18F-FDG gallbladder uptake: observation from a total-body PET/CT scanner.

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 18F-2-fluorodeoxyglucose (18F-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 18F-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 18F-FDG total-body PET/CT were retrospectively reviewed. Subjects were scanned at multiple timepoints up to 3 h post-injection. Gallbladder 18F-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 18F-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 18F-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 18F-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.

Dynamic Positron Emission Tomography/Computed Tomography Imaging Correlate of Nonalcoholic Steatohepatitis.

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 18F-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.

Pericytes, inflammation, and diabetic retinopathy.

Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus, and a common cause of vision impairment and blindness in these patients, yet many aspects of its pathogenesis remain unresolved. Furthermore, current treatments are not effective in all patients, are only indicated in advanced disease, and are associated with significant adverse effects. This review describes the microvascular features of DR, and how pericyte depletion and low-grade chronic inflammation contribute to the pathogenesis of this common ophthalmic disorder. Existing, novel and investigational pharmacological strategies aimed at modulating the inflammatory component of DR and ameliorating pericyte loss to potentially improve clinical outcomes for patients with diabetic retinopathy, are discussed.

Unwell in hospital but not incapable: cross-sectional study on the dissociation of decision-making capacity for treatment and research in in-patients with schizophrenia and related psychoses.

BACKGROUND: Consent to research with decision-making capacity for research (DMC-R) is normally a requirement for study participation. Although the symptoms of schizophrenia and related psychoses are known to affect decision-making capacity for treatment (DMC-T), we know little about their effect on DMC-R.AimsWe aimed to determine if DMC-R differs from DMC-T in proportion and associated symptoms in an in-patient sample of people with schizophrenia and related psychoses. METHOD: Cross-sectional study of psychiatric in-patients admitted for assessment and/or treatment of schizophrenia and related psychoses. We measured DMC-R and DMC-T using 'expert judgement' clinical assessment guided by the MacArthur Competence Assessment Tool for Clinical Research, the MacArthur Competence Assessment Tool for Treatment and the legal framework of the Mental Capacity Act (2005), in addition to symptoms of psychosis. RESULTS: There were 84 participants in the study. Half the participants had DMC-R (51%, 95% CI 40-62%) and a third had DMC-T (31%, 95% CI 21-43%) and this difference was statistically significant (P < 0.01). Thought disorder was most associated with lacking DMC-R (odds ratio 5.72, 95% CI 2.01-16.31, P = 0.001), whereas lack of insight was most associated with lacking DMC-T (odds ratio 26.34, 95% CI 3.60-192.66, P = 0.001). With the exception of improved education status and better DMC-R, there was no effect of sociodemographic variables on either DMC-R or DMC-T. CONCLUSIONS: We have shown that even when severely unwell, people with schizophrenia and related psychoses in in-patient settings commonly retain DMC-R despite lacking DMC-T. Furthermore, different symptoms have different effects on decision-making abilities for different decisions. We should not view in-patient psychiatric settings as a research 'no-go area' and, where appropriate, should recruit in these settings.Declaration of interestNone.

Depression Symptoms in Haemodialysis Patients Predict All-Cause Mortality but Not Kidney Transplantation: A Cause-Specific Outcome Analysis.

Background: Depression is common in haemodialysis (HD) patients and associated with poor outcomes. Purpose: To evaluate whether depression symptoms predict survival and transplantation in a large sample of haemodialysis patients using cause-specific survival models. Methods: Survival data was collected between April 2013 and November 2015, as part of the screening phase of a multicentre randomised placebo-controlled trial of sertraline in HD patients. Depression was measured using the Beck Depression Inventory-II (BDI-II) and the Patient Health Questionnaire-9 (PHQ-9). Demographic and clinical data were collected via a self-report questionnaire and medical records. Competing risk survival analysis involved cause-specific and subdistribution hazard survival models. All models were adjusted for appropriate covariates including co-morbidity and C-reactive protein (CRP) in a subanalysis. Results: Of 707 cases available for analysis, there were 148 deaths. The mean survival time was 787.5 days. Cumulative survival at 12 months was 88.5%. During the study follow-up period, there were 92 transplants. The cumulative transplant event rate at 12 months was 7.8%. In separate adjusted models, depression symptoms predicted mortality (BDI-II HR = 1.03 95% CI 1.01, 1.04; PHQ-9 HR = 1.04 95% CI 1.01, 1.06). With respect to screening cut-off scores, a PHQ-9 ≥ 10 was associated with mortality (HR = 1.51 95% CI 1.01, 2.19) but not a BDI-II ≥ 16. Depression symptoms were not associated with time to transplantation in either cause-specific or subdistribution model. Conclusions: Consistent with past findings in HD patients, depression symptoms predicted survival but were not associated with kidney transplantation. Suitable treatments for depression need further evaluation, and their impact upon quality of life and clinical outcomes determined. Trial Registration Number: (ISRCTN06146268).

Strong and Tunable Spin-Orbit Coupling in a Two-Dimensional Hole Gas in Ionic-Liquid Gated Diamond Devices.

Hydrogen-terminated diamond possesses due to transfer doping a quasi-two-dimensional (2D) hole accumulation layer at the surface with a strong, Rashba-type spin-orbit coupling that arises from the highly asymmetric confinement potential. By modulating the hole concentration and thus the potential using an electrostatic gate with an ionic-liquid dielectric architecture the spin-orbit splitting can be tuned from 4.6-24.5 meV with a concurrent spin relaxation length of 33-16 nm and hole sheet densities of up to 7.23 × 10(13) cm(-2). This demonstrates a spin-orbit interaction of unprecedented strength and tunability for a 2D hole system at the surface of a wide band gap semiconductor. With a spin relaxation length that is experimentally accessible using existing nanofabrication techniques, this result suggests that hydrogen-terminated diamond has great potential for the study and application of spin transport phenomena.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

BACKGROUND: The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. METHODS/DESIGN: The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. DISCUSSION: There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. TRIAL REGISTRATION: ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

Nationwide practice patterns for the use of venous thromboembolism prophylaxis among men undergoing radical prostatectomy.

PURPOSE: To examine the practice patterns and predictors of VTE prophylaxis following radical prostatectomy (RP). METHODS: This was a population-based observational study of 94,709 men with a diagnosis of prostate cancer (ICD-9 code 185) who underwent RP were identified from a hospital-based database from 2000 to 2010, including 68,244 (72.1 %) open RP (ORP) and 26,465 (27.9 %) robotic-assisted laparoscopic RP (RALP). VTE prophylaxis was classified as none, mechanical, pharmacologic, or combination. RESULTS: Following RP, 35,591 (52.2 %) received mechanical, 4,945 (7.2 %) pharmacologic, 7,720 (10.6 %) combination, and 20,438 (30.0 %) no VTE prophylaxis. A total of 245 VTE events (145 DVT, 114 PE) were identified, representing 0.25 % of all procedures. Men with >2 comorbidities (OR = 2.44; 95 % CI 1.78-3.35) and those who were black (OR = 1.44; 95 % CI 1.06-1.97) were more likely to have a VTE. Men who had RALP (OR = 0.61; 95 % CI 0.45-0.99), surgery at high-volume hospitals (OR = 0.45; 95 % CI 0.28-0.73), or received prophylaxis (OR = 0.67; 95 % CI 0.50-0.88) were less likely to develop a VTE. CONCLUSION: Despite the observation that VTE prophylaxis reduces the risk of VTE by 40 %, VTE prophylaxis was not used in almost one-third of men who underwent radical prostatectomy.

Metastatic epidural spinal cord compression among elderly patients with advanced prostate cancer.

BACKGROUND: A recent randomized trial demonstrated that for metastatic epidural spinal cord compression (MESCC), a complication of advanced prostate cancer, surgical decompression may be more effective than external beam radiation therapy (RT). We investigated predictors of MESCC, its treatment, and its impact on hospital length of stay for patients with advanced prostate cancer. METHODS: We used the SEER-Medicare database to identify patients >65 years with stage IV (n = 14,800) prostate cancer. We used polytomous logistic regression to compare those with and without MESCC and those hospitalized for treatment with surgical decompression and/or RT. RESULTS: MESCC developed in 711 (5 %) of patients, among whom 359 (50 %) received RT and 107 (15 %) underwent surgery ± RT. Median survival was 10 months. MESCC was more likely among patients who were black (OR 1.75, 95 %CI 1.39-2.19 vs. white) and had high-grade tumors (OR 3.01, 95 %CI 1.14-7.94), and less likely in those younger; with prior hormonal therapy (OR 0.73, 95 %CI 0.62-0.86); or with osteoporosis (OR 0.63, 95 %CI 0.47-0.83). Older patients were less likely to undergo either RT or surgery, as were those with ≥1 comorbidity. Patients with high-grade tumors were more likely to undergo RT (OR 1.92, 95 %CI 1.25-2.96). Those who underwent RT or surgery spent an additional 11 and 29 days, respectively, hospitalized. CONCLUSIONS: We found that black men with metastatic prostate cancer are more likely to develop MESCC than whites. RT was more commonly utilized for treatment than surgery, but the elderly and those with comorbidities were unlikely to receive either treatment.

Single-Subject Deep-Learning Image Reconstruction With a Neural Optimization Transfer Algorithm for PET-Enabled Dual-Energy CT Imaging.

Combining dual-energy computed tomography (DECT) with positron emission tomography (PET) offers many potential clinical applications but typically requires expensive hardware upgrades or increases radiation doses on PET/CT scanners due to an extra X-ray CT scan. The recent PET-enabled DECT method allows DECT imaging on PET/CT without requiring a second X-ray CT scan. It combines the already existing X-ray CT image with a 511 keV γ -ray CT (gCT) image reconstructed from time-of-flight PET emission data. A kernelized framework has been developed for reconstructing gCT image but this method has not fully exploited the potential of prior knowledge. Use of deep neural networks may explore the power of deep learning in this application. However, common approaches require a large database for training, which is impractical for a new imaging method like PET-enabled DECT. Here, we propose a single-subject method by using neural-network representation as a deep coefficient prior to improving gCT image reconstruction without population-based pre-training. The resulting optimization problem becomes the tomographic estimation of nonlinear neural-network parameters from gCT projection data. This complicated problem can be efficiently solved by utilizing the optimization transfer strategy with quadratic surrogates. Each iteration of the proposed neural optimization transfer algorithm includes: PET activity image update; gCT image update; and least-square neural-network learning in the gCT image domain. This algorithm is guaranteed to monotonically increase the data likelihood. Results from computer simulation, real phantom data and real patient data have demonstrated that the proposed method can significantly improve gCT image quality and consequent multi-material decomposition as compared to other methods.

Kinetic modeling of 18 F-PI-2620 binding in the brain using an image-derived input function with total-body PET.

Accurate quantification of tau binding from 18 F-PI-2620 PET requires kinetic modeling and an input function. Here, we implemented a non-invasive Image-derived input function (IDIF) derived using the state-of-the-art total-body uEXPLORER PET/CT scanner to quantify tau binding and tracer delivery rate from 18 F-PI-2620 in the brain. Additionally, we explored the impact of scan duration on the quantification of kinetic parameters. Total-body PET dynamic data from 15 elderly participants were acquired. Time-activity curves from the grey matter regions of interest (ROIs) were fitted to the two-tissue compartmental model (2TCM) using a subject-specific IDIF derived from the descending aorta. ROI-specific kinetic parameters were estimated for different scan durations ranging from 10 to 90 minutes. Logan graphical analysis was also used to estimate the total distribution volume (V T ). Differences in kinetic parameters were observed between ROIs, including significant reduction in tracer delivery rate (K 1 ) in the medial temporal lobe. All kinetic parameters remained relatively stable after the 60-minute scan window across all ROIs, with K 1 showing high stability after 30 minutes of scan duration. Excellent correlation was observed between V T estimated using 2TCM and Logan plot analysis. This study demonstrated the utility of IDIF with total-body PET in investigating 18 F-PI-2620 kinetics in the brain.

Cloud-based serverless computing enables accelerated monte carlo simulations for nuclear medicine 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 109decays 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.

Development of a Monte Carlo-based scatter correction method for total-body PET using the uEXPLORER PET/CT scanner.

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.

Long-Axial Field-of-View PET Imaging in Patients with Lymphoma: Challenges and Opportunities.

[18F]fluoro-2-deoxy-d-glucose PET/computed tomography has been implemented in the management of patients with lymphoma, offering real-time metabolic information on lymphoma with the promise of more accurate staging, treatment response assessment, prognostication, and early detection of disease recurrence. The clinical management of lymphoproliferative disease has recently, rapidly evolved from initial chemotherapeutic to the use of immunotherapy, targeted agents, and to the use of chimeric antigen receptor T-cell therapies. The implementation of these new systems and imaging protocols together with new tracer development creates, in the field of lymphoproliferative disease, both opportunities and challenges that will be detailed in this comprehensive literature review.

Super-resolution reconstruction of γ-ray CT images for PET-enabled dual-energy CT imaging.

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.

Dose Reduction in Pediatric Oncology Patients with Delayed Total-Body [18F]FDG PET/CT.

Our aim was to define a lower limit of reduced injected activity in delayed [18F]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 [18F]FDG. Five randomly subsampled low-count reconstructions were generated using », 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 SUVmean 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 (SUVmax), 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 [18F]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 [18F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection.

Feasibility of PET-enabled dual-energy CT imaging: First physical phantom and patient results.

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.

Non-invasive quantification of 18F-florbetaben with total-body EXPLORER PET.

BACKGROUND: Kinetic modeling of 18F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic 18F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort. METHODS: 18F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 s after injection. Dynamic time-activity curves (TACs) for 110 min were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (VT, Vs) in key brain regions with early amyloid accumulation. Non-displaceable binding potential ([Formula: see text] was also calculated from the multi-reference tissue model (MRTM). RESULTS: Amyloid-positive (AD) patients showed the highest VT and VS in anterior cingulate, posterior cingulate, and precuneus, consistent with [Formula: see text] analysis. [Formula: see text]and VT from kinetic models were correlated (r² = 0.46, P < 2[Formula: see text] with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. VT from 2TCM was highly correlated ([Formula: see text]= 0.65, P < 2[Formula: see text]) with Logan graphical VT estimation. CONCLUSION: Non-invasive quantification of amyloid binding from total-body 18F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to [Formula: see text]in amyloid-positive and amyloid-negative older individuals.

High-Temporal-Resolution Kinetic Modeling of Lung Tumors with Dual-Blood Input Function Using Total-Body Dynamic PET.

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 18F-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 18F-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.

Racial disparities in the use of palliative therapy for ureteral obstruction among elderly patients with advanced prostate cancer.

OBJECTIVES: Palliative issues are an important but understudied issue for patients with advanced cancer. Ureteral obstruction is a complication of advanced prostate cancer, usually relieved with placement of retrograde ureteral stent (RUS) or percutaneous nephrostomy (PCN) to palliate symptoms associated with obstructive uropathy and/or renal failure. We investigated predictors of receipt of RUS and PCN and their association with survival for older advanced prostate cancer patients. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged 65 or older with stage IV (n = 10,848) or recurrent (n = 7,872) prostate cancer. We used multivariable analysis to compare those with ureteral obstruction treated with RUS or PCN to those not treated and to analyze the association between RUS, PCN, and survival. RESULTS: Sixteen percent (n = 2,958) of the sample developed ureteral obstruction. Compared to no treatment, African Americans were more likely to undergo placement of PCN [odds ratio 1.48, 95 % confidence intervals (CI) 1.03-2.13] than Whites, but equally likely to receive a stent. Subjects of >80 years were less likely to undergo RUS (ages 80-84, 0.41, 95 % CI 0.27-0.63; ages ≥85, 0.30, 95 % CI 0.16-0.54) compared to patients 65-69 years. Subjects who received a PCN were 55 % more likely to die than those who were untreated. There was no difference in survival among those receiving RUS vs untreated. Nine percent of subjects received RUS or PCN within 30 days of dying. CONCLUSIONS: This is the first population-based study to demonstrate a racial disparity in the palliative treatment of advanced prostate cancer. Reasons for disparate care need to be determined so that interventions may be developed.