Length & Fewer Reflections
W. Moses NSS-MIC 2008

27. W. Moses NSS-MIC 2008

28. Time-of-Flight and SNR
Time Resolution (ns) Dx
(cm)
SNR
improvement
(20 cm object)
(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

30. DOI mandatory

31. Optimization: LSO Composition
High Light Out
Short 
Normal LSO
The Good Stuff!
= Ca-doped
0.1%
0.2%
0.4%
0.3%
Ca-Doping Gives High Light Output & Short 

32. Measured Results: LSO Composition
Normal LSO
Scaled by 1/sqrt(I0)
= Ca-doped
0.1%
0.2%
0.4%
0.3%
Ca-Doping Gives Good Timing Resolution
~15% Improvement Over Normal LSO

33. W. Moses NSS-MIC 2008

34. Electronics (W. Moses (IEEE 2008))
Shaper
4 ADCs
CFD
Sum
CERN TDC
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.
Intrinsic Timing Resolution is 63 ps fwhm
With Detectors, Same Timing as NIM Electronics

35. 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

36. J. Va’Vra IEEE 2008

39. 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)

40. S. Majewski

41. Summary and outlook
- prostate cancer detection, diagnosis and staging very difficult
- better radiotracers + multimodality (TOF – PET & MRI (and MRS) can be the solution
- 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 ps timing resolution
- 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