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Preclinical nuclear molecular imaging speeds up the mean time from synthesis to market, in drug development process. Commercial imaging systems have in general high cost, require high-cost service contracts, special facilities and trained staff. In the current work, we present β -eye, a benchtop system for in vivo molecular screening of labeled compounds with Positron Emission Tomography (PET) isotopes. The developed system is based on a dual-head geometry, offering simplicity and decreased cost. The goal of the design is to provide 2D, real-time radionuclide images of mice, allowing the recording of fast frames and thus perform fast kinetic studies, with spatial resolution of ∼ 2 mm. Performance evaluation demonstrates the ability of β -eye to provide quantitative results for injected activities lower than 1.5 MBq, which is adequate for pharmacodynamic studies in small mice.

In this paper, we report for the first time on the performance of the Hamamatsu H13974 flat panel photomultiplier tube (PMT) array. This new photodetector is based on four Hamamatsu H12700A position sensitive PMTs in a $ 2 \times 2$ arrangement providing large sensitive area ( $ {100\times 100}$ mm2) for use in scintimammography or/and medium size mammals imaging. We acquired raw images from three pixellated scintillators for possible positron emission tomography and single photon emission computed tomography applications (BGO with $ {2\times 2\times 6}$ mm3, CsI:Tl with $ {2\times 2\times 4}$ mm3, and CsI:Na with $ {1.45\times 1.45\times 6}$ mm3 pixel sizes) irradiated with 511 keV (68Ga) and 140 keV (99 m Tc), respectively. Different coupling schemes involving optical grease and optical glasses of different thicknesses were used in order to find the scheme that better resolves the crystal elements of the scintillators especially in the dead areas of the flat panel PMT array. We present the results of investigating the basic properties, including energy resolution, intrinsic spatial resolution, detection efficiency, and sensitivity uniformity. The scintillation material, the coupling scheme and the analog readout circuits are the main factors that affect the performance of the detector. The proper combination of these factors should be carefully chosen so as to build a high performance imaging system.

State of the art data acquisition systems for small animal imaging gamma ray detectors often rely on free running Analog to Digital Converters (ADCs) and high density Field Programmable Gate Arrays (FPGA) devices for digital signal processing. In this work, a sub-sampling acquisition approach, which exploits a priori information regarding the shape of the obtained detector pulses is proposed. Output pulses shape depends on the response of the scintillation crystal, photodetector’s properties and amplifier/shaper operation. Using these known characteristics of the detector pulses prior to digitization, one can model the voltage pulse derived from the shaper (a low-pass filter, last in the front-end electronics chain), in order to reduce the desirable sampling rate of ADCs. Fitting with a small number of measurements, pulse shape estimation is then feasible. In particular, the proposed sub-sampling acquisition approach relies on a bi-exponential modeling of the pulse shape. We show that the properties of the pulse that are relevant for Single Photon Emission Computed Tomography (SPECT) event detection (i.e., position and energy) can be calculated by collecting just a small fraction of the number of samples usually collected in data acquisition systems used so far. Compared to the standard digitization process, the proposed sub-sampling approach allows the use of free running ADCs with sampling rate reduced by a factor of 5. Two small detectors consisting of Cerium doped Gadolinium Aluminum Gallium Garnet (Gd3Al2Ga3O12 : Ce or GAGG:Ce) pixelated arrays (array elements: $2\times 2\times 5~\mathrm {mm}^{3}$ and $1\times 1\times 10~\mathrm {mm}^{3}$ respectively) coupled to a Position Sensitive Photomultiplier Tube (PSPMT) were used for experimental evaluation. The two detectors were used to obtain raw images and energy histograms under 140 keV and 661.7 keV irradiation respectively. The sub-sampling acquisition technique (10 MHz sampling rate) was compared with a standard acquisition method (52 MHz sampling rate), in terms of energy resolution and image signal to noise ratio for both gamma ray energies. The Levenberg-Marquardt (LM) non-linear least-squares algorithm was used, in post processing, in order to fit the acquired data with the proposed model. The results showed that analog pulses prior to digitization are being estimated with high accuracy after fitting with the bi-exponential model.

To present a prototype tri-modal imaging system, consisting of a single photon emission computed tomography (SPET), a positron emission tomography (PET), and a computed tomography (CT) subsystem, evaluated in planar mode.The subsystems are mounted on a rotating gantry, so as to be able to allow tomographic imaging in the future. The system, designed and constructed by our group, allows whole body mouse imaging of competent performance and is currently, to the best of our knowledge, unequaled in a national and regional level. The SPET camera is based on two Position Sensitive Photomultiplier Tubes (PSPMT), coupled to a pixilated Sodium Iodide activated with Thallium (NaI(Tl)) scintillator, having an active area of 5x10cmThe scintigraphic mode has a spatial resolution of 1.88mm full width at half maximum (FWHM) and a sensitivity of 107.5cpm/0.037MBq at the collimator surface. The coincidence PET mode has an average spatial resolution of 3.5mm (FWHM) and a peak sensitivity of 29.9cpm/0.037MBq. The X-rays spatial resolution is 3.5lp/mm and the contrast discrimination function value is lower than 2%.A compact tri-modal system was successfully built and evaluated for planar mode operation. The system has an efficient performance, allowing accurate and informative anatomical and functional imaging, as well as semi-quantitative results. Compared to other available systems, it provides a moderate but comparable performance, at a fraction of the cost and complexity. It is fully open, scalable and its main purpose is to support groups on a national and regional level and provide an open technological platform to study different detector components and acquisition strategies.

We present the development of a new fully digital, flexible, cost-efficient data acquisition system (DAQ) suitable for dual head Positron Emission Tomography (PET) scanners for small animal imaging applications. A free-running 12 bit octal channel Analog to Digital Converter (ADC), with 65 MHz sampling rate, was used for the digitization of the detector signals. The digitized data were fed into a Spartan 6 Field Programmable Gate Array (FPGA) for event processing. An embedded system was developed for the acquisition, using Xilinx’s Embedded Development Kit (EDK) and Microblaze processor. A digital version of the Constant Fraction Discriminator (CFD) method was implemented in the FPGA, in order to achieve higher time resolution than the ADC sampling period, eliminating the need of an external mixed-signal device. The obtained information using FPGA includes: event timing, energy determination-discrimination, position determination and coincidence processing. The online processing of potential coincident events, significantly reduces the amount of data that will be transmitted to the computer. Coincident events are written temporarily to an external memory provided on a development board and are transferred to a Personal Computer (PC), via Ethernet link, for image reconstruction. Minimal post processing of the data is required prior to reconstruction. A small detector pair consisting of a BGO array coupled to a Position Sensitive Photomultiplier Tube (PSPMT) was used for the evaluation of the readout system. Obtained results prove that the proposed architecture can be used for the readout of dual head PET detectors for small animal imaging applications.

In this work we report the imaging performance of a small field of view planar scintigraphic system for low and medium energy radiotracers imaging. 99mTc (140 keV) and 67Ga (93 keV (P1, 42%), 184 keV (P2, 21%), 300 keV (P3, 17%), 393 keV (P4, 5%)) radioisotopes were used to evaluate the nuclear imaging detector in terms of non-uniformity, energy resolution, system spatial resolution and system sensitivity. Moreover, detector's ability to reliably quantify activity variations in the useful field of view has been evaluated. Specific collimator for given photon energy range is needed, in order to reduce image degradation due to photon scattering and penetration. Three parallel hole collimators different in geometry were studied. Results show that all of them are suitable for 99mTc and 67Ga molecular imaging applications, given that only the first photopeak in the case of 67Ga has to be used for imaging. In this case, accurate quantitative information is obtained with all 3 collimators for both radioisotopes. For 99mTc the most appropriate collimator is the one with the thinner septa walls and the lower height, while for 67Ga the thickest septa and higher height collimator. Dual isotope imaging is applicable using appropriate energy windows and appropriate collimator depending on the application.

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging. The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes. The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans. Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.

The purpose of this study is to investigate the behavior of the new generation of SensL SiPM arrays, ArrayB and ArrayM, for PET/MR applications. The evaluation of the SiPMs performance underwent with pixelated GaGG and BGO scintillators with 2x2x5 mm3 pixel size and various coupling schemes for 511keV and 662keV energies. To acquire raw images, we used a symmetric resistive voltage division network and the 4x4 SiPMs anodes reduced to 2X and 2Y position signals. A FPGA Spartan 6 LX150T was used for triggering and digital processing of the pulses acquired using free running ADCs. The first step of our work was optimization of the bias voltage of the two SiPM arrays. The optimal bias voltage is a tradeoff between high photon detection efficiency and low excess noise factor. The SiPMs were coupled to homogeneous 16x16x10 mm3 CsITl scintillator and irradiated with 137Cs source. The energy resolution calculated in overvoltages between 26.5V and 30.5V for ArrayB and between 28.3V and 31.3V for ArrayM. The bias voltage with the best energy resolution was used for the evaluation of the SiPMs. The clear visualization of the GaGG and BGO crystal elements is expressed quantitatively by the mean peak-valley ratio of a horizontal profile in the raw images. The best optical coupling for the BGO was 2 mm thick glass. In the case of the GaGG 1 mm thick glass was adequate. The mean energy resolution of the GaGG scintillator is about two times better than the BGO for both type of SiPMs, after applying correction for their non-linear response. The low light output of the BGO scintillator in comparison with the GaGG as well as different emission spectra and the different PDE of the two types of SiPMs explain the differences in the behavior of the tested SiPMs arrays.

Nanoparticle based drug delivery is considered as a new, promising technology for the efficient treatment of various diseases. When nanoparticles are radiolabelled it is possible to image them, using molecular imaging techniques. The use of magnetic nanoparticles in hyperthermia is one of the most promising nanomedicine directions and requires the accurate, non-invasive, monitoring of temperature increase and drug release. The combination of imaging and therapy has opened the very promising Theranostics domain. In this work, we present a digital data acquisition scheme for nuclear medicine dedicated detectors for Theranostic applications.

Purpose In this study, we present the results of the evaluation of the SensL ArraySL-4 photo-detector, coupled to a 6 × 6 GAGG:Ce scintillator array, with 2 × 2 × 5 mm 3 crystal size elements for possible applications in medical imaging detectors with focus in PET applications. Experimental evaluation was carried out with 22 Na and 137 Cs radioactive sources and the parameters studied were energy resolution and peak to valley ratio. Methods ArraySL-4 is a commercially available, 4 × 4 array detector covering an active area of 13.4 mm 2 . The GAGG:Ce scintillator array used in this study has 0.1 mm thickness BaSO 4 reflector material between the crystal elements. A symmetric resistive voltage division matrix was applied, which reduces the 16 outputs of the array to 4 position signals. A Field Programmable Gate Array was used for triggering and digital processing of the signal pulses acquired using free running Analog to Digital Converters. Results Raw images and horizontal profiles of the 6 × 6 GAGG:Ce scintillator array produced under 511 keV and 662 keV excitation are illustrated. Moreover, the energy spectra obtained with 22 Na and 137 Cs radioactive sources from a single 2 × 2 × 5 mm 3 GAGG:Ce scintillator are shown. The peak to valley ratio and the mean energy resolution values are reported. Conclusions The acquired raw image of the GAGG:Ce crystal array under 511 keV excitation shows a clear visualization of all discrete scintillator elements with a mean peak to valley ratio equal to 40. The mean energy resolution was measured equal to 10.5% and 9% respectively under 511 keV and 662 keV irradiation.

In this study we present the performance evaluation of a 6×6 Gd3Al2Ga3O12:Ce (GAGG:Ce) pixellated scintillator with 2×2×5mm3 crystal size elements, coupled to a silicon photomultiplier array (ArraySL-4). Evaluation was carried out with low energy isotopes i.e. 57Co and 99mTc. A symmetric resistive charge division matrix was used reducing array's 16 outputs to 4 position signals. A Field Programmable Gate Array (FPGA) Spartan 6 LX16 was used for triggering and signal processing of the signal pulses acquired using a free running sampling technique. Raw images of the crystals maps were acquired. The mean energy resolution at 140keV and 122.1 keV was 16.1±0.52% and 18.1±0.64% respectively, and the peak to valley ratio was found equal to 17.7±2.7. Comparative measurements of two 3×3×5mm3 CsI:Tl and GAGG:Ce scintillators of same thickness are also presented. All measurements were performed at room temperature ∼25°C, without additional cooling. According to our knowledge this is the first time that the new developed GAGG:Ce scintillator array has been evaluated at low energies.

The aim of this study is to investigate the imaging performance of a silicon photomultiplier array (ArraySL-4) photodetector for possible PET and potentially SPECT applications using BGO and CsI(Na) pixellated scintillators. Our main objectives are: i) the comparison of the ArraySL-4 to the older version SensL's SPMArray4 photo detector in terms of energy resolution and peak to valley ratio of a row profile in the flood image and ii) the study of the effect of different coupling schemes using ultra transmitting glass windows of various thicknesses. We acquired raw images from two pixellated scintillators (BGO with 2 × 2×5 mm3 and CsI:Na with 1 × 1×5 mm3 pixel sizes) irradiated with 511 keV and 1274.5 keV γ-rays from a 22Na source. The SiPM array detector allowed the clear visualization of the discrete 2 × 2 mm2 pixellated BGO and 1 × 1 mm2 CsI:Na scintillator elements at room temperature (no cooling). The energy resolution of the new SensL ArraySL-4 detector for the 2 × 2×5 mm3 BGO pixellated scintillator array is improved for rather 6 percentage points (energy resolution improvement equal to 22%) and the peak to valley ratio is measured higher for both scintillator arrays (for BGO 68% (1.7 × ) and for CsI:Na 154% (2.5 × )) compared with SPMArray4. The clear identification of the 1 × 1 mm2 CsI:Na scintillator elements provides evidence that the combination of those SiPMs with even smaller arrays can be used as an efficient imaging detector module. Optical coupling significantly improves image uniformity, while the use of BK7 ultra transmitting glass window with 1.35 mm thickness provided the best measure energy resolution equal to 21.5%.

Introduction Silicon photomultiplier arrays can be used in dedicated small field of view animal imaging detectors and especially in those used to head PET/MR studies in mice due to their small size and flexibility. Ce doped LGSO scintillator crystal is based on a mixture of LSO and GSO orthosilicates (Lu 2x-_ Gd 2-2x_ SiO 5 :Ce – LGSO:Ce) and has attracted researcher’s attention because of high density of 7 g/cm 3 , high light output (∼32000 ph/MeV) and fast scintillation decay time (∼40 ns). Purpose The purpose of this study is to investigate the behavior of the ArraySL-4 (4 × 4 element array of 3 × 3 mm 2 silicon photomultipliers) optical detector coupled to a 6 × 6 LGSO:Ce scintillator array, with 1.9 × 1.9 × 5 mm 3 crystal size elements, for possible applications in small field of view PET imaging detectors. Evaluation was carried out with 137 Cs radioactive source and results regarding energy resolution and peak to valley ratio are presented. Materials and methods We have developed a symmetric resistive charge division circuit to read out the signal outputs of 4 × 4 pixel SiPM array reducing the 16 pixel outputs to 4 position signals. The 4 position signals were acquired using a free running sampling technique. An FPGA (Spartan 6 LX150T) was used for triggering and signal processing of the pulses acquired using free running Analog to Digital Converters. Results and conclusion Evaluation shows a clear visualization of all discrete scintillator elements. The mean peak to valley ratio of the profiles on the image was measured equal to 13 while the mean energy resolution was measured equal to 18%.

The aim of this study is to design and apply a symmetric resistive voltage division matrix to read out the compact silicon photomultiplier array (SPMArray2 by SensL) photodetector for possible applications as gamma or PET probes for localization of cancer tumors. We applied a symmetric resistive voltage division circuit, reducing the 16 voltage outputs, which are provided from SensL's evaluation board, to 4 position signals. We acquired raw images and crystal maps from various pixilated scintillators under 99mTc and 22Na excitation, emitting mainly at 140KeV and 511KeV, respectively. The exact values of the resistors as well as the summing amplifiers used in the summation and division stages are given. Moreover, experimental evaluation in terms of energy and spatial resolution is reported. A clear visualization of the discrete 2mm2 pixilated CsI:Tl scintillator elements under 140keV excitation - with better than 23% energy resolution - was achieved. Raw images of the crystals maps acquired shown visualization of the discrete 1mm2 CsI:Na scintillator elements under 511keV irradiation. Under 511keV excitation we achieve an energy resolution of ∼35% for BGO and 18% for CsI:Na pixilated scintillators, respectively. All measurements were carried out at room temperature (∼25°C), without additional cooling.

The aim of this study is to propose and evaluate a simple, open source, data acquisition (DAQ) tool, which provides accurate results for nuclear imaging applications. For this purpose a Xilinx Spartan3E Starter Kit, which is one of the simplest Field Programmable Gate Arrays (FPGA) evaluation boards, was used. The system has been evaluated using a positionsensitive photo-multiplier (PSPMT) at the energy produced by 99m Tc sources. Two dual channel, external, 12-bit analog to digital converters (ADC) with a sampling rate of 1Msps per channel were used. The tool was designed using Xilinx's Embedded Development Kit (EDK) and was based in Xilinx's Microblaze soft-core processor. A reference multiparameter based data acquisition system using nuclear instrumentation modules (NIM) was used for the evaluation of the proposed system. Two different algorithms for pulse height estimation were applied; the maximum height approximation method and the Gaussian approximation. A second PSPMT and a Silicon Photomultiplier (SiPM) were used for further evaluation of image quality and energy spectrum respectively. Results have shown that the FPGA based data acquisition system i) provides accurate digitization of the PSPMTs anode signals in various conditions and ii) gives similar energy spectra when SiPMs are used.

Silicon Photomultiplier (SiPM) detectors are attractive candidates for the replacement of Photomultipliers in nuclear imaging. They are compact, provide high gain with low V bias and have fast response. In addition, SiPMs are not influenced by strong magnetic fields, allowing their use in the emerging field of PET-MRI. The development of small prototypes based on SiPMs posses several design challenges, since it is necessary to optimize scintillator and SiPM coupling, as well as signal amplification and digitization. The aim of this work is the characterization of two SiPM modules, in terms of energy resolution using 3 different scintillator materials and variable V bias . We have used SensL's SPMM3020 and SPMM3035 combined with LYSO, CsI:Tl and BGO, irradiated with99mTc and 137Cs sources The best energy resolution for Tc was 18% and achieved for the SPMM3020, coupled to CsI:Tl at 31V. For 137Cs energy resolution was 10.0% and achieved for the SPMM3020 coupled to CsI(Tl) at 32.5V.

In this work we present the design and development of a prototype SPECT/PET/CT system, suitable for whole body small animal imaging, which is unique not only in national but also in regional level. The integrated SPECT/PET/CT system has three components and is mounted on a rotating gantry, which is designed specifically for such applications. The system is unique on national and regional level. The SPECT component has a 2mm spatial resolution, the PET components a 2.5mm spatial resolution and the X-ray component was recently purchased and is now mounted on the existing gantry and will be evaluated. The complete design of the system and evaluation results are presented.

The combination of imaging and therapy has opened the very promising Theranostics domain with magnetic hyperthermia being a very promising domain. However, imaging systems should not interact with the magnetic field. In this work we have tested the recent C-series of SensL SiPM with 3mm pixel size, 4×4 arrays, coupled to different scintillators and irradiated with various gamma energies. The evaluation of the SiPM arrays shows that 1x1mm pixel size can be clearly resolved at PET energies for GAGG:Ce and CsI:Na and 1.5×1.5mm in SPECT imaging for CsI:Na. The best energy resolution was measured equal to 10.5% under 511keV irradiation for the 2×2mm GAGG:Ce; 16% under 511keV irradiation for the 1×1mm GAGG:Ce and 22% under 120keV irradiation for the 1×1mm CsI:Na. In addition, measurements with position sensitive photomultipliers have been carried out, to evaluate the effect of the magnetic field on the imaging performance of the system. While the effect of the magnetic field outside the coil is small, optimal images will be obtained if the imaging system is placed inside the coil, something that can be achieved only by using SiPMs.

Silicon photomultiplier (SiPMs) detectors are attractive candidates for replacing position sensitive photomultipliers in nuclear imaging. They are compact, they provide high gain with low bias voltage and show better response. The development of dedicated imaging prototypes based on SiPMs possesses several design challenges, since it is necessary to optimize scintillator and SiPM coupling, as well as signal amplification and digitization. In this work, we have investigated the performance of three SiPM modules constructed by SensL coupled on three scintillators (CsI:Tl, BGO, LYSO:Ce), which are used in SPECT and PET imaging. Irradiation was carried out using different sources, which covered a wide range of energies from 88 to 1275 keV. The parameters measured were output pulses' width and height, energy resolution and linearity as a function of bias voltage and sources energy.

The development and assessment of a readout system based on field programmable gate arrays (FPGA) for dedicated nuclear medicine cameras is presented. We have used Xilinx Spartan3E starter kit, which is one of the simplest FPGA evaluation boards. The aim of this work is to offer a simple, open source, data acquisition tool, which provides accurate results for nuclear imaging applications. The system has been evaluated using three different experimental setups: pulses from two position-sensitive photo-multipliers (PSPMTs) and a silicon photo-multiplier (SiPM) were recorded, using 99mTc sources. Two dual channel, external, 12 bit analog to digital converters with a sampling rate of 1 Msps per channel were used. The tool was designed using Xilinx's embedded development kit and was based in Xilinx's Microblaze soft-core processor. A reference multiparameter-based data acquisition system using nuclear instrumentation modules was used for the evaluation of the proposed system. A number of tests were carried out to assess different algorithms for pulse maximum estimation and Gaussian fitting provided optimal results. The results have shown that the FPGA data acquisition system (i) provides accurate digitization of the PSPMT anode signals under various conditions and (ii) gives similar energy spectra when SiPMs are used.