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We report a PET detector module (DM) designed for developing a preclinical positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) hybrid system. The DM consists of a linear array of eight detector units, each of which is a 12×12 array of lutetium–yttrium oxyorthosilicate (LYSO) crystals read by a 4×4 silicon photomultiplier (SiPM) array. The crystal size is approximately 1.0×1.0×10 mm3. All surfaces of the crystal are polished; except for that coupled to SiPMs they are also covered with BaSO4 to reduce light loss. The pitches of the LYSO and SiPM arrays are about 1.05 mm and 3.2 mm, respectively. The front face of the resulting DM is about 1.28×10.24 cm2 in extext and its thickness is approximately 1.8 cm. A highly multiplexing readout is devised to produce only six outputs for a DM, including two outputs that are derived from the SiPM cathode signals for determining the event time and the active DU, and four outputs that are derived from the SiPM anode signals for determining the event energy and the active crystal within the active DU. At present, these outputs are acquired by waveform sampling and analyzed offline. We have successfully developed two DMs, both showing well discriminated DUs and crystals, and an average energy resolution of about 15%. Even though time-of-flight (ToF) is not needed for the proposed system, our data shows that the DM can potentially achieve a 300-400 ps ToF resolution.

Objective. X-ray scatter leads to signal bias and degrades the image quality in Computed Tomography imaging. Conventional real-time scatter estimation and correction methods include the scatter kernel superposition (SKS) methods, which approximate x-ray scatter field as a convolution of the scatter sources and scatter propagation kernels to reflect the spatial spreading of scatter x-ray photons. SKS methods are fast to implement but generally suffer from low accuracy due to the difficulties in determining the scatter kernels. Approach. To address such a problem, this work describes a new scatter estimation and correction method by combining the concept of SKS methods and convolutional neural network. Unlike conventional SKS methods which estimate the scatter amplitude and the scatter kernel based on the value of an individual pixel, the proposed method generates the scatter amplitude maps and the scatter width maps from projection images through a neural network, from which the final estimated scatter field is calculated based on a convolution process. Main Results. By incorporating physics in the network design, the proposed method requires fewer trainable parameters compared with another deep learning-based method (Deep Scatter Estimation). Both numerical simulations and physical experiments demonstrate that the proposed SKS-inspired convolutional neural network outperforms the conventional SKS method and other deep learning-based methods in both qualitative and quantitative aspects. Significance. The proposed method can effectively correct the scatter-related artifacts with a SKS-inspired convolutional neural network design.

A recent trend in PET instrumentation is the use of silicon photomultipliers (SiPMs) for high resolution and time-of-flight (TOF) detection. Due to its small size, a PET system can use a large number of SiPMs and hence effective and scalable multiplexing readout methods become important. Unfortunately, multiplexing readout generally degrades the fast timing properties necessary for TOF, especially at high channel reduction. Previously, we developed a stripline (SL)-based readout method for PET that uses a time-based multiplexing mechanism. This method maintains fast timing by design and has been successfully used for TOF PET detectors. In this article, we present a more systematic study in which we examine how two important design parameters of the readout—the number of inputs on an SL ( $n_{\mathrm {SL}}$ ) and the pathlength between adjacent input positions ( $\Delta \ell $ )—affect its detection performance properties for PET. Our result shows that up to $n_{\mathrm {SL}}=32$ the readout can achieve accurate pixel discrimination and causes little degradation in the energy resolution. The TOF resolution is compromised mildly and a coincidence resolving time on the order of 300-ps FWHM can be achieved for lutetium–yttrium oxyorthosilicate- and SiPM-based detectors. We also discuss strategies in using the readout to further reduce the number of electronic channels that a PET system would otherwise need.

Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC (18F had the highest maximum %RC (> 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A larger SOR were measured in water with 11C and 68Ga compared to 18F on all systems. SOR in air reflected image reconstruction and data correction performance. Large variation in image quantification was observed, with maximal errors of 22.73% (89Zr, Inveon), 17.54% (89Zr, RAYCAN) and − 14.87% (68Ga, Molecubes). Conclusions The systems performed most optimal in terms of NEMA image quality parameters when using 18F, where 11C and 89Zr performed slightly worse than 18F. The performance was least optimal when using 68Ga, due to large positron range. The large quantification differences prompt optimization not only by terms of image quality but also quantification. Further investigation should be performed to find an appropriate calibration and harmonization protocol and the evaluation should be conducted on a multi-scanner and multi-center level.

Previously we reported the development of a positron emission tomography (PET) and electron paramagnetic resonance (EPR) combined imaging system. The combined imaging system aimed to investigate the potential of PET hypoxia imaging by using EPR oxygen imaging as a reference. Simultaneous PET/EPR data acquisition is important to make sure of recording the same biological changes in both imaging modalities as well as to shorten imaging time. Our current system does not have magnetic or RF shielding. During the initial simultaneous PET/EPR operation, we observed that the EPR RF pulsing induced spurious noise events in the PET, and significantly affected the PET detector performance. We developed a method to reject the EPR RF noise events in off-line data processing. The method is to exploit the waveform sampling capable PET data acquisition implemented in a multi-voltage-threshold (MVT) board, and to use the pulse shape difference found in the MVT waveforms between scintillation and RF noise events. Experiments were conducted to evaluate the effectiveness of the proposed method in rejecting RF noise events. Preliminary results indicate that the rejection method works effectively to enable simultaneous data acquisition of the PET/EPR system.

Additional file 1: Fig. S1. Construction scheme of the NEMA phantom with a photograph of the phantom. Data S1. Effect of using the standard 20 minute acquisition time for 11C and 68Ga. Data S1, Table S1. Recovery coefficients of the phantom rods with different radionuclides and acquisition times. Data S1, Table S2. Percentage standard deviation of recovery coefficients of the phantom rods with different radionuclides and acquisition times. Data S1, Table S3. The mean activity and the percentage standard deviation measured from the uniform compartment of the phantom with different acquisition times. Data S1, Fig. S2. Image quality comparison for 11C and 68Ga using the 20 minute acquisition time. Data S1, Fig. S3. Recovery coefficients with 11C and 68Ga only. Data S2. Effect of different reconstruction algorithms and parameters. Data S2, Table S4. Image reconstruction parameters and data corrections used for the reconstruction evaluation. Data S2, Fig. S4. Dependency of image quality parameters on the amount of iterations. Data S2, Table S5. Recovery coefficients of the phantom rods with different radionuclides and reconstruction options. Data S2, Table S6. Percentage standard deviation of recovery of the phantom rods with different radionuclides and reconstruction options. Data S2, Table S7. The mean radioactivity with percentage standard deviation and relative difference in the uniform compartment with the spill-over-ratios and their percentage standard deviations with different reconstruction schemes..

We present a combined imaging system of positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI) developed for assessing tumor hypoxia. Tumor hypoxia has been known to be resistant for cancer treatment such as radiation therapy. Therefore, precise quantitative measurement of tumor hypoxia is important for effective cancer treatment planning in radiation therapy. In clinic, PET imaging by using 18F-fluoromisonidazole (F-MISO) have been performed to delineate tumor hypoxia. However, the effectiveness of PET imaging based hypoxia targeting in radiation therapy was not yet firmly established. EPRI is a non-invasive imaging method capable of measuring the partial pressure of oxygen (pO 2 ) in tissue precisely. However, EPRI is not available for clinical use currently. The combined imaging system is to use EPRI as a gold standard to measure the pO 2 in hypoxic tumor in animal, and aims to evaluate the validity of PET imaging in tumor hypoxia by simultaneously acquired EPRI. The PET component of the combined system, which was originally developed as an insert for MRI, consists of total 14 detector modules. Each PET detector module uses of 8x4 LYSO arrays (3x3x10 mm3) coupled to Hamamatsu S13361 MPPC arrays (3.2 mm pitch). The detector modules are encased in a cylindrical plastic holder with 60 mm inner diameter and 115 mm outer diameter in a ring configuration. The axial field of view of the PET is 25.6 mm. The EPRI component of the system is built with two permanent magnets (25 mT), three gradient field coils for spatial encoding (the maximum 15 mT/m) and a RF resonator. The PET is installed to fit into the two EPR magnets (12 cm distance apart) so that the PET detector center is aligned to the magnet center. The compatibility of two imaging modalities were tested by using a 22Na point source and imaging phantoms. Animal imaging with F-MISO and FDG were also performed by running the PET/EPR simultaneously. Initial imaging results are reported.

Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using $^{18}$F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system., Comment: 12 pages, 6 figures

We report the development of a compact, highly modular SiPM-based PET detector that outputs digital data via a standard serial network interface and the use of such detectors in conjunction with a software platform to obtain a scalable system architecture for PET. The detector, approximately 2.5 cm wide and 10 cm long, is made of 4 LYSO/SiPM arrays arranged in a row. Each LYSO/SiPM array is consisted of a 13x13 LYSO array optically coupled to a 6x6 array of SensL MicroFC-30035 SiPMs. For the LYSO array, the crystal size is 1.89x1.89x13 mm3 and the pitch is 2.0 mm. For the SiPM array, the pixel size and pitch are 3.2 mm and 4.2 mm, respectively. The intrinsic resolution, energy resolution and coincidence time resolution of the detector are measured to be about 1.91 mm, 15% and 1.4 ns, respectively. Crystals in a detector exhibit rather uniform performance characteristics. Two demonstration systems are developed using the developed detectors and proposed architecture, including a single-ring system (~10.4 cm diameter, 10 cm length) using 12 detectors and a two-ring system (~19 cm diameter, 20 cm length) using 48 detectors. Imaging data are successfully obtained by using these systems and the results indicate that approximately 1 mm image resolution is achieved.

We present for the first time a simulation framework based on GEANT4 and dedicated to the digital Plug and Imaging (P&I) sensor system for Positron Emission Tomography. We manufactured a a prototype of Digital Brain Positron Emission Tomography and we compared the experimental results with the simulation model in terms of sensitivity and space resolution estimation.

Recently, we have developed a stripline (SL) readout method and amulti-voltage threshold (MVT) digitizer for PET. The SL readout is amultiplexing method for reading multiple input signals that is easy toimplement and can support timeof-flight (TOF) detection. The MVT methodsdigitally samples a PET signal pulse with respect to a number of voltagethresholds and can be implemented by using the field programmable gate array(FPGA). The use of these two methods can greatly simplify the electroniccomplexity of a TOF PET detector. In this paper, we investigate theperformance properties of the SL readout when applied to different numbersof silicon photomultipliers (SiPM) from SensL. Outputs of the SL readout areacquired by using a 72-ch FPGA MVT board. Our results show that up to 36pixels per SL can be discriminated, a pixel energy resolution of 11-21%can be obtained, and a coincidence resolving time (CRT) of 520 ps can beachieved. Previously, we obtained 320ps CRT when applied the MVT to a singlepixel made of LYSO and SiPM. Therefore, we believe the CRT can be furtherimproved after optimization.

Positron Emission Tomography (PET) is one of the most promising non-invasive in vivo imaging techniques for the proton therapy verification. In this paper we investigate the feasibility of using an all-digital PET technology platform for in-beam or in-room imaging for proton therapy. We performed a series of experiments using phantom and biological tissue. Our initial results demonstrate the PET technology platform is promising for verification of proton therapy.

We are developing a MR insert PET detector using SiPM for small animal imaging. Our detector design is based on the strip-line signal readout that we have developed to efficiently handle large amount signals for SiPM-based TOF PET. The stripline readout has an advantageous feature suitable for building PET integrated within MR. In strip-line readout, the signal digitization is accomplished remotely from the detection module, thereby the front-end electronics of the detector within MR is minimal; the interference between two systems, e.g., magnetic field distortion due to PET, can be minimized accordingly. The feasibility of the strip-line readout for PET/MR has been demonstrated in our previous study. The current prototype MR insert PET is comprised of 8 detector modules, which are installed in a plastic cylindrical supporting structure. Each detector module consists of 8x4 LYSO arrays (3x3x10 mm3each) and two Hamamatsu S13361–3050NE-04 MPPC arrays (4x4, 3.2 mm pitch); 32 SiPM signals are routed in 4 strip-lines so that 8 LYSO/SiPM signals in a row are connected to each strip-line. The signals from strip-lines are fed to a 72-ch multi-voltage threshold (MVT) digitizer, which digitizes the input by TDCs implemented in FPGA. Experiments have been carried out to evaluate the detector performance, and image reconstruction also has been performed for a simple shape object. In the paper, the detail on the development of the MR insert PET are explained, and preliminary test results are presented.

Signal multiplexing for SiPM-based TOF PET to achieve high multiplexing ratio and keep the fast timing performance is a challenging issue. We have developed a multiplexing method using a strip-line; multiple SiPMs are connected to a single micro-strip transmission line, and the position of hit SiPM is determined by the signal arrival time difference on the strip-line. The strip-line method is scalable; high multiplexing ratio can be easily achieved by increasing the number of SiPMs connected on a strip-line. To test the scalable feature of the strip-line readout systematically, we have implemented several strip-lines with different trace lengths and varied the number of SiPMs (Hamamatsu S13361-3050NE) on the strip-lines up to 32. Experimental tests have been conducted to assess the influences of the strip-lines on detector performance: position, energy, and coincidence time resolution. Preliminary results from the study are presented, and our ongoing efforts on strip-line readout for TOF PET are discussed.

One key issue in proton beam therapy is to ensure precise delivery of the concentrated radiation dose to the target. A promising method that is under active study and development is the use of position emission tomography (PET) for range verification or monitoring. In this work, we test the use of a digital PET system developed on the basis of a Plug-and-Imaging architecture for a proton therapy system. We analyze technical features of the proposed PET technology and experimentally demonstrate the possibility to imaging positron decays in a phantom immediately after proton irradiation. The experiment results agree with the expectation according to the physical properties of proton beam interaction with hydrocarbons.

We report the development of a modularized compact positron emission tomography (PET) detector that outputs serial streams of digital samples of PET event pulses via an Ethernet interface using the UDP/IP protocol to enable rapid configuration of a PET system by connecting multiple such detectors via a network switch to a computer. Presently, the detector is [Formula: see text] in extent (excluding I/O connectors) and contains an [Formula: see text] array of [Formula: see text] one-to-one coupled lutetium-yttrium oxyorthosilicate/silicon photomultiplier pixels. It employs cross-wire and stripline readouts to merge the outputs of the 216 detector pixels to 24 channels. Signals at these channels are sampled using a built-in 24-ch, 4-level field programmable gate arrays-only multivoltage threshold digitizer. In the computer, software programs are implemented to analyze the digital samples to extract event information and to perform energy qualification and coincidence filtering. We have developed two such detectors. We show that all their pixels can be accurately discriminated and measure a crystal-level energy resolution of 14.4% to 19.4% and a detector-level coincidence time resolution of 1.67 ns FWHM. Preliminary imaging results suggests that a PET system based on the detectors can achieve an image resolution of [Formula: see text].

We have developed a signal multiplexing method for a SiPM-based time-of-flight (TOF) positron emission tomography (PET). In the method, multiple SiPM signals are connected to a single strip-line, and the position of hit SiPM is decoded from the arrival time difference measured at the two ends of a strip-line. Since the position resolution on strip-line is directly proportional to the accuracy of the measured time, a high speed (≥ 1 GSPS) waveform sampling electronics, e.g., Domino Ring Sampler (DRS4), has been used to determine the time stamp of the strip-line signal as precise as possible: e.g., the electronic time resolution of the DRS4 is measured to be 5 ps. Although the DRS4 waveform sampling provides a good timing accuracy, its large latency time required for digitizing samples could be a limiting factor for high count rate operation. Therefore, in an effort to increase the counting performance, we have come up with a new design of the strip-line board that can work with commonly used time-to-digital converters (TDC) with 50-100 ps electronic time resolution, which provide high counting capability. Hamamatsu MPPC 4×4 arrays (S12642-0404PA-50, 3×3 mm2 area for each) are employed in the new strip-line board; 32 MPPC signals are routed to 4 strip-lines on the board. For verification purpose, we have conducted experimental tests to readout the current strip-line board by using the OpenPET electronics, which is a general purpose data acquisition developed for nuclear medicine research community. In the test, LYSO scintillator arrays (3×3×20 mm3 each) are coupled to MPPCs on the strip-line board, and the detector is irradiated by a 22Na source with 10 μCi activity. The initial results obtained by using OpenPET are very promising: each MPPC on the strip-line is well identified with 1.2 mm FWHM resolution, and 13.0% FWHM of energy resolution for 511 keV gamma. The results are comparable to the ones by using DRS4 waveform sampler running at 2.5 GSPS.

We are developing a time-of-flight (TOF) positron emission tomography (PET) scanner for brain imaging using SiPMs. In our development, we have adopted a strip-line based signal multiplexing method for efficient channel reduction for SiPMs; the method is using a single strip-line on which multiple SiPMs are connected for sharing readout, and the position of hit SiPM is decoded from the arrival time difference measured at the two ends of the strip-line. We have conducted experimental tests for evaluating the performance of the detectors based on the strip-line signal readout. Hamamatsu MPPC array (S12642-0404PA-50, 3.2 mm pitch) is employed in the detector module; 32 MPPC signals from two MPPCs arrays are routed to 4 strip-lines on the current strip-line board. For the tests, two detectors are used in a coincidence setup, and an array of 4×4 LYSO scintillator (3×3×20 mm3, 3.2 mm pitch) is coupled to the MPPC array in each detector. A 22Na source with 3 μCi activity is used, and the waveform of the detectors signals are collected by using a Domino Ring Sampler (DRS4) evaluation board running at 2.5 giga sampling rate. The preliminary results show that the position on the strip-line is determined with ∼1.0 mm precision from the measured differential time on the strip-line. The average energy and coincidence time resolution are measured to be ∼13% FWHM and ∼726 ps FWHM, respectively, at 511 keV photo-peak. A systematic investigation of the effects of strip-line on detector performance is carried out in parallel by using a specially designed strip-line board. The test results is presented in the paper.

WE have previously demonstrated a stripline readout for TOFPET detectors that can achieve significant reduction in the number of readout channels while maintaining good detection performance [1-3]. The principle of this time-based multiplexing readout is depicted in Figs. 1(a) and 1(b). As shown, a stripline receives the outputs of several photodetectors (PD). When a PD produces a signal at time t e , two identical pulses are created at the position of the PD but travel in opposite directions along the stripline, arriving the ends at time, say, t 1 and t 2 . Evidently, t 1 = t e + l 1 /v and t 2 = t e + l 2 /v = t 2 + (L − l 1 )/v, where l 1 and l 2 are the path lengths from the PD to the ends, L is the total length of the stripline, and v is the pulse propagation speed on the stripline. It follows that dt = t 2 − t 1 = L/v − 2(l 1 /v) and t = (t 1 + t 2 )/2 = t e + L/2v. As L and v are fixed numbers, the differential time (DT), dt, thus encodes the PD's position on the stripline and the average time, t, the event time. The pulses are highly correlated; therefore, the size of the pulse, which is related to the event energy in PET, can be measured off either one of the pulses by using the peak or integrated amplitude. Now, the path-length between neighboring PDs on the strpiline can be small, for example, 3–6 mm. The propagation speed of the pulse, on the other hand, is approximately half the speed of light. Thus, the difference in the DT reading of two adjacent PDs can be on the order of 20–40 picoseconds (ps) and the DT measurement needs to be highly precise. To achieve this, we proposed to digitally sample the pulses at 2–5 GHz by employing an inexpensive, low power-comsumption waveform-sampling technology such as the DRS4 from the Paul Sherrer Institut (PSI) (see Fig. 1(c)) and apply digital-signal processing to extract accurate time information. Subject to the count-rate requirement, multiple striplines can be simply connected to increase the number of SiPMs per line and therefore the readout is scalable. Also, with the stripline readout the data-acquisition (DAQ) electronics can be detached from the detector (the use of up to 10-meter long cables to connect the DAQ electronics and detector have been successfully tested); this feature can be useful for developing systems that are subject to tight space constraints.

Based on the multi-voltage threshold (MVT) method, we have proposed the FPGA-only implementation for positron emission tomography (PET) detectors. It realizes required comparators and time-to-digital convertors (TDCs) on FPGAs. Thus, its performance can be easily enhanced by optimizing the inside algorithm without hardware modifications or improved with the development of FPGA technologies. In this paper, we leverage the advantages of the FPGA-only implementation to develop a new digitizer board that can provide 72 digitizing channels. This digitizer board significantly increases its readout density than before. And the power consumption is also reduced from 330 mW per channel to 150 mW per channel. By connecting the board to a pair of 6 × 6 LYSO/SiPM arrays, a micro-system, useful for coincidence detection and imaging small objects, is built. We also introduce a TDC multiplexing method when implementing MVT digitizers which apparently reduces the required FPGA resources by 70%. These freed resources can be reused to further improve the integration of readout system. With the micro-system, our preliminary results indicate a coincidence timing resolution of ∼530 ps (FWHM) and an energy resolution of ∼15% (at 511 keV) when the signal rate is 0.9 Mcps, regardless whether TDC multiplexing method is used.