1. October 16thPicosecond Lyon1 INNOTEP Project Using HEP technologies to improve TEP imaging: Development of innovative schemes for front-end electronic, readout and DAQ architecture  Check of HEP R&D (LHC, ILC,..) for medical imaging instrumentation  To go beyond the state of art independently of the industry  To federate French labs effort in the domain of intrumentation applied to TEP imaging

2. October 16thPicosecond Lyon2 INNOTEP project covers following R&D domains where techniques could be transfered to medical imaging Use of compact segmented Photodetectors: APD, MAPMT, MCPPMT ? Front-end Electronic –Fast, low noise,low power preamp –Fast Sampling ADCs Signal Filtering –Optimum filtering for pulse’s time and amplitude estimation –Signal analysis Read-Out/DAQ –Pipeline and parallel read-out, –Use of high bandwith system (microTCA and ATCA) for trigger and on-line treatment

3. October 16thPicosecond Lyon3 How to improve performances of clinical TEP One exemple = Use of Time of Flight (TOF)  Philips, Gemini TF™, Siemens  Reduction of backgrounds  Improvment of image quality  Decrease time of acquisition GEMINI TF™, Philips TruFlight™ ∆t ~ 550 ps PET scanner LYSO : 4 x 4 x 22 mm 3 28,338 cristaux, 420 PMTs cristal gap: 0.75 µm 2  = 4 ns couronne 70-cm, 18-cm FOV CT scanner Brilliance™ 16 or 64 slice

4. October 16thPicosecond Lyon4 J. Karp, University of Pennsylvania Advantage of TOF Contrast improvment for detection of small structures in background

5. October 16thPicosecond Lyon5 Advantage of TOF J. Karp, University of Pennsylvania Dose injected=9.8 mCi Non-TOF TOF CTCT/TEP

6. October 16thPicosecond Lyon6 Second Application Novel Imaging Systems for in vivo Monitoring and Quality Control during Tumour Ion Beam Therapy (proton, carbon) Advantages of hadrontherapy for localized treatment of tumors :  More localized energy deposition in target due to the Bragg peak  Better biological efficiency of hadrons compared to photons

7. October 16thPicosecond Lyon7 Many hadrontherapy centers planned worldwide:  Protons :  Carbon : GSI, Heidelberg, CNAO, ETOILE, Medaustron…. Hadrontherapy Treatement Protocol :  Decomposition of the volume to be treated in voxels  Maximum Energy in each voxel using Bragg peak  Adjustement of the beam in energy and position to locate the Bragg peak in the voxel

8. October 16thPicosecond Lyon8 Peripheral nucleus-nucleus-collisions, nuclear reactions 12 C: E = 212 AMeV Target: PMMA 15 O, 11 C, 13 N... 11 C, 10 C Penetration depth / mm Arbitrary units 16 O: E = 250 AMeV Target: PMMA 15 O, 11 C, 13 N... 15 O, 14 O, 13 N, 11 C … Therapy beam 1H1H 3 He 7 Li 12 C 16 ONuclear medicine Activity density / Bq cm -3 Gy -1 6600530030601600103010 4 – 10 5 Bq cm -3 Z  6 Target fragmentsProjectile fragmentsTarget fragments Z < 6 1 H: E = 110 MeV Target: PMMA 15 O, 11 C, 13 N... 3 He: E = 130 AMeV Target: PMMA 15 O, 11 C, 13 N... Arbitrary units Penetration depth / mm 7 Li: E = 129 AMeV Target: PMMA Physics

9. October 16thPicosecond Lyon9 What do we have?  In-beam PET Rationale Proportional to dose 3D Non invasive Real time Time efficient In situ Tomography Highly penetrable signal Separation of the signal from the therapeutic irradiation X- or  -rays Signal with: well defined energy spatial correlation time correlation time delay Annihilation  -rays, Positron Emitters PET High detection efficiency ? ? 11 C 11 B + e + + e T 1/2 180 deg  t = 0 E  = 511 keV

10. October 16thPicosecond Lyon10 12 C   Off-beam PET: 1 H-therapy at MGH Boston In-beam PET: 12 C-therapy at GSI Darmstadt In-beam PET and Off beam PET

11. October 16thPicosecond Lyon11 In-beam PET Clinical implementation at GSI 0 1 T Time S(t)S(t) Accelerator: Synchrotron d  60 m Particle beam: pulsed T  5 s,  ≤ 2 s   PET data, list mode: {K 1, K 2, S}(t) Irradiation- time course: {E, I, d}(t)

12. October 16thPicosecond Lyon12 Presence of a large background noise comming mainly from the beam but also :  large rate of high energy prompt gammas from nuclear desexcitation, as well of neutrons  large rate of randoms Pause : P Out of mbunch: A 2 In mbunch: B 2 Main experimental Constraints P ExtractionA2A2 B2B2 At GSI  : acquisition out of beam delivery period in correlation with in beam detector But low « true coincidence» statistic to recover dose monitoring

13. October 16thPicosecond Lyon13 Pause : P Out of  bunch: A2 In  bunch: B 2

14. October 16thPicosecond Lyon14 Clinical implementation Ion range verification Treatment plan: dose distribution  + -activity: prediction  + -activity: measurement

15. October 16thPicosecond Lyon15  PET allows for a - beam delivery independent, - simultaneous or close to therapy (in-beam, offline, resp.), - non-invasive control of tumour irradiations by means of ion beams  An in-vivo measurement of the ion range  The validation of the physical model of the treatment planning In-beam PET Advantages

16. October 16thPicosecond Lyon16  The evaluation of the whole physical process of the treatment from planning to the dose application - new ion species - new components, algorithms - high precision irradiations  The detection and estimation of unpredictable deviations between planned and actually applied dose distributions due to - mispositioning - anatomical changes - mistakes and incidents In-beam PET Advantages (II)

17. October 16thPicosecond Lyon17 The ENVISION Project (European Novel imaging systems for in vivo monitoring and quality control during tumour ion beam) Upcoming FP7 call HEALTH-2008-1.2-4 The focus should be to develop novel imaging instruments, methods and tools for monitoring, in vivo and preferably in real time, the 3-dimensional distribution of the radiation dose effectively delivered within the patient during ion beam therapy of cancer. The ions should be protons or heavier ions. The system should typically be able to quantify the radiation dose delivered, to determine the agreement between the planned target volume and the actually irradiated volume, and for decreasing localisation uncertainties between planned and effective positions (e.g. of tissues or organs), and between planned and effective dose distribution during irradiation. It should aim at improving quality assurance, increasing target site (tumour) to normal tissue dose ratio and better sparing normal tissue.

18. October 16thPicosecond Lyon18 What do we need? WP1: Time-of-flight in-beam PET -Aim: Remove the influence of limited angle tomographic sampling to quantitative imaging -Subtask 1.1.: Development of a demonstrator of an in-beam TOF positron camera : ▪ 2t < 200 ps  the more the time resolution, the faster and efficient dose reconstruction ▪ h singles > 50 % ▪ Dx < 5 mm  detector technology  DAQ - Subtask 1.2.: Tomographic reconstruction and prediction of measured activity distributions from treatment planning  real-time TOF reconstruction  simulation TP  TOF IBPET

19. October 16thPicosecond Lyon19 Main Partners involved in ENVISION project INFN, TERA Project, CERN, IN2P3, GSI, Heidelberg, Louvain, Birmingham, Oxford, Valencia IBA, OncoRay, Icx, Siemens