Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity.

Objective.Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed. Novel research demonstrated significant improvements in the reachable timing resolutions when combining conventional calibration approaches with machine learning, with the disadvantage of extensive calibration times infeasible for a clinical application. In this work, we made the first steps towards an in-system application and analyzed the effects of varying data sparsity on a machine learning timing calibration, aiming to accelerate the calibration time. Furthermore, we demonstrated the versatility of our calibration concept by applying the procedure for the first time to analog readout technology.Approach.We modified experimentally acquired calibration data used for training regarding their statistical and spatial sparsity, mimicking reduced measurement time and variability of the training data. Trained models were tested on unseen test data, characterized by fine spatial sampling and rich statistics. In total, 80 decision tree models with the same hyperparameter settings, were trained and holistically evaluated regarding data scientific, physics-based, and PET-based quality criteria.Main results.The calibration procedure can be heavily reduced from several days to some minutes without sacrificing quality and still significantly improving the timing resolution from(304±5)psto(216±1)pscompared to conventionally used analytical calibration methods.Significance.This work serves as the first step in making the developed machine learning-based calibration suitable for an in-system application to profit from the method's capabilities on the system level. Furthermore, this work demonstrates the functionality of the methodology on detectors using analog readout technology. The proposed holistic evaluation criteria here serve as a guideline for future evaluations of machine learning-based calibration approaches.

[Direct Positron Emission Imaging Using Ultrafast Timing Performance Detectors].

This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.

Development of a novel phantom for tau PET imaging.

PURPOSE: The cortical uptake of tau positron emission tomography (PET) tracers corresponds to the Braak stage and reflects the distribution and progression of tau neurofibrillary tangles. The present study aimed to develop and validate the basic performance of a novel tau PET phantom, as well as to establish standard test procedures and analytical methods. METHODS: The tau PET phantom consisted of a brain simulation section simulated medial temporal lobe region and resolution and uniformity sections. The brain simulation section and hot rods and uniformity section contained 4 and 2 kBq/mL of 18F, respectively and images were acquired three times for 20 min with a PET/CT scanner. The resolution section was visually assessed with two sets of hot and cold rods. Recovery coefficients (RCs) as a quantitative value and coefficient of variation (CV) as image noise were determined based on the brain simulation and the uniformity section, respectively. RESULTS: Preparation of activity in the phantom was repeatable among three measurements. The quality of images in the brain simulation and uniformity section with the rods was good. The 5- or 6-mm rods were detected separately. The mean RCs calculated based on the VOI template were between 0.75 and 0.83. The CV at the center slice of uniformity section was 5.54%. CONCLUSIONS: We developed a novel tau PET phantom to assess quantitative value, image noise, and detectability and resolution from brain simulation section, uniformity section, and rods, respectively. This phantom will contribute to the standardization and harmonization of tau PET imaging.

Investigation of intra-fractionated range guided adaptive proton therapy: I. On-line PET imaging and range measurement.

Objective.Develop a prototype on-line positron emission tomography (PET) scanner and evaluate its capability of on-line imaging and intra-fractionated proton-induced radioactivity range measurement.Approach.Each detector consists of 32 × 32 array of 2 × 2 × 30 mm3Lutetium-Yttrium Oxyorthosilicate scintillators with single-scintillator-end readout through a 20 × 20 array of 3 × 3 mm2Silicon Photomultipliers. The PET can be configurated with a full-ring of 20 detectors for conventional PET imaging or a partial-ring of 18 detectors for on-line imaging and range measurement. All detector-level readout and processing electronics are attached to the backside of the system gantry and their output signals are transferred to a field-programable-gate-array based system electronics and data acquisition that can be placed 2 m away from the gantry. The PET imaging performance and radioactivity range measurement capability were evaluated by both the offline study that placed a radioactive source with known intensity and distribution within a phantom and the online study that irradiated a phantom with proton beams under different radiation and imaging conditions.Main results.The PET has 32 cm diameter and 6.5 cm axial length field-of-view (FOV), ∼2.3-5.0 mm spatial resolution within FOV, 3% sensitivity at the FOV center, 18%-30% energy resolution, and ∼9 ns coincidence time resolution. The offline study shows the PET can determine the shift of distal falloff edge position of a known radioactivity distribution with the accuracy of 0.3 ± 0.3 mm even without attenuation and scatter corrections, and online study shows the PET can measure the shift of proton-induced positron radioactive range with the accuracy of 0.6 ± 0.3 mm from the data acquired with a short-acquisition (60 s) and low-dose (5 MU) proton radiation to a human head phantom.Significance.This study demonstrated the capability of intra-fractionated PET imaging and radioactivity range measurement and will enable the investigation on the feasibility of intra-fractionated, range-shift compensated adaptive proton therapy.

Design and implementation of continuous bed motion (CBM) in Xtrim preclinical PET scanner for whole-body Imaging: MC simulation and experimental measurements.

PURPOSE: Preclinical PET scanners often have limited axial field-of-view for whole-body (WB) scanning of the small-animal. Step-and-shoot(S&S) acquisition mode requires multiple bed positions (BPs) to cover the scan length. Alternatively, in Continuous Bed Motion(CBM) mode, data acquisition is performed while the bed is continuously moving. In this study, to reduce acquisition time and enhance image quality, the CBM acquisition protocol was optimized and implemented on the Xtrim-PET preclinical scanner for WB imaging. METHODS: The over-scan percentage(OS%) in CBM mode was optimized by Monte Carlo simulation. Bed movement speed was optimized considering ranges from 0.1 to 2.0 mm s-1, and absolute system sensitivities with the optimal OS% were calculated. The performance of the scanner in CBM mode was measured, and compared with S&S mode based on the NEMA-NU4 standard. RESULTS: The optimal trade-off between absolute sensitivity and uniformity of sensitivity profile was achieved at OS-50 %. In comparison to S&S mode with maximum ring differences (MRD) of 9 and 23, the calculated equivalent speeds in CBM(OS-50 %) mode were 0.3 and 0.14 mm s-1, respectively. In terms of data acquisition with equal sensitivity in both CBM(OS-50 %) and S&S(MRD-9) modes, the total scan time in CBM mode decreased by 25.9 %, 47.7 %, 54.7 %, and 58.2 % for scan lengths of 1 to 4 BPs, respectively. CONCLUSION: The CBM mode enhances WB PET scans for small-animals, offering rapid data acquisition, high system sensitivity, and uniform axial sensitivity, leading to improved image quality. Its efficiency and customizable scan length and bed speed make it a superior alternative.

Optical crosstalk of protective cover on MPPC array for TOF PET detector.

Objective. Time-of-flight (TOF) is an important factor that directly affects the image quality of PET systems, and various attempts have been made to improve the coincidence resolving time (CRT) of PET detectors. For independent readout detectors, the timing is acquired for each silicon photomultiplier (SiPM), so they are less sensitive to diffused scintillation light, resulting in a better CRT. Further improvement can be expected if the light can be focused on a single SiPM. However, existing SiPM arrays have a thin protective cover on the SiPM and the gap between the SiPMs is filled with either air or the protective cover, so the light must diffuse through the cover. In this work, we investigated optical crosstalk in the protective cover to improve the CRT.Approach. We used 3.1 × 3.1 × 20 mm3fast LGSO crystals and 3 mm square 8 × 8 multi pixel photon counter (MPPC) arrays. Pitch of the MPPCs was 3.2 mm and thickness of the protective cover on them was 150µm. To reduce diffusion of scintillation light in the protective cover, the part of the inactive areas on the MPPC array were optically separated using reflective material. Specifically, 50, 100, 150, and 350µm deep grid-shaped slits were made along the inactive area of the MPPCs and they were filled with BaSO4powder as the reflective material.Main results. Coincidence counts were measured with a pair of TOF detectors, and the CRT was shorter with a deeper slit depth. The CRT before improvement was 235 ps, and using the cover having the 350µm deep slits filled with reflective material lowered the CRT to 211 ps.Significance. Up to 10% of the scintillation light was diffused to other MPPCs by the protective cover, and the CRT was degraded by 10% due to optical crosstalk of the cover. The proposed method promises to improve the CRT of the TOF detector.

Animal PET scanner with a large field of view is suitable for high-throughput scanning of rodents.

OBJECTIVE: In preclinical studies, high-throughput positron emission tomography (PET) imaging, known as simultaneous multiple animal scanning, can reduce the time spent on animal experiments, the cost of PET tracers, and the risk of synthesis of PET tracers. It is well known that the image quality acquired by high-throughput imaging depends on the PET system. Herein, we investigated the influence of large field of view (FOV) PET scanner on high-throughput imaging. METHODS: We investigated the influence of scanning four objects using a small animal PET scanner with a large FOV. We compared the image quality acquired by four objects scanned with the one acquired by one object scanned using phantoms and animals. We assessed the image quality with uniformity, recovery coefficient (RC), and spillover ratio (SOR), which are indicators of image noise, spatial resolution, and quantitative precision, respectively. For the phantom study, we used the NEMA NU 4-2008 image quality phantom and evaluated uniformity, RC, and SOR, and for the animal study, we used Wistar rats and evaluated the spillover in the heart and kidney. RESULTS: In the phantom study, four phantoms had little effect on imaging quality, especially SOR compared with that for one phantom. In the animal study as well, four rats had little effect on spillover from the heart muscle and kidney cortex compared with that for one rat. CONCLUSIONS: This study demonstrated that an animal PET scanner with a large FOV was suitable for high-throughput imaging. Thus, the large FOV PET scanner can support drug discovery and bridging research through rapid pharmacological and pathological evaluation.

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Innovations in dedicated PET instrumentation: from the operating room to specimen imaging.

This review casts a spotlight on intraoperative positron emission tomography (PET) scanners and the distinctive challenges they confront. Specifically, these systems contend with the necessity of partial coverage geometry, essential for ensuring adequate access to the patient. This inherently leans them towards limited-angle PET imaging, bringing along its array of reconstruction and geometrical sensitivity challenges. Compounding this, the need for real-time imaging in navigation systems mandates rapid acquisition and reconstruction times. For these systems, the emphasis is on dependable PET image reconstruction (without significant artefacts) while rapid processing takes precedence over the spatial resolution of the system. In contrast, specimen PET imagers are unburdened by the geometrical sensitivity challenges, thanks to their ability to leverage full coverage PET imaging geometries. For these devices, the focus shifts: high spatial resolution imaging takes precedence over rapid image reconstruction. This review concurrently probes into the technical complexities of both intraoperative and specimen PET imaging, shedding light on their recent designs, inherent challenges, and technological advancements.

Transformer-CNN hybrid network for improving PET time of flight prediction.

Objective.In positron emission tomography (PET) reconstruction, the integration of time-of-flight (TOF) information, known as TOF-PET, has been a major research focus. Compared to traditional reconstruction methods, the introduction of TOF enhances the signal-to-noise ratio of images. Precision in TOF is measured by full width at half maximum (FWHM) and the offset from ground truth, referred to as coincidence time resolution (CTR) and bias.Approach.This study proposes a network combining transformer and convolutional neural network (CNN) to utilize TOF information from detector waveforms, using event waveform pairs as inputs. This approach integrates the global self-attention mechanism of Transformer, which focuses on temporal relationships, with the local receptive field of CNN. The combination of global and local information allows the network to assign greater weight to the rising edges of waveforms, thereby extracting valuable temporal information for precise TOF predictions. Experiments were conducted using lutetium yttrium oxyorthosilicate (LYSO) scintillators and silicon photomultiplier (SiPM) detectors. The network was trained and tested using the waveform datasets after cropping.Main results.Compared to the constant fraction discriminator (CFD), CNN, CNN with attention, long short-term memory (LSTM) and Transformer, our network achieved an average CTR of 189 ps, reducing it by 82 ps (more than 30%), 13 ps (6.4%), 12 ps (6.0%), 16 ps (7.8%) and 9 ps (4.6%), respectively. Additionally, a reduction of 10.3, 8.7, 6.7 and 4 ps in average bias was achieved compared to CNN, CNN with attention, LSTM and Transformer.Significance.This work demonstrates the potential of applying the Transformer for PET TOF estimation using real experimental data. Through the integration of both CNN and Transformer with local and global attention, it achieves optimal performance, thereby presenting a novel direction for future research in this field.

Depth-encoding using optical photon TOF in a prism-PET detector with tapered crystals.

BACKGROUND: High-resolution brain positron emission tomography (PET) scanner is emerging as a significant and transformative non-invasive neuroimaging tool to advance neuroscience research as well as improve diagnosis and treatment in neurology and psychiatry. Time-of-flight (TOF) and depth-of-interaction (DOI) information provide markedly higher PET imaging performance by increasing image signal-to-noise ratio and mitigating spatial resolution degradation due to parallax error, respectively. PET detector modules that utilize light sharing can inherently carry DOI information from the multiple timestamps that are generated per gamma event. The difference between two timestamps that are triggered by scintillation photons traveling in opposite directions signifies the event's depth-dependent optical photon TOF (oTOF). However, light leak at the crystal-readout interface substantially degrades the resolution of this oTOF-based depth encoding. PURPOSE: We demonstrate the feasibility of oTOF-based depth encoding by mitigating light leak in single-ended-readout Prism-PET detector modules using tapered crystals. Minimizing light leak also improved both energy-based DOI and coincidence timing resolutions. METHODS: The tapered Prism-PET module consists of a 16  × $\times$  16 array of 1.5  × $\times$  1.5  × $\times$  20  mm 3 ${\rm {mm}}^3$ lutetium yttrium oxyorthosillicate (LYSO) crystals, which are tapered down to 1.2  × $\times$  1.2  mm 2 ${\rm {mm}}^2$ at the crystal-readout interface. The LYSO array couples 4-to-1 to an 8  × $\times$  8 array of 3  × $\times$  3  mm 2 ${\rm {mm}}^2$ silicon photomultiplier (SiPM) pixels on the tapered end and to a segmented prismatoid light guide array on the opposite end. Performance of tapered and non-tapered Prism-PET detectors was experimentally characterized and evaluated by measuring flood histogram, energy resolution, energy-, and oTOF-based DOI resolutions, and coincidence timing resolution. Sensitivities of scanners using different Prism-PET detector designs were simulated using Geant4 application for tomographic emission (GATE). RESULTS: For the tapered (non-tapered) Prism-PET module, the measured full width at half maximum (FWHM) energy, timing, energy-based DOI, and oTOF-based DOI resolutions were 8.88 (11.18)%, 243 (286) ps, 2.35 (3.18) mm, and 5.42 (13.87) mm, respectively. The scanner sensitivities using non-tapered and tapered crystals, and 10 rings of detector modules, were simulated to be 30.9 and 29.5 kcps/MBq, respectively. CONCLUSIONS: The tapered Prism-PET module with minimized light leak enabled the first experimental report of oTOF-based depth encoding at the detector module level. It also enabled the utilization of thinner (i.e., 0.1 mm) inter-crystal spacing with barium sulfate as the reflector while also improving energy-based DOI and timing resolutions.

Performance evaluation of the FastIC readout ASIC with emphasis on Cherenkov emission in TOF-PET.

Objective.The efficient usage of prompt photons like Cherenkov emission is of great interest for the design of the next generation, cost-effective, and ultra-high-sensitivity time-of-flight positron emission tomography (TOF-PET) scanners. With custom, high power consuming, readout electronics and fast digitization the prospect of sub-300 ps FWHM with PET-sized BGO crystals have been shown. However, these results are not scalable to a full system consisting of thousands of detector elements.Approach.To pave the way toward a full TOF-PET scanner, we examine the performance of the FastIC ASIC with Cherenkov-emitting scintillators (BGO), together with one of the most recent SiPM detector developments based on metal trenching from FBK. The FastIC is a highly configurable ASIC with 8 input channels, a power consumption of 12 mW ch-1and excellent linearity on the energy measurement. To put the timing performance of the FastIC into perspective, comparison measurements with high-power consuming readout electronics are performed.Main results.We achieve a best CTR FWHM of 330 ps for 2 × 2 × 3 mm3and 490 ps for 2 × 2 × 20 mm3BGO crystals with the FastIC. In addition, using 20 mm long LSO:Ce:Ca crystals, CTR values of 129 ps FWHM have been measured with the FastIC, only slightly worse to the state-of-the-art of 95 ps obtained with discrete HF electronics.Significance.For the first time, the timing capability of BGO with a scalable ASIC has been evaluated. The findings underscore the potential of the FastIC ASIC in the development of cost-effective TOF-PET scanners with excellent timing characteristics.

Development of the quantitative PET prostate phantom (Q3P) for improved quality assurance of 18F-PSMA PET imaging in metastatic prostate cancer.

BACKGROUND: Phantoms are commonly used to evaluate and compare the performance of imaging systems given the known ground truth. Positron emission tomography (PET) scanners are routinely validated using the NEMA image quality phantom, in which lesions are modeled using 10 to 37 mm fillable spheres. The NEMA phantom neglects, however, to model focal (3-10-mm), high-uptake lesions that are increasingly observed in prostate-specific membrane antigen (PSMA) PET images. PSMA-targeting radiopharmaceuticals allow for enhanced detection of metastatic prostate cancers. As such, there is significant need to develop an updated phantom which considers both the quantitative and lesion detectability of this new paradigm in oncological PET imaging. PURPOSE: In this work, we present the Quantitative PET Prostate Phantom (Q3P); a portable and modular phantom that can be used to improve and harmonize imaging protocols for 18F-PSMA PET scans. METHODS: A one-piece cylindrical phantom was designed effectively in two halves, which we call modules. Module 1 was designed to mimic lesions in the presence of background, and Module 2 mimicked very high contrast conditions (i.e., very low background) that can be observed in 18F-PSMA PET scans. Shell-less radioactive spheres (3-16-mm) were cast using epoxy resin mixed with sodium-22 (22Na), a long half-life positron emitter with positron range similar to 18F. To establish realistic lesion contrast, the 22Na spheres were mounted in a cylindrical chamber that can be filled with an 18F background (module 1). Thirteen exchangeable spherical cavity inserts (3-37-mm) were machined in two parts and solvent welded together, and filled with 18F (50 kBq/mL) to model lesions with very high contrast (module 2). Five 2.5-min PET scans were acquired on a 5-ring GE Discovery MI PET/CT scanner (General Electric, USA). Lesions were segmented using 41% of SUVmax fixed thresholding (41% FT) and recovery coefficients (RCs) were computed from 5 noise realizations. RESULTS: The manufactured phantom is portable (5.7 kg) and scan preparation takes less than 40 min. The total 22Na activity is 250 kBq, allowing it to be shipped as an exempt package under International Atomic Energy Agency (IAEA) regulations. Recovery coefficients, computed using PSF modeling and no post-reconstruction smoothing, were 130.3% (16 mm), 147.1% (10 mm), 87.2% (6 mm), and 7.0% (3 mm) for RCmax, which decreased to 91.1% (16 mm), 90.6% (10 mm), 53.2% (6 mm), and 3.6% (3 mm) for RCmean in the 22Na spheres. Comparatively, 18F sphere recovery was 110.7% (17 mm), 123.6% (10 mm), 106.5% (7 mm), and 23.3% (3 mm) for RCmax, which was reduced to 76.7% (17 mm), 77.7% (10 mm), 66.8% (7 mm), and 13.5% (3 mm), for RCmean. CONCLUSIONS: A standardized imaging phantom was developed for lesion quantification assessment in 18F-PSMA PET images. The phantom is configurable, providing users with the opportunity to modify background activity levels or sphere sizes according to clinical demands. Distributed to the community, the Q3P phantom has the potential to enable better assessment of lesion quantification and harmonization of 18F-PSMA PET imaging, which may lead to more robust predictive metrics and better outcome prediction in metastatic prostate cancer.

A finely segmented semi-monolithic detector tailored for high-resolution PET.

BACKGROUND: Preclinical research and organ-dedicated applications use and require high (spatial-)resolution positron emission tomography (PET) detectors to visualize small structures (early) and understand biological processes at a finer level of detail. Researchers seeking to improve detector and image spatial resolution have explored various detector designs. Current commercial high-resolution systems often employ finely pixelated or monolithic scintillators, each with its limitations. PURPOSE: We present a semi-monolithic detector, tailored for high-resolution PET applications with a spatial resolution in the range of 1 mm or better, merging concepts of monolithic and pixelated crystals. The detector features LYSO slabs measuring (24 × 10 × 1) mm3, coupled to a 12 × 12 readout channel photosensor with 4 mm pitch. The slabs are grouped in two arrays of 44 slabs each to achieve a higher optical photon density despite the fine segmentation. METHODS: We employ a fan beam collimator for fast calibration to train machine-learning-based positioning models for all three dimensions, including slab identification and depth-of-interaction (DOI), utilizing gradient tree boosting (GTB). The data for all dimensions was acquired in less than 2 h. Energy calculation was based on a position-dependent energy calibration. Using an analytical timing calibration, time skews were corrected for coincidence timing resolution (CTR) estimation. RESULTS: Leveraging machine-learning-based calibration in all three dimensions, we achieved high detector spatial resolution: down to 1.18 mm full width at half maximum (FWHM) detector spatial resolution and 0.75 mm mean absolute error (MAE) in the planar-monolithic direction, and 2.14 mm FWHM and 1.03 mm MAE for DOI at an energy window of (435-585) keV. Correct slab interaction identification in planar-segmented direction exceeded 80%, alongside an energy resolution of 12.7% and a CTR of 450 ps FWHM. CONCLUSIONS: The introduced finely segmented, high-resolution slab detector demonstrates appealing performance characteristics suitable for high-resolution PET applications. The current benchtop-based detector calibration routine allows these detectors to be used in PET systems.

Whole Reconstruction-Free System Design for Direct Positron Emission Imaging From Image Generation to Attenuation Correction.

Direct positron emission imaging (dPEI), which does not require a mathematical reconstruction step, is a next-generation molecular imaging modality. To maximize the practical applicability of the dPEI system to clinical practice, we introduce a novel reconstruction-free image-formation method called direct µCompton imaging, which directly localizes the interaction position of Compton scattering from the annihilation photons in a three-dimensional space by utilizing the same compact geometry as that for dPEI, involving ultrafast time-of-flight radiation detectors. This unique imaging method not only provides the anatomical information about an object but can also be applied to attenuation correction of dPEI images. Evaluations through Monte Carlo simulation showed that functional and anatomical hybrid images can be acquired using this multimodal imaging system. By fusing the images, it is possible to simultaneously access various object data, which ensures the synergistic effect of the two imaging methodologies. In addition, attenuation correction improves the quantification of dPEI images. The realization of the whole reconstruction-free imaging system from image generation to quantitative correction provides a new perspective in molecular imaging.

Applicability of [18F]FDG/PET for investigating rosmarinic acid preconditioning efficacy in a global stroke model in mice

ABSTRACT Positron emission tomography (PET) is a non-invasive nuclear imaging technique that uses radiotracers to track cell activity. The radiopharmaceutical 18F-fluoro-2-deoxyglucose ([18F] FDG) is most commonly used in nuclear medicine for the diagnosis of various diseases, including stroke. A stroke is a serious condition with high mortality and morbidity rates. Rosmarinic acid (RA) is a promising therapeutic agent that exerts neuroprotective effects against various neurological diseases. Therefore, this study aimed to evaluate the applicability of [18F]FDG/PET for investigating the neuroprotective effects of RA in case of a global stroke model in mice. The [18F]FDG/PET technique facilitates the observation of ischemia and reperfusion injuries in the brain. Moreover, the recovery of glucose metabolism in three specific brain regions, the striatum, superior colliculus, and inferior colliculus, was observed after preconditioning with RA. It was concluded that the [18F]FDG/PET technique may be useful for stroke diagnosis and the assessment of treatment response. In addition, a long-term longitudinal study using biochemical analysis in conjunction with functional imaging may provide further conclusive results regarding the effect of RA on cerebral ischemia.

Uso del filtro hidrofóbico estéril de 0, 2 micras para fraccionamiento y dispensación de fludesoxiglucosa (18f-fdg) en el dispensador automático con celda caliente de flujo laminar blindada con filtro hepa / Use of sterile 0, 2 micron hydrophobic filter for fractionation and dispensing of fludeoxyglucose (18f-fdg) in the automatic dispenser with laminar flow hot cell shielded with hepa filter

INTRODUCCIÓN: La tomografía por emisión de positrones (PET) es un examen imagenológico que a través de un scanner para PET, la inyección intravenosa de un radiomarcador o radiosonda nos permite realizar exploraciones para detectar cáncer o determinar si hubo metástasis, evaluar la efectividad del tratamiento contra el cáncer o su recurrencia y evaluar pronóstico. Dentro de los radiomarcadores utilizados para el uso de PET la fludesoxiglucosa (18F-FDG) es un análogo de la glucosa y se acumula en células que utilizan glucosa como fuente primaria de energía y sobre todo las células que tienen un alto intercambio de glucosa como las células oncológicas. Su síntesis se lleva a cabo a través de un equipo especial que requiere de otros insumos para poder lograr en la fase final el fraccionamiento y dispensación exacta de este marcador. Para ello se utilizan filtros hidrofóbicos los cuales son individuales y se colocan en la celda caliente del equipo. En INEN durante el 2021 se estuvieron realizando diariamente PETs en la nueva torre cuya inversión incluyó la adquisición del equipo para la síntesis, fraccionamiento y dispensación del 18F-FDG; sin embargo, actualmente ya no se cuenta con el filtro hidrofóbico que se coloca en el equipo y logra la fase final del procedimiento de obtención de 18F-FDG. Para el correcto funcionamiento se requerirían según lo coordinado con el área usuaria un promedio de 400 filtros adquiridos anualmente. METODOLOGÍA: Se realizó una búsqueda sistemática de la información y una búsqueda dirigida en las principales entidades que elaboran tecnologías sanitarias y guías relacionadas al tema. Con respecto a la búsqueda dirigida se encontró 02 guías de entidades reconocidas a nivel internacional, en una de ellas no se encontró información sobre el procedimiento de síntesis, pero en otra si se encontró y se especificaban las características y la importancia de contar con un filtro hidrofóbico que permita obtener una muestra estéril y fraccionada en cantidades exactas para el paciente. En la búsqueda sistemática se encontró 02 revisiones narrativas que mencionan la importancia de utilizar los filtros hidrofóbicos como parte de la calidad del procedimiento de síntesis del radiofármaco para PET. A pesar de que sean revisiones narrativas, en ambos casos se brinda información con respecto al fraccionamiento, dispensación, esterilidad y la necesidad de filtros hidrofóbicos para la protección del personal de salud que realiza el procedimiento. DISCUSIÓN: Se agregó información sobre el uso de tomografía por emisión de positrones. Este ambiente que incluye el equipo entro en funcionamiento cuando se apertura la torre nueva en INEN. Por ello, la adquisición de los equipos que participan para lograr un adecuado uso del TEM formaron parte del presupuesto del proyecto de la torre nueva y ello incluyo el equipo de celda caliente que tiene como dificultad la necesidad de usar un filtro exclusivo que permita el fraccionamiento y dispensación del radiofármaco usado para el TEM. Durante los primeros meses como se disponía del dispositivo se ha venido trabajando de manera normal; sin embargo, a la actualidad solamente se está usando el TEM cuando el paciente cuenta de manera personal con el radiofármaco (18F-FDG) ya fraccionado y en dosis exactas individualizadas. Por otro lado, si el INEN adquiriera el radiomarcador fraccionado el precio se eleva comparado a adquirirlo para fraccionar a nivel institucional y el fraccionar a nivel institucional permite un uso más racional de las dosis que vienen en un vial. CONCLUSIONES: Finalmente; a pesar de que no se cuente con evidencia de alta calidad con respecto a la utilidad de los filtros hidrofóbicos, la evidencia encontrada aboga por la necesidad de que se apruebe su adquisición debido a que es un dispositivo necesario dentro de la última etapa de dispensación y fraccionamiento del FDG18 y el correcto funcionamiento del equipo de celda caliente en INEN.

Validation technique and improvements introduced in a new dedicated brain positron emission tomograph (CareMiBrain).

The goal of developing a PET dedicated to the brain (CareMiBrain) has evolved from its initial approach to diagnosis and monitoring of dementias, to the more ambitious of creating a revolutionary clinical pathway for the knowledge and personalized treatment of multiple neurological diseases. The main innovative feature of CareMiBrain is the use of detectors with continuous crystals, which allow a high resolution determination of the depth of annihilation photons interaction within the thickness of the scintillation crystal. The technical validation phase of the equipment consisted of a pilot, prospective and observational study whose objective was to obtain the first images (40 patients), analyze them and make adjustments in the acquisition, reconstruction and correction parameters, comparing the image quality of the CareMiBrain equipment with that of the whole-body PET/CT. Thanks to the team meetings and the joint analysis of the images, it was possible to detect its weak points and some of its causes. The calibration, acquisition and processing processes, as well as the reconstruction, were optimized, the number of iterations was set to achieve the best signal-to-noise ratio, the random correction was optimized and a post-processing algorithm was included in the reconstruction algorithm. The main technical improvements implemented in this phase of technical validation carried out through collaboration of the Services of Nuclear Medicine and Neurology of the Hospital Clínico San Carlos with the Spanish company Oncovision will be exposed in a project financed with funds from the European Union (Horizon 2020 innovation program, 713323).