Evaluation of Various Scintillator Materials in Radiation Detector Design for Positron Emission Tomography (PET)

Article Evaluation of Various Scintillator Materials in Radiation Detector Design for Positron Emission Tomography (PET)

Siwei Xie 1, Xi Zhang 2, Yibin Zhang 1, Gaoyang Ying 2, Qiu Huang 3, Jianfeng Xu 2,* and Qiyu Peng 1,4,*

1 Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen 518107, China; [email protected] (S.X.); [email protected] (Y.Z.) 2 State Key Lab of Digital Manufacturing Equipment & Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China; [email protected] (X.Z.); [email protected] (G.Y.) 3 School of Biomedical Engineering, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200025, China; [email protected] 4 Department of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Cyclotron Road, Berkeley, CA 94720, USA * Correspondence: [email protected] (J.X.); [email protected] (Q.P.); Tel.: +1-510-486-4422 (Q.P.); Fax: +1-510-486-4422 (Q.P.) Received: 6 August 2020; Accepted: 23 September 2020; Published: 25 September 2020

Abstract: The performance of radiation detectors used in positron-emission tomography (PET) is determined by the intrinsic properties of the scintillators, the geometry and surface treatment of the scintillator crystals and the electrical and optical characteristics of the photosensors. Experimental studies were performed to assess the timing resolution and energy resolution of detectors constructed with samples of different scintillator materials (LaBr3, CeBr3, LFS, LSO, LYSO: Ce, Ca and GAGG) that were fabricated into different shapes with various surface treatments. The saturation correction of SiPMs was applied for tested detectors based on a Tracepro simulation. Overall, we tested 28 pairs of different forms of scintillators to determine the one with the best CTR and light output. Two common high-performance silicon photomultipliers (SiPMs) provided by SensL (J-series, 6 mm) or AdvanSiD (NUV, 6 mm) were used for photodetectors. The PET detector constructed with 6 mm CeBr3 cubes achieved the best CTR with a FWHM of 74 ps. The 4 mm co-doped LYSO: Ce, Ca pyramid crystals achieved 88.1 ps FWHM CTR. The 2 mm, 4 mm and 6 mm 0.2% Ce, 0.1% Ca co-doped LYSO cubes achieved 95.6 ps, 106 ps and 129 ps FWHM CTR, respectively. The scintillator crystals with unpolished surfaces had better timing than those with polished surfaces. The timing resolution was also improved by using certain geometric factors, such as a pyramid shape, to improve light transportation in the scintillator crystals.

Keywords: coincidence timing resolution; positron emission tomography; time of ﬂight; light output; energy resolution; radiation detector

1. Introduction Positron emission tomography (PET) has become commercially available with successful applications in oncology, cardiology and neurology [1,2]. The radiation detector is the core component of any PET system; its performance (timing resolution, depth of interaction measurement, light output, decoding accuracy) determines the performance of the PET system [3–6]. There are continuous eﬀorts to improve the spatial resolution, sensitivity and signal-to-noise ratio (SNR) in the reconstructed

Crystals 2020, 10, 869; doi:10.3390/cryst10100869 www.mdpi.com/journal/crystals Crystals 2020, 10, 869 2 of 15

PET images since improvements in these characteristics could significantly facilitate the clinical and preclinical applications of PET imaging [7–12]. The SNR in conventional PET images are limited by the sensitivity of the scanner. There are two strategies to improve the sensitivity of a PET scanner. The first strategy is to increase the geometric sensitivity of the scanner by increasing its axial extent to achieve total body coverage [13–16]. This strategy not only improves sensitivity, but it also allows the collection of metabolic and chemical target information simultaneously from multiple organs in the body, such as the brain, lungs, heart, liver and kidneys. The second strategy is to incorporate the additional time-of-flight (TOF) information into the reconstruction to increase the effective sensitivity and SNR in the reconstructed images [9,10,17]. The timing resolution of a PET system is largely determined by the performance of the individual detector modules. Many factors may affect the timing resolution of the detector modules, including the structure of detector [18–22], the properties of the scintillator crystal (luminosity and decay time) [23,24]; the optical properties (refractive index and optical attenuation length) of the light guides and coupling materials (air, MeltmountTM, optical glues, etc.) [25]; the surface treatment of the scintillator crystals and light guides (saw-cutting, chemical etching and mechanical polishing to varying degrees); the optical reflectance properties (specular and/or diffuse reflection and spectral reflection coefficient) of the reflectors (Teflon tapes, ESR films, Lumirror films, Tyvek papers, titanium dioxide paint, multilayer dielectric high-reflector coating, etc.); the electric and optical characteristics of the photon detectors (photon detection efficiency, size and fill factor, etc.) [26]; and the performance of the readout electronics (bandwidth, slew rate, signal–noise ratio, etc.) [27,28]. Photonic crystals can change the propagation path of scintillation photons by adding microstructures on the crystal surface, thus improving the time and energy performance of PET detector [29]. Enabled by the developments of lutetium oxyorthosilicate (LSO) and lutetium–yttrium oxyorthosilicate (LYSO) scintillators, all three major PET manufacturers have introduced commercial TOF PET cameras that achieve 200~600 ps full-width half-maximum (FWHM) coincidence timing resolution (CTR). Many studies have indicated that a sub-100 ps CTR is achievable. However, there is no literature reported clinic PET systems with a timing resolution better than 200 ps yet. In order to help break through the barrier, we have performed extensive experimental studies to assess the CTR of PET detectors constructed with samples of different scintillators from different vendors that were fabricated into different shapes with various surface treatments. The basic reasoning of the approach chosen in this study is that the CTR is a function of the photon density detected in the initial moment of an event [20–22]. Hence the CTR can be improved through the enhancement of the light collection efficiency by optimizing the geometry and surface treatment of the scintillator. This article not only describes these studies in much greater detail than we previously presented at the IEEE Nuclear Science Symposium and Medical Imaging Conference [30], but also analyzes the experimental data in depth and compares the performances of the detectors constructed with various scintillator materials, vendors, shapes, surface treatments and silicon photomultipliers systematically. Practical conclusions are drawn, based on the in-depth analyses and the systematic comparisons of the experimental data, to provide a useful guidance to the design of PET detectors with high timing resolution.

2. Materials and Methods

2.1. PET Detector Characterization

2.1.1. Type of Scintillators Twenty-eight pairs of scintillators with various types, sizes, shapes, surface treatments, and manufacturers were tested for the CTR, light output and energy resolution. Six diﬀerent types of scintillator cuboids—including LYSO (Suzhou Jtcrystal, JTC), LFS (Zecotek), LSO (Siemens), GAGG (Kinheng), LaBr3 (Saint Gobain, SG) and CeBr3 (SG)—with various sizes were tested. The coupling surface of the scintillator cubes was polished and the other surfaces were unpolished. As shown in Crystals 2020, 10, x 869 FOR PEER REVIEW 3 of 16 15 surface of the scintillator cubes was polished and the other surfaces were unpolished. As shown in Figure1a, the scintillators were mounted to the center of two SiPMs (MicroFJ-60035-TSV, SensL) with Figure 1a, the scintillators were mounted to the center of two SiPMs (MicroFJ-60035-TSV, SensL) with MeltMount optical glue (refractive index: 1.53). The 6 mm LaBr3 (Saint Gobain, SG) cube and 2 mm MeltMount optical glue (refractive index: 1.53). The 6 mm LaBr3 (Saint Gobain, SG) cube and 2 mm GAGG (Kinheng) cubes are shown in Figure1b,c. The parameters and labels of those crystals are listed GAGG (Kinheng) cubes are shown in Figure 1b,c. The parameters and labels of those crystals are in Table1. listed in Table 1.

(a)

(b) (c)

3 Figure 1. ((aa)) Silicon Silicon photomultipliers (SiPMs)(SiPMs) andand scintillators;scintillators; ( b(b)) packaged packaged 6 6 mm mm LaBr LaBr3 cubes cubes (LaBr-6) (LaBr- 6)crystals; crystals; (c) ( GAGG-2c) GAGG-2 crystals. crystals.

Table 1.1.Parameters Parameters of of the the lutetium–yttrium lutetium–yttrium oxyorthosilicate oxyorthosilicate (LYSO), (LYSO), lutetium lutetium oxyorthosilicate oxyorthosilicate (LSO), LFS, GAGG, LaBr and CeBr crystals. (LSO), LFS, GAGG,3 LaBr3 and3 CeBr3 crystals.

Size (mm) Size (mm) Surface Treatment of No. Labels Labels Crystal Crystal Surface Treatment of Uncoupled Surfaces (L × W × H) (L W H) Uncoupled Surfaces × × 01 LYSOA-4 4 × 4 × 4 01 LYSOA-4 LYSO: 0.2% Ce, 0.1% Ca co-doped 4 4 4 LYSO: 0.2% Ce, 0.1% Ca co-doped × × 0202 LYSOA-6 LYSOA-6 6 × 6 × 6 6 6 6 03 LSO-6L3.7 6 × 6 × 3.7 × × LSO 0403 LSO-6L3.7 LSO-6 6 × 6 × 6 6 6 3.7 LSO × × 0504 LFS-2 LSO-6 2 × 2 × 2 6 6 6 × × Unpolished 0605 LFS-3.7 LFS-2 LFS 3.7 × 3.7 × 3.7 2 2 2 × × Unpolished 0706 LFS-4 LFS-3.7 LFS 4 × 4 × 4 3.7 3.7 3.7 × × 0807 GAGG-2 LFS-4 GAGG 2 × 2 × 2 4 4 4 09 LaBr-6 LaBr3 6 × 6 × 6 × × 08 GAGG-2 GAGG 2 2 2 10 CeBr-6 CeBr3 6 × 6 × 6 × × 09 LaBr-6 LaBr 6 6 6 3 × × 2.1.2.10 Size, Doping CeBr-6 and Surface Treatment CeBr 6 6 6 3 × × Eight pairs of LYSO crystals were tested to study the timing resolutions for different sizes and surface2.1.2. Size, treatments. Doping andThese Surface “label Treatment LYSOA” crystals were made of co-doped LYSO: 0.2% Ce, 0.1% Ca provided by JTC. The parameters of the 4 mm and 6 mm cubes (LYSOA-4 and LYSOA-6) are listed Eight pairs of LYSO crystals were tested to study the timing resolutions for different sizes and in Table 1. The parameters of the other six sample LYSOA crystals are listed in Table 2. Samples surface treatments. These “label LYSOA” crystals were made of co-doped LYSO: 0.2% Ce, 0.1% Ca LYSOA-2 (Figure 2 left), LYSOA-4 (Figure 2 middle), LYSOA-5.5 and LYSOA-6 (Figure 2 right) were provided by JTC. The parameters of the 4 mm and 6 mm cubes (LYSOA-4 and LYSOA-6) are listed in used to compare the timing resolutions of the scintillators of different sized cubes. Samples LYSOA- Table1. The parameters of the other six sample LYSOA crystals are listed in Table2. Samples LYSOA-2 6 and LYSOA-6L3 were used to compare the timing resolutions of the scintillators of different lengths. (Figure2 left), LYSOA-4 (Figure2 middle), LYSOA-5.5 and LYSOA-6 (Figure2 right) were used to These “sample LYSOB” crystals were made of co-doped LYSO: 0.1% Ce, 0.1% Ca provided by compare the timing resolutions of the scintillators of different sized cubes. Samples LYSOA-6 and JTC. Samples LYSOA and LYSOB were used to compare the timing resolutions of the scintillators LYSOA-6L3 were used to compare the timing resolutions of the scintillators of different lengths. with different-doped values, when comparing crystals with the same shape and size (LYSOA-4 to LYSOB-4, LYSOA-6 to LYSOB-6).Similarly, samples LYSOA-6 (LYSOA-4) and LYSOP-6 (LYSOP-4)

Crystals 2020, 10, x FOR PEER REVIEW 4 of 16 were used to compare the timing performance of the crystals of different surface treatments. When testing these 6 mm crystal cubes (LYSOA-6 and LYSOP-6), the bias voltage and trigger level added Crystals 2020, 10, 869 4 of 15 to the Sensl SiPM ranged from 26 V to 32.5 V and 20 mV to 140 mV, respectively.

Table 2. Parameters of the LYSO cubecube crystals.crystals.

SizeSize (mm) (mm) SurfaceSurface Treatment Treatment of of No. No.Label Label Crystal Crystal (L ×(L W ×W H) H) UncoupledUncoupled Surfaces Surfaces × × 01 01LYSOA-2 LYSOA-2 2 × 22 × 22 2 × × 02 02 LYSOA-5.5LYSOA-5.5 LYSO:LYSO: 0.2% 0.2% Ce, Ce, 0.1% Ca 5.5 5.5× 5.5 5.5× 5.5 5.5 × × 03 LYSOA-6L3 co-doped (JTC) 6 6 3 03 LYSOA-6L3 Ca co-doped (JTC) 6 × 6 ×× 3 × Unpolished 04 LYSOA-3L6 3 3 6 Unpolished 04 LYSOA-3L6 3 × 3 ×× 6 × 05 LYSOB-4 LYSO: 0.1% Ce, 0.1% Ca 4 4 4 05 LYSOB-4 LYSO: 0.1% Ce, 0.1% 4 × 4 ×× 4 × 06 LYSOB-6co-doped (JTC) 6 6 6 06 LYSOB-6 Ca co-doped (JTC) 6 × 6 ×× 6 × 07 LYSOP-4 LYSO: 0.2% Ce, 0.1% Ca 4 4 4 07 LYSOP-4 LYSO: 0.2% Ce, 0.1% 4 × 4 ×× 4 × Polished 08 LYSOP-6co-doped (JTC) 6 6 6 Polished 08 LYSOP-6 Ca co-doped (JTC) 6 × 6 ×× 6 ×

Figure 2.2. LYSOLYSO cubes cubes with with sizes sizes of 2of 22 × 2 mm× 2 3mm(left3 (),left 4 ),4 4 ×4 4 mm × 43 (mmmiddle3 (middle) and 6) and6 66 × mm 6 ×3 (6right mm).3 × × × × × × (right). These “sample LYSOB” crystals were made of co-doped LYSO: 0.1% Ce, 0.1% Ca provided by JTC.2.1.3. Samples Shape LYSOA and LYSOB were used to compare the timing resolutions of the scintillators with different-doped values, when comparing crystals with the same shape and size (LYSOA-4 to LYSOB-4, Scintillation crystals were fabricated into different shapes (cubes, cuboids, pyramids and frusta) LYSOA-6 to LYSOB-6).Similarly, samples LYSOA-6 (LYSOA-4) and LYSOP-6 (LYSOP-4) were used to to investigate the effects of geometric shapes on the detector performance. Cuboid-shaped crystals compare the timing performance of the crystals of different surface treatments. When testing these have the disadvantage of requiring most of the photons to be reflected multiple times before being 6 mm crystal cubes (LYSOA-6 and LYSOP-6), the bias voltage and trigger level added to the Sensl SiPM absorbed by the photodetector, which can reduce timing resolution. Therefore, we also designed and ranged from 26 V to 32.5 V and 20 mV to 140 mV, respectively. tested some crystals with a pyramid shape. The scintillating photons reflected from the pyramid 2.1.3.surface Shape will change their flight angle and emit directly to the coupling surface, which may increase the light output and improve timing resolution. Similarly, scintillating photons in a crystal with a zigzagScintillation slope may crystals also be were reflected fabricated by the into slope different and shapesdirectly (cubes, emit to cuboids, the coupling pyramids surface. and frusta) Table to3 investigateshows the theparameters effects of geometricof the six shapesodd-shaped on the detectorscintillation performance. crystals, where Cuboid-shaped LYSOP indicates crystals have the thepyramid-shaped disadvantage crystal, of requiring LYSOH most indicates of the photons the crysta to bel with reflected a pyramid-shaped multiple times top, before LYSOF being indicates absorbed a byfrustum-shaped the photodetector, crystal, which LYSOT can indicates reduce timing a pyramid-shaped resolution. Therefore,top crystal wewith also a sawtooth designed surface and tested and someLYSOTP crystals indicates with athe pyramid crystals shape. with The two scintillating pyramids. photons Figure reflected3a,b show from the the pictures pyramid of surface LYSOF-6, will changeLYSOH-6, their LYSOP-4 flight angle and and LYSOT-6 emit directly and LYSOTP-6 to the coupling crystals, surface, respectively. which may Figure increase 4 shows the light the outputdesign anddimensions improve of timing various resolution. shaped crystals. Similarly, scintillating photons in a crystal with a zigzag slope may also be reflected by the slope and directly emit to the coupling surface. Table3 shows the parameters of the six odd-shaped scintillation crystals, where LYSOP indicates the pyramid-shaped crystal, LYSOH indicates the crystal with a pyramid-shaped top, LYSOF indicates a frustum-shaped crystal, LYSOT indicates a pyramid-shaped top crystal with a sawtooth surface and LYSOTP indicates the crystals with two pyramids. Figure3a,b show the pictures of LYSOF-6, LYSOH-6, LYSOP-4 and LYSOT-6 and LYSOTP-6 crystals, respectively. Figure4 shows the design dimensions of various shaped crystals.

2.1.4. Position and Manufacturer Four pairs of scintillators were tested to investigate differences in boule position and manufacturers. When a crystal is cut from different positions of the scintillator boule, its performance may also be di fferent. Therefore, we tested two 2 mm, 0.2% co-doped LYSO with Ce and Ca crystal cuboids (LYSOAH-2 and LYSOAT-2), which were taken from the tail or head of the same crystal boule. CrystalsCrystals 20202020,, 1010,, xx FORFOR PEERPEER REVIEWREVIEW 55 ofof 1616 Crystals 2020, 10, 869 5 of 15

TableTable 3.3. ParametersParameters ofof thethe odd-shapedodd-shaped LYSOLYSO crystals.crystals. Table 3. Parameters of the odd-shaped LYSO crystals. SurfaceSurface TreatmentTreatment ofof No.No. LabelLabel Crystal Crystal Size Size SurfaceUncoupledUncoupled Treatment SurfacesSurfaces of No. Label Crystal Size 0101 LYSOP-4LYSOP-4 FigureFigure 4a4a Uncoupled Surfaces 02 LYSOP-6 Figure 4b 02 01LYSOP-6 LYSOP-4 FigureFigure 44ba Polished 03 02LYSOH-6 LYSOP-6 LYSO: 0.2% Ce, 0.1% Ca co- Figure Figure 44cb Polished 03 LYSOH-6 LYSO: 0.2% Ce, 0.1% Ca co- Figure 4c Polished 0404 03LYSOF-6LYSOF-6 LYSOH-6 LYSO:dopeddoped 0.2% Ce,(JTC)(JTC) 0.1% Ca Figure Figure Figure 4d44dc 05 04LYSOT-6 LYSOF-6 co-doped (JTC) Figure Figure 44ed 05 LYSOT-6 Figure 4e Unpolished 05 LYSOT-6 Figure4e Unpolished 0606 LYSOTP-6LYSOTP-6 Figure Figure 4f4f Unpolished 06 LYSOTP-6 Figure4f

((aa))

((bb))

FigureFigure 3. 3. ((aa)) LYSOF-6 LYSOF-6 (left), ((left),left), LYSOH-6LYSOH-6 (( middlemiddle)) andand LYSOP-4LYSOP-4 ( (rightright)) crystals; crystals; (( bb)) LYSOT-6LYSOT-6 ( (leftleft)) and and LYSOTP-6LYSOTP-6 ((rightrightright))) crystals.crystals.crystals.

((aa)) ((bb)) ((cc))

((dd)) ((ee)) ((ff)) Figure 4. Shape and size of the odd-shaped scintillator configurations. (a) LYSOP-4 crystal, (b) Figure 4.4.Shape Shape and and size size of theof odd-shapedthe odd-shaped scintillator scintillator conﬁgurations. configurations. (a) LYSOP-4 (a) LYSOP-4 crystal, (bcrystal,) LYSOP-6 (b) LYSOP-6 crystal, (c) LYSOH-6 crystal, (d) LYSOF-6 crystal, (e) LYSOT-6 crystal and (f) LYSOTP-6 crystal,LYSOP-6 (c )crystal, LYSOH-6 (c) crystal,LYSOH-6 (d) crystal, LYSOF-6 (d crystal,) LYSOF-6 (e) LYSOT-6 crystal, ( crystale) LYSOT-6 and (f )crystal LYSOTP-6 and crystal.(f) LYSOTP-6 crystal.crystal.

2.1.4.2.1.4. PositionPosition andand ManufacturerManufacturer

Crystals 2020, 10, x FOR PEER REVIEW 6 of 16

Four pairs of scintillators were tested to investigate differences in boule position and manufacturers. When a crystal is cut from different positions of the scintillator boule, its performance may also be different. Therefore, we tested two 2 mm, 0.2% co-doped LYSO with Ce and Ca crystal cuboids (LYSOAH-2 and LYSOAT-2), which were taken from the tail or head of the same crystal boule. Finally, sample C crystals were made of LYSO crystal provided by SG. These crystals were used to compare the timing resolution of equivalent LYSO crystals from different manufacturers. The parameters of those crystals are listed in Table 4. Crystals 2020, 10, 869 6 of 15

Table 4. Parameters of the LYSO taken from different positions of the crystal boule. Finally, sample C crystals were made of LYSO crystal provided by SG. These crystals were Size (mm) Surface Treatment of Uncoupled No. Label Crystal used to compare the timing resolution of equivalent LYSO(Lcrystals × W × H) from different manufacturers.Surfaces 01 The LYSOAH-2 parameters of 0.2% those Ce crystals co-doped are LYSO listed (from in Tablehead boule)4. 2 × 2 × 2 02 LYSOAT-2 0.2% Ce co-doped LYSO (from tail boule) Unpolished 03 LYSOC-3.7Table 4. Parameters of the LYSO taken from different3.7 positions × 3.7 × 3.7 of the crystal boule. LYSO crystal (SG) 04 LYSOC-5 5 × 5 × 5 Size (mm) Surface Treatment of No. Label Crystal (L W H) Uncoupled Surfaces × × 2.2. Experimental Setting 0.2% Ce co-doped LYSO 01 LYSOAH-2 An experimental system with(from excellent head boule) timing resolution2 2 2was constructed in this study. As 0.2% Ce co-doped LYSO × × 02 LYSOAT-2 Unpolished shown in Figure 5, the system consists(from tail of boule) two PET detectors, a Keithley 2400 source meter, two custom-designed03 LYSOC-3.7amplifier boards, two leading edge discriminators3.7 3.7 3.7 (LEDs), a time-to-amplitude LYSO crystal (SG) × × converter (TAC),04 an LYSOC-5 NI PCI-7833R board and a PC. Each custom-designed 5 5 5 amplifier board split the × × signal from the SiPM into an energy signal and a timing signal and then amplified them. Two stages of current2.2. Experimental feedback Setting amplifiers (AD8000, Analog Devices, Inc.) were used to amplify the timing signals withAn experimentala total gain systemof 200. with The excellent−3 dB bandwidth timing resolution and the was slew constructed rate of inthe this amplifier study. As are shown 1.5 GHz and in4100 Figure V/5μ,s, the respectively. system consists The of two amplified PET detectors, timing a Keithley signals 2400 were source fed meter,to two two LEDs custom-designed (CANBERRA®, Modelamplifier 454). Note boards, that two the leading Model edge 454 discriminatorsis a device with (LEDs), four channels a time-to-amplitude of conventional converter constant (TAC), anfractional NI discriminatorsPCI-7833R board(CFDs). and We a PC.have Each modified custom-designed its internalamplifier circuits and board converted split the the signal four from CFDs the into SiPM LEDs. The intooutputs an energy of the signal LEDs and were a timing fed signalto the and TAC then (ORTEC amplified®, Model them. Two 566), stages which of currentmeasured feedback the time intervalamplifiers between (AD8000, pulses Analog to Devices,its start Inc.) and were stop used inputs to amplify and thegenerated timing signals an analog with a total output gain ofpulse 200. The 3 dB bandwidth and the slew rate of the amplifier are 1.5 GHz and 4100 V/µs, respectively. proportional− to the measured time. The full scale of the TAC was set to 50 ns and the FWHM of the The amplified timing signals were fed to two LEDs (CANBERRA®, Model 454). Note that the Model timing resolution of the Model 566 TAC was 10 ps for all ranges according to the datasheet. The 454 is a device with four channels of conventional constant fractional discriminators (CFDs). We have outputs of the TAC and the amplified energy signals were connected to the NI PCI-7833R board, a modified its internal circuits and converted the four CFDs into LEDs. The outputs of the LEDs were PCI-basedfed to the reconfigurable TAC (ORTEC® I/O, Model device 566), with which a FPGA measured and the eight time analog-to-digital interval between pulses converters to its start on-board. and stopA LabVIEW inputs and program generated was an analogdeveloped output to pulse control proportional the FPGA to to the perform measured event time. triggering The full scale and of read out thethe TACenergy was and set totiming 50 ns andsignals. the FWHM The timing of the timingresolution resolution of the of readout the Model electronics 566 TAC was were 10 calibrated ps for withall pulses ranges generated according from to the a datasheet.signal generator. The outputs The oftiming the TAC resolution and the amplifiedof the readout energy electronic signals were system was connected12.7 ps ± to0.1 the ps NI (mean PCI-7833R ± standard board, a PCI-baseddeviation), reconfigurable which is only I/O deviceslightly with worse a FPGA than and the eight timing resolutionanalog-to-digital of the Model converters 566 TAC. on-board.

FigureFigure 5. Schematic 5. Schematic of of the the experimental experimental setupsetup with with readout readout electronics. electronics.

A LabVIEW program was developed to control the FPGA to perform event triggering and read out the energy and timing signals. The timing resolution of the readout electronics were calibrated with pulses generated from a signal generator. The timing resolution of the readout electronic system was Crystals 2020, 10, 869 7 of 15

12.7 ps 0.1 ps (mean standard deviation), which is only slightly worse than the timing resolution of ± ± the Model 566 TAC. The new high-density (HD) cell SiPM (AdvanSiD) coupled to 6 mm LaBr3 crystal cubes (Table1) was tested at different bias voltages and trigger levels. This is a highly sensitive photon detector in the near-ultraviolet (NUV) and blue light regions. The SiPM size was 6 6 mm2 with 40,000 cells of × 20 20 µm2 cell pitch. The bias voltage and trigger level added to the AdvanSiD SiPM ranged from × 36 V to 39 V and 10 mV to 350 mV, respectively. The bias voltage and trigger level added to the Sensl SiPM ranged from 26 V to 32.5 V and 20 mV to 140 mV, respectively. The energy spectrum and time spectrum of each experiment were recorded. Two detectors using identical scintillator crystal configurations were mounted head-to-head with a 10 mm gap with a 22Na point source (Eckert and Ziegler, 0.74 MBq) centrally located between them for coincidence imaging. Unless otherwise stated, the scintillators were wrapped with the same reflector (Teflon tape), coupled with using the same optical glue (MeltMount) with the same pair of SiPMs (6 mm SensL J-series) and tested with the same readout electronics with identical settings in terms of bias voltage (31.5 V), amplifier gain (200) and trigger level (40 mV). Note that we used MeltMount glue to construct the detectors. Thus, we were able to mount and unmount the scintillators conveniently and use the same pair of SiPMs repeatedly. Approximately one million coincidence events were acquired for each coincidence pair of scintillator crystals within the energy window of 450 keV to 550 keV and were analyzed for the time spectrum and calculation of CTR. The trigger time differs for coincidence events with the same rise time, but different energy peaks. Therefore, the timing measurements were not accurate when the leading-edge discriminator was implemented, especially for the large range of energy windows. Therefore, the energy value of coincidence events was used to correct the time signal. The timing resolution was raised by approximately 10% after compensation. Typically, the FWHM of the peak of the time spectrum was calculated as the timing resolution of the coincidence event.

2.3. Saturation Correction The saturation correction of SiPMs was applied for all the tested detectors based on Tracepro simulation; the correction process is shown in Figure6a. First, the Tracepro was used to optically simulate the interaction of gamma photons in the scintillators, track the scintillation photons and get the simulated light output. The characteristic parameters of those scintillators in the simulation are shown in Table5, which was provided by the vendors. The SiPM has di fferent detection efficiency for photons with different wavelength (λ). In the simulation, when λ is 420 nm, the detection efficiency is up to 52%. Depending on the crystal specifications, scintillation photons from 2300 to 7000 (the area between the two red vertical lines) can eventually reach the coupled SiPM. Second, according to the cross-sectional area of the scintillators, the conversion function between the reached photons number and the detected photons number was obtained through Matlab modeling. The SensL MicroFJ-60035-TSV SiPM has 22,292 microcells. Figure6b shows the conversion function curves when the crystal coupling area are 2 2 mm2, 4 4 mm2 and 6 6 mm2, respectively, taking into × × × account of the influence of the thickness of optical glue (0.1 mm) and protective glass (0.35 mm) on SiPM, corresponding coupling microcells are about 5.8 k, 15.9 k and 22 k, respectively. In the simulation, we assume that the scintillating photons simultaneously reach the avalanche diode in the SiPM. Third, the light output obtained by the Tracepro was converted into the light output actually detected by SiPM through the conversion function. Finally, the uncorrected measured energy spectrum was converted into corrected energy spectrum by matching the peak position of 511 keV with simulated light output. The corrected light outputs and energy resolutions were calculated from the corrected energy spectrum. Crystals 2020, 10, x FOR PEER REVIEW 8 of 16 Crystals 2020, 10, 869 8 of 15 Crystals 2020, 10, x FOR PEER REVIEW 8 of 16

(a()a ) (b()b )

FigureFigure 6. 6. (a ()a )Flowchart Flowchart of of thethe saturationsaturation correction;correction; ( b(b) )conversion conversion function. function. Figure 6. (a) Flowchart of the saturation correction; (b) conversion function.

TableTableTable 5. 5. 5. CharacteristicCharacteristic Characteristic parameters ofof of the the the tested tested tested crystals. crystals. crystals. PeakPeak Emission Emission Refractive DecayDecay Time Time AbsoluteAbsolute Light Light Output Output CrystalCrystal Peak Emission Absolute Light Output Crystal Refractive Index Decay Time (ns) 3 3 WavelengthWavelengthWavelength (nm) (nm) (nm) Index (ns)(ns) (10(10(10 Photon/MeV) 3Photon/MeV)Photon/MeV) 0.2%0.2% co-doped co-doped LYSO LYSO 420 420 1.82 35 35 32 32 0.2% co-doped LYSO 420 1.82 35 32 0.1%0.1% co-doped co-doped LYSO LYSO 420 420 1.82 41 41 39 39 0.1% co-doped LYSO 420 1.82 41 39 LFS 420 1.82 35 38 LFSLFS 420420 1.821.82 35 3538 38 LSOLSOLSO 420420420 1.821.82 4040 4030 30 30 GAGGGAGGGAGG 530530530 1.91.9 5050 5032 32 32 LaBr3 370 1.9 16 60 LaBrLaBr3 3 370370 1.91.9 1616 60 60 CeBr3 380 1.9 17 68 CeBrCeBr3 3 380380 1.91.9 1717 68 68

3. Results 3.3. Results Results 3.1. Photodetectors 3.1.3.1. Photodetectors Photodetectors First, we compared the performance of the 6 mm SensL J-series SiPMs (Figure 7a) with the 6 mm First, we compared the performance of the 6 mm SensL J-series SiPMs (Figure 7a) with the 6 mm AdvanSiDFirst, we comparedNUV SiPMs the (Figure performance 7b) by using of the a pair 6 mm of 6 SensL mm LaBr J-series3 cubes SiPMs (LaBr-6). (Figure The7 FWHMa) with CTRs the 6 mm AdvanSiDAdvanSiDwere represented NUV NUV SiPMs SiPMs by the (Figure (Figure colors7 b) 7b)and by by contour using using alines.a pairpair The ofof 66SensL mmmm LaBrSiPM3 3withoutcubescubes (LaBr-6). time (LaBr-6). walk The compensation The FWHM FWHM CTRs CTRs werewereachieved represented represented its best by bycoincidence the the colors colors timing andand contourcontour resolution lines. of 77 The The ps SensLFWHM SensL SiPM SiPMwhen without the without bias timevoltage time walk walk was compensation 31.5 compensation V and achievedachievedthe trigger its its best best level coincidencecoincidence was 40 mV. Similarly,timing timing resolution resolution the AdvanSiD of of77 77SiPMps FWHM ps without FWHM when time when the walk bias the compensation voltage bias voltage was achieved 31.5 was V and 31.5 V andtheits the trigger best trigger CTR level of level was 75 ps 40 was FWHM mV. 40 Similarly,mV. when Similarly, the the bias AdvanSiD voltag the AdvanSiDe was SiPM 38.5 without V SiPMand the time without trigger walk level timecompensation was walk 75 mV. compensation achieved These achievedits resultsbest CTR its showed best of 75 CTR thatps FWHM the of 75two ps when SiPMs FWHM the had bias whenno voltagsignificant thee biaswas differences 38.5 voltage V and wasin the timing 38.5 trigger resolution. V andlevel the was Therefore, trigger 75 mV. level Thesethe was results showed that the two SiPMs had no significant differences in timing resolution. Therefore, the 75 mV.6 mm These SensL results SiPMs showed were used that in all the of two the SiPMstests described had no below. signiﬁcant diﬀerences in timing resolution. 6 mm SensL SiPMs were used in all of the tests described below. Therefore, the 6 mm SensL SiPMs were used in all of the tests described below.

(a) (b) Figure 7. Contour plots(a) of the FWHM CTR. (a) SensL J-series SiPMs; (b) AdvanSiD(b) NUV HD SiPMs.

FigureFigure 7. 7.Contour Contour plotsplots ofof thethe FWHM CTR. ( (aa)) SensL SensL J-series J-series SiPMs; SiPMs; (b ()b AdvanSiD) AdvanSiD NUV NUV HD HD SiPMs. SiPMs.

Crystals 2020, 10, x FOR PEER REVIEW 9 of 16

3.2. Surface Treatment LYSO samples LYSOA-6 and LYSOP-6 were used to compare the timing resolution of the crystals of different surface treatments. For these tests, the bias voltage and trigger level added to the Crystals 2020, 10, 869 9 of 15 SiPM ranged from 26 V to 32.5 V and 20 mV to 140 mV, respectively. The best CTR of the polished crystal was 146 ps with a bias voltage of 31 V and a trigger level of 40 mV (Figure 8a). The best CTR of3.2. the Surface unpolished Treatment crystal was 129 ps with a bias voltage of 31.5 V and a trigger level of 40 mV (Figure 8b). Clearly, the timing resolution of the unpolished crystal is better than that of the polished crystal, LYSO samples LYSOA-6 and LYSOP-6 were used to compare the timing resolution of the crystals regardless of the bias voltage and the trigger level. When the cubic crystal surface is absolutely of diﬀerent surface treatments. For these tests, the bias voltage and trigger level added to the SiPM smooth, nearly half of the scintillating photons are not received by the SiPM due to total internal ranged from 26 V to 32.5 V and 20 mV to 140 mV, respectively. The best CTR of the polished crystal reflection (TIR). In contrast, the unpolished surface can change the flight angle of the scintillating was 146 ps with a bias voltage of 31 V and a trigger level of 40 mV (Figure8a). The best CTR of the photons, thereby breaking the limit of the TIR and increasing the light output and timing resolution. unpolished crystal was 129 ps with a bias voltage of 31.5 V and a trigger level of 40 mV (Figure8b).

(a) (b)

Figure 8. 8. ContourContour plots plots of ofthe the FWHM FWHM CTR CTR of 0.2% of 0.2% co-doped co-doped LYSO. LYSO. (a) Polished (a) Polished crystal; crystal; (b) unpolished(b) unpolished crystal. crystal.

3.3. TimingClearly, and the Energy timing resolution of the unpolished crystal is better than that of the polished crystal, regardless of the bias voltage and the trigger level. When the cubic crystal surface is absolutely 3.3.1.smooth, Type nearly of Scintillators half of the scintillating photons are not received by the SiPM due to total internal reflection (TIR). In contrast, the unpolished surface can change the flight angle of the scintillating The cubic crystals listed in Tables 1 and 2 were used to investigate how the CTR varied with the photons, thereby breaking the limit of the TIR and increasing the light output and timing resolution. scintillator material. The CTRs of those cubic crystals are shown in Figure 9a. The timing resolution of3.3. the Timing halogen and crystal Energy (LaBr-6:77 ps, CeBr-6:74 ps) was the best as shown in Figure 9b and the GAGG crystal (193 ps) was the worst. The timing resolution of the other crystals were at the same level. In detail,3.3.1. Typethe CTRs of Scintillators of LFS-2, LFS-3.7 and LFS-4 were 119 ps, 126.4 ps and 142.8 ps, respectively, which was worse than those of the 0.2% Ce, 0.1% Ca co-doped LYSO for the same size. The CTRs of LYSO- The cubic crystals listed in Tables1 and2 were used to investigate how the CTR varied with the 3.7 (SG), LYSO-5 (SG) and LSO-6 were 110.1 ps, 126.7 ps and 132.9 ps, respectively. In general, the scintillator material. The CTRs of those cubic crystals are shown in Figure9a. The timing resolution of larger the cubic crystal, the worse the timing resolution tends to be. The relative light outputs and the halogen crystal (LaBr-6:77 ps, CeBr-6:74 ps) was the best as shown in Figure9b and the GAGG crystal energy resolutions of cubic crystals with the same surface treatments are shown in Figure 9c,d with (193 ps) was the worst. The timing resolution of the other crystals were at the same level. In detail, corrected for saturation effects of SiPMs. The light output of the 4 mm 0.2% co-doped LYSO cubic the CTRs of LFS-2, LFS-3.7 and LFS-4 were 119 ps, 126.4 ps and 142.8 ps, respectively, which was (LYSOA-4) crystal was used as a reference and it was set to 100%. Similar, the larger the cubic crystal, worse than those of the 0.2% Ce, 0.1% Ca co-doped LYSO for the same size. The CTRs of LYSO-3.7 the worse the light output tend to be. (SG), LYSO-5 (SG) and LSO-6 were 110.1 ps, 126.7 ps and 132.9 ps, respectively. In general, the larger the cubic crystal, the worse the timing resolution tends to be. The relative light outputs and energy resolutions of cubic crystals with the same surface treatments are shown in Figure9c,d with corrected for saturation effects of SiPMs. The light output of the 4 mm 0.2% co-doped LYSO cubic (LYSOA-4) crystal was used as a reference and it was set to 100%. Similar, the larger the cubic crystal, the worse the light output tend to be.

3.3.2. Size, Doping and Surface Treatment Figure 10a shows the CTR for the cuboid-shaped LYSO crystals listed in Table2. Investigating the size of the crystal cubes, the CTR of the 2 mm cube crystal was better than that of the 6 mm cube crystal and the CTRs of the 4 mm cube crystals were in between (Figure 10a). In long crystals, the time distribution of the photons (particularly the ﬁrst photons) reaching the photodetector is wider, due to a larger distribution of the photon pathways. Thus, larger time jitters were introduced in the long crystals. Consistently, the larger the scintillator, the lower the light output (Figure 10b). The 4 mm cubic crystal achieved the best energy resolution as shown in Figure 10c. Crystals 2020, 10, x FOR PEER REVIEW 10 of 16

3.3. Timing and Energy

3.3.1. Type of Scintillators The cubic crystals listed in Tables 1 and 2 were used to investigate how the CTR varied with the scintillator material. The CTRs of those cubic crystals are shown in Figure 9a. The timing resolution of the halogen crystal (LaBr-6:77 ps, CeBr-6:74 ps) was the best as shown in Figure 9b and the GAGG crystal (193 ps) was the worst. The timing resolution of the other crystals were at the same level. In detail, the CTRs of LFS-2, LFS-3.7 and LFS-4 were 119 ps, 126.4 ps and 142.8 ps, respectively, which was worse than those of the 0.2% Ce, 0.1% Ca co-doped LYSO for the same size. The CTRs of LYSO- 3.7 (SG), LYSO-5 (SG) and LSO-6 were 110.1 ps, 126.7 ps and 132.9 ps, respectively. In general, the larger the cubic crystal, the worse the timing resolution tends to be. The relative light outputs and energy resolutions of cubic crystals with the same surface treatments are shown in Figure 9c,d with corrected for saturation effects of SiPMs. The light output of the 4 mm 0.2% co-doped LYSO cubic (LYSOA-4) crystal was used as a reference and it was set to 100%. Similar, the larger the cubic crystal, Crystalsthe2020 worse, 10, 869 the light output tend to be. 10 of 15

(a) (c)

(d)

FigureFigure 9. (a )9. CTR (a) CTR values, values (b, ()b time) time spectrum spectrum of of the the 6 6mm mm Ce CeBrBr3 cube3 cube;; (c) relative (c) relative light outputs light outputs and (d) and (d) energyenergy resolutions resolutions ofof cubic crystal. crystal. Crystals 2020, 10, x FOR PEER REVIEW 11 of 16 3.1.2. Size, Doping and Surface Treatment Figure 10a shows the CTR for the cuboid-shaped LYSO crystals listed in Table 2. Investigating the size of the crystal cubes, the CTR of the 2 mm cube crystal was better than that of the 6 mm cube crystal and the CTRs of the 4 mm cube crystals were in between (Figure 10a). In long crystals, the time distribution of the photons (particularly the first photons) reaching the photodetector is wider, due to a larger distribution of the photon pathways. Thus, larger time jitters were introduced in the long crystals. Consistently, the larger the scintillator, the lower the light output (Figure 10b). The 4 mm cubic crystal achieved the best energy resolution as shown in Figure 10c.

(a) (b)

(c)

Figure 10.Figure(a) CTRs, 10. (a) ( bCTRs,) relative (b) relative light light outputs outputs and and (c )(c energy) energy resolutions of of2 mm, 2 mm, 4 mm 4 mmand 6 and mm 6 mm side side LYSO cubes crystal. LYSO cubes crystal. Investigating the size of the rectangular-prism crystals, the CTRs of LYSOA-6L3, LYSOA-3L6 and LSO-6L3.7 were 119 ps, 128.4 ps and 127.8 ps, respectively. By comparing LYSOA-6L3 and LYSOA-6, it can be inferred that a short crystal length can achieve a better timing resolution when the cross section is the same.

3.3.3. Shape The CTR and relative light output of six types of odd-shaped 0.2% co-doped LYSO crystals (LYSOH-6, LYSOP-4, LYSOF-6, LYSOP-6, LYSOT-6, LYSOTP-6) are shown in Figure 11a. The CTR and light output of the LYSOP-4 and LYSOP-6 crystals were better than those of the reference sample LYSOA-6 crystal, which illustrates that the tapered structure may contribute to improve timing resolution and light output. However, the performance of several other odd-shaped crystals (LYSOF- 6, LYSOH-6, LYSOT-6, LYSOTP-6) were on the same level as the 6 mm crystal cube. The typical time spectrum of the LYSOP-4 crystal is shown in Figure 11b.

Crystals 2020, 10, 869 11 of 15

Investigating the doping and surface treatment, the timing resolution of the 0.2% Ce co-doped LYSO crystals (LYSOA-4 and LYSOA-6) were better than that of the matching 0.1% Ce co-doped LYSO crystals (LYSOB-4 and LYSOB-6). However, the light output of the 0.2% Ce co-doped crystals were lower than that of 0.1% Ce co-doped LYSO crystals. The energy resolution of the 0.2% Ce co-doped LYSO were similar with that of 0.1% Ce co-doped LYSO crystals. In addition, the unpolished 4 mm and 6 mm crystal cubes (LYSOA-4 and LYSOA-6, the black line in Figure 10a,b) had better light output and timing performance than that of the equivalent polished crystals (LYSOP-4 and LYSOP-6, the red line in Figure 10a,b). Investigating the size of the rectangular-prism crystals, the CTRs of LYSOA-6L3, LYSOA-3L6 and LSO-6L3.7 were 119 ps, 128.4 ps and 127.8 ps, respectively. By comparing LYSOA-6L3 and LYSOA-6, it can be inferred that a short crystal length can achieve a better timing resolution when the cross section is the same.

3.3.3. Shape The CTR and relative light output of six types of odd-shaped 0.2% co-doped LYSO crystals (LYSOH-6, LYSOP-4, LYSOF-6, LYSOP-6, LYSOT-6, LYSOTP-6) are shown in Figure 11a. The CTR and light output of the LYSOP-4 and LYSOP-6 crystals were better than those of the reference sample LYSOA-6 crystal, which illustrates that the tapered structure may contribute to improve timing resolution and light output. However, the performance of several other odd-shaped crystals (LYSOF-6, LYSOH-6, LYSOT-6, LYSOTP-6) were on the same level as the 6 mm crystal cube. The typical time Crystalsspectrum 2020, 10, ofx FOR the LYSOP-4PEER REVIEW crystal is shown in Figure 11b. 12 of 16

FigureFigure 11. ( 11.a) CTR(a) CTR and and the the relative relative light light output output of sixsix typestypes of of odd odd crystals crystals (blue (blue points); points); (b) time(b) time spectrumspectrum of LYSOP-4. of LYSOP-4. 3.3.4. Position and Manufacturer 3.3.4. Position and Manufacturer Investigating the scintillator manufacturers, the CTRs of the cubic crystals LYSOC-3.7 and LYSOC-5.5Investigating supplied the scintillator by SG were manufacturers, 110.1 ps and 126.7 the ps, CTRs respectively. of the Thiscubic result crystals conﬁrms LYSOC-3.7 that the and LYSOC-5.5smaller thesupplied crystal cube,by SG the were better 110.1 the timing ps and resolution. 126.7 ps, The respectively. crystal was at This the same result level confirms as the timing that the smallerresolution the crystal and light cube, output the ofbetter the crystal the timing provided resolution. by JTC. The crystal was at the same level as the timing resolutionInvestigating and the light position output of theof the crystal crystal within provided the boule, by the JTC. CTRs of LYSOAH-2 and LYSOAT-2 wereInvestigating 110.2 ps and the 99.1 position ps, respectively. of the crystal These within crystals the were boule, taken the from CTRs diﬀ erentof LYSOAH-2 positions of and the LYSOAT- same 2 werecrystal 110.2 boule, ps and which 99.1 shows ps, respectively. that crystal taken These from crystals the tail were of the taken crystal from boule different may achieve positions a better of the sametiming crystal resolution. boule, which shows that crystal taken from the tail of the crystal boule may achieve a better timing resolution.

Table 6. Testing results of all the scintillator detectors.

Relative Surface Cube Size (mm) Energy CTR No. Label Light Treatment (L × W× H) Resolution (ps) Output 1 LYSOA-4 4 × 4 × 4 8.4% 1 106 2 LYSOA-6 6 × 6 × 6 8.9% 0.88 129 3 LSO-6L3.7 6 × 6 × 3.7 10.7% 0.88 127.8 4 LSO-6 6 × 6 × 6 10.4% 0.85 132.9 5 LFS-2 Unpolished 2 × 2 × 2 12.5% 1.14 119 6 LFS-3.7 3.7 × 3.7 × 3.7 8.9% 1.04 126.4 7 LFS-4 4 × 4 × 4 10.2% 0.93 142.8 8 GAGG-2 2 × 2 × 2 10.7% 0.65 193 9 LaBr-6 6 × 6 × 6 6.4% 1.75 77

Crystals 2020, 10, 869 12 of 15

4. Summary and Discussion The CTRs, corrected energy resolution and corrected relative light outputs of the tested scintillator detectors are summarized in Table6. The sample CeBr-6 achieved the best CTR (74 ps) and the GAGG-2 crystal achieved the worst CTR (193 ps). The LaBr-6 crystal achieved the best relative light output (1.75) and the GAGG-2 crystal achieved the worst relative light output (0.65). The LaBr-6 crystal achieved the best energy resolution (6.4%) and the LYSOTP-6 crystal achieved the worst energy resolution (12.9%). Figure 12 shows a comparison of the CTR and the light output for all of test crystals except LaBr-6 and CeBr-6. There is a general trend, that the larger the light output of the crystal, the better the time performance. The timing resolution and light output of several rhenium silicate-based crystals (LYSO, LFS, LFS, etc.) are at the same level. The CTR of the 2 mm GAGG cubes was 193 ps. However, we note that the SensL SiPM had a much lower photon detection efficiency (PDE) for 530 nm compared to that for 420 nm. Thus, the measured light output from GAGG was 47% lower than that of LYSO. According to the relationship between the CTR and the light output of the crystal, the CTR of the 2 mm GAGG cubes improves to 117 ps if the effect of the low PDE for 530 nm was compensated. The idea for an odd-shaped crystal came from the study of photonics crystals, which are a kind of micronano structure on the crystal surface that guides and controls the propagation of scintillating photons to increase the light output and time performance of the detector. The macroscopic structure does not meet the expectations, but it is possible when the profiled structure is on the nanometer scale.

Table 6. Testing results of all the scintillator detectors.

Surface Cube Size (mm) Energy Relative Light No. Label CTR (ps) Treatment (L W H) Resolution Output × × 1 LYSOA-4 4 4 4 8.4% 1 106 × × 2 LYSOA-6 6 6 6 8.9% 0.88 129 × × 3 LSO-6L3.7 6 6 3.7 10.7% 0.88 127.8 × × 4 LSO-6 6 6 6 10.4% 0.85 132.9 × × 5 LFS-2 2 2 2 12.5% 1.14 119 Unpolished × × 6 LFS-3.7 3.7 3.7 3.7 8.9% 1.04 126.4 × × 7 LFS-4 4 4 4 10.2% 0.93 142.8 × × 8 GAGG-2 2 2 2 10.7% 0.65 193 × × 9 LaBr-6 6 6 6 6.4% 1.75 77 × × 10 CeBr-6 6 6 6 NA NA 74 × × 11 LYSOA-2 2 2 2 11.8% 1.03 95.6 × × 12 LYSOA-5.5 5.5 5.5 5.5 8.4% 0.87 127 × × 13 LYSOA-6L3 6 6 3 9.8% 0.78 119 Unpolished × × 14 LYSOA-3L6 3 3 6 9.5% 0.94 128.4 × × 15 LYSOB-4 4 4 4 8.7% 1.14 127.1 × × 16 LYSOB-6 6 6 6 9.7% 1.01 138.9 × × 17 LYSO-P4 4 4 4 7.8% 0.90 124 Polished × × 18 LYSO-P6 6 6 6 8.3% 0.82 146 × × 19 LYSOP-4 Figure4a 7.6% 1.21 88.1 20 LYSOP-6 Figure4b 7.7% 1.25 94.5 21 LYSOH-6 Figure4c 10.8% 0.83 131.5 Polished 22 LYSOF-6 Figure4d 11.2% 0.83 125.8 23 LYSOT-6 Figure4e 10.6% 0.79 165 24 LYSOTP-6 Figure4f 12.9% 0.83 187.6 25 LYSOAH-2 2 2 2 12.2% 0.98 110.2 × × 26 LYSOAT-2 2 2 2 12.9% 0.92 99.1 Unpolished × × 27 LYSOC-3.7 3.7 3.7 3.7 10.6% 0.98 110.1 × × 28 LYSOC-5 5 5 5 9.9% 0.89 126.7 × × Crystals 2020, 10, x FOR PEER REVIEW 13 of 16

10 CeBr-6 6 × 6 × 6 NA NA 74 11 LYSOA-2 2 × 2 × 2 11.8% 1.03 95.6 12 LYSOA-5.5 5.5 × 5.5 × 5.5 8.4% 0.87 127 13 LYSOA-6L3 6 × 6 × 3 9.8% 0.78 119 Unpolished 14 LYSOA-3L6 3 × 3 × 6 9.5% 0.94 128.4 15 LYSOB-4 4 × 4 × 4 8.7% 1.14 127.1 16 LYSOB-6 6 × 6 × 6 9.7% 1.01 138.9 17 LYSO-P4 4 × 4 × 4 7.8% 0.90 124 Polished 18 LYSO-P6 6 × 6 × 6 8.3% 0.82 146 19 LYSOP-4 Figure 4a 7.6% 1.21 88.1 20 LYSOP-6 Figure 4b 7.7% 1.25 94.5 21 LYSOH-6 Figure 4c 10.8% 0.83 131.5 Polished 22 LYSOF-6 Figure 4d 11.2% 0.83 125.8 23 LYSOT-6 Figure 4e 10.6% 0.79 165 24 LYSOTP-6 Figure 4f 12.9% 0.83 187.6 25 LYSOAH-2 2 × 2 × 2 12.2% 0.98 110.2 26 LYSOAT-2 2 × 2 × 2 12.9% 0.92 99.1 Unpolished Crystals 2020, 1027, 869 LYSOC-3.7 3.7 × 3.7 × 3.7 10.6% 0.98 110.1 13 of 15 28 LYSOC-5 5 × 5 × 5 9.9% 0.89 126.7

Figure 12. Comparison of the CTR and corrected light output for tested crystals. Figure 12. Comparison of the CTR and corrected light output for tested crystals. The CTR of the 2 mm GAGG cubes was 193 ps. However, we note that the SensL SiPM had a In thismuch study, lower the photon number detection of samples efficiency for (PDE) all conﬁgurationsfor 530 nm compared is small, to that andfor 420 some nm. resultsThus, the may not be representative. Especially when the crystals were taken from diﬀerent positions of the crystal boule

(LYSOAH-2 and LYSOAT-2), the diﬀerence of CTR may not be as big as tested. The sensitivity of the PET scanners is related to the length of the crystal. In a typical commercial PET scanner, the length of the crystal is approximately 20 mm. It is possible to build a TOF-PET detector with three layers of scintillators. While the detector meets the sensitivity requirements of the PET scanner, the measured CTRs are expected to drop below 70 ps.

5. Conclusions In summary, we can conclude from the testing results that: (1) a 74 ps FWHM CTR was measured with a pair of 6 mm side CeBr3 cubes. It is possible to achieve a CTR below 50 ps if the PET detector is constructed by smaller LaBr3 crystals; (2) an 88.1 ps FWHM CTR was measured with a pair of 4 mm LYSO: Ce, Ca pyramids, which shows that a change in the shape of the crystal can improve the timing resolution; (3) the two SiPMs from SensL and AdvanSiD have no significant differences with respect to timing resolutions; (4) the crystals with unpolished surfaces have better timing than those with polished surfaces; (5) LYSO: Ce, Ca from different venders and LSO from Siemens have similar performances; (6) 0.2% co-doped LYSO crystals have a better CTR than that of 0.1% Ce co-doped LYSO; (7) 0.2% co-doped LYSO crystals have a better timing resolution than that of LFS; (8) the CTR measurements are related to the size of the crystals. The 2 mm crystals have better timing than 4 mm crystals and the 4 mm crystals have better timing than 6 mm crystals. The conclusions drawn from these experimental studies provide some practical guidance in terms of the design of PET detectors with high timing resolution. However, many other practical factors, including costs, detector efficiency or stopping power, accuracy of the decoding of the positions of gamma interaction and effects of Compton scatters, need to be considered and carefully balanced, Crystals 2020, 10, 869 14 of 15 when designing PET detectors for different applications such as the whole-body imaging and the organ-specific imaging.

Author Contributions: Conceptualization, Q.P. and S.X.; methodology, X.Z.; formal analysis, Y.Z.; investigation, G.Y.; data curation, Q.H.; writing—original draft preparation, S.X.; writing—review and editing, J.X.; funding acquisition, Q.P. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by National Natural Science Foundation of China (grant number 51627807), the 111 Project (grant number B16019), Hubei International Cooperation Project (grant number 2018AHB001) and the National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering (grant number R01EB006085). The APC was funded by Shenzhen Bay Laboratory. Conﬂicts of Interest: The authors declare no conﬂict of interest.

References

1. Hoh, C.K. Clinical use of FDG PET. Nucl. Med. Boil. 2007, 34, 737–742. [CrossRef] 2. Kitson, S.L.; Cuccurullo, V.; Ciarmiello, A.; Salvo, D.; Mansi, L. Clinical applications of positron emission tomography (PET) imaging in medicine: Oncology, brain diseases and cardiology. Curr. Radiopharm. 2009, 2, 224–253. [CrossRef] 3. Lamprou, E.; Gonzalez, A.J.; Sanchez, F.; Benlloch, J.M. Exploring TOF capabilities of PET detector blocks based on large monolithic crystals and analog SiPMs. Phys. Med. 2020, 70, 10–18. [CrossRef][PubMed] 4. Xie, S.; Zhang, X.; Peng, H.; Yang, J.; Huang, Q.; Xu, J.; Peng, Q. PET detectors with 127 ps CTR for the Tachyon-II time-of-flight PET scanner. Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 2019, 933, 48–55. [CrossRef] 5. Alekhin, M.S.; De Haas, J.T.M.; Khodyuk, I.V.; Krämer, K.W.; Menge, P.R.; Ouspenski, V.; Dorenbos, P. 3+ 2+ 2+ Improvement of γ-ray energy resolution of LaBr3: Ce scintillation detectors by Sr and Ca co-doping. Appl. Phys. Lett. 2013, 102, 161915. [CrossRef] 6. Gundacker, S.; Acerbi, F.; Auffray, E.; Ferri, A.; Gola, A.; Nemallapudi, M.V.; Paternoster, G.; Piemonte, C.; Lecoq, P. State of the art timing in TOF-PET detectors with LuAG, GAGG and L(Y)SO scintillators of various sizes coupled to FBK-SiPMs. J. Instrum. 2016, 11, P08008. [CrossRef] 7. Conti, M. State of the art and challenges of time-of-flight PET. Phys. Med. 2009, 25, 1–11. [CrossRef] 8. Moses, W.W. Recent advances and future advances in time-of-flight PET. Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 2007, 580, 919–924. [CrossRef] 9. Surti, S.; Karp, J.S. Advances in time-of-flight PET. Phys. Med. 2016, 32, 12–22. [CrossRef] 10. Conti, M.; Bendriem, B. The new opportunities for high time resolution clinical TOF PET. Clin. Transl. Imaging 2019, 7, 139–147. [CrossRef] 11. Hsu, D.F.C.; Ilan, E.; Peterson, W.T.; Uribe, J.; Lubberink, M.; Levin, C.S. Studies of a next-generation silicon-photomultiplier–based time-of-flight PET/CT system. J. Nucl. Med. 2017, 58, 1511–1518. [CrossRef] [PubMed] 12. Vandenberghe, S. [I180] Recent developments in time-of-flight PET. Phys. Med. Eur. J. Med. Phys. 2018, 52, 69. [CrossRef] 13. Lyu, Y.; Lv, X.; Liu, W.; Judenhofer, M.S.; Zwingenberger, A.; Wisner, E.R.; Berg, E.; McKenney, S.E.; Leung, E.K.; Spencer, B.A.; et al. Mini EXPLORER II: A prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning. Phys. Med. Boil. 2019, 64, 075004. [CrossRef] 14. Zhang, X.; Zhou, J.; Cherry, S.R.; Badawi, R.D.; Qi, J. Quantitative image reconstruction for total-body PET imaging using the 2-meter long EXPLORER scanner. Phys. Med. Boil. 2017, 62, 2465–2485. [CrossRef] 15. Badawi, R.D.; Shi, H.; Hu, P.; Chen, S.; Xu, T.; Price, P.M.; Ding, Y.; Spencer, B.A.; Nardo, L.; Liu, W.; et al. First human imaging studies with the EXPLORER total-body PET scanner. J. Nucl. Med. 2019, 60, 299–303. [CrossRef] 16. Cherry, S.R.; Jones, T.; Karp, J.S.; Qi, J.; Moses, W.W.; Badawi, R.D. Total-body PET: Maximizing sensitivity to create new opportunities for clinical research and patient care. J. Nucl. Med. 2017, 59, 3–12. [CrossRef] 17. Lecoq, P. Pushing the limits in time-of-flight PET imaging. IEEE Trans. Radiat. Plasma Med. Sci. 2017, 1, 473–485. [CrossRef] 18. Guo, L.; Tian, J.; Chen, P.; Derenzo, S.E.; Choong, W.-S. Improving timing performance of double-ended readout in TOF-PET detectors. J. Instrum. 2020, 15, P01003. [CrossRef] Crystals 2020, 10, 869 15 of 15

19. Gundacker, S.; Knapitsch, A.; Auffray, E.; Jarron, P.; Meyer, T.; Lecoq, P. Time resolution deterioration with increasing crystal length in a TOF-PET system. Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 2014, 737, 92–100. [CrossRef] 20. Carrier, C.; LeComte, R. Effect of geometrical modifications and crystal defects on light collection in ideal rectangular parallelepipedic BGO scintillators. Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 1990, 294, 355–364. [CrossRef] 21. Huber, J.S.; Moses, W.W.; Andreaco, M.S.; Loope, M.; Melcher, C.L.; Nutt, R. Geometry and surface treatment dependence of the light collection from LSO crystals. Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 1999, 437, 374–380. [CrossRef] 22. Danevich, F.A.; Kobychev, V.V.; Kobychev, R.V.; Kraus, H.; Mikhailik, V.B.; Mokina, V.M.; Solsky, I.M. Impact of geometry on light collection efficiency of scintillation detectors for cryogenic rare event searches. Nucl. Instrum. Methods Phys. Res. Sect. B Beam Interact. Mater. At. 2014, 336, 26–30. [CrossRef] 23. Chen, J.; Mao, R.; Zhang, L.; Zhu, R.-Y. Large size LSO and LYSO crystals for future high energy physics experiments. IEEE Trans. Nucl. Sci. 2007, 54, 718–724. [CrossRef] 24. Mao, R.; Zhang, L.; Zhu, R.-Y. Optical and scintillation properties of inorganic scintillators in high energy physics. IEEE Trans. Nucl. Sci. 2008, 55, 2425–2431. [CrossRef] 25. Janecek, M.; Moses, W.W. Measuring light reflectance of BGO crystal surfaces. EEE Trans. Nucl. Sci. 2008, 55, 2443–2449. [CrossRef] 26. Wagatsuma, K.; Miwa, K.; Sakata, M.; Oda, K.; Ono, H.; Kameyama, M.; Toyohara, J.; Ishii, K. Comparison between new-generation SiPM-based and conventional PMT-based TOF-PET/CT. Phys. Med. 2017, 42, 203–210. [CrossRef] 27. Sui, T.; Zhao, Z.; Xie, S.; Xie, Y.; Zhao, Y.; Huang, Q.; Xu, J.; Peng, Q. A 2.3-ps RMS Resolution Time-to-Digital Converter Implemented in a Low-Cost Cyclone V FPGA. IEEE Trans. Instrum. Meas. 2019, 68, 3647–3660. [CrossRef] 28. Song, Z.; Zhao, Z.; Yu, H.; Yang, J.; Zhang, X.; Sui, T.; Xu, J.; Xie, S.; Huang, Q.; Peng, Q. An 8.8 ps RMS Resolution Time-To-Digital Converter Implemented in a 60 nm FPGA with Real-Time Temperature Correction. Sensors 2020, 20, 2172. [CrossRef] 29. Salomoni, M.; Pots, R.; Auffray, E.; Lecoq, P. Enhancing light extraction of inorganic scintillators using photonic crystals. Crystals 2018, 8, 78. [CrossRef] 30. Peng, Q.; Xie, S.; Sui, T.; Yang, M.; Huang, Q.; Xu, J. Experimental assessments of the timing performances of detectors constructed with LaBr3, CeBr3, LFS, LSO, LYSO, GAGG scintillators. In Proceedings of the 2017 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), Atlanta, GA, USA, 21–28 October 2017; pp. 1–2.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).