a liquid xenon Compton camera 3 g medical imaging with a liquid xenon Compton camera and Scandium-44 radionuclide. J.P. Cussonneau on behalf of XEMIS project Subatech (IMT-Atlantique, In2p3/CNRS, Nantes University)

Outline XEMIS project 3γ Imaging XEMIS1: performances XEMIS2: small animal imaging Image - Simulation Conclusion

XEMIS (Xenon Medical Imaging System) (β+, γ) emitter for functional imaging, e.g. 44Sc • Liquid xenon Compton camera Time projection chamber (TPC) - Direct 3D location of the radioactive source - Administered dose reduction &/or shorter acquisition time XEMIS1 R&D XEMIS2 XEMIS3 Human body imaging Small animal imaging 3γ : 20 kBq 100+ times less of injected activity Large field-of-view High sensitivity 30 kg LXe 200 kg LXe

3 imaging with Compton telescope (E1, x1, y1, z1) (E2, x2, y2, z2) LOR θ Δ γ 511keV Compton Telescope  E0 Cone Emitter (β+,γ) Reconstructed  direction Spatial resolution cone axis (∆) Energy resolution opening angle () - Direct 3D location of the radioactive source: res. along LOR ~ 1 cm (FWHM) - Reduction of injected activity: 100 times less Both new radiopharmaceutical and new camera technology !

3g imaging using 44Sc based pharmaceuticals 44Sc is the best candidate β+ 94.3 % γ e+ Emission β+ Emax = 1.474 MeV T1/2 = 4 h Range in H2O ~ 2.8mm B.R. ~ 100% 1.157 MeV  Good for Compton imaging Fast emission Precise time coincidence Production: ARRONAX cyclotron Radiopharmaceutical : CRCINA/INSERM Ready for tests with [44Sc]-DOTA

XEMIS1: Compton camera XEMIS1 is a single phase liquid xenon TPC Field rings XEMIS1 is a single phase liquid xenon TPC PMT 30 kg ultra pure LXe @ -110°C Active volume 2.5 x 2.5 x 12 (or 6) cm3 1” square UV sensitive PMT Segmented anode (2.5 x 2.5 cm2 active) in 64 pixels Frisch grid. Gap 0.5 (or 1) mm Field shaping rings for homogeneous drift field up to 2.5 kV/cm 12 cm Frisch grid Anode

Why liquid xenon? Neon Argon Krypton Xenon LXe provides: Atomic number 10 18 36 54 Density (g/cm3) 1.2 1.4 2.4 3 Boiling Point (K) 27.1 87.3 119.8 165.0 Light yield (UV/MeV) ( ) 30000 40000 25000 42000 Ionization yield (/MeV) ( ) 46000 49000 64000 Decay Time (ns) 10, 15400 6.3, 1500 7.0, 85 2.2 , 27 , 45 Wavelength (nm) 85 128 150 178 J.A. Nikkel et al. 2012 JINST LXe provides: Simpler cryogenics Simultaneous production of a scintillation and an ionization signal Fast decay, high scintillation light yield and high ionization yield

XEMIS1: Time Projection Chamber Particle interaction in the active volume produces prompt scintillation light and ionization electrons Scintillation light (PMT) t0 LXe γ Field rings Cathode Anode PMT LXe PMT Fast scintillation Decay times: 2.2, 27, 45 ns + Cathode Ionization (Frisch grid, Anode, FEE) Energy + (x, y) + t1 LXe λ = 178 nm λ = 178 nm Field rings UV z Vdrift is known ~ 2 mm/ms Z = vdrift.(t1 - t0) Frisch Grid Anode γ Energy + 3D Positions of each interaction z x y

XEMIS1: FEE - Ionization read-out Noise (RMS): 85 +/- 5 e- (@ -100 C ) IDEF-X Asics Developed for CdTe @ IrFU (Gevin et al. 2006) Adapted by Subatech for LXe 511 keV (@1 kV/cm)  27200 e- LXe Anode 64 pixels 3.1 x 3.1 mm2

Ionization : signal @ 511 keV for Photoelectrics 1 ch. = 80 ns c

Ionization : signal @ 511 keV for Compton 1 ch. = 80 ns c

XEMIS1: Ionization results @ 511 keV Energy res.(s)= 4.92 ± 0.04 % @ 1 kV/cm Primary electron E  102 keV thermalization Secondary electrons Tertiary electrons E2 E1 E0 Thomas et al. 1989 Phys. Rev. A Recombination in LXe: E0  5 eV E1  5 keV E2  20 keV Thomas Imel Model is not so good! MC simulations required… NEST/Geant4 M Szydagis et al. 2011 Jinst. , Oct 2011

XEMIS1: Drift time – spatial resolution Photoelectric events @ 511 keV and 1 kV/cm Beginning γ End Drift time resolution: ∼ 50 ns Z resolution: ∼ 100 μm Drift velocity ~ 2 mm/ms

XEMIS1: Angular resolution Acceptance & resolution limited by active area of XEMIS1 Improvement expected at higher electric field XEMIS2 is the key Equivalent to ΔL = 8.2 mm (FWHM) for a 5 cm distant source α 0.75 kV/cm Source: 22Na (E0 = 1.274 MeV) BaF2 BaF2 LXe TPC Gallego et al. NIMA 2015

XEMIS2: Small animals imaging Purification ReStoX XEMIS2 Camera Purification ReStoX XEMIS2 XEMIS2 at Nantes Hospital: 1st image: 1st semester 2018 preclinical researches: until 2020

Install a liquid xenon camera in a hospital ? XEMIS2: ReStoX ReStoX: Recovery and Storage system of Xenon Scientific collaboration: Install a liquid xenon camera in a hospital ? XEMIS2 ReStoX Xenon cryogenics of XEMIS2 : - compact (210 kg capacity) safe (from -110°C to RT) High cooling power LN2(10 kW) ultra clean (~ppb impurities)

XEMIS2 : ReStoX commissioning ~9.5 days In case of LN2 failure, RT should be reached in ~ 1 year

Commissioning: camera filling (XEMIS2 is pre-cooled @ LXe temp.) 125 kg filled in ~ 1 hour at 30 nl/mn thanks to the pump. GXe flows through getters

Commissioning : assisted gravity recovering Bypass of the circulation circuit, direct connection of gaseous phases LN2 valve closed on ReStoX End of LXe Recovering 125 kg LXe recovered in less than 9 mn ! (w/o cooling power)

From XEMIS1 to XEMIS2 XEMIS2: Full liquid xenon cylindrical camera dedicated to small animal imaging Scintillation What we have learnt from XEMIS1: 380 x 1’’ PMTs in LXe LXe: 200 kg cathode - Drift time resolution: < 50 ns - 3D spatial resolution: < 1 mm - Energy resolution (s): ~ 4% @ 511 keV - Very low elec. noise: 85 e- (~ 1.5 keV) - Ionization, attenuation length: > 1 m Field Rings LXe Air 120mm 120mm - Frisch grid / gap properties affect: - Charge collection - Signal shape - Charge and time measurement Vacuum LXe TPC Ionization Active volume ‐ axial : 2 x 12 cm ‐ radius : 7 -> 19 cm - Optimal time and charge measurement → CFD method: XTRACT front-end 2.104 pixels: 3.1 x 3.1 mm

XEMIS2 : DAQ for Ionization IDeF-X HD_LXe Imaging Detector Front-end XTRACT: Xemis TPC Readout for Acquisition of Charge and Time ∼20000 electronic channels Challenge: continuous read-out with negligible dead-time XTRACT v2 for summer 2017

XEMIS2 : ionization DAQ scheme Vacuum LXe Cooled directly by LXe Air PU X 8 IDEF-X XTRAC X 32 XTRACT pixels 6 x FPGA Board 20480 80 LVDS > 2m 8 x 32A 2A+1D 640x Idef-X (32W) 50mW/chip 640x XTRACT (32W) 50mW/Chip 80 x PU (40W) 500mW/PU TIdef-X = -100°C TXtract = -80°C TPU = -30°C Challenge : Continuous read-out with negligible dead-time Goal : record on disc ~104 charge and time signals/pixel/s

XEMIS2: full Gate/Geant4 simulation 3g detection efficiency MOUSE PHANTOM   Cylinder: radius = 2.6 cm length = 12 cm Sphere: radius = 5 mm SOURCE 44Sc Total: 20.0 kBq Hot Sphere: 0.5 kBq Contrast  = 15 XEMIS2 CAMERA TPC active area Radius: 7 -> 19cm Axial length: 24 cm Liquid Xenon Acquisition time : tA = 20 min PMTs Mouse Phantom Cathode Anodes 3g detection efficiency At least 4 Hits in LXe : 1 for each 511 keV photons 2 for 1157 keV photon Phantom length Phantom radius Quite homogeneous !

XEMIS2 image reconstruction 20 kBq, 20 mn Image reconstruction -> Iterative ML-EM assuming Poisson Distribution Reconstructed images @ 23 iterations. Central transverse slices (x,y) Simulated true distribution It’s completely new and it works ! Expected resolution : [2-3 mm] all over the field of view A lot of works for the future …

Conclusion 3g imaging can be a new medical modality thanks to LXe technology. Big challenges and innovations for the design of the camera. XEMIS2 is under construction and will demonstrates the potential of LXe for medical imaging. Expected image qualities are very promising: - very low injected activity, - good spatial resolution all over the FOV, - reduced acquisition time on a large FOV. LXe technology is scalable: design of large whole body camera could be investigated.