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

Abstract Background: Lung herniation has been described in case reports or series. There are scare data in the form of original research studies to systematically evaluate this condition. Objective: Our aim was to evaluate lung hernias with a focus on their natural history. Methods: This is a retrospective study at our institution of patients who were found to have lung herniation on imaging between September 2010 and November 2022. Electronic medical record review was performed to extract clinical information regarding patients. Computed tomographic imaging was used to evaluate hernia size and size progression over time with a median follow-up time of 3.8 years. Results: Thirty-eight patients were eligible for analysis. Majority of patients were overweight or obese (31/38), smokers (31/38), had prior thoracic surgery (30/38), and were asymptomatic (33/38). Twenty of 38 patients had stability in hernia size, 12 of 38 patients had hernia size progression, and 6 of 38 patients showed hernia size regression. Younger age was found to be predictive of hernia size progression with age of 60 years being the cut-off for its prediction. Conclusion: Lung hernias typically either remain stable in size or show size progression. Younger age (60 years cut-off) was found to be predictive of size progression. This is the largest systematic investigation at a medical institution to the best of our knowledge of lung hernias which used computed tomographic imaging to follow up lung hernias. Further information could be given to patients with this condition and to clinicians for potential management guidance.

Background Pericardial disease can be a manifestation of infection and imaging can have a role in its diagnosis. coccidioidomycosis endemic fungal infection has been more frequently reported over the past few decades. Other than case reports or series, there has been no systemic study evaluating pericardial imaging findings in patients with coccidioidomycosis to the best of our knowledge. The purpose of this study was to evaluate intrathoracic computed tomographic (CT) imaging abnormalities in patients with coccidioidal infection with specific emphasis on the pericardium. Methods Retrospective review of radiology reports and clinical chart review was performed to identify patients with coccidioidomycosis between January 2000 and September 2021 at our medical center. Diagnosis of infection was confirmed predominately with serology. Patients were excluded if a CT was not performed within 3 months of confirmed diagnosis date and if there was concomitant additional granulomatous or fungal infection. Chest CT was reviewed for pericardial and additional intrathoracic findings. Results The final retrospective cohort consisted of 37 patients. Imaging findings included lung nodules (N = 33/37), consolidation (N = 25/37), mediastinal or hilar lymphadenopathy (N = 20/37) and pleural effusions (N = 13/37). Eleven of 37 patients (30%) had either trace pericardial fluid (N = 3/37) or small pericardial effusions (N = 8/37). One patient had pericardial enhancement/thickening and history of pericardial tamponade. No other patient had clinical pericarditis or pericardial tamponade. Pericardial calcifications were not seen in any patient. Pericardial effusion was statistically associated with presence of pleural effusion as 9/13 patients with pleural effusion had pericardial effusion versus 2/26 patients without pleural effusion had pericardial effusion (p < 0.001). Otherwise patients with and without pericardial imaging findings were similar in terms of demographics, comorbidities and other imaging findings. Conclusion Pulmonary parenchymal pathology is a common manifestation of coccidioidal infection. Most patients with coccidioidomycosis do not have pericardial imaging abnormalities on CT.

Introduction Our aim was to characterize the diagnostic accuracy indices for nodal (N)-staging with [ 18 F]FDG Total-Body (TB) and short-axial field-of-view (SAFOV) PET/CT in non-small cell lung cancer (NSCLC) patients referred for staging or restaging. Methods In this prospective single center cross-over head-to-head comparative study 48 patients underwent [ 18 F]FDG TB and SAFOV PET/CT on the same day. In total 700 lymph node levels (1R/L, 2R/L, 3a/p, 4R/L, 5, 6, 7, 8R/L, 9R/L, 10-14R/L) of 28 patients could be correlated to a composite reference standard (histopathological correlation, imaging after localized or systemic treatment), which allowed determination of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) lesions. Lymph nodes were characterized semi-quantitatively by maximum standardized uptake value (SUV max ), tumor-to-background ratio (TBR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) leading to threshold for each scanner. Results TB and SAFOV PET/CT showed high diagnostic accuracy indices for patient-based N-staging. Sensitivity and specificity were 86.0% (CI: 77.0–95.0%) and 98.3% (CI: 97.3–99.3%) for TB; 77.2% (CI: 66.3–88.1%) and 97.4% (CI: 96.1–98.6%) for SAFOV PET. Positive predictive value was higher for TB (81.7%, CI: 71.9–91.5%) compared to SAFOV PET (72.1%, CI: 60.9–83.4%). However, this finding was not statistically significant ( p  = 0.08). Negative predictive values for TB (98.6%, CI: 97.9–99.6%) and SAFOV PET/CT (98.0%, CI: 96.9–99.1%) were comparable. Overall, NSCLC N-staging was affected in six cases on SAFOV and only in one case on TB PET/CT. Semi-quantitative analysis revealed a threshold of SUV max 3.0 to detect TP lesions on both scanners. However, TBR, MTV and TLG thresholds were lower on TB compared to SAFOV PET (TBR: 1.2 vs. 1.7, MTV: 0.5 ml vs. 1.0 ml and TLG: 1.0 ml vs. 3.0 ml). Conclusion TB and SAFOV PET/CT showed high diagnostic accuracy indices for N-staging in NSCLC patients. Sensitivity and PPV on TB PET/CT were slightly higher, compared to SAFOV PET/CT without statistical significance. However, TB PET/CT showed lower rate of incorrect N-staging and lower semi-quantitative thresholds for the detection positive mediastinal lymph nodes. Therefore, TB PET/CT might be advantageous in detecting small and low [ 18 F]FDG-avidity mediastinal lymph node metastases in NSCLC patients.

ObjectivesThe objectives of the study are (1) to distinguish lipoma (L) from atypical lipomatous tumor (ALT) using MRI qualitative features, (2) to assess the value of contrast enhancement, and (3) to evaluate the reproducibility and confidence level of radiological readings.Materials and methodsPatients with pathologically proven L or ALT, who underwent MRI within 3 months from surgical excision were included in this retrospective multicenter international study. Two radiologists independently reviewed MRI centrally. Impressions were recorded as L or ALT. A third radiologist was consulted for discordant readings. The two radiologists re-read all non-contrast sequences; impression was recorded; then post-contrast images were reviewed and any changes were recorded.ResultsA total of 246 patients (135 females; median age, 59 years) were included. ALT was histopathologically confirmed in 70/246 patients. In multivariable analysis, in addition to the lesion size, deep location, proximal lower limb lesions, demonstrating incomplete fat suppression, or increased architectural complexity were the independent predictive features of ALT; but not the contrast enhancement. Post-contrast MRI changed the impression in a total of 5 studies (3 for R1 and 4 for R2; 2 studies are common); all of them were incorrectly changed from Ls to ALTs. Overall, inter-reader kappa agreement was 0.42 (95% CI 0.39–0.56). Discordance between the two readers was statistically significant for both pathologically proven L (p < 0.001) and ALT (p = 0.003).ConclusionMost qualitative MR imaging features can help distinguish ALTs from BLs. However, contrast enhancement may be limited and occasionally misleading. Substantial discordance on MRI readings exists between radiologists with a relatively high false positive and negative rates.

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.

Background/Objectives: Quantitative analysis of amyloid PET imaging plays a crucial role in diagnosing Alzheimer’s disease (AD), particularly in cases where visual interpretation is equivocal. Multiple commercial software tools are available for this purpose, yet differences in their quantification and diagnostic performance remain understudied, especially for Neurophet SCALE PET. Methods: We retrospectively analyzed 18F-florbetaben PET/CT scans from 129 patients with cognitive impairment, comprising 39 patients with AD and 90 with non-AD diagnoses, using three software tools: MIMneuro, CortexID Suite, and Neurophet SCALE PET. Standardized uptake value ratios (SUVRs) were obtained for six brain regions known for amyloid accumulation. Diagnostic accuracy was evaluated using ROC curve analysis, while inter-software correlations and reliability were assessed via Pearson correlation coefficients and intraclass correlation coefficients (ICC). Results: All three software programs significantly distinguished AD from non-AD patients in most brain regions. MIMneuro and Neurophet SCALE PET demonstrated the highest diagnostic performance, with MIMneuro achieving an AUC of 1.000 in the anterior cingulate gyrus. While MIMneuro and Neurophet SCALE PET showed moderate-to-strong SUVR correlations (r = 0.715–0.865), CortexID Suite showed limited correlation with the other tools. Inter-software reliability was moderate only in selected regions (ICC ≈ 0.5), indicating potential variability in SUVR measurements across platforms. Conclusions: MIMneuro, CortexID Suite, and Neurophet SCALE PET are effective for the semi-quantitative analysis of amyloid PET and can aid in the diagnosis of AD. However, clinicians should be cautious when interpreting SUVRs across different software tools due to limited inter-software consistency. Standardization efforts or consistent use of a single platform are recommended to avoid diagnostic discrepancies.

Background/Objectives: Quantitative analysis of amyloid PET imaging plays a crucial role in diagnosing Alzheimer’s disease (AD), particularly in cases where visual interpretation is equivocal. Multiple commercial software tools are available for this purpose, yet differences in their quantification and diagnostic performance remain understudied, especially for Neurophet SCALE PET. Methods: We retrospectively analyzed [sup.18]F-florbetaben PET/CT scans from 129 patients with cognitive impairment, comprising 39 patients with AD and 90 with non-AD diagnoses, using three software tools: MIMneuro, CortexID Suite, and Neurophet SCALE PET. Standardized uptake value ratios (SUVRs) were obtained for six brain regions known for amyloid accumulation. Diagnostic accuracy was evaluated using ROC curve analysis, while inter-software correlations and reliability were assessed via Pearson correlation coefficients and intraclass correlation coefficients (ICC). Results: All three software programs significantly distinguished AD from non-AD patients in most brain regions. MIMneuro and Neurophet SCALE PET demonstrated the highest diagnostic performance, with MIMneuro achieving an AUC of 1.000 in the anterior cingulate gyrus. While MIMneuro and Neurophet SCALE PET showed moderate-to-strong SUVR correlations (r = 0.715–0.865), CortexID Suite showed limited correlation with the other tools. Inter-software reliability was moderate only in selected regions (ICC ≈ 0.5), indicating potential variability in SUVR measurements across platforms. Conclusions: MIMneuro, CortexID Suite, and Neurophet SCALE PET are effective for the semi-quantitative analysis of amyloid PET and can aid in the diagnosis of AD. However, clinicians should be cautious when interpreting SUVRs across different software tools due to limited inter-software consistency. Standardization efforts or consistent use of a single platform are recommended to avoid diagnostic discrepancies.

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.