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Purpose: The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes.Methods: Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Three observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software.Results: Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472).Conclusion: Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival. [ABSTRACT FROM AUTHOR]

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 K i ' is equal to the standard Patlak K i (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 18 F-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 K i ' was highly correlated with the standard Patlak K i in lesions and major organs, demonstrating its quantitative potential across subjects. Compared with conventional SUVs, the K i ' 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., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Background & Aims: Brown adipose tissue (BAT) has been mainly investigated as a potential target against cardiometabolic disease, but it has also been linked to cancer-related outcomes. Although preclinical data support that BAT and the thermogenic adipocytes in white adipose tissue may play an adverse role in the pathogenesis of cancer cachexia, results from studies in patients have reported inconsistent results. The purpose of this study was to examine the interrelationship between presence of detectable BAT, changes in body weight, and cachexia in patients with cancer. We hypothesized that evidence of BAT at cancer diagnosis would be associated with greater weight loss and risk of cancer cachexia up to a year after cancer diagnosis., Methods: We conducted a retrospective cohort study in treatment-naïve patients with detectable BAT (BAT+, n = 57) and without evidence of BAT (BAT-, n = 73) on 2-deoxy-2-[ 18 F]fluoro-d-glucose positron emission tomography-computed tomography ( 18 F-FDG-PET-CT) imaging performed for cancer staging (2004-2020). Patients' clinical, demographic, and anthropometric characteristics were extracted from their electronic medical record for up to a year after diagnosis. The two groups were a priori matched for demographic, anthropometric, and disease-related characteristics at diagnosis, as well as for season and outdoor temperature on the day of the PET-CT scan. Cancer cachexia was defined as weight loss greater than 5 % or 2 % if body mass index was lower than 20 kg/m 2 . Poisson regression models were fitted to estimate the relative risk (RR) for developing cancer cachexia over the 1-year follow-up among BAT+ compared to BAT- patients., Results: The BAT+ group experienced a lower magnitude of weight loss compared with the BAT- group during the 1-year follow-up (p = 0.014 for interaction between BAT status and time). The risk for cancer cachexia was 44 % lower in the BAT+ than the BAT- group, adjusted for age, sex, outdoor temperature on the day of the 18 F-FDG-PET-CT imaging, cancer site and stage (RR: 0.56, 95 % CI: 0.32 to 0.97)., Conclusion: Contrary to our original hypothesis, evidence of BAT assessed by 18 F-FDG-PET-CT imaging at cancer diagnosis was associated with greater body weight maintenance and lower risk for developing cancer cachexia up to one year after diagnosis. Larger, prospective studies and mechanistic experiments are needed to expand and identify the causal factors of our observations., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 [ 18 F]FDG were performed over 13 h, covering phantom activities of 1.3-177 MBq. Furthermore, a uniform cylindric phantom filled with 558 MBq of 11 C 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- 18 F)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one ([ 18 F]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., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Inflammatory disorders historically have been difficult to monitor with conventional PET imaging due to limitations including radiation exposure, lack of validated imaging biomarkers, low spatial resolution, and long acquisition durations. However, the recent development of long-axial field-of-view (LAFOV) PET/CT scanners may allow utilization of novel noninvasive biomarkers to diagnose, predict outcomes, and monitor therapeutic response of inflammatory conditions. LAFOV PET scanners can image most of the human body (if not the entire body) simultaneously in one bed position, with improved signal collection efficiency compared to conventional PET scanners. This allows for imaging with shorter acquisition durations, decreased injected radiotracer dose, prolonged uptake times, or a combination of any of these. In addition, LAFOV PET scanners enable whole-body dynamic imaging. Altogether, these intrinsically superior capabilities in assessing both local and systemic diseases, have allowed these scanners to make increasingly significant contributions to the assessment of inflammatory conditions. This review aims to further explore the role and benefits of LAFOV scanners for imaging various inflammatory conditions while addressing future developments and challenges faced by this technology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: UC Davis has a research agreement and a sales-based revenue sharing agreement with United Imaging Healthcare, the manufacturer of the total-body PET/CT scanner. No other potential conflicts of interest relevant to this article exist including employment, royalties, stock options, or patents. The authors would like to acknowledge funding from the National Institutes of Health via grants R01 AR076088, R01 AR085314 and R01 CA206187. Lorenzo Nardo is principal investigator of a service agreement with United Imaging Healthcare. Lorenzo Nardo has been the PI of more than 1 service agreements with United Imaging Healthcare. Lorenzo Nardo is mentioned in a recurrent gift from United Imaging Healthcare that support the American Board of Radiology Alternate Pathway at UC Davis. Lorenzo Nardo is site PI of clinical trials supported by Novartis Pharmaceuticals Corporation. Lorenzo Nardo is PI of a clinical trial supported by Telix Pharmaceuticals. Lorenzo Nardo is PI of clinical trial supported by Lantheus Medical Imaging. Lorenzo Nardo is PI of a clinical trials supported by Curium Pharma Healthcare. Lorenzo Nardo is Co-I of a clinical trial supported by Lilly. Lorenzo Nardo has a SPEAKING ENGAGEMENT AGREEMENT with Lilly. Lorenzo Nardo is associate editor for Current Problems in Cancer. Lorenzo Nardo served a panel reviewer for the European Health and Digital Executive Agency. Lorenzo Nardo served a panel reviewer for the National Cancer Center Network (NCCN) – multiple panels. Lorenzo Nardo served a panel reviewer for the National Institutes for Health (NIH). Lorenzo Nardo is PI and co-PI of multiple National Institutes for Health (NIH) grants. Lorenzo Nardo served a committee member for the American Board of Radiology - multiple committees. Ramsey Badawi is an investigator with Lilly. Ramsey Badawi is an investigator with United Imaging Healthcare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 were 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 joint (75%), entheseal (79%) and nail (65%) pathology. TB-PET was positive for an additional 15% joints, 20% entheses and 13% 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

X-ray computed tomography (CT) in PET/CT is commonly operated with a single energy, resulting in a limitation of lacking tissue composition information. Dual-energy (DE) spectral CT enables material decomposition by using two different x-ray energies and may be combined with PET for improved multimodality imaging, but would either require hardware upgrade or increase radiation dose due to the added second x-ray CT scan. Recently proposed PET-enabled DECT method allows dual-energy spectral imaging using a conventional PET/CT scanner without the need for a second x-ray CT scan. A gamma-ray CT (gCT) image at 511 keV can be generated from the existing time-of-flight PET data with the maximum-likelihood attenuation and activity (MLAA) approach and is then combined with the low-energy x-ray CT image to form dual-energy spectral imaging. To improve the image quality of gCT, a kernel MLAA method was further proposed by incorporating x-ray CT as a priori information. The concept of this PET-enabled DECT has been validated using simulation studies, but not yet with 3D real data. In this work, we developed a general open-source implementation for gCT reconstruction from PET data and use this implementation for the first real data validation with both a physical phantom study and a human subject study on a uEXPLORER total-body PET/CT system. These results have demonstrated the feasibility of this method for spectral imaging and material decomposition.

Purpose: Dual-energy (DE) CT enables material decomposition by using two different x-ray energies and may be combined with PET for improved multimodality imaging. However, this increases radiation dose and may require a hardware upgrade due to the added second x-ray CT scan. The recently proposed PET-enabled DECT method allows dual-energy imaging using a conventional PET/CT scanner without the need to change scanner hardware or increase radiation exposure. Here we demonstrate the first-time physical phantom and patient data evaluation of this method., Methods: The PET-enabled DECT method reconstructs a gamma-ray CT (gCT) image at 511 keV from the time-of-flight PET data with the maximum-likelihood attenuation and activity (MLAA) approach and then combines this image with the low-energy x-ray CT images to form a dual-energy image pair for material decomposition. To improve the image quality of gCT, a kernel MLAA method was developed using the x-ray CT as a priori information. Here we developed a general open-source implementation for gCT reconstruction and used this implementation for the first real data validation using both physical phantom study and human-subject study. Results from PET-enabled DECT were compared using x-ray DECT as the reference. Further, we applied the PET-enabled DECT method in another patient study to evaluate bone lesions., Results: Compared to the standard MLAA, results from the kernel MLAA showed significantly improved image quality. PET-enabled DECT with the kernel MLAA was able to generate fractional images that were comparable to the x-ray DECT, with high correlation coefficients for both the phantom study and human subject study (R > 0.99). The application study also indicates that PET-enabled DECT has potential to characterize bone lesions., Conclusion: Results from this study have demonstrated the feasibility of this PET-enabled method for CT imaging and material decomposition. PET-enabled DECT shows promise to provide comparable results to x-ray DECT., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by Institution Review Board at University of California, Davis (IRB#: 1374902). Consent to participate: Informed consent was obtained from all participants enrolled in the study. Consent for publication: Consent to publish has been received from all participants. Conflict of interest: UC Davis has a revenue-sharing agreement with United Imaging Healthcare. No other potential conflicts of interest relevant to this article exist., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective. Penalty parameters in penalized likelihood positron emission tomography (PET) reconstruction are typically determined empirically. The cross-validation log-likelihood (CVLL) method has been introduced to optimize these parameters by maximizing a CVLL function, which assesses the likelihood of reconstructed images using one subset of a list-mode dataset based on another subset. This study aims to validate the efficacy of the CVLL method in whole-body imaging for cancer patients using a conventional clinical PET scanner. Approach. Fifteen lung cancer patients were injected with 243.7 ± 23.8 MBq of [ 18 F]FDG and underwent a 22 min PET scan on a Biograph mCT PET/CT scanner, starting at 60 ± 5 min post-injection. The PET list-mode data were partitioned by subsampling without replacement, with 20 minutes of data for image reconstruction using an in-house ordered subset expectation maximization algorithm and the remaining 2 minutes of data for cross-validation. Two penalty parameters, penalty strength β and Fair penalty function parameter δ , were subjected to optimization. Whole-body images were reconstructed, and CVLL values were computed across various penalty parameter combinations. The optimal image corresponding to the maximum CVLL value was selected by a grid search for each patient. Main results. The δ value required to maximize the CVLL value was notably small (⩽10 -6 in this study). The influences of voxel size and scan duration on image optimization were investigated. A correlation analysis revealed a significant inverse relationship between optimal β and scan count level, with a correlation coefficient of -0.68 ( p -value = 3.5 × 10 -5 ). The optimal images selected by the CVLL method were compared with those chosen by two radiologists based on their diagnostic preferences. Differences were observed in the selection of optimal images. Significance. This study demonstrates the feasibility of incorporating the CVLL method into routine imaging protocols, potentially allowing for a wide range of combinations of injected radioactivity amounts and scan durations in modern PET imaging., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Quantitative total-body PET imaging of blood flow can be performed with freely diffusible flow radiotracers such as 15 O-water and 11 C-butanol, but their short half-lives necessitate close access to a cyclotron. Past efforts to measure blood flow with the widely available radiotracer 18 F-fluorodeoxyglucose (FDG) were limited to tissues with high 18 F-FDG extraction fraction. In this study, we developed an early-dynamic 18 F-FDG PET method with high temporal resolution kinetic modeling to assess total-body blood flow based on deriving the vascular transit time of 18 F-FDG and conducted a pilot comparison study against a 11 C-butanol reference., Methods: The first two minutes of dynamic PET scans were reconstructed at high temporal resolution (60×1 s, 30×2 s) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate ( K 1 ) as a surrogate of blood flow, our method directly estimates blood flow using a distributed kinetic model (adiabatic approximation to the tissue homogeneity model; AATH). To validate our 18 F-FDG measurements of blood flow against a flow radiotracer, we analyzed total-body dynamic PET images of six human participants scanned with both 18 F-FDG and 11 C-butanol. An additional thirty-four total-body dynamic 18 F-FDG PET scans of healthy participants were analyzed for comparison against literature 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 by the Akaike Information Criterion at different temporal resolutions., Results: 18 F-FDG blood flow was in quantitative agreement with flow measured from 11 C-butanol across same-subject regional measurements (Pearson R=0.955, p<0.001; linear regression y=0.973x-0.012), 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 literature ranges (e.g., healthy cohort average: 0.51±0.12 ml/min/cm 3 in the cerebral cortex and 2.03±0.64 ml/min/cm 3 in the lungs, respectively). High temporal resolution (1 to 2 s) was critical to enabling AATH modeling over standard compartment modeling., Conclusions: Total-body blood flow imaging was feasible using early-dynamic 18 F-FDG PET with high-temporal resolution kinetic modeling. Combined with standard 18 F-FDG PET methods, this method may enable efficient single-tracer flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience., Competing Interests: Disclosure The University of California, Davis has a research agreement and a revenue sharing agreement with United Imaging Healthcare. This work was supported in part by National Institutes of Health (NIH) grants R01 EB033435 and R61 AT012187. The image data of healthy participants were acquired under the support of NIH R01 CA206187 and P30 CA093373. The other authors declare no competing interests.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18 F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18 F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of 18 F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers., Competing Interests: Competing interests The University of California, Davis has a research agreement and a revenue sharing agreement with United Imaging Healthcare. The other authors declare no competing interests.

Standard Patlak plot is widely used to describe FDG kinetics for dynamic PET imaging. Whole-body Patlak parametric imaging remains constrained due to the need for a full-time input function. Here, 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 clinical 20-min scan acquired in list-mode. We demonstrated that the RP intercept b' is equivalent to a ratio of standardized uptake value relative to the blood, while the RP slope Ki' is equal to the standard Patlak Ki multiplied by a global scaling factor for each subject. One challenge in applying RP to a short scan duration (20 min) is the high noise in parametric images. We applied a 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 with uEXPLORER in 22 human subjects who underwent a 1-h dynamic 18F-FDG scan. The RP method was also applied to the dynamic data regenerated from a clinical standard 20-min scan either at 1-h or 2-h post-injection for two cancer patients. We demonstrated that it is feasible to obtain high-quality parametric images from 20-min dynamic scans using the RP plot with a self-supervised deep-kernel noise reduction strategy. The RP Ki' highly correlated with Ki in lesions and major organs, demonstrating its quantitative potential across subjects. Compared to conventional SUVs, the Ki' images significantly improved lesion contrast and enabled visualization of the myocardium for potential cardiac assessment. The application of RP parametric imaging to two clinical scans also showed similar benefits. Total-body PET with the RP plot is feasible to generate parametric images from the dynamic data of a 20-min clinical scan.

Brown adipose tissue (BAT) in rodents appears to be an important tissue for the clearance of plasma branched-chain amino acids (BCAAs) contributing to improved metabolic health. However, the role of human BAT in plasma BCAA clearance is poorly understood. Here, we evaluate patients with prostate cancer who underwent positron emission tomography-computed tomography imaging after an injection of 18 F-fluciclovine (L-leucine analog). Supraclavicular adipose tissue (AT; primary location of human BAT) has a higher net uptake rate for 18 F-fluciclovine compared to subcutaneous abdominal and upper chest AT. Supraclavicular AT 18 F-fluciclovine net uptake rate is lower in patients with obesity and type 2 diabetes. Finally, the expression of genes involved in BCAA catabolism is higher in the supraclavicular AT of healthy people with high BAT volume compared to those with low BAT volume. These findings support the notion that BAT can potentially function as a metabolic sink for plasma BCAA clearance in people., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Our aim was to define a lower limit of reduced injected activity in delayed [ 18 F]FDG total-body (TB) PET/CT in pediatric oncology patients. Methods: In this single-center prospective study, children were scanned for 20 min with TB PET/CT, 120 min after intravenous administration of a 4.07 ± 0.49 MBq/kg dose of [ 18 F]FDG. Five randomly subsampled low-count reconstructions were generated using ¼, ⅛, [Formula: see text], and [Formula: see text] of the counts in the full-dose list-mode reference standard acquisition (20 min), to simulate dose reduction. For the 2 lowest-count reconstructions, smoothing was applied. Background uptake was measured with volumes of interest placed on the ascending aorta, right liver lobe, and third lumbar vertebra body (L3). Tumor lesions were segmented using a 40% isocontour volume-of-interest approach. Signal-to-noise ratio, tumor-to-background ratio, and contrast-to-noise ratio were calculated. Three physicians identified malignant lesions independently and assessed the image quality using a 5-point Likert scale. Results: In total, 113 malignant lesions were identified in 18 patients, who met the inclusion criteria. Of these lesions, 87.6% were quantifiable. Liver SUV mean did not change significantly, whereas a lower signal-to-noise ratio was observed in all low-count reconstructions compared with the reference standard ( P < 0.0001) because of higher noise rates. Tumor uptake (SUV max ), tumor-to-background ratio, and total lesion count were significantly lower in the reconstructions with [Formula: see text] and [Formula: see text] of the counts of the reference standard ( P < 0.001). Contrast-to-noise ratio and clinical image quality were significantly lower in all low-count reconstructions than with the reference standard. Conclusion: Dose reduction for delayed [ 18 F]FDG TB PET/CT imaging in children is possible without loss of image quality or lesion conspicuity. However, our results indicate that to maintain comparable tumor uptake and lesion conspicuity, PET centers should not reduce the injected [ 18 F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. This study investigates the potential of cloud-based serverless computing to accelerate Monte Carlo (MC) simulations for nuclear medicine imaging tasks. MC simulations can pose a high computational burden-even when executed on modern multi-core computing servers. Cloud computing allows simulation tasks to be highly parallelized and considerably accelerated. Approach. We investigate the computational performance of a cloud-based serverless MC simulation of radioactive decays for positron emission tomography imaging using Amazon Web Service (AWS) Lambda serverless computing platform for the first time in scientific literature. We provide a comparison of the computational performance of AWS to a modern on-premises multi-thread reconstruction server by measuring the execution times of the processes using between105and2·1010simulated decays. We deployed two popular MC simulation frameworks-SimSET and GATE-within the AWS computing environment. Containerized application images were used as a basis for an AWS Lambda function, and local (non-cloud) scripts were used to orchestrate the deployment of simulations. The task was broken down into smaller parallel runs, and launched on concurrently running AWS Lambda instances, and the results were postprocessed and downloaded via the Simple Storage Service. Main results. Our implementation of cloud-based MC simulations with SimSET outperforms local server-based computations by more than an order of magnitude. However, the GATE implementation creates more and larger output file sizes and reveals that the internet connection speed can become the primary bottleneck for data transfers. Simulating 10 9 decays using SimSET is possible within 5 min and accrues computation costs of about $10 on AWS, whereas GATE would have to run in batches for more than 100 min at considerably higher costs. Significance. Adopting cloud-based serverless computing architecture in medical imaging research facilities can considerably improve processing times and overall workflow efficiency, with future research exploring additional enhancements through optimized configurations and computational methods., (© 2024 IOP Publishing Ltd.)

Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation., Methods: The conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using 18 F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored., Results: The estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method., Conclusion: The proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging., Competing Interests: Declaration of competing interest UC Davis has a revenue-sharing agreement with United Imaging Healthcare. No other potential conflicts of interest relevant to this article exist., (Copyright © 2024. Published by Elsevier Inc.)

The lungs are supplied by both the pulmonary arteries carrying deoxygenated blood originating from the right ventricle and the bronchial arteries carrying oxygenated blood downstream from the left ventricle. However, this effect of dual blood supply has never been investigated using PET, partially because the temporal resolution of conventional dynamic PET scans is limited. The advent of PET scanners with a long axial field of view, such as the uEXPLORER total-body PET/CT system, permits dynamic imaging with high temporal resolution (HTR). In this work, we modeled the dual-blood input function (DBIF) and studied its impact on the kinetic quantification of normal lung tissue and lung tumors using HTR dynamic PET imaging. Methods: Thirteen healthy subjects and 6 cancer subjects with lung tumors underwent a dynamic 18 F-FDG scan with the uEXPLORER for 1 h. Data were reconstructed into dynamic frames of 1 s in the early phase. Regional time-activity curves of lung tissue and tumors were analyzed using a 2-tissue compartmental model with 3 different input functions: the right ventricle input function, left ventricle input function, and proposed DBIF, all with time delay and dispersion corrections. These models were compared for time-activity curve fitting quality using the corrected Akaike information criterion and for differentiating lung tumors from lung tissue using the Mann-Whitney U test. Voxelwise multiparametric images by the DBIF model were further generated to verify the regional kinetic analysis. Results: The effect of dual blood supply was pronounced in the high-temporal-resolution time-activity curves of lung tumors. The DBIF model achieved better time-activity curve fitting than the other 2 single-input models according to the corrected Akaike information criterion. The estimated fraction of left ventricle input was low in normal lung tissue of healthy subjects but much higher in lung tumors (∼0.04 vs. ∼0.3, P < 0.0003). The DBIF model also showed better robustness in the difference in 18 F-FDG net influx rate [Formula: see text] and delivery rate [Formula: see text] between lung tumors and normal lung tissue. Multiparametric imaging with the DBIF model further confirmed the differences in tracer kinetics between normal lung tissue and lung tumors. Conclusion: The effect of dual blood supply in the lungs was demonstrated using HTR dynamic imaging and compartmental modeling with the proposed DBIF model. The effect was small in lung tissue but nonnegligible in lung tumors. HTR dynamic imaging with total-body PET can offer a sensitive tool for investigating lung diseases., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Quantitative PET attenuation correction (AC) for cardiac PET/CT and PET/MR is a challenging problem. We propose and evaluate an AC approach that uses coincidences from a relatively weak and physically fixed sparse external source, in combination with that from the patient, to reconstruct μ -maps based on physics principles alone. The low 30 cm3 volume of the source makes it easy to fill and place, and the method does not use prior image data or attenuation map assumptions. Our supplemental transmission aided maximum likelihood reconstruction of attenuation and activity (sTX-MLAA) algorithm contains an attenuation map update that maximizes the likelihood of terms representing coincidences originating from tracer in the patient and a weighted expression of counts segmented from the external source alone. Both external source and patient scatter and randoms are fully corrected. We evaluated performance of sTX-MLAA compared to reference standard CT-based AC with FDG PET/CT phantom studies; including modeling a patient with myocardial inflammation. Through an ROI analysis we measured ≤ 5 % bias in activity concentrations for PET images generated with sTX-MLAA and a TX source strength ≥ 12.7 MBq, relative to CT-AC. PET background variability (from noise and sparse sampling) was substantially reduced with sTX-MLAA compared to using counts segmented from the transmission source alone for AC. Results suggest that sTX-MLAA will enable quantitative PET during cardiac PET/CT and PET/MR of human patients.

Objective. This study presents and evaluates a robust Monte Carlo-based scatter correction (SC) method for long axial field of view (FOV) and total-body positron emission tomography (PET) using the uEXPLORER total-body PET/CT scanner. Approach. Our algorithm utilizes the Monte Carlo (MC) tool SimSET to compute SC factors in between individual image reconstruction iterations within our in-house list-mode and time-of-flight-based image reconstruction framework. We also introduced a unique scatter scaling technique at the detector block-level for optimal estimation of the scatter contribution in each line of response. First image evaluations were derived from phantom data spanning the entire axial FOV along with image data from a human subject with a large body mass index. Data was evaluated based on qualitative inspections, and contrast recovery, background variability, residual scatter removal from cold regions, biases and axial uniformity were quantified and compared to non-scatter-corrected images. Main results. All reconstructed images demonstrated qualitative and quantitative improvements compared to non-scatter-corrected images: contrast recovery coefficients improved by up to 17.2% and background variability was reduced by up to 34.3%, and the residual lung error was between 1.26% and 2.08%. Low biases throughout the axial FOV indicate high quantitative accuracy and axial uniformity of the corrections. Up to 99% of residual activity in cold areas in the human subject was removed, and the reliability of the method was demonstrated in challenging body regions like in the proximity of a highly attenuating knee prosthesis. Significance. The MC SC method employed was demonstrated to be accurate and robust in TB-PET. The results of this study can serve as a benchmark for optimizing the quantitative performance of future SC techniques., (© 2024 Institute of Physics and Engineering in Medicine.)

Dual-energy computed tomography (DECT) enables material decomposition for tissues and produces additional information for PET/CT imaging to potentially improve the characterization of diseases. PET-enabled DECT (PDECT) allows the generation of PET and DECT images simultaneously with a conventional PET/CT scanner without the need for a second x-ray CT scan. In PDECT, high-energy γ -ray CT (GCT) images at 511 keV are obtained from time-of-flight (TOF) PET data and are combined with the existing x-ray CT images to form DECT imaging. We have developed a kernel-based maximum-likelihood attenuation and activity (MLAA) method that uses x-ray CT images as a priori information for noise suppression. However, our previous studies focused on GCT image reconstruction at the PET image resolution which is coarser than the image resolution of the x-ray CT. In this work, we explored the feasibility of generating super-resolution GCT images at the corresponding CT resolution. The study was conducted using both phantom and patient scans acquired with the uEXPLORER total-body PET/CT system. GCT images at the PET resolution with a pixel size of 4.0 mm × 4.0 mm and at the CT resolution with a pixel size of 1.2 mm × 1.2 mm were reconstructed using both the standard MLAA and kernel MLAA methods. The results indicated that the GCT images at the CT resolution had sharper edges and revealed more structural details compared to the images reconstructed at the PET resolution. Furthermore, images from the kernel MLAA method showed substantially improved image quality compared to those obtained with the standard MLAA method.

The world's first total-body PET/CT system has been in routine clinical and research use at UC Davis since 2019. The uEXPLORER total-body PET scanner has been designed with an axial field-of-view long enough to completely encompass most human subjects (194 cm or 76 inches long), allowing for a 15-68-fold gain in the PET signal collection efficiency over conventional PET scanners. A high-sensitivity PET scanner that can image the entire subject with a single bed position comes with new benefits and challenges to consider for efficient and practical use. In this chapter, we discuss the common clinical and research imaging protocols implemented at our institution, along with the appropriate technical and practical considerations of total-body PET imaging., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Tissue perfusion can be affected by physiology or disease. With the advent of total-body PET, quantitative measurement of perfusion across the entire body is possible. [ 11 C]-butanol is a perfusion tracer with a superior extraction fraction compared with [ 15 O]-water and [ 13 N]-ammonia. To develop the methodology for total-body perfusion imaging, a pilot study using [ 11 C]-butanol on the uEXPLORER total-body PET/CT scanner was conducted. Methods: Eight participants (6 healthy volunteers and 2 patients with peripheral vascular disease [PVD]) were injected with a bolus of [ 11 C]-butanol and underwent 30-min dynamic acquisitions. Three healthy volunteers underwent repeat studies at rest (baseline) to assess test-retest reproducibility; 1 volunteer underwent paired rest and cold pressor test (CPT) studies. Changes in perfusion were measured in the paired rest-CPT study. For PVD patients, local changes in perfusion were investigated and correlated with patient medical history. Regional and parametric kinetic analysis methods were developed using a 1-tissue compartment model and leading-edge delay correction. Results: Estimated baseline perfusion values ranged from 0.02 to 1.95 mL·min -1 ·cm -3 across organs. Test-retest analysis showed that repeat baseline perfusion measurements were highly correlated (slope, 0.99; Pearson r = 0.96, P < 0.001). For the CPT subject, the largest regional increases were in skeletal muscle (psoas, 142%) and the myocardium (64%). One of the PVD patients showed increased collateral vessel growth in the calf because of a peripheral stenosis. Comorbidities including myocardial infarction, hypothyroidism, and renal failure were correlated with variations in organ-specific perfusion. Conclusion: This pilot study demonstrates the ability to obtain reproducible measurements of total-body perfusion using [ 11 C]-butanol. The methods are sensitive to local perturbations in flow because of physiologic stressors and disease., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Conventional whole-body static 18 F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18 F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18 F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18 F-FDG delivery rate [Formula: see text] and the phosphorylation rate k 3 , as well as the macroparametric 18 F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18 F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18 F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18 F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18 F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. Contrast recovery coefficient (CRC) is essential for image quality (IQ) assessment in positron emission tomography (PET), typically measured according to the National Electrical Manufacturers Association (NEMA) NU 2 standard. This study quantifies systematic uncertainties of the CRC measurement by a numerical investigation of the effects from scanner-independent parameters like voxel size, region-of-interest (ROI) misplacement, and sphere position on the underlying image grid. Approach. CRC measurements with 2D and 3D ROIs were performed on computer-generated images of a NEMA IQ-like phantom, using voxel sizes of 1-4 mm for sphere diameters of 5-40 mm-first in absence of noise and blurring, then with simulated spatial resolution and image noise with varying noise levels. The systematic uncertainties of the CRC measurement were quantified from above variations of scanner-independent parameters. Subsampled experimental images of a NEMA IQ phantom were additionally used to investigate the impact of ROI misplacement at different noise levels. Main results. In absence of noise and blurring, systematic uncertainties were up to 28.8% and 31.0% with 2D and 3D ROIs, respectively, for the 10 mm sphere, with the highest impact from ROI misplacement. In all cases, smaller spheres showed higher uncertainties with larger voxels. Contrary to prior assumptions, the use of 3D ROIs did not exhibit less susceptibility for parameter changes. Experimental and computer-generated images both demonstrated considerable variations on individual CRC measurements when background coefficient-of-variation exceeded 20%, despite negligible effects on mean CRC. Significance. This study underscores the effect of scanner-independent parameters on reliability, reproducibility, and comparability of CRC measurements. Our findings highlight the trade-off between the benefits of smaller voxel sizes and noise-induced CRC fluctuations, which is not considered in the current version of the NEMA IQ standards. The results furthermore warrant adjustments to the standard to accommodate the advances in sensitivity and spatial resolution of current-generation PET scanners., (© 2023 Institute of Physics and Engineering in Medicine.)

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8 + T cell biodistribution in humans. A 89 Zr-labeled CD8-targeted minibody ( 89 Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals ( N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients ( N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

Total-body PET/CT images can be rendered to produce images of a subject's face and body. In response to privacy and identifiability concerns when sharing data, we have developed and validated a workflow that obscures (defaces) a subject's face in 3-dimensional volumetric data. Methods: To validate our method, we measured facial identifiability before and after defacing images from 30 healthy subjects who were imaged with both [ 18 F]FDG PET and CT at either 3 or 6 time points. Briefly, facial embeddings were calculated using Google's FaceNet, and an analysis of clustering was used to estimate identifiability. Results: Faces rendered from CT images were correctly matched to CT scans at other time points at a rate of 93%, which decreased to 6% after defacing. Faces rendered from PET images were correctly matched to PET images at other time points at a maximum rate of 64% and to CT images at a maximum rate of 50%, both of which decreased to 7% after defacing. We further demonstrated that defaced CT images can be used for attenuation correction during PET reconstruction, introducing a maximum bias of -3.3% in regions of the cerebral cortex nearest the face. Conclusion: We believe that the proposed method provides a baseline of anonymity and discretion when sharing image data online or between institutions and will help to facilitate collaboration and future regulatory compliance., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

We introduce the Fast Algorithm for Motion Correction (FALCON) software, which allows correction of both rigid and nonlinear motion artifacts in dynamic whole-body (WB) images, irrespective of the PET/CT system or the tracer. Methods: Motion was corrected using affine alignment followed by a diffeomorphic approach to account for nonrigid deformations. In both steps, images were registered using multiscale image alignment. Moreover, the frames suited to successful motion correction were automatically estimated by calculating the initial normalized cross-correlation metric between the reference frame and the other moving frames. To evaluate motion correction performance, WB dynamic image sequences from 3 different PET/CT systems (Biograph mCT, Biograph Vision 600, and uEXPLORER) using 6 different tracers ( 18 F-FDG, 18 F-fluciclovine, 68 Ga-PSMA, 68 Ga-DOTATATE, 11 C-Pittsburgh compound B, and 82 Rb) were considered. Motion correction accuracy was assessed using 4 different measures: change in volume mismatch between individual WB image volumes to assess gross body motion, change in displacement of a large organ (liver dome) within the torso due to respiration, change in intensity in small tumor nodules due to motion blur, and constancy of activity concentration levels. Results: Motion correction decreased gross body motion artifacts and reduced volume mismatch across dynamic frames by about 50%. Moreover, large-organ motion correction was assessed on the basis of correction of liver dome motion, which was removed entirely in about 70% of all cases. Motion correction also improved tumor intensity, resulting in an average increase in tumor SUVs by 15%. Large deformations seen in gated cardiac 82 Rb images were managed without leading to anomalous distortions or substantial intensity changes in the resulting images. Finally, the constancy of activity concentration levels was reasonably preserved (<2% change) in large organs before and after motion correction. Conclusion: FALCON allows fast and accurate correction of rigid and nonrigid WB motion artifacts while being insensitive to scanner hardware or tracer distribution, making it applicable to a wide range of PET imaging scenarios., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Tracer kinetic modeling in dynamic PET has the potential to improve the diagnosis, prognosis, and research of lung diseases. The advent of total-body PET systems with much greater detection sensitivity enables high-temporal-resolution (HTR) dynamic PET imaging of the lungs. However, existing models may become insufficient for modeling the HTR data. In this paper, we investigate the necessity of additional corrections to the input function for HTR lung kinetic modeling. Methods: Dynamic scans with HTR frames of as short as 1 s were performed on 13 healthy subjects with a bolus injection of about [Formula: see text] of 18 F-FDG using the uEXPLORER total-body PET/CT system. Three kinetic models with and without time-delay and dispersion corrections were compared for the quality of lung time-activity curve fitting using the Akaike information criterion. The impact on quantification of 18 F-FDG delivery rate [Formula: see text], net influx rate [Formula: see text] and fractional blood volume [Formula: see text] was assessed. Parameter identifiability analysis was also performed to evaluate the reliability of kinetic quantification with respect to noise. Correlation of kinetic parameters with age was investigated. Results: HTR dynamic imaging clearly revealed the rapid change in tracer concentration in the lungs and blood supply (i.e., the right ventricle). The uncorrected input function led to poor time-activity curve fitting and biased quantification in HTR kinetic modeling. The fitting was improved by time-delay and dispersion corrections. The proposed model resulted in an approximately 85% decrease in [Formula: see text], an approximately 75% increase in [Formula: see text], and a more reasonable [Formula: see text] (∼0.14) than the uncorrected model (∼0.04). The identifiability analysis showed that the proposed models had good quantification stability for [Formula: see text], [Formula: see text], and [Formula: see text] The [Formula: see text] estimated by the proposed model with simultaneous time-delay and dispersion corrections correlated inversely with age, as would be expected. Conclusion: Corrections to the input function are important for accurate lung kinetic analysis of HTR dynamic PET data. The modeling of both delay and dispersion can improve model fitting and significantly impact quantification of [Formula: see text], [Formula: see text], and [Formula: see text]., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases <1 cm, detection of cancer-associated vascular complications, effective assessment of post-therapy changes, as well as bone metabolism and osteoporosis assessment. As a result of recent advances in PET/CT instrumentation, new systems now offer a long-axial field-of-view (LAFOV) to image between 106 cm and 194 cm (i.e., total-body PET) of the patient's body simultaneously and feature higher physical sensitivity and spatial resolution compared to standard PET/CT systems. LAFOV PET could overcome the forementioned limitations of conventional imaging and provide valuable global disease assessment, allowing for improved patient-tailored care. This article provides a comprehensive overview of these and other potential applications of LAFOV PET/CT imaging for patients with gynecological malignancies.

Conventional whole-body 18 F-FDG PET imaging provides a semi-quantitative evaluation of overall glucose metabolism without gaining insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18 F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19)., Methods: The study included thirteen healthy subjects and twelve recovering COVID-19 subjects within eight weeks of confirmed diagnosis. Each subject had a dynamic 18 F-FDG scan on the uEXPLORER total-body PET/CT system for one hour. Semiquantitative standardized uptake value (SUV) and SUV ratio relative to blood (SUVR) were calculated for regions of interest (ROIs) in different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify microparametric rate constants K 1 and k 3 that characterize 18 F-FDG blood-to-tissue delivery and intracellular phosphorylation, respectively, and a macroparameter K i that represents 18 F-FDG net influx rate. Statistical tests were performed to examine differences between the healthy controls and recovering COVID-19 subjects. Impact of COVID-19 vaccination was investigated. We further generated parametric images to confirm the ROI-based analysis., Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and K i in the recovering COVID-19 subjects, indicating an improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 , but not with the delivery rate K 1 , which suggests it is glucose phosphorylation, not glucose delivery, that drives the observed difference of glucose metabolism in the lungs. Meanwhile, there was no or little difference in bone marrow metabolism measured with SUV, SUVR and K i , but a significant increase in bone-marrow 18 F-FDG delivery rate K 1 in the COVID-19 group ( p < 0.05), revealing a difference of glucose delivery in this immune-related organ. The observed differences were lower or similar in vaccinated COVID-19 subjects as compared to unvaccinated ones. The organ ROI-based findings were further supported by parametric images., Conclusions: Higher lung glucose metabolism and bone-marrow glucose delivery were observed with total-body multiparametric 18 F-FDG PET in recovering COVID-19 subjects as compared to healthy subjects, which suggests continued inflammation due to COVID-19 during the early stages of recovery. Total-body multiparametric PET of 18 F-FDG delivery and metabolism can provide a more sensitive tool and more insights than conventional static whole-body 18 F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

Ultrasensitive, high-resolution, extended-field-of-view total-body (TB) PET using the first-of-its-kind 194-cm axial-field-of-view uEXPLORER may facilitate the interrogation of biologic hallmarks of hitherto difficult-to-evaluate low-signal vessel wall pathology in cardiovascular disease. Methods: Healthy volunteers were imaged serially for up to 12 h after a standard dose of 18 F-FDG ( n  = 15) or for up to 3 h after injection of a very low dose (about 5% of a standard dose; n  = 15). A cohort undergoing standard 18 F-FDG PET ( n  = 15) on a conventional scanner with a 22-cm axial field of view served as a comparison group. Arterial wall signal, crosstalk with hematopoietic and lymphoid organs, and image quality were analyzed using standardized techniques. Results: TB PET depicted the large vessel walls with excellent quality. The arterial wall could be imaged with high contrast up to 12 h after tracer injection. Ultralow-dose TB 18 F-FDG images yielded a vessel wall signal and target-to-background ratio comparable to those of conventional-dose, short-axial-field-of-view PET. Crosstalk between vessel wall and lymphoid organs was identified with better accuracy in both TB PET cohorts than in conventional PET. Conclusion: TB PET enables detailed assessment of in vivo vessel wall biology and its crosstalk with other organs over an extended time window after tracer injection or at an ultralow tracer dose. These initial observations support the feasibility of serial imaging in low-risk populations and will stimulate future mechanistic studies or therapy monitoring in atherosclerosis and other vessel wall pathologies., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Image reconstruction of low-count positron emission tomography (PET) data is challenging. Kernel methods address the challenge by incorporating image prior information in the forward model of iterative PET image reconstruction. The kernelized expectation-maximization (KEM) algorithm has been developed and demonstrated to be effective and easy to implement. A common approach for a further improvement of the kernel method would be adding an explicit regularization, which however leads to a complex optimization problem. In this paper, we propose an implicit regularization for the kernel method by using a deep coefficient prior, which represents the kernel coefficient image in the PET forward model using a convolutional neural-network. To solve the maximum-likelihood neural network-based reconstruction problem, we apply the principle of optimization transfer to derive a neural KEM algorithm. Each iteration of the algorithm consists of two separate steps: a KEM step for image update from the projection data and a deep-learning step in the image domain for updating the kernel coefficient image using the neural network. This optimization algorithm is guaranteed to monotonically increase the data likelihood. The results from computer simulations and real patient data have demonstrated that the neural KEM can outperform existing KEM and deep image prior methods.

Background: Total-body positron emission tomography/computed tomography (PET/CT) scanners are characterized by higher signal collection efficiency and greater spatial resolution compared to conventional scanners, allowing for delayed imaging and improved image quality. These advantages may also lead to better detection of physiological processes that diagnostic imaging professionals should be aware of. The gallbladder (GB) is not usually visualized as an 18 F-2-fluorodeoxyglucose ( 18 F-FDG)-avid structure in routine clinical PET/CT studies; however, with the total-body PET/CT, we have been increasingly visualizing GB activity without it being involved in an inflammatory or neoplastic process. The aim of this study was to report visualization rates and characteristics of GB 18 F-FDG uptake observed in both healthy and oncological subjects scanned on a total-body PET/CT system., Materials and Methods: Scans from 73 participants (48 healthy and 25 with newly diagnosed lymphoma) who underwent 18 F-FDG total-body PET/CT were retrospectively reviewed. Subjects were scanned at multiple timepoints up to 3 h post-injection. Gallbladder 18 F-FDG activity was graded using liver uptake as a reference, and the pattern was qualified as present in the wall, lumen, or both. Participants' characteristics, such as age, sex, body-mass index, blood glucose, and other clinical parameters, were collected to assess for any significant correlation with GB 18 F-FDG uptake., Results: All 73 subjects showed GB uptake at one or more imaging timepoints. An increase in uptake intensity overtime was observed up until the 180-min scan, and the visualization rate of GB 18 F-FDG uptake was 100% in the 120- and 180-min post-injection scans. GB wall uptake was detected in a significant number of patients (44/73, 60%), especially at early timepoint scans, whereas luminal activity was detected in 71/73 (97%) subjects, especially at later timepoint scans. No significant correlation was found between GB uptake intensity/pattern and subjects' characteristics., Conclusion: The consistent observation of GB 18 F-FDG uptake recorded in this study in healthy participants and subjects with a new oncological diagnosis indicates that this is a normal physiologic finding rather than representing an exception., (© 2023. The Author(s).)

We introduce multiple-organ objective segmentation (MOOSE) software that generates subject-specific, multiorgan segmentation using data-centric artificial intelligence principles to facilitate high-throughput systemic investigations of the human body via whole-body PET imaging. Methods: Image data from 2 PET/CT systems were used in training MOOSE. For noncerebral structures, 50 whole-body CT images were used, 30 of which were acquired from healthy controls (14 men and 16 women), and 20 datasets were acquired from oncology patients (14 men and 6 women). Noncerebral tissues consisted of 13 abdominal organs, 20 bone segments, subcutaneous fat, visceral fat, psoas muscle, and skeletal muscle. An expert panel manually segmented all noncerebral structures except for subcutaneous fat, visceral fat, and skeletal muscle, which were semiautomatically segmented using thresholding. A majority-voting algorithm was used to generate a reference-standard segmentation. From the 50 CT datasets, 40 were used for training and 10 for testing. For cerebral structures, 34 18 F-FDG PET/MRI brain image volumes were used from 10 healthy controls (5 men and 5 women imaged twice) and 14 nonlesional epilepsy patients (7 men and 7 women). Only 18 F-FDG PET images were considered for training: 24 and 10 of 34 volumes were used for training and testing, respectively. The Dice score coefficient (DSC) was used as the primary metric, and the average symmetric surface distance as a secondary metric, to evaluate the automated segmentation performance. Results: An excellent overlap between the reference labels and MOOSE-derived organ segmentations was observed: 92% of noncerebral tissues showed DSCs of more than 0.90, whereas a few organs exhibited lower DSCs (e.g., adrenal glands [0.72], pancreas [0.85], and bladder [0.86]). The median DSCs of brain subregions derived from PET images were lower. Only 29% of the brain segments had a median DSC of more than 0.90, whereas segmentation of 60% of regions yielded a median DSC of 0.80-0.89. The results of the average symmetric surface distance analysis demonstrated that the average distance between the reference standard and the automatically segmented tissue surfaces (organs, bones, and brain regions) lies within the size of image voxels (2 mm). Conclusion: The proposed segmentation pipeline allows automatic segmentation of 120 unique tissues from whole-body 18 F-FDG PET/CT images with high accuracy., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Autoimmune inflammatory arthritides (AIA), such as psoriatic arthritis and rheumatoid arthritis, are chronic systemic conditions that affect multiple joints of the body. Recently, total-body (TB) PET/CT scanners exhibiting superior technical characteristics (total-body coverage, geometric sensitivity) that could benefit AIA evaluation, compared with conventional PET/CT systems, have become available. The objectives of this work were to assess the performance of an ultra-low-dose, 18 F-FDG TB PET/CT acquisition protocol for evaluating systemic joint involvement in AIA and to report the association of TB PET/CT measures with joint-by-joint rheumatologic examination and standardized rheumatologic outcome measures. Methods: Thirty participants (24 with AIA and 6 with osteoarthritis) were prospectively enrolled in this single-center, observational study. All participants underwent a TB PET/CT scan for 20 min starting at 40 min after intravenous injection of 78.1 ± 4.7 MBq of 18 F-FDG. Qualitative and quantitative evaluation of 18 F-FDG uptake and joint involvement were performed from the resulting images and compared with the rheumatologic assessments. Results: TB PET/CT enabled the visualization of 18 F-FDG uptake at joints of the entire body, including those of the hands and feet, in a single bed position, and in the same phase of radiotracer uptake. A range of pathologies consistent with AIA (and non-AIA in the osteoarthritis group) were visualized, and the feasibility of extracting PET measures from joints examined by rheumatologic assessments was demonstrated. Of 1,997 evaluable joints, there was concordance between TB PET qualitative assessments and joint-by-joint rheumatologic evaluation in the AIA and non-AIA cohorts for 69.9% and 91.1% joints, respectively, and an additional 20.1% and 8.8% joints, respectively, deemed negative on rheumatologic examination showed PET positivity. On the other hand, 10.0% and 0% joints in the AIA and non-AIA cohorts, respectively, were positive on rheumatologic evaluation but negative on TB PET. Quantitative measures from TB PET in the AIA cohort demonstrated a moderate-to-strong correlation (Spearman ρ  = 0.53-0.70, P  < 0.05) with the rheumatologic outcome measures. Conclusion: Systemic joint evaluation in AIA (and non-AIA) is feasible with a TB PET/CT system and an ultra-low-dose protocol. Our results provide the foundation for future larger studies to evaluate the possible improvements in AIA joint assessment via the TB PET/CT technology., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Quantitative kinetic modeling requires an input function. A noninvasive image-derived input function (IDIF) can be obtained from dynamic PET images. However, a robust IDIF location (e.g., aorta) may be far from a tissue of interest, particularly in total-body PET, introducing a time delay between the IDIF and the tissue. The standard practice of joint estimation (JE) of delay, along with model fitting, is computationally expensive. To improve the efficiency of delay correction for total-body PET parametric imaging, this study investigated the use of pulse timing methods to estimate and correct for delay. Methods: Simulation studies were performed with a range of delay values, frame lengths, and noise levels to test the tolerance of 2 pulse timing methods-leading edge (LE) and constant fraction discrimination and their thresholds. The methods were then applied to data from 21 subjects (14 healthy volunteers, 7 cancer patients) who underwent a 60-min dynamic total-body 18 F-FDG PET acquisition. Region-of-interest kinetic analysis was performed and parametric images were generated to compare LE and JE methods of delay correction, as well as no delay correction. Results: Simulations demonstrated that a 10% LE threshold resulted in biases and SDs at tolerable levels for all noise levels tested, with 2-s frames. Pooled region-of-interest-based results ( n = 154) showed strong agreement between LE (10% threshold) and JE methods in estimating delay (Pearson r = 0.96, P < 0.001) and the kinetic parameters v b ( r = 0.96, P < 0.001), K i ( r = 1.00, P < 0.001), and K 1 ( r = 0.97, P < 0.001). When tissues with minimal delay were excluded from pooled analyses, there were reductions in v b (69.4%) and K 1 (4.8%) when delay correction was not performed. Similar results were obtained for parametric images; additionally, lesion K i contrast was improved overall with LE and JE delay correction compared with no delay correction and Patlak analysis. Conclusion: This study demonstrated the importance of delay correction in total-body PET. LE delay correction can be an efficient surrogate for JE, requiring a fraction of the computational time and allowing for rapid delay correction across more than 10 6 voxels in total-body PET datasets., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Quantitative dynamic PET with compartmental modeling has the potential to enable multiparametric imaging and more accurate quantification than static PET imaging. Conventional methods for parametric imaging commonly use a single kinetic model for all image voxels and neglect the heterogeneity of physiologic models, which can work well for single-organ parametric imaging but may significantly compromise total-body parametric imaging on a scanner with a long axial field of view. In this paper, we evaluate the necessity of voxelwise compartmental modeling strategies, including time delay correction (TDC) and model selection, for total-body multiparametric imaging. Methods: Ten subjects (5 patients with metastatic cancer and 5 healthy volunteers) were scanned on a total-body PET/CT system after injection of 370 MBq of 18 F-FDG. Dynamic data were acquired for 60 min. Total-body parametric imaging was performed using 2 approaches. One was the conventional method that uses a single irreversible 2-tissue-compartment model with and without TDC. The second approach selects the best kinetic model from 3 candidate models for individual voxels. The differences between the 2 approaches were evaluated for parametric imaging of microkinetic parameters and the 18 F-FDG net influx rate, K i Results: TDC had a nonnegligible effect on kinetic quantification of various organs and lesions. The effect was larger in lesions with a higher blood volume. Parametric imaging of K i with the standard 2-tissue-compartment model introduced vascular-region artifacts, which were overcome by the voxelwise model selection strategy. Conclusion: The time delay and appropriate kinetic model vary in different organs and lesions. Modeling of the time delay of the blood input function and model selection improved total-body multiparametric imaging., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. This work assessed the relationship between image signal-to-noise ratio (SNR) and total-body noise-equivalent count rate (NECR)-for both non-time-of-flight (TOF) NECR and TOF-NECR-in a long uniform water cylinder and 14 healthy human subjects using the uEXPLORER total-body PET/CT scanner. Approach. A TOF-NEC expression was modified for list-mode PET data, and both the non-TOF NECR and TOF-NECR were compared using datasets from a long uniform water cylinder and 14 human subjects scanned up to 12 h after radiotracer injection. Main results. The TOF-NECR for the uniform water cylinder was found to be linearly proportional to the TOF-reconstructed image SNR 2 in the range of radioactivity concentrations studied, but not for non-TOF NECR as indicated by the reduced R 2 value. The results suggest that the use of TOF-NECR to estimate the count rate performance of TOF-enabled PET systems may be more appropriate for predicting the SNR of TOF-reconstructed images. Significance. Image quality in PET is commonly characterized by image SNR and, correspondingly, the NECR. While the use of NECR for predicting image quality in conventional PET systems is well-studied, the relationship between SNR and NECR has not been examined in detail in long axial field-of-view total-body PET systems, especially for human subjects. Furthermore, the current NEMA NU 2-2018 standard does not account for count rate performance gains due to TOF in the NECR evaluation. The relationship between image SNR and total-body NECR in long axial FOV PET was assessed for the first time using the uEXPLORER total-body PET/CT scanner., (© 2022 Institute of Physics and Engineering in Medicine.)

Total-body PET has come a long way from its first conception to today, with both total-body and long axial field of view (> 1m) scanners now being commercially available world-wide. The conspicuous signal collection efficiency gain, coupled with high spatial resolution, allows for higher sensitivity and improved lesion detection, enhancing several clinical applications not readily available on current conventional PET/CT scanners. This technology can provide (a) reduction in acquisition times with preservation of diagnostic quality images, benefitting specific clinical situations (i.e. pediatric patients) and the use of several existing radiotracers that present transient uptake over time and where small differences in acquisition time can greatly impact interpretation of images; (b) reduction in administered activity with minimal impact on image noise, thus reducing effective dose to the patient, improving staff safety, and helping with logistical concerns for short-lived radionuclides or long-lived radionuclides with poor dosimetry profiles that have had limited use on conventional PET scanners until now; (c) delayed scanning, that has shown to increase the detection of even small and previously occult malignant lesions by improved clearance in regions of significant background activity and by reduced visibility of coexisting inflammatory processes; (d) improvement in image quality, as a consequence of higher spatial resolution and sensitivity of total-body scanners, implying better appreciation of small structures and clinical implications with downstream prognostic consequences for patients; (e) simultaneous total-body dynamic imaging, that allows the measurement of full spatiotemporal distribution of radiotracers, kinetic modeling, and creation of multiparametric images, providing physiologic and biologically relevant data of the entire body at the same time. On the other hand, the higher physical and clinical sensitivity of total-body scanners bring along some limitations and challenges. The strong impact on clinical sensitivity potentially increases the number of false positive findings if the radiologist does not recalibrate interpretation considering the new technique. Delayed scanning causes logistical issues and introduces new interpretation questions for radiologists. Data storage capacity, longer processing and reconstruction time issues are other limitations, but they may be overcome in the near future by advancements in reconstruction algorithms and computing hardware., Competing Interests: Declaration of Competing Interest Lorenzo Nardo has is principal investigator of a service agreement with United Imaging Healthcare. UC Davis has a revenue-sharing agreement with United Imaging Healthcare that is based on uEXPLORER sales. The authors thank all the EXPLORER team at UC Davis. The authors acknowledge NIH R01CA249422-01., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using 18 F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or 18 F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different 18 F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

The current generation of total-body positron emission tomography (PET) scanners offer significant sensitivity increase with an extended axial imaging extent. With the large volume of lutetium-based scintillation crystals that are used as detector elements in these scanners, there is an increased flux of background radiation originating from 176 Lu decay in the crystals and higher sensitivity for detecting it. Combined with the ability of scanning the entire body in a single bed position, this allows more effective utilization of the lutetium background as a transmission source for estimating 511 keV attenuation coefficients. In this study, utilization of the lutetium background radiation for attenuation correction in total-body PET was studied using Monte Carlo simulations of a 3D whole-body XCAT phantom in the uEXPLORER PET scanner, with particular focus on ultralow-dose PET scans that are now made possible with these scanners. Effects of an increased acceptance angle, reduced scan durations, and Compton scattering on PET quantification were studied. Furthermore, quantification accuracy of lutetium-based attenuation correction was compared for a 20-min scan of the whole body on the uEXPLORER, a one-meter-long, and a conventional 24-cm-long scanner. Quantification and lesion contrast were minimally affected in both long axial field-of-view scanners and in a whole-body 20-min scan, the mean bias in all analyzed organs of interest were within a ±10% range compared to ground-truth activity maps. Quantification was affected in certain organs, when scan duration was reduced to 5 min or a reduced acceptance angle of 17° was used. Analysis of the Compton scattered events suggests that implementing a scatter correction method for the transmission data will be required, and increasing the energy threshold from 250 keV to 290 keV can reduce the computational costs and data rates, with negligible effects on PET quantification. Finally, the current results can serve as groundwork for transferring lutetium-based attenuation correction into research and clinical practice., Competing Interests: Conflict of interest UC Davis has a research agreement and a sales-based revenue-sharing agreement with United Imaging Healthcare. RB and SC are principal investigators on a research grant funded by United Imaging Healthcare. EL is a full-time employee at UIH America, Inc. The remaining authors declare that the research was conducted in the absence of any other commercial or financial relationships that could be construed as a potential conflict of interest.

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease characterized by lobular inflammation and hepatocyte injury and is a key determinant of clinical outcome. 1 Liver biopsy remains the gold standard for diagnosis but is limited by risks of the procedure and interobserver variability. Although magnetic resonance imaging (MRI)-based technology may provide novel means to identify NASH, 2 there remains a significant need for other modalities to diagnose NASH noninvasively. Glucose transport, an integral tissue process altered in NASH, 3 is measurable with 18 F-fluorodeoxyglucose positron emission tomography (FDG PET). Because unenhanced computed tomography (CT) scan can detect hepatic steatosis quite reliably, 4 and PET combines unenhanced CT for attenuation correction, we hypothesized that measurement of the combination of glucose transport by PET and steatosis by CT could yield a reliable radiologic correlate of NASH., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Absolute quantification of regional tissue concentration of radioactivity in positron emission tomography (PET) is a critical parameter-of-interest across various clinical and research applications and is affected by a complex interplay of factors including scanner calibration, data corrections, and image reconstruction. The emergence of long axial field-of-view (FOV) PET systems widens the dynamic range accessible to PET and creates new opportunities in reducing scan time and radiation dose, delayed or low radioactivity imaging, as well as kinetic modeling of the entire human. However, these imaging regimes impose challenging conditions for accurate quantification due to constraints from image reconstruction, low count conditions, as well as large and rapidly changing radioactivity distribution across a large axial FOV. We comprehensively evaluated the quantitative accuracy of the uEXPLORER total-body scanner in conditions that encompass existing and potential imaging applications (such as dynamic imaging and ultralow-dose imaging) using a set of total-body specific phantom and human measurements. Through these evaluations we demonstrated a relative count rate accuracy of ±3%-4% using the NEMA NU 2-2018 protocol, an axial uniformity spread of ±3% across the central 90% axial FOV, and a 3% activity bias spread from 17 to 474 MBq 18 F-FDG in a 210 cm long cylindrical phantom. Region-of-interest quantification spread of 1% was found by simultaneously scanning three NEMA NU 2 image quality phantoms, as well as relatively stable volume-of-interest quantification across 0.2%-100% of total counts through re-sampled datasets. In addition, an activity bias spread of -2% to +1% post-bolus injections in human subjects was found. Larger bias changes during the bolus injection phase in humans indicated the difficulty in providing accurate PET data corrections for complex activity distributions across a large dynamic range. Our results overall indicated that the quantitative performance achieved with the uEXPLORER scanner was uniform across the axial FOV and provided the accuracy necessary to support a wide range of imaging applications., (© 2021 Institute of Physics and Engineering in Medicine.)

Myocardial blood flow (MBF) and flow reserve are usually quantified in the clinic with positron emission tomography (PET) using a perfusion-specific radiotracer (e.g. 82 Rb-chloride). However, the clinical accessibility of existing perfusion tracers remains limited. Meanwhile, 18 F-fluorodeoxyglucose (FDG) is a commonly used radiotracer for PET metabolic imaging without similar limitations. In this paper, we explore the potential of 18 F-FDG for myocardial perfusion imaging by comparing the myocardial FDG delivery rate K 1 with MBF as determined by dynamic 82 Rb PET in fourteen human subjects with heart disease. Two sets of FDG K 1 were derived from one-hour dynamic FDG scans. One was the original FDG K 1 estimates and the other was the corresponding K 1 values that were linearly normalized for blood glucose levels. A generalized Renkin-Crone model was used to fit FDG K 1 with Rb MBF, which then allowed for a nonlinear extraction fraction correction for converting FDG K 1 to MBF. The linear correlation between FDG-derived MBF and Rb MBF was moderate ( r = 0.79) before the glucose normalization and became much improved ( r > 0.9) after glucose normalization. The extraction fraction of FDG was also similar to that of Rb-chloride in the myocardium. The results from this pilot study suggest that dynamic cardiac FDG-PET with tracer kinetic modeling has the potential to provide MBF in addition to its conventional use for metabolic imaging., (© 2021 Institute of Physics and Engineering in Medicine.)

Background: To prospectively demonstrate the feasibility of performing dual-phase SPECT/CT for the assessment of the small joints of the hands of rheumatoid arthritis (RA) patients, and to evaluate the reliability of the quantitative and qualitative measures derived from the resulting images., Methods: A SPECT/CT imaging protocol was developed in this pilot study to scan both hands simultaneously in participants with RA, in two phases of 99m Tc-MDP radiotracer uptake, namely the soft-tissue blood pool phase (within 15 minutes after radiotracer injection) and osseous phase (after 3 hours). Joints were evaluated qualitatively (normal vs. abnormal uptake) and quantitatively [by measuring a newly developed metric, maximum corrected count ratio (MCCR)]. Qualitative and quantitative evaluations were repeated to assess reliability., Results: Four participants completed seven studies (all four were imaged at baseline, and three of them at follow-up after 1-month of arthritis therapy). A total of 280 joints (20 per hand) were evaluated. The MCCR from soft-tissue phase scans was significantly higher for clinically abnormal joints compared to clinically normal ones; P<0.001, however the MCCR from the osseous phase scans were not different between the two joint groups. Intraclass Correlation Coefficient (ICC) for MCCR was excellent [0.9789, 95% confidence interval (CI): 0.9734-0.9833]. Intra-observer agreement for qualitative SPECT findings was substantial for both the soft-tissue phase (kappa =0.78, 95% CI: 0.72-0.83) and osseous-phase (kappa =0.70, 95% CI: 0.64-0.76) scans., Conclusions: Extracting reliable quantitative and qualitative measures from dual-phase 99mTc-MDP SPECT/CT hand scans is feasible in RA patients. SPECT/CT may provide a unique means for assessing both synovitis and osseous involvement in RA joints using the same radiotracer injection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-996). Dr. RDB reports grants from Philips Healthcare, during the conduct of the study. Dr. AJC reports grants from Philips Healthcare, grants from National Institute of Health, during the conduct of the study. The other authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Nuclear medical imaging devices, such as those enabling photon emission imaging (gamma camera, single photon emission computed tomography, or positron emission imaging), that are typically used in today's clinics are optimized for assessing large portions of the human body, and are classified as whole-body imaging systems. These systems have known limitations for organ imaging, therefore application-specific devices have been designed, constructed and evaluated. These devices, given their compact nature and superior technical characteristics, such as their higher detection sensitivity and spatial resolution for organ imaging compared to whole-body imaging systems, have shown promise for niche applications. Several of these devices have further been integrated with complementary anatomical imaging devices. The objectives of this review article are to (1) provide an overview of such application-specific nuclear imaging devices that were developed over the past two decades (in the twenty-first century), with emphasis on brain, cardiac, breast, and prostate imaging; and (2) discuss the rationale, advantages and challenges associated with the translation of these devices for routine clinical imaging. Finally, a perspective on the future prospects for application-specific devices is provided, which is that sustained effort is required both to overcome design limitations which impact their utility (where these exist) and to collect the data required to define their clinical value., (© 2021 Institute of Physics and Engineering in Medicine.)