Introduction to the ClearPEM projects Joao Varela LIP, Lisbon On behalf of the ClearPEM Collaboration Jornadas LIP Universidade do Minho, 7-9 January 2010

The ClearPEM Projects High performance PET scanner for breast cancer detection. Scanner is in clinical tests. Other applications to brain imaging and PET animal are being pursued Projects developed by the ClearPEM consortium, in the framework of Crystal Clear at CERN IP licensed to PETsys, SA

The ClearPEM scanner Good spatial resolution ( ~1.5 mm in whole FoV) Fine crystal segmentation (2x2 mm) DoI measurement with good resolution (FWHM ~2 mm) Dual APD readout of individual crystal pixels High Sensitivity ( ~ 40 cps/kBq in center FoV) Long LYSO crystals (20 mm) Two detector plates with large active area Reduced Random Background (~30%) Large flux of single photons (up to 10 MHz) Coincidence time resolution of ~4 ns FWHM

The ClearPEM scanner

The ClearPEM detector Two detector plates: 6144 LYSO 2x2x20 mm3 crystals 12288 APD pixel channels Dual readout of crystal pixels for DoI measurement 160x180 mm2 active area Water cooling 75% of detector channels presently installed

ASIC Performance Pulse Shape Noise Amplifier rise time: 20ns Variation of baseline and pulse shape 1-2% Noise Pedestal RMS = 2.2 ADC Counts = 5keV ENC = 1300 e- r.m.s. Inter-channel dispersion ~ 8% Response to test pulse Noise measurement

Data Acquisition Performance Trigger Performance Events in coincidence up to 1.5MHz (This involves computation of energy and time, Compton grouping and transmission to the trigger processor) Acquisition rate up to 0.8MHz (This involves readout of the event dataframe after issuing a trigger) Disk storage rate ~ 400MB/s High performance useful for fast calibration runs Needed for other PET applications

Ancillary Systems Cooling Bias Voltages Water cooling of detector plates at 18 oC Stability of temperature ± 0.1 oC Bias Voltages Regulation of APD bias voltages on the detector heads (64 regulation channels) Long-term stability of HV ~ 28 mV rms r.m.s. ~28 mV 40 hours

Energy Resolution Energy measurements: 137Cs Na-22 spectra summed for all crystals Energy measurements: Average energy resolution at 511 keV for the full scanner is 16.0% Dispersion of energy resolution of individual crystals is 8.8% Good energy linearity (~ up to few percent) 137Cs Resolution ~12.5% Photopeak measurements

Time Resolution Time measurement: Typical pulse sampling Time measurement: Photon time is extracted from the pulse samples fitted by the function: Coincidence time resolution of the whole scanner is 5.2 ns FWHM 137Cs 50 MHz sampling Resolution ~12.5% Time difference in coincidence events All scanner coincidences

Energy in bottom vs top APDs DoI Resolution Asymmetry distributions for different impact points in the crystal Depth of interaction measurement DoI is measured from light asymmetry in crystal dual readout From direct measurement (collimated photons): DoI resolution ~ 2 mm FWHM for light asymmetry ±40% Lu-176 background in crystals is used for DoI calibration in whole scanner Average light asymmetry is ±59% Energy in bottom vs top APDs

Energy Dependence on DoI Photopeak position as a function of DoI Energy is independent of DoI: E[keV]=Kabs.(Etop+Krel.Ebottom) Z[mm]=CDOI.((Etopkrel.Ebottom)/(Etop+krel.Ebottom)) Photopeak position is independent of DoI (up to few percent) Energy resolution does not depend on DoI 137Cs Resolution ~12.5% Energy resolution as a function of DoI

Scanner Calibration Energy: Depth of interaction (Lu-176 background): Distribution of energy calibrations Energy: Dispersion of channel gains 15.3% Depth of interaction (Lu-176 background): Dispersion of DoI calibration constants 7.8% Time calibration: Two pulse shape parameters per channel Dispersion of time calibration constants 2% ~4600 crystals Distribution of pulse peak time ~4600 crystals

ClearPEM Sensitivity 14 Sensitivity measurement: Na-22 source A(22Na) = 2.73 µCi ± 0.3% (101kBq) Sensitivity at center of FoV for 10 cm Detector Head opening is 1.0% (350-700 keV, 20 ns) Correction factors: Incomplete (75%) detector: 1.3 In-detector Comptons: ~2 Corrected sensitivity: ~2.6% Monte Carlo estimation: 3.1% Count rate scan Sensitivity (100 mm ): 1.0% 14

ClearPEM Spatial Resolution With DoI Point source imaging Na-22 point source in a grid with 5mm pitch Energy window 400-600 keV Sinograms of 16 source positions are added Reconstruction with 3D-OSEM / STIR Spatial resolution Transaxial 1.2 mm FWHM (corrected for source size ~1mm) DoI effect Images without using DoI information show considerable blurring 5 mm 1 mm Without DoI

ClearPEM Image Uniformity Images of uniform Ge-68 source Reconstruction with 4 orientations of the detector plates Absorption, scatter and corrections are not applied Image artifacts due to detector effects are corrected Good image uniformity Cylinder filled with positron emitter Ge-68 EW=400-700keV TW=4 ns 6 iterations 3D-OSEM

Clinical Tests Program Scanner Installation Hospital IPO, Porto Phase 1 (present) Patients indicated for PET/CT (other disease) Negative breast exams Tuning the image reconstruction with real cases 11 exams done Phase 2 Patients with positive indication from x-rays mammography Assessment of PEM sensitivity / specificity Comparison to mammography and MRI ClearPEM scanner at IPO Porto

Initial clinical exams Example of typical exam: dose 8 mCi 150 mm detector plate opening 4 angular orientations coincidence window ±4 ns energy window 400-650 keV fraction of randoms in FoV is 35% Reconstruction: 3D-OSEM randoms, attenuation and scatter corrections not applied simple normalization correction on-going work to reduce statistical noise

ClearPEM and Ultrasound Dualmodal PET – US CERIMED , Hospital Marseille, other partners Ultra-sound probe with elastography capabilities Cross-reference system and PET-US image fusion Construction of second ClearPEM machine is well advanced ClearPEM-Sonic

PET Animal Pre-clinical studies with small and medium size animals PET/MR insert Texas Institute of Preclinical Studies Application to brain imaging /EPFL 35 cm 60 cm 4.5 cm Cooling plates Detector modules Version with DoI

High performance PET Improvements to Electronics/DAQ Optical S-link (under test) ASICv4 (in design) Intelligent Front End Board (in project) PET Ring Trigger (hw ready) PET Time-of-Flight (FWHM ~200 ps) SiPM and TOF ASIC (collaboration with Torino and CERN) SPAD single-photon detectors integrated with TDCs (collaboration with TUDelft and CERN)

The ClearPEM Collaboration E. Albuquerque1, F. G. Almeida2,13, P. Almeida3, E. Auffray10, J. Barbosa2, A. L. Bastos9, V. Bexiga1, R. Bugalho4, C. Cardoso4, S. Carmona8, J.F. Carneiro2, B. Carriço4, C. S. Ferreira4, N. C. Ferreira5, M. Ferreira4, M. Frade4, F. Gonçalves1, C. Guerreiro5, P. Lecoq10, C. Leong1, P. Lousã6, P. Machado1, M. V. Martins3, N. Matela3, R. Moura4, J. Neves4, P. Neves6, N. Oliveira3, C. Ortigão4, F. Piedade6, J. F. Pinheiro4, P. Relvas6, A. Rivetti , P. Rodrigues4, I. Rolo4, A. I. Santos8, J. Santos2, M. M. Silva1, S. Tavernier11, I. C. Teixeira1,9, J. P. Teixeira1,9, J. C. Silva4,10, R. Silva4, A. Trindade4, J. Varela4, 12   1 INESC-ID, 2 INEGI, 3 IBEB/FCUL, 4 LIP, 5 IBILI/FMUC, 6 INOV, 8 HGO, 9 IPO, 10CERN, 11VUB Funded by