Imaging the blood-brain barrier (BBB) permeability of molecular PET tracers may allow pathway-specific assessment of the diverse transport mechanisms expressed at the BBB. However, PET quantification of BBB permeability typically requires dual-tracer protocols involving a flow tracer, increasing methodological complexity and clinical burden. We evaluated a single-tracer dynamic PET method for quantifying the BBB permeability-surface area (PS) of [18F]fluorodeoxyglucose (FDG) against the conventional dual-tracer method. Our method uses high-temporal resolution imaging (1 s/frame), an image-derived arterial input function, and distributed kinetic modelling to simultaneously estimate cerebral blood flow (CBF) and transvascular transport rate K1, from which BBB PS is calculated via the Renkin-Crone equation. Single-tracer and conventional dual-tracer PS estimates were compared in 18 volunteers scanned with the flow-tracer [11C]butanol and [18F]FDG PET. Single-tracer [18F]FDG PS estimates had 3.7% mean bias and 4.2% standard deviation of differences compared to dual-tracer estimates. This was enabled by strong agreement between [18F]FDG and [11C]butanol CBF estimates (Pearson R = 0.85, p < 0.001; mean difference: -0.057 ± 0.078 mL/min/cm3). These results demonstrate that high-temporal resolution dynamic PET enables single-tracer quantification of both CBF and BBB PS without a dedicated flow tracer, expanding opportunities for quantitative studies of molecular BBB transport across a broad range of tracers and disorders.

In positron emission tomography (PET), time-of-flight (TOF) information localizes source positions along lines of response. Cherenkov-radiator-integrated microchannel-plate photomultiplier tubes have achieved 30-ps TOF resolution, demonstrating cross-sectional imaging without reconstruction. Such ultrafast TOF detectors would free PET from conventional ring geometries. Therefore, this study aimed at investigating imaging characteristics of a dual-panel PET with ultrafast TOF detectors using Geant4 simulation. Two detector panels (137 & times; 137 mm(2)), which consisted of 5.0-mm thick bismuth germanate pixelized crystals with a 5.75-mm pitch, were placed face-to-face at a 300-mm distance. Imaging characteristics with various TOF resolutions from 30 to 90 ps were evaluated. Because, degraded efficiency may cancel TOF gain in image quality, detection efficiency was also parameterized by reducing coincidence counts. Data acquisitions for a numerical multirod and uniform phantom (21 MBq) and a modified NEMA NU2 image quality phantom were simulated for 600 s. Results of the maximum likelihood expectation maximization (MLEM) reconstruction were compared with those of a backprojection (i.e., no reconstruction). The dual-panel PET required a 40-ps TOF resolution to have a similar spatial resolution to that of a non-TOF ring PET (300-mm in diameter) for the same detection efficiency. TOF showed benefit in the reconstruction of image quality phantom with 40% efficiency, and the image noise with 20% efficiency at 30-ps TOF was similar to the complete efficiency at 40-ps TOF. MLEM provided better imaging performance than backprojection, even at 30-ps TOF. The feasibility of the proposed dual-panel PET was shown.

We present a large whole-body and total-body curated dataset of dual-modality 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) studies, consisting of 1,683 PET/CT images and the corresponding CT-derived segmentations of 130 target regions. This multi-center dataset includes images from individuals without overt disease and patients with a range of malignant and inflammatory pathologies, including arthritis, lymphoma, and melanoma, as well as cancers of the lung, head-neck, and genito-urinary tract. Target regions were first automatically segmented from CT images using an in-house software and subsequently verified and corrected by physicians-in-training. In total, the segmented regions encompass 130 volumes, including abdominal organs, muscles, bones, cardiac subregions, vessels, adipose tissue, and skeletal muscle around the third lumbar vertebra. PET/CT images and corresponding CT-derived segmentations are provided in anonymized NIfTI format. The dataset can be used for deep learning training, validation, or multi-modality image analysis and thus fills an important gap in available resources to advance the use of PET/CT data in clinical management.

Precise measurement of radiation has long played a vital role in a wide range of research and industrial fields, from fundamental physics beyond the Standard Model to medical imaging such as time-of-flight positron emission tomography. Developing radiation detectors that achieve high timing precision-on the order of a few tens of picoseconds-and energy measurement capabilities remains indispensable yet challenging. In this study, we developed two types of scintillator-integrated microchannel plate photomultiplier tubes (SCI-IMPs), one incorporating barium fluoride, and the other bismuth germanate, to enable simultaneous high-precision timing and energy measurements. To evaluate their performance over a wide energy range from keV- to GeV-scale, electron-positron annihilation gamma rays and cosmic ray muons were used. For energy measurements, both detectors achieved an energy resolution of approximately 35% at 511 keV. For timing measurements using 511 keV, coincidence time resolutions (CTRs) of approximately 50 ps full width at half maximum (FWHM) were obtained for both detectors. In contrast, for cosmic ray muon experiments where cosmic ray muon energy is typically on the order of GeV, CTRs were measured to be 25.1 and 16.8 ps FWHM for barium fluoride- and bismuth germanate-based detectors, respectively. The versatile scintillator-integration technique established in this study can broaden the applicability of the newly developed SCI-IMPs. In particular, these results demonstrate that the developed detectors push the boundaries of timing performance while retaining energy measurement and hold promise for future applications in fundamental physics experiments and medical imaging.

Objectives To test the hypothesis that recently-developed total body-positron emission tomography (TB-PET) imaging with integrated computed tomography (CT) will enable low-dose, quantitative, domain-specific evaluation of the total inflammatory burden of psoriatic arthritis (PsA) and associate with established outcome measures of the clinical domains of PsA.Methods Seventy-one adult participants (40 with PsA, 16 with rheumatoid arthritis (RA), and 15 with osteoarthritis (OA)) underwent 20-min TB-PET/CT scans using [18F]FDG, a glucose analogue radiotracer. [18F]FDG uptake was assessed qualitatively and quantitatively. Rheumatological examinations were performed prior to the scan. For both evaluations, domain-specific assessments included 68 joints, 6 entheses, 20 nails, axial disease and dactylitis.Results [18F]FDG PET uptake consistent with joint involvement and enthesitis was noted in 100% of participants with PsA. Other features included nail matrix pathology (53%), spinal involvement (60%), active sacroiliitis (13%) and dactylitis (10%). Patterns of [18F]FDG uptake in PsA differed from those in participants with RA or OA. There was a high concordance between TB-PET measures and the domain-specific assessments of the joint (75%), entheseal (79%) and nail (65%) pathology. TB-PET was positive for an additional 15% of joints, 20% of entheses and 13% of nails that were negative on clinical assessments.Conclusion TB-PET/CT identified inflammatory pathologies characteristic to all clinical domains of PsA and thus provided an in vivo evaluation of systemic PsA inflammatory burden. This promising tool may further contribute to identifying pathologies that may be occult, provide biomarkers to diagnose and differentiate PsA at an early stage, and to monitor early treatment response.

Positron emission tomography (PET) detectors suffer from time-walk when the leading edge discriminator is employed for timing pick-off as well as a timing-shift when thick crystals are utilized due to the depth-of-interaction (DOI) effect. In this study, a combined time-walk and timing-shift correction method was proposed for dual-ended readout PET detectors. To evaluate the proposed method, a pair of dual-ended readout PET detectors was constructed. Each detector was based on two Hamamatsu S14161-3050-08 silicon photomultiplier (SiPM) arrays coupled to both ends of an 8 × 8 arrays of 3.1 × 3.1 × 20 mm3 LYSO crystals with a 3.2 mm pitch. By employing the relationship between the energies and detected time differences of events, the time-walk and timing-shift were effectively corrected. The coincidence time resolution of the two detectors improved from 260.7 ± 1.0 ps to 229.4 ± 1.0 ps when a 400-650 keV energy window was used to select events. These results demonstrate the effectiveness of the proposed time-walk and timing-shift correction method.

Neuroimaging of blood-brain barrier permeability has been instrumental in identifying its broad involvement in neurological and systemic diseases. However, current methods evaluate the blood-brain barrier mainly as a structural barrier. Here we developed a non-invasive positron emission tomography method in humans to measure the blood-brain barrier permeability of molecular radiotracers that cross the blood-brain barrier through its molecule-specific transport mechanism. Our method uses high-temporal resolution dynamic imaging and kinetic modeling for multiparametric imaging and quantification of the blood-brain barrier permeability-surface area product of molecular radiotracers. We show, in humans, our method can resolve blood-brain barrier permeability across three radiotracers and demonstrate its utility in studying brain aging and brain-body interactions in metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to effectively study the molecular permeability of the human blood-brain barrier in vivo using the large catalogue of available molecular positron emission tomography tracers.

Objective. Position-sensitive silicon photomultipliers (PS-SiPMs) are promising photodetectors for ultra-high spatial resolution small-animal positron emission tomography (PET) scanners. This paper evaluated the performance of the latest generation of linearly-graded SiPMs (LG-SiPMs), a type of PS-SiPM, for ultra-high spatial resolution PET applications using LYSO arrays from two vendors.Approach. Two dual-ended readout detectors were developed by coupling LG-SiPMs to both ends of the two LYSO arrays. Each LG-SiPM has an active area of 9.8 × 9.8 mm2. Both LYSO arrays consist of 20 × 20 arrays of 0.44 × 0.44 × 20 mm3polished LYSOs with a pitch of 0.5 mm. The performance of the two detectors was compared in terms of flood histogram, energy resolution, timing resolution, and depth-of-interaction (DOI) resolutions.Main results. Flood histograms showed clear identification of all LYSO elements except for some edge crystals due to the larger size of the LYSO arrays compared to the active area of the LG-SiPMs and the misalignment between LG-SiPMs and LYSO arrays in the assembled detectors. At a bias voltage of 37.0 V, the detectors utilizing the Tianle LYSO array and EBO LYSO array provided energy resolutions of 17.5 ± 2.2 and 18.6 ± 2.0%, timing resolutions of 0.75 ± 0.03 and 0.78 ± 0.03 ns, and DOI resolutions of 2.16 ± 0.15 and 2.31 ± 0.12 mm, respectively.Significance. The results presented in this paper demonstrate that the new generation LG-SiPMs are promising photodetectors for ultra-high spatial resolution small-animal PET scanner applications.

The standard Patlak plot, a simple yet efficient model, is widely used to describe irreversible tracer kinetics for dynamic PET imaging. Its widespread application to whole-body parametric imaging remains constrained because of the need for a full-time-course input function (e.g., 1 h). In this paper, we demonstrate the relative Patlak (RP) plot, which eliminates the need for the early-time input function, for total-body parametric imaging and its application to 20-min clinical scans acquired in list mode. Methods: We conducted a theoretic analysis to indicate that the RP intercept b' is equivalent to a ratio of the SUV relative to the plasma concentration, whereas the RP slope Ki' is equal to the standard Patlak Ki (net influx rate) multiplied by a global scaling factor for each subject. One challenge in applying RP to a short scan duration (e.g., 20 min) is the resulting high noise in the parametric images. We applied a self-supervised deep-kernel method for noise reduction. Using the standard Patlak plot as the reference, the RP method was evaluated for lesion quantification, lesion-to-background contrast, and myocardial visualization in total-body parametric imaging in 22 human subjects (12 healthy subjects and 10 cancer patients) who underwent a 1-h dynamic 18F-FDG scan. The RP method was also applied to the dynamic data reconstructed from a clinical standard 20-min list-mode scan either at 1 or 2 h after injection for 2 cancer patients. Results: We demonstrated that it is feasible to obtain high-quality parametric images from 20-min scans using RP parametric imaging with a self-supervised deep-kernel noise-reduction strategy. The RP slope Ki' was highly correlated with the standard Patlak Ki in lesions and major organs, demonstrating its quantitative potential across subjects. Compared with conventional SUVs, the Ki' images significantly improved lesion contrast and enabled visualization of the myocardium for potential cardiac assessment. The application of the RP parametric imaging to the 2 clinical scans also showed similar benefits. Conclusion: Using total-body PET with the RP approach, it is feasible to generate parametric images using data from a 20-min clinical list-mode scan.

Past efforts to measure blood flow with the widely available radiotracer 18F-FDG were limited to tissues with high 18F-FDG extraction fraction. In this study, we developed an early dynamic 18F-FDG PET method with high-temporal-resolution (HTR) kinetic modeling to assess total-body blood flow based on deriving the vascular phase of 18F-FDG transit and conducted a pilot comparison study against a 11C-butanol flow-tracer reference. Methods: The first 2 min of dynamic PET scans were reconstructed at HTR (60 × 1 s/frame, 30 × 2 s/frame) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate as a surrogate of blood flow, our method directly estimated blood flow using a distributed kinetic model (adiabatic approximation to tissue homogeneity [AATH] model). To validate our 18F-FDG measurements of blood flow against a reference flow-specific radiotracer, we analyzed total-body dynamic PET images of 6 human participants scanned with both 18F-FDG and 11C-butanol. An additional 34 total-body dynamic 18F-FDG PET images of healthy participants were analyzed for comparison against published blood-flow ranges. Regional blood flow was estimated across the body, and total-body parametric imaging of blood flow was conducted for visual assessment. AATH and standard compartment model fitting was compared using the Akaike information criterion at different temporal resolutions. Results: 18F-FDG blood flow was in quantitative agreement with flow measured from 11C-butanol across same-subject regional measurements (Pearson correlation coefficient, 0.955; P < 0.001; linear regression slope and intercept, 0.973 and -0.012, respectively), which was visually corroborated by total-body blood-flow parametric imaging. Our method resolved a wide range of blood-flow values across the body in broad agreement with published ranges (e.g., healthy cohort values of 0.51 ± 0.12 mL/min/cm3 in the cerebral cortex and 2.03 ± 0.64 mL/min/cm3 in the lungs). HTR (1-2 s/frame) was required for AATH modeling. Conclusion: Total-body blood-flow imaging was feasible using early dynamic 18F-FDG PET with HTR kinetic modeling. This method may be combined with standard 18F-FDG PET methods to enable efficient single-tracer multiparametric flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience.

Combined PET/CT imaging provides critical insights into both anatomic and molecular processes, yet traditional single-tracer approaches limit multidimensional disease phenotyping; to address this, we developed the PET Unified Multitracer Alignment (PUMA) framework-an open-source, postprocessing tool that multiplexes serial PET/CT scans for comprehensive voxelwise tissue characterization. Methods: PUMA utilizes artificial intelligence-based CT segmentation from multiorgan objective segmentation to generate multilabel maps of 24 body regions, guiding a 2-step registration: affine alignment followed by symmetric diffeomorphic registration. Tracer images are then normalized and assigned to red-green-blue channels for simultaneous visualization of up to 3 tracers. The framework was evaluated on longitudinal PET/CT scans from 114 subjects across multiple centers and vendors. Rigid, affine, and deformable registration methods were compared for optimal coregistration. Performance was assessed using the Dice similarity coefficient for organ alignment and absolute percentage differences in organ intensity and tumor SUVmean Results: Deformable registration consistently achieved superior alignment, with Dice similarity coefficient values exceeding 0.90 in 60% of organs while maintaining organ intensity differences below 3%; similarly, SUVmean differences for tumors were minimal at 1.6% ± 0.9%, confirming that PUMA preserves quantitative PET data while enabling robust spatial multiplexing. Conclusion: PUMA provides a vendor-independent solution for postacquisition multiplexing of serial PET/CT images, integrating complementary tracer data voxelwise into a composite image without modifying clinical protocols. This enhances multidimensional disease phenotyping and supports better diagnostic and therapeutic decisions using serial multitracer PET/CT imaging.

The image quality of positron emission tomography (PET) can be significantly enhanced by using time-of-flight (TOF) and depth-of-interaction (DOI) information. PET detectors are pivotal in determining the TOF and DOI capabilities of PET scanners. This study developed and evaluated TOF-DOI PET detectors based on the dual-ended readout method and lutetium-yttrium oxyorthosilicate (LYSO) arrays with two different pitches and reflector configurations. Specifically, the performance of detectors based on three types of LYSO arrays with 20 mm thickness, 8 × 8 arrays with a 3.2 mm pitch, 16 × 16 arrays with a 1.6 mm pitch and normal reflectors, and 16 × 16 arrays with a 1.6 mm pitch and partial short reflectors, were assessed. Hamamatsu S14161-3050-08 silicon photomultiplier arrays were used as the photodetectors, and PETsys TOFPET2 was used as the readout electronics. The flood histograms showed that all crystals in the three types of LYSO arrays were clearly resolved. The detectors based on the 8 × 8 LYSO arrays provided a coincidence timing resolution (CTR) of 207 ± 5 ps and a DOI resolution of 3.9 ± 0.6 mm. The detectors based on the 16 × 16 LYSO arrays with normal reflectors provided a CTR of 218 ± 7 ps and a DOI resolution of 2.6 ± 0.2 mm. In comparison, the detector based on the 16 × 16 LYSO arrays with partial short reflectors provided a CTR of 228 ± 11 ps and a DOI resolution of 2.9 ± 0.3 mm, and superior crystal resolvability compared to the detectors based on the 16 × 16 LYSO arrays with normal reflectors. These detectors are promising candidates for developing whole-body and brain PET scanners, offering effective sensitivity and uniform spatial resolution improvements across the field-of-view.

Positron emission tomography (PET) is the most sensitive biomedical imaging modality for noninvasively detecting and visualizing positron-emitting radiopharmaceuticals within a subject. In PET, measuring the time-of-flight (TOF) information for each pair of 511 keV annihilation photons improves effective sensitivity but requires high timing resolution. Hybrid materials that emit both scintillation and Cherenkov photons, such as bismuth germanate, recently offer the potential for more precise timing information from Cherenkov photons while maintaining adequate energy resolution from scintillation photons. However, a significant challenge in using such hybrid materials for TOF PET applications lies in the event-dependent timing spread caused by the mixed detection of Cherenkov and scintillation photons due to relatively lower production of Cherenkov photons. This study introduces an innovative approach by segmenting silicon photomultiplier (SiPM) pixels coupled to a single crystal, rather than using traditional SiPMs that are as large as or larger than the crystals they read. We demonstrated that multiple timestamps and photon counts obtained from the segmented SiPM can classify events by providing temporal photon density, effectively addressing this challenge. The approach and findings would lead to new opportunities in applications that require precise timing and photon counting.

Quantitative molecular imaging with PET can offer insights into physiologic and pathologic processes and is widely used for studying brain disorders. The NeuroEXPLORER is a recently developed dedicated brain PET system offering high spatial resolution and high sensitivity with an extended axial length. This study evaluated the quantitative precision and accuracy of the NeuroEXPLORER with phantom and human data for a variety of imaging conditions that are relevant to dynamic neuroimaging studies. Methods: Thirty-minute scans of an image quality (IQ) phantom and a 3-dimensional Hoffman brain phantom filled with [18F]FDG were performed over 13 h, covering phantom activities of 1.3-177 MBq. Furthermore, a uniform cylindric phantom filled with 558 MBq of 11C was scanned for 4 h. Quantitative accuracy was assessed using the contrast recovery coefficient (CRC), background variability, and background bias in the IQ phantom, the recovery coefficients (RCs) in the Hoffman phantom, and the bias in the uniform phantom. Results were compared at delayed time points, with different reconstruction parameters and frame lengths down to 1 s. Moreover, randomly subsampled frames of 2 imaging time points (0-2 min and 60-90 min) from a dynamic scan of a healthy volunteer with a 177-MBq injected dose of (R)-4-(3-fluoro-5-(fluoro-18F)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one ([18F]SynVesT-1) were used to assess quantification of brain uptake and image-derived input function extraction. Results: Negligible effects were observed on CRC and background bias with 3-177 MBq in the IQ phantom, and bias was less than 5% with 1-558 MBq in the uniform phantom. RC variations were within ±1% with 2-169 MBq in the Hoffman phantom, showcasing the system's high spatial resolution and high sensitivity. Short-frame reconstructions of the 60- to 90-min healthy-volunteer scan showed a ±1% mean difference in quantification of brain uptake for frame lengths down to 30 s and demonstrated the feasibility of measuring image-derived input function with mean absolute differences below 10% for frame lengths down to 1 s. Conclusion: The NeuroEXPLORER, with its high detection sensitivity, maintains high precision and accuracy across a wide range of imaging conditions beyond those evaluated in standard performance tests. These results demonstrate its potential for quantitative neuroimaging applications.

Semi monolithic detector designs with a series of stacked thin monolithic scintillator plates and side readout are an attractive approach for potentially achieving very high performance in a positron emission tomography (PET) scanner. In this work, a simulation study of a single layer monolithic detector module was performed with side read out of scintillation light using GATEv8.2. In this design, a single layer LSO crystal was used with dimensions 40 mm*40 mm*40 mm, with 0.60 mm thickness of the ESR (enhanced specular reflector) films covering the crystal's top and bottom surfaces. The photons generated in the scintillation process induced by the gamma ray hitting the crystal were detected by four 1*8 SiPM (silicon photomultiplier) arrays placed along the four sides of the crystal. The scintillation light distribution detected by all of the 32 SiPMs surrounding the crystal layer was then used to extract the gamma-crystal interaction location based on machine learning analysis. In this work, the spatial resolution of the detector module was explored when analog signals from each of the 32 SiPMs were summed to 28, 24, 20, 16, 12, 8, and 4 total outputs. This study showed that good spatial resolution can be achieved even when the number of read out channels is decreased by multiplexing, which can reduce the overall detector manufacturing cost.

We present a novel anti-coincidence technique combined with active shielding to reduce crosstalk from PET tracers to SPECT data acquisition in a proposed simultaneous PET/SPECT scanner. By detecting coincidence events between PET and SPECT detectors, the method identifies and rejects scattered photons during event acquisition. It is compatible with conventional scatter correction algorithms and remains effective in lowactivity scenarios. To evaluate the effectiveness of this technique, we implemented the technique in a simulated simultaneous PET/SPECT system using GEANT4. Simulation results demonstrate a $\boldsymbol{\sim} \mathbf{85\%}$ reduction in down-scattered events, leading to substantial improvements in projection-domain image quality: SNR increased from 0.29 to 1.48, and NECR improved from 41 cps to 89.3 cps, compared to the results without using anticoincidence and active shielding. In the reconstructed phantom images, CNR improved from 7.25 to $\mathbf{28.23}$. These results highlight the technique's potential to significantly enhance image quality in hybrid PET/SPECT systems and therefore allow imaging of lowactivity single photon emitters (such as therapeutic alpha-emitters) with simultaneous PET acquisition.