RPC TOF-PET (An Unlikely Approach) Good afternoon. My name is Miguel Couceiro, and will present the Human RPC TOF-PET, which is really an unlikely approach. Currently supported by RadForLife (QREN)

The RPC–PET Team Researchers and engineers Technicians 02/23 The RPC–PET Team Alberto Blanco12, Antero Abrunhosa7, Custódio Loureiro2, Filomena Clemêncio2, Francisco Caramelo3, Grzegorz Korcyl11, Isabel Prata6, Jan Michel8, Jorge Landeck2, M. Kajetanowicz13, Marek Palka11, Michael Traxler4, Miguel Couceiro2,10,12, Nuno Chichorro3,7, Orlando Oliveira12, Paulo Crespo2,12, Paulo Fonte10,12, Paulo Martins12, Rui Alves12, Rui F. Marques2,12 Researchers and engineers Américo Pereira12, Carlos Silva12, João Silva12, Joaquim Oliveira12, Nuno Carolino12, Ricardo Caeiro12 Technicians Past collaborations Adriano Rodrigues3,7, C.M.B.A. Correia1,2, C. Gil9, Carlos Silvestre10, Durval Costa5, J.J. Pedroso de Lima12, L. Fazendeiro12, Luís Mendes3, M.F. Ferreira Marques9,10, M. P. Macedo1,10, Miguel Oliveira12 1 CEI, Centro de Electrónica e Instrumentação da Universidade de Coimbra, Coimbra, Portugal 2 FCTUC, Departamento de Física da Faculdade de Ciências e Tecnologia da Universidade de Coimbra, Coimbra, Portugal 3 FMUC, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal 4 GSI, Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany 5 HPP, Hospitais Privados de Portugal, Porto, Portugal 6 IBILI, Instituto Biomédico de Investigação da Luz e Imagem da FMUC, Coimbra, Portugal 7 ICNAS, Instituto de Ciências Nucleares Aplicadas à Saúde da Universidade de Coimbra, Coimbra, Portugal 8 IKF, Institut für Kernphysik, Goethe-Universität, Frankfurt, Germany 9 ICEMS, Instituto de Ciência e Engenharia de Materiais e Superfícies de Coimbra, Coimbra, Portugal 10 ISEC, Instituto Superior de Engenharia de Coimbra, Coimbra, Portugal 11 JU, Jagiellonian University of Cracow, Cracow, Poland 12 LIP, Laboratório de Instrumentação e Física Experimental de Partículas, Coimbra, Portugal 13 NE, Nowoczesna Elektronika, Cracow, Poland

Toward a human wide axial field of view PET scanner with RPC detectors 03/23 Toward a human wide axial field of view PET scanner with RPC detectors Current PET scanners CT Low geometric efficiency [D.B.Crosetto, 2000] Full-body, wide axial field of view PET scanner concept CT High geometric efficiency Low detection efficiency (< 0.4% @ 511 keV) No energy resolution (but energy sensitivity) Reasonable time resolution (300 ps) Low cost (glass + electronics) High detection efficiency Good energy resolution (~ 12% @ 511 keV) Low time resolution (~ 600 ps) High cost (cristal + PMTs + electronics) SIEMENS Commercial PET scanner have a reduced Axial Field of View. As a consequence, several bed positions must be acquired in order to obtain a full body image. Moreover, due to the limited axial field of view, a large number of useful events are lost. This process is time consuming, increases the injected activity, and introduces discontinuities in the uptake signal. However, image reconstruction is fairly easy to perform.

Toward a human wide axial field of view PET scanner with RPC detectors 04/23 Toward a human wide axial field of view PET scanner with RPC detectors Glass layers separated by N gaps impinged by perpendicular photons (simulation in GEANT4) [A. Blanco, et al., 2009] Increasing the detection efficiency (~ 20% for 20 detectors, each with 10 gaps) Increased scatter in the detector Commercial PET scanner have a reduced Axial Field of View. As a consequence, several bed positions must be acquired in order to obtain a full body image. Moreover, due to the limited axial field of view, a large number of useful events are lost. This process is time consuming, increases the injected activity, and introduces discontinuities in the uptake signal. However, image reconstruction is fairly easy to perform. Detection efficiency depends also on the photon incidence angle, and detector design (materials and number of active gaps between electrodes)

Toward a human wide axial field of view PET scanner with RPC detectors 05/23 Toward a human wide axial field of view PET scanner with RPC detectors Extraction efficiencies for a single 400 m thick glass plate (GEANT4) M. Couceiro (PhD Thesis submitted on July 2013) Commercial PET scanner have a reduced Axial Field of View. As a consequence, several bed positions must be acquired in order to obtain a full body image. Moreover, due to the limited axial field of view, a large number of useful events are lost. This process is time consuming, increases the injected activity, and introduces discontinuities in the uptake signal. However, image reconstruction is fairly easy to perform.

Toward a human wide axial field of view PET scanner with RPC detectors 06/23 Toward a human wide axial field of view PET scanner with RPC detectors First prototype of detection head with 3030 cm2  8 gaps Efficiency as expected from GEANT4 Time resolution – 300 ps FWHM Detection efficiency depends both on: Photon interaction probability in the converter plate And electron extraction probability from the converter plate Therefore, we must chose converter plates with high interaction probability, optimize thickness, for optimum electron extraction, and then stack several plates to increase efficiency [A. Blanco et al., 2009]

Toward a human wide axial field of view PET scanner with RPC detectors 07/23 Toward a human wide axial field of view PET scanner with RPC detectors Detailed Simulations (Software and physics) Simulation concerning spatial resolution GEANT4 release 9.1, patch 2 Standard Energy Physics (SEP) package for electromagnetic processes (photons, electrons and positrons), and without hadron, ion and decay physics Simulation concerning Scatter Fraction and Noise Equivalent Count Rate GEANT4 release 9.2, patch 4 Standard Energy Physics (SEP) package for electromagnetic processes (photons, electrons and positrons), hadron, ion and decay physics, and Rayleigh scatter provided by Low Energy Physics based on the Livermore libraries Positron annihilation physics provided by GEANT4 assuming perfect collinear photons GATE assuming photon non-collinearity as a Gaussian blur in the polar angle with 0.58 FWHM, corresponding to values measured in water [S. Jan et al., 2004]

Toward a human wide axial field of view PET scanner with RPC detectors 08/23 Toward a human wide axial field of view PET scanner with RPC detectors Commercial PET scanner have a reduced Axial Field of View. As a consequence, several bed positions must be acquired in order to obtain a full body image. Moreover, due to the limited axial field of view, a large number of useful events are lost. This process is time consuming, increases the injected activity, and introduces discontinuities in the uptake signal. However, image reconstruction is fairly easy to perform. The scanner consists in a hollow parallelepiped with 4 detection heads Each detection head has a stack of 20 RPC detectors in the radial direction Each detector consists of 2 RPC modules, each with 5 gaps and independent axial electrodes, but sharing a common transaxial electrode

Toward a human wide axial field of view PET scanner with RPC detectors 09/23 Toward a human wide axial field of view PET scanner with RPC detectors Axial direction Transaxial direction Each detector has 10 independent readout sections (a total of 800 independent readout sections for the scanner) with a: 0.2 s non-paralyzable dead time for timing signals (ts) and coarse position readout ps paralyzable dead time (currently 3.0 s) for fine axial and transaxial position readout Fine axial position readout 2400 mm Time and coarse position readout Fine transaxial position readout 1000 mm 1 2 ts (0,2 s) 3 1 Event 1 2 Event 2 1 2 3 ps,1 ps,2+3 ps,2 ps,3 Fine position (3.44 mm pitch in the radial direction and 2 mm pitch in the axial and transaxial directions) Both events rejected or accepted with coarse position (3.44 mm pitch in the radial direction, 30 mm pitch in the transaxial direction, following a 10 mm  Gaussian distribution in the axial direction)

Toward a human wide axial field of view PET scanner with RPC detectors 10/23 Toward a human wide axial field of view PET scanner with RPC detectors [P.Crespo et al., 2012] We also computed the sensitivity according to the NEMA 2001 standards, and found that it could be more than fifty times greater then that achievable with conventional PET scanners

Toward a human wide axial field of view PET scanner with RPC detectors 11/23 Toward a human wide axial field of view PET scanner with RPC detectors Spatial resolution obtained for a 1 m diameter spherical source centered in a 1 mm diameter water sphere DOI + 2.0 mm Binning Mean = 2.1 mm DOI + 1.0 mm Binning Mean = 1.4 mm Only DOI Mean = 0.8 mm [M.Couceiro et al, 2012] We processed data taking into account some possible values for the detector granularity In the first image, only depth of interaction granularity of 3.4 mm was considered, and mean spatial resolution was found to be 0.8 mm. Considering also the readout granularity in a plane parallel to the detector surface, we found a mean spatial resolution of 1.4 mm for a 1.0 mm readout binning, and a mean spatial resolution of 2.1 mm for a readout binning of 2.0 mm. This values are better then those obtained by commercial PET scanners, which are of the order of 3 to 4 mm.

Toward a human wide axial field of view PET scanner with RPC detectors 12/23 Toward a human wide axial field of view PET scanner with RPC detectors Scatter fraction axial profiles (NEMA NU2–2001) 200 mm 700 mm Phantom center Line source with 3.2 mm inside diameter filled with 18F diluted in water (Dimensions in scale) 45 mm Polyethylene

Toward a human wide axial field of view PET scanner with RPC detectors 13/23 Toward a human wide axial field of view PET scanner with RPC detectors NECR – Noise Equivalent Count Rate (NEMA NU2–2001) NECR [kcps] NECR gain Activity concentration [kBq/cm3] 700 mm long phantom 1800 mm long phantom

A full scanner for mice 14/23 Expected quantum efficiency and resolution

15/23 A full scanner for mice Almost finished

Readout meant for accuracy 16/23 A full scanner for mice Readout meant for accuracy DAQ Provided by the HADES DAQ group GSI, IKF (Germany) and JU (Poland). 192 charge amplifiers optimized for large Cin 192 channels 12 bit streaming ADC Digital Pulse Processing by software Few channels of 100ps TDC also used Not so much hardware  low cost

RMS pedestal ~7 ADC units RMS pedestal/strip ~2 ADC units SNR ~ 45 17/23 A full scanner for mice Typical charge spectra with gammas Pedestals (sum of 7 strips with larger signal) Mean Q ~320 ADC units RMS pedestal ~7 ADC units RMS pedestal/strip ~2 ADC units SNR ~ 45 RMS pedestal/strip “TOFtracker” (RPC2012) 36 µm resolution tracking cosmic rays

Resolution tests in simplified geometry 18/23 A full scanner for mice Resolution tests in simplified geometry Two detectors with XY localization Detector a Step Motor Acceptance ±56º Detector b Needle source, 0.2 mm  int. Planar (disk) source

Resolution tests (needle source) 19/23 A full scanner for mice Resolution tests (needle source) Full area, all angles (up to 56º), all gaps (DOI) MLEM reconstruction Reconstructed activity profile across the black line shown in the upper left panel. Resolution ~0.4mm FWHM + background (Note: source is 0.2mm diam.) Joint reconstruction of the source in 2 positions separated by 1mm. ~130k LORs in 3.5M 25m voxels. Color maps: planar profiles including peak density point. Isosufaces: 50% rel. activity

Resolution tests (planar source) 20/23 A full scanner for mice Resolution tests (planar source) Profiles across image (0.5 mm FWHM) 22Na planar source edge-on all angles, all gaps 1mm “mathematical” separation MLEM reconstruction Isosufaces: 50% relative activity

Resolution in final geometry (2 heads only, needle source) 21/23 A full scanner for mice Resolution in final geometry (2 heads only, needle source) X’ PRELIMINARY Calibration not done in full.

22/23 Conclusions RPC–PET is a Falloff of HEP into Nuclear Medicine [Blanco et al. NIMA 2003] Disadvantages in comparison to crystal based detectors Much smaller detection efficiency No energy resolution, although energy sensitivity Advantages Inexpensive Suitable for large area detectors, covering a large solid angle, increasing system sensitivity [Couceiro et al. NIMA 2007, Crespo et al. MIC 2009] Increased position accuracy, allowing full 3D detection, minimizing gross parallax errors Excellent timing resolution of 300 ps FWHM for 511 keV photon pair, allowing TOF-PET Simulation results indicate that RPC detectors may be successfully used in human full–body TOF–PET, outperforming current commercial PET scanners in what concerns sensitivity, spatial resolution and NECR Experimental results for a full mice scanner have shown a high spatial resolution, that outperforms current ones In conclusion RPC-PET is a fallof of high energy physics into Nuclear Medicine, which presents two important disadvantages in comparison to crystal based detectors: - a much smaller detection efficiency - and the lack of energy resolution, although having energy sensitivity However, these drawbacks could be compensated by the fact that RPCs are inexpensive, and suitable for large area detectors, allowing to cover large solid angles, which will increase sensitivity. Besides, RPCs have an increased position accuracy, compared to crystal detectors used in commercial PET scanners, allowing full 3D detection, and minimizing gross parallax errors. RPCs also have good timing resolutions, allowing TOF-PET. Simulations indicate that RPCs may be successfully used in full body TOF PET scanners.

23/23 Acknowledgments The team greatly acknowledge the Laboratory for Advanced Computing of the University of Coimbra for the generous computation time provided in the milipeia cluster. The team also acknowledge to Dr. Miguel Oliveira, formerly in LIPCA and responsible for Coimbra Grid facilities. In conclusion RPC-PET is a fallof of high energy physics into Nuclear Medicine, which presents two important disadvantages in comparison to crystal based detectors: - a much smaller detection efficiency - and the lack of energy resolution, although having energy sensitivity However, these drawbacks could be compensated by the fact that RPCs are inexpensive, and suitable for large area detectors, allowing to cover large solid angles, which will increase sensitivity. Besides, RPCs have an increased position accuracy, compared to crystal detectors used in commercial PET scanners, allowing full 3D detection, and minimizing gross parallax errors. RPCs also have good timing resolutions, allowing TOF-PET. Simulations indicate that RPCs may be successfully used in full body TOF PET scanners.