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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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

Parametric imaging has been shown to provide better quantitation physiologically than SUV imaging in PET. With the increased sensitivity from a recently developed total-body PET scanner, whole-body scans with higher temporal resolution become possible for dynamic analysis and parametric imaging. In this paper, we focus on deriving the parameter k 1 using compartmental modeling and on developing a method to acquire whole-body 18 F-FDG PET parametric images using only the first 90 s of the postinjection scan data with the total-body PET system. Methods: Dynamic projections were acquired with a time interval of 1 s for the first 30 s and a time interval of 2 s for the following minute. Image-derived input functions were acquired from the reconstructed dynamic sequences in the ascending aorta. A 1-tissue-compartment model with 4 parameters ( k 1 , k 2 , blood fraction, and delay time) was used. A maximum-likelihood-based estimation method was developed with the 1-tissue-compartment model solution. The accuracy of the acquired parameters was compared with the ones estimated using a 2-tissue-compartment irreversible model with 1-h-long data. Results: All 4 parametric images were successfully calculated using data from 2 volunteers. By comparing the time-activity curves acquired from the volumes of interest, we showed that the parameters estimated using our method were able to predict the time-activity curves of the early dynamics of 18 F-FDG in different organs. The delay-time effects for different organs were also clearly visible in the reconstructed delay-time image with delay variations of as large as 40 s. The estimated parameters using both 90-s data and 1-h data agreed well for k 1 and blood fraction, whereas a large difference in k 2 was found between the 90-s and 1-h data, suggesting k 2 cannot be reliably estimated from the 90-s scan. Conclusion: We have shown that with total-body PET and the increased sensitivity, it is possible to estimate parametric images based on the very early dynamics after 18 F-FDG injection. The estimated k 1 might potentially be used clinically as an indicator for identifying abnormalities., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of 18 F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the 18 F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Within the EXPLORER Consortium, the construction of the world's first total-body PET/CT scanner has recently been completed. The 194-cm axial field of view of the EXPLORER PET/CT scanner is sufficient to cover, for the first time, the entire human adult body in a single acquisition in more than 99% of the population and allows total-body pharmacokinetic studies with frame durations as short as 1 s. The large increase in sensitivity arising from total-body coverage as well as increased solid angle for detection at any point within the body allows whole-body 18 F-FDG PET studies to be acquired with unprecedented count density, improving the signal-to-noise ratio of the resulting images. Alternatively, the sensitivity gain can be used to acquire diagnostic PET images with very small amounts of activity in the field of view (25 MBq, 0.7 mCi or less), with very short acquisition times (∼1 min or less) or at later time points after the tracer's administration. We report here on the first human imaging studies on the EXPLORER scanner using a range of different protocols that provide initial evidence in support of these claims. These case studies provide the foundation for future carefully controlled trials to quantitatively evaluate the improvements possible through total-body PET imaging., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

We describe a long axial field-of-view (FOV) PET scanner for high-sensitivity and total-body imaging of nonhuman primates and present the physical performance and first phantom and animal imaging results. Methods: The mini-EXPLORER PET scanner was built using the components of a clinical scanner reconfigured with a detector ring diameter of 43.5 cm and an axial length of 45.7 cm. National Electrical Manufacturers Association (NEMA) NU-2 and NU-4 phantoms were used to measure sensitivity and count rate performance. Reconstructed spatial resolution was investigated by imaging a radially stepped point source and a Derenzo phantom. The effect of the wide acceptance angle was investigated by comparing performance with maximum acceptance angles of 14°-46°. Lastly, an initial assessment of the in vivo performance of the mini-EXPLORER was undertaken with a dynamic 18 F-FDG nonhuman primate (rhesus monkey) imaging study. Results: The NU-2 total sensitivity was 5.0%, and the peak noise-equivalent count rate measured with the NU-4 monkey scatter phantom was 1,741 kcps, both obtained using the maximum acceptance angle (46°). The NU-4 scatter fraction was 16.5%, less than 1% higher than with a 14° acceptance angle. The reconstructed spatial resolution was approximately 3.0 mm at the center of the FOV, with a minor loss in axial spatial resolution (0.5 mm) when the acceptance angle increased from 14° to 46°. The rhesus monkey 18 F-FDG study demonstrated the benefit of the high sensitivity of the mini-EXPLORER, including fast imaging (1-s early frames), excellent image quality (30-s and 5-min frames), and late-time-point imaging (18 h after injection), all obtained at a single bed position that captured the major organs of the rhesus monkey. Conclusion: This study demonstrated the physical performance and imaging capabilities of a long axial FOV PET scanner designed for high-sensitivity imaging of nonhuman primates. Further, the results of this study suggest that a wide acceptance angle can be used with a long axial FOV scanner to maximize sensitivity while introducing only minor trade-offs such as a small increase in scatter fraction and slightly degraded axial spatial resolution., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: In 2005, 8 Imaging Response Assessment Teams (IRATs) were funded by the National Cancer Institute (NCI) as supplemental grants to existing NCI Cancer Centers. After discussion among the IRATs regarding the need for increased standardization of clinical and research PET/CT methodology, it became apparent that data acquisition and processing approaches differ considerably among centers. To determine the variability in detail, a survey of IRAT sites and IRAT affiliates was performed., Methods: A 34-question instrument evaluating patient preparation, scanner type, performance approach, display, and analysis was developed. Fifteen institutions, including the 8 original IRATs and 7 institutions that had developed affiliate IRATs, were surveyed., Results: The major areas of variation were (18)F-FDG dose (259-740 MBq [7-20 mCi]) uptake time (45-90 min), sedation (never to frequently), handling of diabetic patients, imaging time (2-7 min/bed position), performance of diagnostic CT scans as a part of PET/CT, type of acquisition (2-dimensional vs. 3-dimensional), CT technique, duration of fasting (4 or 6 h), and (varying widely) acquisition, processing, display, and PACS software--with 4 sites stating that poor-quality images appear on PACS., Conclusion: There is considerable variability in the way PET/CT scans are performed at academic institutions that are part of the IRAT network. This variability likely makes it difficult to quantitatively compare studies performed at different centers. These data suggest that additional standardization in methodology will be required so that PET/CT studies, especially those performed quantitatively, are more comparable across sites.

Unlabelled: We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging., Methods: The system consisted of a lutetium oxyorthosilicate-based dual-planar head PET camera (crystal size, 3 x 3 x 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with (18)F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated., Results: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal., Conclusion: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

Unlabelled: The aim of this work was to develop a rigorous evaluation methodology to assess performance of different acquisition and processing methods for variable patient sizes in the context of lesion detection in whole-body (18)F-FDG PET., Methods: Fifty-nine bed positions were acquired in 32 patients in 2-dimensional (2D) and 3-dimensional (3D) modes 1-4 h after (18)F-FDG injection (740 MBq) using a BGO PET scanner. Three spheres (1.0-, 1.3-, and 1.6-cm diameter) containing (68)Ge were also imaged separately in air, at locations corresponding to possible lesion sites in 2D and 3D (590 targets per condition). Each bed position was acquired for 7 min in 2D and 6 min in 3D and corrected for randoms using delayed window randoms subtraction (DWS) or randoms variance reduction (RVR). Sphere sinograms were attenuated using the 2D or 3D attenuation map derived from the transmission scan of the patient, after scaling 2D and 3D sinograms with identical factors to ensure marginal detectability. Resulting 2D sinograms were reconstructed with filtered backprojection (FBP) and ordered-subsets expectation maximization (OSEM) without any scatter or attenuation correction (FBP-NATS and OSEM-NATS) or corrected for scatter and attenuation and reconstructed using FBP (FBP-ATT) or attenuation-weighted OSEM (AWOSEM). 3D sinograms were processed identically after Fourier rebinning. Next, reconstructed volumes were compared on the basis of performance of a 3-channel Hotelling observer (CHO-SNR [SNR is signal-to-noise ratio]) in detecting the presence of a sphere of unknown size on an anatomic background while modeling observer noise. The noise equivalent count (NEC) rate was computed in 2D and 3D for 3 different phantoms sizes (40, 60, and 95 kg) and compared with lesion detection SNR., Results: 3D imaging yielded better lesion detectability than 2D (P < 0.025, 2-tailed paired t test) in patients of normal size (body mass index [BMI] < or = 31). However, 2D imaging yielded better lesion detectability than 3D in large patients (BMI > 31), as 3D performance deteriorated in large patients (P < 0.05). 2D and 3D yielded similar results for different lesion sizes. CHO-SNR were 40% greater for AWOSEM, FBP-ATT, and FBPNAT than for OSEM (P < 0.05), and AWOSEM yielded significantly better lesion detectability than did FBP. In all patients, RVR yielded a systematic improvement in CHO-SNR over DWS in both 2D and 3D. radicalNEC was characterized by a behavior similar to that of SNR(CHO) for the 3 different phantom sizes considered in this study.

Unlabelled: Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph., Methods: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph. Data acquisition (350-650 keV, 6 ns) started 99 +/- 12 min (mean +/- SD) after injection of 624 +/- 76 MBq (18)F-FDG. Bias caused by tracer redistribution and decay was eliminated by acquiring dynamic data over a single-bed position using a protocol that alternated between septa-in and septa-out modes (2D, 3D, 2D, 3D, 2D, 3D). Frames were combined to form 8 statistically independent sinograms: four 2D replicates (105 s) and four 3D replicates (90 s). The different frame durations in 2D and 3D compensated for the different number of overlapping bed positions required for an 85-cm whole-body study. Images were reconstructed with either 2D or fully 3D ordered-subsets expectation maximization (2 iterations and 8 subsets; 2D 6-mm gaussian, 3D 5- and 6-mm gaussian). Image target-to-background ratio was assessed by dividing the lesion maximum by the mean within a neighboring background region. Image noise was assessed by applying background regions of interest to the replicate images and calculating the within-patient coefficient of variation., Results: The difference in target-to-background ratio between the 2D and 3D images, when they were filtered with 6-mm and 5-mm gaussian filters, respectively, was not highly statistically significant (P = 0.16). The mean ratio of 3D to 2D image values was 0.94 with 95% limits of agreement of 0.63-1.41. The within-patient coefficients of variation for the 2D and 3D images were 13% +/- 15% and 9% +/- 10%, respectively (P = 0.0005)., Conclusion: Under conditions of matched target to-to-background ratios, the 3D mode was found to produce images with significantly less variability than the 2D mode. These data provide support for the use of 3D acquisition with LSO detectors to reduce scan times in whole-body (18)F-FDG applications.