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

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

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

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

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

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

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

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

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 67.5 - 80% PSA level > 4.0 ng/ml 60 - 70% 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: 1452-1455, 2004 **Langer JE et al. Semin Roentgenol 34: 284-294,,2004

Prostate Cancer

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

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

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

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

TOF issues W. Moses NSS-MIC 2008

W. Moses NSS-MIC 2008

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

W. Moses NSS-MIC 2008

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

DOI mandatory

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 

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

W. Moses NSS-MIC 2008

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

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 - 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 150-250 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