1. FP 7 Collaborative Project Novel MR-compatible PET detectors for simultaneous PET/MRI imaging FP7-HEALTH-2009-single-stage - Scope - Issues - Actions - Deadline(s)

2. HEALTH-2009-1.2-3 Novel MR-compatible PET detectors for simultaneous PET/MRI imaging FP7-HEALTH-2009-single-stage The focus should be to develop novel magnetic-field-compatible nuclear detectors for PET imaging, aimed at maximizing the benefits of simultaneous PET/MRI acquisition, which can also be used efficiently and implemented in stand alone PET or SPECT applications. These detectors should operate in high magnetic fields, as used in MRI, without performance degradation, and have high spatial and time resolution. A dedicated integrated readout of high quality should also be developed. The full detector should be compact so as to allow good integration with an MRI system. Globally, it should allow fully exploiting the advantages of both PET and MR technologies in a simultaneous imaging modality and for implementation in both preclinical and clinical/human PET stand-alone systems beyond the state-of-theart. Active participation of industry, especially SMEs, could lead to an increate impact of the research proposed, and this will be considered in the evaluation of the proposal. Funding scheme: Collaborative Project (Large scale integrating project).

3. FP7 PET-MRI ISS INFN UnivR ome (MRI) Italy RomeGenova Bari Germany Portugal Belgium Switz. Slovenia Russia Industries Wurz. Julich. Munich Cern ESPL Lisbon (J.Varela) Brussel (S.Tavernier) P. Jarron P. Krizan (Lubjian) R. Gruetter Y. Lusienko (Moskow) Siemens ? PETsys, ClearPET ? Management G. Cozzone (3i Consulting Gent l (S.)

4. The Istituto Superiore di Sanità (ISS) is the leading technical and scientific public body of the Italian National Health Service. Its activities include research, control, training and consultation in the interest of public health protection.

5. ISS-INFN Rome group - Physics (in the farmework of int. and INFN Bari (and more recently Genova, Catania) Electron scattering (Saclay, Nikhef, Desy (Hermes), Jefferson Lab mainly: electroproduction of kaons on proton and nuclei (high resolution hypernculear spectroscopy), spin structorue of neutron - Apparatuses - Gas and aerogel threshold detectors, RICH detectors (proximity focusing CsI/freon, aerogel (Hermes) waerfall target, superconducting septum magnets… - Applications; - Aerial platform for large scale radioactive contamination - Diagnostic chamber for proton therapy beam -…. - Molecular imaging with radionuclides

6. Hall A - Two High Resolution Spectrometers QDQ - Momentum Range: 0.3 –4 GeV/c  p/p : 1 x 10-4 –  p = =-5% -  –  mr 1 (+1) Cherenkov threshold aerogels + RICH in the hadron spectrometer + septum magnet

9. Spectroscopy analysis of 12 B  : Aerogel vs. RICH K-selection Aerogel Kaon selection RICH Kaon selection 12 C(e,e’K) 12 B  Freon/CsI RICH detector (like ALICE) Hermes areogel RICH

12. Participants in Large-scale integrating projects are required to conclude a consortium agreement Large-scale integrating projects: the requested EC contribution shall be over € 6 million and not exceed € 12 million unless otherwise indicated in the topic description

13. Molecular Imaging Modalities CT Tissue Density, Z A 20-50 µm  -galactocidase 0.1 µmole H / µmole 31 P MRIA H Concentration MF BOLD, DCE 0.1 mm UltrasoundStructure A F Doppler Optical (Bioluminescence, fluorescence) A Topography M ~10 3 cells  quantitative µm to mm PET/SPECTRadiotracer M ~1-2 mm <10 -12 mole = quantitative F Unique !!

14. control Detecting vulnerable plaques (coll. Johns Hopkins, Jefferson Lab)

15. - Optical 10 e15 to 10e17 mol/l - PET,SPECT 10 e11 to 10e12 mol/l - MRI 10 e5 mol/l alternative approach: stable transfection of cells with a reporter gene, such as herpes simplex virus type-1thymidine kinase (HSV1-tk), whose expression can be visualized using a radioactive PET or SPECT reporter probe (phosfphorilates --> TK --> triphosphate --> cells) PET and SPECT imaging can be used to assess cell trafficking, function, and efficacy, using methods which are easily translatable to humans. Reporter gene approaches are particularly valuable, as they provide information not only on cell trafficking, but also on cellular function and survival direct labeling: labels may be diluted upon cell division, making these cells invisible; and labels may efflux from cells or may be degraded over time.

16. - Optical imaging techniques provide high spatial resolution and permit tracking of stem cells but are limited to preclinical use - Magnetic resonance imaging methods permit good spatial resolution but limited detectability - Nuclear techniques, including reporter genes and direct cellular radiolabeling, afford very good detectability but more limited spatial resolution A multimodality approach using combined PET or SPECT and MRI agents may ultimately prove most useful in clinical settings. Dual labeling P. Acton and al.

17. and Multimodality (Zhou, Acton) SPECT/MRI OPTICAL/PET (Gambir)

18. Outlook -the challenge:120 pixel/100 mm, 8 modules 150 X 100 mm 2 ---> FOV 50 x 33 (M=3))

19. Readout Improvements : 1) Higher sensibility: the trigger can be generated by the single channel whose uniformity is achieved by the variable gain. 2) Lower channel correlation: by definition, each channel is read independently; this improve the quality of the acquired signal and consequently the Signal to Noise Ratio, 3) Higher flexibility: better channel-to-channel unformity and transparent “hot channel” suppression, 4) High processing capability: data can be processed in more detailed and accurate way, compensating for distorsion and improving quality parameters minimizing collateral effects on other parameters. 5) Higher speed (> 10 KHz)

20. - 10 trials - 7 “negative” - 2 big tumors - 1 small tumor 2 University clinics (Rome TOV and Napoli)

21. 8 – Fotomoltiplicatori H 9500 H 8500 " Italian Patent Pending No. RM2008A000541".

22. FP7 PET/SPECT MRI: what we shoudl do to be successfull ? - good (new???) detectors - “perfect” integration in multimodality (hardware and software) - loking at applications (“added value” by combining the modalities) - PET/SPECT - high m. field and low m. field - “smart layout (s)” - What to propose ? - TOF – PET  scintillator, electronics, sensor - Management and careful writing of the proposal (only 1/3 of the evaluation is on “technical/scientific)!!

23. What we have to study  design What we have to build PET-SPECT MRI Low field High field - a prototype of SPECT/PET – MRI (low field) for - breast - small animal - a prototype of SPECT/PET – MRI (high field) for - brain - heart (W.B.)

24. Time-of-Flight in PET Can localize source along line of flight. Time of flight information reduces noise in images. Variance reduction given by 2D/c  t. 500 ps timing resolution  5x reduction in variance! c = 30 cm/ns 500 ps timing resolution  7.5 cm localization Time of Flight Provides a Huge Performance Increase! Largest Improvement in Large Patients Time of Flight Provides a Huge Performance Increase! Largest Improvement in Large Patients D

25. Many other applications:

26. Benefit of Time-of-Flight in PET: Experimental and Clinical Results Joel S. Karp, Suleman Surti, Margaret E. Daube-Witherspoon, and Gerd Muehllehner Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

30. W. Moses NSS-MIC 2008

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

35. Time Resolution (ns)  x (cm) SNR improvement (20 cm object ) SNR improvement (40 cm object) 0.11.53.75.2 0.34.52.13.0 0.57.51.62.3 1.218.01.11.5 Time-of-Flight and SNR

39. DOI mandatory

40. SPECT/PET - mixed ring, “trivial” - full ring - at the same time?  reducing too much the sensitivity - consecutively? How to build this? Scintillator  LaBr3 - fast - light yield but - hygroscopic - density Different layout possible for A and B - continuous single slice (for Pet) or several slices (with equal or increasing thickness) - pixellated - modules of 50 x 50 x 20 (30) mm3 with pixels 2 x2 or 3 x3 or 4 x 4 mm2 (problems with DOI) - same scheme - modules of 50 x 50 mm2 with pixel “cubes” of 2 x2 x2 mm3 (or 3 x 3 x 3 mm3) (brute force) (diverging number of channels?) SPECT PET 5 mm 15-25 mm AB

42. W. Moses NSS-MIC 2008

43. Detector Requirements Detect 511 keV Photons With (in order of importance): >85% efficiency <5 mm spatial resolution “low” cost (<$100 / cm 2 ) “low” dead time (<1 µs cm 2 ) <5 ns fwhm timing resolution <100 keV energy resolution Based on Current PET Detector Modules Patient port ~60 cm diameter 24 to 48 layers, covering 15 cm axially. 4–5 mm fwhm spatial resolution. ~2% solid angle coverage $1 – $2 million dollars.

44. Brain and Whole Body 25 -30 cm 5 cm spect pet “HRRT like” Small animals and breast