Citations

Abstract Introduction Quantitative interpretation of pediatric brain [ 18 F]-FDG PET is limited by the lack of age-matched normative reference databases, despite substantial developmental variation in cerebral glucose metabolism. This study aimed to construct a large-scale normative pediatric [ 18 F]-FDG PET database and develop an age-specific z-score mapping framework for quantitative evaluation of pediatric epilepsy. Method Pediatric brain PET data were retrospectively derived from clinically acquired whole-body or dedicated [ 18 F]-FDG PET examinations in participants 0–19 years of age without neurologic disease or visible brain abnormalities. A total of 417 PET scans from 341 participants were stratified into five developmental age groups: infancy, early childhood, middle childhood/school age, adolescence, and late adolescence. SUVR maps were generated using whole-brain atlas and brainstem reference regions. Voxel-wise t-test analyses were performed to characterize age- and sex-related metabolic differences. Age-specific voxel-wise mean and standard deviation maps were generated from the normative cohort and used to calculate age-matched hypometabolic z-score maps in 14 pediatric patients with epilepsy. The resulting abnormalities were qualitatively evaluated for concordance with epileptogenic findings identified on clinical MRI and/or PET by expert image review. Results Voxel-wise analyses demonstrated prominent age-dependent SUVR differences, particularly between infancy and older age groups. With whole-brain atlas normalization, older children showed progressively higher relative SUVR in cortical and cerebellar gray matter regions, whereas infancy showed relatively higher SUVR in the occipital cortex, white matter, thalamus, and brainstem. Brainstem normalization produced distinct developmental patterns, emphasizing higher white matter SUVR in infancy and broader gray matter differences in older groups. Sex-related differences were limited and regionally specific. Whole-brain atlas normalization showed lower variability than brainstem normalization and was selected for z-score mapping. In representative epilepsy cases, age-matched z-score maps identified focal or regional hypometabolism corresponding to malformations of cortical development, focal cortical dysplasia, mesial temporal sclerosis, nonlesional MRI cases, remote insult, tumor-related abnormalities, and Sturge-Weber syndrome. Discussion A large-scale normative pediatric [18F]-FDG PET database can support developmentally appropriate quantitative interpretation of pediatric brain PET. Age-matched z-score mapping may complement visual assessment by highlighting abnormal cerebral glucose metabolism in pediatric epilepsy, although findings should be interpreted with MRI, EEG, seizure semiology, and other presurgical data.

Objective To investigate the utility of tumoral and peritumoral [ 18 F]-fluorodeoxyglucose PET-based radiomics models for predicting tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC). Methods A total of 104 patients with NSCLC were retrospectively included and classified as STAS-positive or STAS-negative according to postoperative histopathology. Three radiomics models were developed based on tumoral and peritumoral volumes of interest (VOIs). Peritumoral models were constructed by defining VOIs with 5 and 10 mm expansions from the tumor margin (PR-5 and PR-10). Conventional PET-derived parameters were calculated. Each group was randomly divided into training (70%) and testing (30%) sets. For prediction, five machine learning algorithms were applied. Model performance was assessed by area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. Results Of the 104 patients, 60 (57.7%) were in the STAS-positive group, and 44 (42.3%) were in the STAS-negative group. Statistically significant differences were found in 27 tumoral, 62 PR-5, and 89 PR-10 radiomic features between the groups. Support Vector Machine achieved the best performance for the tumoral model (AUC: 0.70), whereas Logistic Regression was optimal for the PR-5 and PR-10 models, with AUCs of 0.79 and 0.74, respectively. The mean F1 score values for the tumoral, PR-5, and PR-10 models were 0.67, 0.72, and 0.68, respectively. Maximum standardized uptake value (SUV max ), SUV mean , and SUV peak did not differ significantly between groups. Tumor size, total lesion glycolysis, and metabolic tumor volume were significantly higher in the STAS-positive group. Conclusion Our findings suggest that peritumoral PET-based radiomics may help predict STAS status in NSCLC. The PR-5 model demonstrated the highest predictive performance, while conventional SUV-based parameters showed limited predictive value.

Abstract INTRODUCTION Centiloid (CL) scaling standardizes amyloid positron emission tomography (PET) quantification across tracers and platforms; however, variability across software implementations may affect diagnostic classification. This study evaluated inter‐software variability and diagnostic performance across five platforms using identical 1 8 F‐florbetapir datasets. METHODS Retrospectively, 192 patients undergoing 1 8 F‐florbetapir PET/computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. CL values were generated using four US Food and Drug Administration (FDA) ‐cleared platforms and an in‐house Centiloid standard pipeline. Agreement was assessed using intraclass correlation coefficient, with bias and limits of agreement evaluated by linear modeling and Bland–Altman analysis. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and classification against visual interpretation. RESULTS Agreement was excellent (intraclass correlation coefficient [ICC] 0.969; 95%CI 0.961–0.975). Some platforms produced systematically higher CL values versus others slightly lower. LoA reached ± 30 CL. Diagnostic accuracy was high (area under the curve [AUC]: 0.949–0.975), with sensitivity 0.923–0.968 and specificity 0.667–0.806. DISCUSSION Despite excellent agreement, systematic differences persist and may affect classification near thresholds, supporting consistent use of a single processing pipeline.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

6123 Background: Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735) with 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR) for Cohort A but was amended to clinical benefit rate (CBR=SD+PR+CR) due to prolonged SD in several pts. Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. Exploratory analyses in Cohort A1 (post-amendment pts) included PSMA PET imaging and circulating PSMA extravesicles (EVs) as a biomarker. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 20 pts (11 Cohort A + 9 Cohort A1) were enrolled from August 2021-Feb 2025. All 20 patients were eligible and received ≥ 1 cycle of treatment. Median age was 60.5 yrs, 50% male, performance status 0 (80%) or 1 (20%). 11 pts had no prior therapies (55.0%). The remaining pts had 1 (35%) or 2 (10%) prior lines of therapy. 75% of pts had no prior ICI. In Cohort A, the ORR was 0% (0 of 11). Cohort A1 met criteria for success based on CBR with 1 PR (12.5%) and 5 SD (62.5%) in the first 8 pts. For the whole cohort of 20 patients, the ORR was 5% (95% CI: 0.1-24.9) and the CBR rate was 75% (95% CI: 51-91) with 1 PR and 14 pts with SD. The duration of response for the 1 PR patient was 12.4 months. The median duration of response for the 15 pts with SD was 7.5 (2.0-29.7) months. 3 pts (15%) had PD and 2 pts (10%) went off prior to response assessment. Median cycles of treatment was 4 (2-30). In the 17 pts who discontinued, treatment was stopped in 9 (53%) for PD, 4 (23.5%) due to adverse events (AE), and 4 (23.5%) due to physician/patient preference. With a median follow-up of 14.5 months (1.5-39.2), the 1-year PFS rate is 52.1% (32.6 – 83.2%) and the OS rate is 82.1% (95% CI: 65.6 – 100%). The overall grade 3+ AE rate regardless of attribution was 80% (16/20). The most common grade 3 AEs were lymphocyte count decrease (40%), hypertension (20%), fatigue (10%), and pneumonitis (10%). 2 pts had a grade 4 AE (lymphocyte count decrease and thrombotic thrombocytopenic purpura). There were no treatment-related deaths. Analysis of correlative studies for Cohort A1 with PSMA imaging and EV biomarker ongoing. Conclusions: PTX and PMB has modest activity in pts with R/M ACC with CBR of 75% and prolonged benefit for some patients. Clinical trial information: NCT04895735 .

Background: Cardiac biomarkers are recognized as potential indicators for brain function, emotion regulation, and psychiatric risk. While research in adults has suggested associations between cardiac variables of autonomic function and neural changes, little is known about these relationships in children and young adults with psychiatric conditions. This systematic review aimed to examine the evidence linking cardiac biomarkers with structural, functional, and connectivity-based brain changes in this population. Methods: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Multiple databases were searched for studies examining associations between any cardiac biomarker and neuroimaging findings in individuals under 21 years old with psychiatric diagnoses. After screening and full-text review, 11 eligible studies were included. Results: The included studies investigating a range of psychiatric conditions and cardiac biomarkers were associated with brain changes across three domains: structure, connectivity, and neural responses. Associations were most consistent between higher vagal tone and structural and functional integrity of emotion-regulating regions such as the prefrontal cortex, amygdala, and insula. However, findings were heterogeneous and potentially moderated by symptom severity or environmental stressors. Conclusions: This review supports the potential of cardiac biomarkers, particularly high-frequency heart rate variability and root mean square of the successive differences, as proxies of brain changes in youth with psychiatric disorders. While promising, current evidence is too limited and variable for clinical applications. Future research should prioritize large-scale, longitudinal studies using harmonized protocols and wearable technologies to validate these indices as translational tools in child and adolescent psychiatry.

Abstract Background Immigrants to the United States often face challenges from limited healthcare access and less healthy environments which contribute to rising obesity and cardiovascular risk. Purpose To assess the feasibility and effectiveness of a community-based social network intervention for cardiovascular risk reduction among Hispanic and Somali adults. Methods A social network-informed, community-based participatory research-derived health promotion intervention was delivered by Hispanic and Somali lay health promoters (HPs) to members of their social networks over 1 year (12 biweekly sessions in months 0-6; 12 biweekly check-ins in months 7-12). Using a closed-cohort stepped wedge cluster randomized design, social networks were randomly assigned to receive the intervention immediately or after a delay of 1 year. Measurements at baseline, 6 months, and 12 months were derived from 6 of the American Heart Association’s “Life’s Simple 7”: BMI, blood pressure, fasting glucose, cholesterol, physical activity and dietary quality (range 0-12, with higher values indicating lower cardiovascular risk). Waist circumference and proportion of participants who achieved >5% body weight loss were also assessed. Results Four hundred seventy-five participants were enrolled among 51 HPs (29 Hispanic; 22 Somali). There was a statistically significant improvement in cardiovascular risk in the intervention group (n = 246) compared with controls (n = 229) at 6 months (0.4 [1.8] vs. −0.1 [1.7]; P = .03) that was not sustained at 12 months (0.5 [1.9] vs. 0.3 [1.8]; P = .38). There was a statistically significant higher proportion of participants who lost >5% of body weight in the intervention group compared with controls at 12 months (37% [15] vs. 18% [7.9]; P = .02). Reductions in weight and waist circumference in the intervention group compared with controls did not achieve statistical significance. Conclusion A social network intervention, delivered by lay HPs was feasible and resulted in a modest improvement of cardiovascular risk and clinically significant weight loss. Clinical Trial Identification Number NCT05136339.

Background Psychiatric comorbidities are increasingly recognised in demyelinating diseases, yet their frequency and timing in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well defined. We aimed to characterise the spectrum and temporal pattern of psychiatric illness in MOGAD and compare to multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-IgG). Methods We conducted a cross-sectional study of patients with MOGAD (n=388), age-matched and sex-matched MS (n=257) and AQP4-IgG-positive NMOSD (n=58) evaluated at Mayo Clinic (1991–2025). Psychiatric diagnoses, timing relative to the first attack and patient-reported outcomes were extracted from electronic health records (EHRs). Complementary analyses were conducted using the NeuroBlu real-world EHR database. Results Among 388 patients with MOGAD, 54.8% had ≥1 psychiatric disorder, most commonly anxiety (47.7%), depression (36.6%) and attention-deficit/hyperactivity disorder (ADHD, 9%). After the first attack, 33.3% of patients with MOGAD developed a new psychiatric disorder, often within the first year. MOGAD showed a lower frequency of depression versus MS (36.6% vs 47.5%, p=0.02) but similar rates of anxiety and ADHD. Temporal patterns differed: psychiatric disorders often appeared years before onset in MS but clustered shortly after onset in MOGAD. NeuroBlu analyses supported high rates of psychiatric disorders across the three conditions. Conclusion Psychiatric comorbidities are common in MOGAD, particularly depression and anxiety, typically emerging close after onset, whereas in MS they often preceded onset by years. These findings underscore the need for routine psychiatric screening in MOGAD and highlight unresolved questions regarding whether, and to what extent, MOG-IgG-mediated inflammatory demyelination contributes to psychiatric vulnerability.