Diagnostic Accuracy of 18 F-FES PET/CT for the Detection of Recurrent and Metastatic Breast Cancer.

PURPOSE: To evaluate the diagnostic value of 16α- 18 F-fluoro-17ß-fluoroestradiol ( 18 F-FES) PET/CT for distant metastasis or recurrence in patients with estrogen receptor (ER)-positive breast cancer. METHODS: Patients with ER-positive breast cancer and suspected of de novo metastasis or recurrence were retrospectively identified from a prospective cohort enrolled for a postmarketing surveillance study of 18 F-FES at our institution. Per-patient diagnostic accuracy was assessed using pathology or 2 or more standard-of-care imaging procedures with a minimum of 6 months of follow-up as the reference standard. The per-region detection rate of 18 F-FES PET/CT was evaluated and compared with that of standard-of-care imaging. RESULTS: Of the 162 included patients, 104 and 58 were suspected to have recurrence or de novo metastasis, respectively. The overall sensitivity and specificity of 18 F-FES PET/CT were 95% (95% confidence interval [CI], 89%-98%) and 89% (95% CI, 76%-96%), respectively. When stratified according to clinical settings, the sensitivity and specificity were 95% (95% CI, 88%-99%) and 96% (95% CI, 78%-100%), respectively, for detecting recurrence, and 94% (95% CI, 81%-99%) and 82% (95% CI, 60%-95%) for detecting distant metastasis. In region-based analysis, the overall detection rate of 18 F-FES PET/CT was significantly higher than that of standard-of-care imaging (92% [95% CI, 89%-94%] vs 83% [95% CI, 79%-87%], P < 0.001). CONCLUSIONS: 18 F-FES PET/CT showed excellent diagnostic performance in patients with ER-positive breast cancer suspected of de novo metastasis or recurrence.

Impact of 18F-FES PET/CT on Clinical Decisions in the Management of Recurrent or Metastatic Breast Cancer.

The clinical impact of 16α-18F-fluoro-17ß-estradiol (18F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor-positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18F-FES PET/CT. In 139 (40%) patients,18F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18F-FES-negative (44% [36/81]) than 18F-FES-positive (30% [51/172]) or mixed 18F-FES-positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.

Effect of Evogliptin on the Progression of Aortic Valvular Calcification.

BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).

miR-133b as a potential regulator of a synaptic NPTX2 protein in Alzheimer's disease.

A synaptic protein, Neuronal Pentraxin 2 (NPTX2), has emerged as a pivotal biomarker for Alzheimer's dementia (AD). We identified candidate miRNAs targeting NPTX2 and performed association and mediation analyses using multi-omics data (N = 702). Among 44 candidate miRNAs, miR-133b was significantly associated with AD and Braak positivity. Higher miR-133b expression was also associated with higher NPTX2 gene expression and better cognition. Mediation analysis showed that miR-133b partially influences AD and cognition through the NPTX2 protein. Our integrated approach suggests a potential role of miR-133b in synaptic integrity and offers new insights into AD pathogenesis.

Prognostic Value of Bone Scintigraphy in Cardiac Amyloidosis: A Systematic Review and Meta-analysis.

OBJECTIVES: The prognostic value of bone scintigraphy in cardiac amyloidosis (CA) remains undetermined. We conducted a systematic review and meta-analysis on the association of cardiac uptake on bone scintigraphy with mortality in known or suspected CA. PATIENTS AND METHODS: PubMed, Embase, and Cochrane library databases were searched up to November 2023 for studies that evaluated cardiac uptake on bone scintigraphy as a prognostic factor in the workup of CA. Hazards ratios (HRs) of high cardiac uptake for outcomes of all-cause or cardiac death were pooled and analyzed with stratifications according to the study populations, analytical methodologies, and radiotracers. RESULTS: Fourteen studies (3325 patients) were finally included. In studies regarding known or suspected CA, visual grades were not prognostically significant, regardless of the threshold used, with pooled HRs of 2.25 (95% confidence interval [CI], 0.93-5.48), 1.55 (95% CI, 0.89-2.68), and 1.53 (95% CI, 0.95-2.47) for visual grades ≥1, ≥2, and ≥3, respectively. By contrast, high cardiac uptake on semiquantitative measurements (heart-to-contralateral lung ratio, n = 6; heart-to-whole-body ratio, n = 1) was associated with increased mortality (pooled HR = 2.27 [95% CI, 1.87-2.76] for all semiquantitative measurements; 2.26 [1.86-2.74] for heart-to-contralateral lung ratio only). No difference in prognostic significance was found across 3 different 99mTc-radiotracers (P = 0.619). However, high cardiac uptake was not predictive of mortality in aortic stenosis-related CA (pooled HR = 1.13 [95% CI, 0.96-1.32]). CONCLUSIONS: High semiquantitative cardiac uptake on bone scintigraphy is associated with an increased risk of mortality in patients with known or suspected CA.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Hearing impairment increases the risk of hip fracture-related mortality and recurrent hip fractures: A propensity score matching analysis.

PURPOSE: Despite the ongoing rise in hip fractures and the adverse effects of hearing impairment (HI) on increased mortality and morbidity, research addressing the influence of HI on mortality risk or complications in patients with hip fractures remains absent. This study aimed to analyze the effects of HI on mortality and treatment outcomes among patients with hip fracture. METHODS: We retrospectively collected data from consecutive patients diagnosed with hip fractures between January 2007 and March 2022 who had auditory examination records. From the initially enrolled 265 patients, data for 58 with HI and 58 without HI (control group) were extracted using a 1:1 propensity score matching. The primary outcome included comparison of mortality rates, and the secondary outcome encompassed the comparison of postoperative medical and surgical complications. RESULTS: The 1-year cumulative mortality rate was not significantly different between the HI and control groups, but the overall cumulative mortality rate was significantly higher in the HI than in the control group (63.0 % and 48.6, respectively; P = 0.046) in a follow-up period of up to 16 years. The HI group had a significantly higher incidence of "second hip fractures due to falls" than the control group (P = 0.016), although no differences in other medical and surgical complications were revealed. CONCLUSIONS: Awareness of the long-term risk of higher mortality when managing patients with hip fracture and HI is important. To reduce the risk of second hip fractures, paying more attention to fall prevention education and taking a more proactive approach, especially for those with HI.

Impact of white matter hyperintensity volumes estimated by automated methods using deep learning on stroke outcomes in small vessel occlusion stroke.

Introduction: Although white matter hyperintensity (WMH) shares similar vascular risk and pathology with small vessel occlusion (SVO) stroke, there were few studies to evaluate the impact of the burden of WMH volume on early and delayed stroke outcomes in SVO stroke. Materials and methods: Using a multicenter registry database, we enrolled SVO stroke patients between August 2013 and November 2022. The WMH volume was estimated by automated methods using deep learning (VUNO Med-DeepBrain, Seoul, South Korea), which was a commercially available segmentation model. After propensity score matching (PSM), we evaluated the impact of WMH volume on early neurological deterioration (END) and poor functional outcomes at 3-month modified Ranking Scale (mRS), defined as mRS score >2 at 3 months, after an SVO stroke. Results: Among 1,718 SVO stroke cases, the prevalence of subjects with severe WMH (Fazekas score ≥ 3) was 68.9%. After PSM, END and poor functional outcomes at 3-month mRS (mRS > 2) were higher in the severe WMH group (END: 6.9 vs. 13.5%, p < 0.001; 3-month mRS > 2: 11.4 vs. 24.7%, p < 0.001). The logistic regression analysis using the PSM cohort showed that total WMH volume increased the risk of END [odd ratio [OR], 95% confidence interval [CI]; 1.01, 1.00-1.02, p = 0.048] and 3-month mRS > 2 (OR, 95% CI; 1.02, 1.01-1.03, p < 0.001). Deep WMH was associated with both END and 3-month mRS > 2, but periventricular WMH was associated with 3-month mRS > 2 only. Conclusion: This study used automated methods using a deep learning segmentation model to assess the impact of WMH burden on outcomes in SVO stroke. Our findings emphasize the significance of WMH burden in SVO stroke prognosis, encouraging tailored interventions for better patient care.

Semi-Quantitative Analysis of Lung Perfusion SPECT/CT for Evaluation of Response to Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension.

Purpose: We aimed to investigate the response to balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) using semi-quantitative analysis of lung perfusion SPECT/CT. Methods: This is a single-center retrospective study of patients with CTEPH who underwent BPA and pre- and post-BPA lung perfusion SPECT/CT between 2015 and 2022. Segmental defects on SPECT/CT were visually assessed and semi-quantitatively scored as 1 (large defect) or 0.5 (moderate defect) in accordance with modified PIOPED II criteria. The perfusion defect score was defined as (Σ segmental defect scores/18) × 100 (%). Associations between perfusion defect score and hemodynamic or functional parameters including WHO functional class, six-minute walking distance (6MWD), serum B-type natriuretic peptide (BNP), mean arterial pulmonary pressure (mPAP), pulmonary vascular resistance (PVR), and tricuspid regurgitation pressure gradient (TRPG) on echocardiography were statistically analyzed. Results: A total of 24 consecutive patients were included. The perfusion defect score significantly improved after BPA (median 58.3% vs. 47.2%, P < 0.001), in conjunction with the WHO functional class, 6MWD, serum BNP, mPAP, and TRPG. Perfusion defect scores were significantly correlated with 6MWD (rho = - 0.583, P < 0.001), serum BNP (rho = 0.514, P < 0.001), mPAP (rho = 0.583, P < 0.001), and PVR (rho = 0.575, P < 0.001). The improvement in the perfusion defect score was significantly associated with improvement in mPAP (rho = 0.844, P < 0.001). Conclusion: Our results suggest that semi-quantitative analysis of lung perfusion SPECT/CT can provide a potential imaging biomarker for monitoring the efficacy of BPA. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-024-00858-1.

Fully Automatic Quantitative Measurement of Equilibrium Radionuclide Angiocardiography Using a Convolutional Neural Network.

PURPOSE: The aim of this study was to generate deep learning-based regions of interest (ROIs) from equilibrium radionuclide angiography datasets for left ventricular ejection fraction (LVEF) measurement. PATIENTS AND METHODS: Manually drawn ROIs (mROIs) on end-systolic and end-diastolic images were extracted from reports in a Picture Archiving and Communications System. To reduce observer variability, preprocessed ROIs (pROIs) were delineated using a 41% threshold of the maximal pixel counts of the extracted mROIs and were labeled as ground-truth. Background ROIs were automatically created using an algorithm to identify areas with minimum counts within specified probability areas around the end-systolic ROI. A 2-dimensional U-Net convolutional neural network architecture was trained to generate deep learning-based ROIs (dlROIs) from pROIs. The model's performance was evaluated using Lin's concordance correlation coefficient (CCC). Bland-Altman plots were used to assess bias and 95% limits of agreement. RESULTS: A total of 41,462 scans (19,309 patients) were included. Strong concordance was found between LVEF measurements from dlROIs and pROIs (CCC = 85.6%; 95% confidence interval, 85.4%-85.9%), and between LVEF measurements from dlROIs and mROIs (CCC = 86.1%; 95% confidence interval, 85.8%-86.3%). In the Bland-Altman analysis, the mean differences and 95% limits of agreement of the LVEF measurements were -0.6% and -6.6% to 5.3%, respectively, for dlROIs and pROIs, and -0.4% and -6.3% to 5.4% for dlROIs and mROIs, respectively. In 37,537 scans (91%), the absolute LVEF difference between dlROIs and mROIs was <5%. CONCLUSIONS: Our 2-dimensional U-Net convolutional neural network architecture showed excellent performance in generating LV ROIs from equilibrium radionuclide angiography scans. It may enhance the convenience and reproducibility of LVEF measurements.

Deep learning-based measurement of split glomerular filtration rate with 99mTc-diethylenetriamine pentaacetic acid renal scan.

PURPOSE: To develop a deep learning (DL) model for generating automated regions of interest (ROIs) on 99mTc-diethylenetriamine pentaacetic acid (DTPA) renal scans for glomerular filtration rate (GFR) measurement. METHODS: Manually-drawn ROIs retrieved from a Picture Archiving and Communications System were used as ground-truth (GT) labels. A two-dimensional U-Net convolutional neural network architecture with multichannel input was trained to generate DL ROIs. The agreement between GFR values from GT and DL ROIs was evaluated using Lin's concordance correlation coefficient (CCC) and slope coefficients for linear regression analyses. Bias and 95% limits of agreement (LOA) were assessed using Bland-Altman plots. RESULTS: A total of 24,364 scans (12,822 patients) were included. Excellent concordance between GT and DL GFR was found for left (CCC 0.982, 95% confidence interval [CI] 0.981-0.982; slope 1.004, 95% CI 1.003-1.004), right (CCC 0.969, 95% CI 0.968-0.969; slope 0.954, 95% CI 0.953-0.955) and both kidneys (CCC 0.978, 95% CI 0.978-0.979; slope 0.979, 95% CI 0.978-0.979). Bland-Altman analysis revealed minimal bias between GT and DL GFR, with mean differences of - 0.2 (95% LOA - 4.4-4.0), 1.4 (95% LOA - 3.5-6.3) and 1.2 (95% LOA - 6.5-8.8) mL/min/1.73 m² for left, right and both kidneys, respectively. Notably, 19,960 scans (81.9%) showed an absolute difference in GFR of less than 5 mL/min/1.73 m². CONCLUSION: Our DL model exhibited excellent performance in the generation of ROIs on 99mTc-DTPA renal scans. This automated approach could potentially reduce manual effort and enhance the precision of GFR measurement in clinical practice.

Humanin activates integrin αV-TGFß axis and leads to glioblastoma progression.

The role of mitochondria peptides in the spreading of glioblastoma remains poorly understood. In this study, we investigated the mechanism underlying intracranial glioblastoma progression. Our findings demonstrate that the mitochondria-derived peptide, humanin, plays a significant role in enhancing glioblastoma progression through the intratumoral activation of the integrin alpha V (ITGAV)-TGF beta (TGFß) signaling axis. In glioblastoma tissues, humanin showed a significant upregulation in the tumor area compared to the corresponding normal region. Utilizing multiple in vitro pharmacological and genetic approaches, we observed that humanin activates the ITGAV pathway, leading to cellular attachment and filopodia formation. This process aids the subsequent migration and invasion of attached glioblastoma cells through intracellular TGFßR signaling activation. In addition, our in vivo orthotopic glioblastoma model provides further support for the pro-tumoral function of humanin. We observed a correlation between poor survival and aggressive invasiveness in the humanin-treated group, with noticeable tumor protrusions and induced angiogenesis compared to the control. Intriguingly, the in vivo effect of humanin on glioblastoma was significantly reduced by the treatment of TGFBR1 inhibitor. To strengthen these findings, public database analysis revealed a significant association between genes in the ITGAV-TGFßR axis and poor prognosis in glioblastoma patients. These results collectively highlight humanin as a pro-tumoral factor, making it a promising biological target for treating glioblastoma.

Distinguishing thymic cysts from low-risk thymomas via [18F]FDG PET/CT.

BACKGROUND: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. METHODS: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). CONCLUSIONS: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.

Clinical [18F]FSPG Positron Emission Tomography Imaging Reveals Heterogeneity in Tumor-Associated System xc- Activity.

BACKGROUND: (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography/computed tomography (PET/CT) provides a readout of system xc- transport activity and has been used for cancer detection in clinical studies of different cancer types. As system xc- provides the rate-limiting precursor for glutathione biosynthesis, an abundant antioxidant, [18F]FSPG imaging may additionally provide important prognostic information. Here, we performed an analysis of [18F]FSPG radiotracer distribution between primary tumors, metastases, and normal organs from cancer patients. We further assessed the heterogeneity of [18F]FSPG retention between cancer types, and between and within individuals. METHODS: This retrospective analysis of prospectively collected data compared [18F]FSPG PET/CT in subjects with head and neck squamous cell cancer (HNSCC, n = 5) and non-small-cell lung cancer (NSCLC, n = 10), scanned at different institutions. Using semi-automated regions of interest drawn around tumors and metastases, the maximum standardized uptake value (SUVmax), SUVmean, SUV standard deviation and SUVpeak were measured. [18F]FSPG time-activity curves (TACs) for normal organs, primary tumors and metastases were subsequently compared to 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT at 60 min post injection (p.i.). RESULTS: The mean administered activity of [18F]FSPG was 309.3 ± 9.1 MBq in subjects with NSCLC and 285.1 ± 11.3 MBq in those with HNSCC. The biodistribution of [18F]FSPG in both cohorts showed similar TACs in healthy organs from cancer patients. There was no statistically significant overall difference in the average SUVmax of tumor lesions at 60 min p.i. for NSCLC (8.1 ± 7.1) compared to HNSCC (6.0 ± 4.1; p = 0.29) for [18F]FSPG. However, there was heterogeneous retention between and within cancer types; the SUVmax at 60 min p.i. ranged from 1.4 to 23.7 in NSCLC and 3.1-12.1 in HNSCC. CONCLUSION: [18F]FSPG PET/CT imaging from both NSCLC and HNSCC cohorts showed the same normal-tissue biodistribution, but marked tumor heterogeneity across subjects and between lesions. Despite rapid elimination through the urinary tract and low normal-background tissue retention, the diagnostic potential of [18F]FSPG was limited by variability in tumor retention. As [18F]FSPG retention is mediated by the tumor's antioxidant capacity and response to oxidative stress, this heterogeneity may provide important insights into an individual tumor's response or resistance to therapy.

Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment.

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine.

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (p < 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (p < 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (p < 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.

Prognostic value of left ventricular mechanical dyssynchrony indices derived from gated myocardial perfusion SPECT in coronary artery disease: a systematic review and meta-analysis.

PURPOSE: Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor in coronary artery disease. A growing body of evidence indicates that LVMD parameters derived from phase analysis of gated myocardial SPECT may allow risk stratification for future cardiac events. We performed a systematic review and meta-analysis on the prognostic value of LVMD on gated SPECT in patients with coronary artery disease. METHODS: PubMed, Embase, and the Cochrane library were searched until August 25, 2022, for studies reporting the prognostic value of LVMD on gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE) in patients with coronary artery disease. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. RESULTS: Nine studies (26,750 patients) were included in a qualitative synthesis. Among the SPECT LVMD parameters used in various studies, high phase standard deviation, phase bandwidth, and phase entropy were widely evaluated and reported to be associated with high rates of all-cause death, cardiac death, or MACE. For five studies (23,973 patients) in the quantitative synthesis, the pooled HR of LVMD for predicting MACE was 2.81 (95% CI 2.03-3.88). Studies using combined phase parameters to define LVMD showed higher HRs than a study using phase entropy (p = 0.0180). CONCLUSION: LVMD from gated myocardial SPECT is a significant prognostic factor for coronary artery disease. Phase analysis of gated SPECT may be useful for accurate risk stratification and could be applied for clinical decision-making in such patients.

Diagnostic Performance of Perfusion-Only SPECT/CT for Chronic Thromboembolic Pulmonary Hypertension in Comparison With Ventilation-Perfusion Planar, SPECT, and SPECT/CT Imaging.

PURPOSE: The aim of this study was to assess the diagnostic performance of perfusion-only SPECT/CT (Q SPECT/CT) in comparison with that of ventilation/perfusion planar scintigraphy (V/Q planar), perfusion SPECT with ventilation scan (V/Q SPECT), and perfusion SPECT/CT with ventilation scan (V/Q SPECT/CT) in chronic thromboembolic pulmonary hypertension (CTEPH). PATIENTS AND METHODS: Patients with pulmonary hypertension who underwent ventilation-perfusion planar and SPECT/CT were retrospectively recruited. Two nuclear medicine physicians interpreted V/Q planar, V/Q SPECT, V/Q SPECT/CT, and Q SPECT/CT according to the European Association of Nuclear Medicine criteria. The diagnostic accuracy of these modalities for CTEPH was compared using a composite reference standard of pulmonary angiography, imaging test, cardiorespiratory assessment, and follow-up. RESULTS: A total of 192 patients were enrolled, including 85 with CTEPH. The sensitivity of Q SPECT/CT was 98.8%, which similar to that of V/Q planar (97.6%), V/Q SPECT (96.5%), or V/Q SPECT/CT (100.0%). In contrast, Q SPECT/CT exhibited significantly lower specificity (73.8%) compared with V/Q planar (86.9%, P = 0.001), V/Q SPECT (87.9%, P < 0.001), and V/Q SPECT/CT (88.8%, P < 0.001). The significantly lower specificity of Q SPECT/CT, compared with the 3 others, was observed in the subgroup aged ≥50 years ( P < 0.001 for all), but not in those <50 years. CONCLUSIONS: Q SPECT/CT exhibited lower specificity compared with V/Q planar, V/Q SPECT, and V/Q SPECT/CT in diagnosing CTEPH. It might underscore the essential role of a ventilation scan in patients with PH, even with the introduction of SPECT/CT.

Comparison of SUVA/V and SUVA-V for Evaluating Atherosclerotic Inflammation in 18F-FDG PET/CT.

Purpose: This study aimed to compare the clinical significance of two parameters, division of standardized uptake value (SUV) of target arterial activity by background venous blood pool activity (SUVA/V) and subtraction of background venous blood pool activity from SUV of target arterial activity (SUVA-V) of carotid arteries with atherosclerotic plaques using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). Methods: Patients aged 50 years or more who were diagnosed with carotid artery stenosis of 50% or more with carotid Doppler ultrasonography and had torso 18F-FDG PET/CT were enrolled retrospectively and classified patients who developed cerebrovascular events (CVEs) within 5 years after 18F-FDG PET/CT scan as the active group and patients who did not experience the CVE within 5 years as an inactive group. We calculated SUVA/V and SUVA-V using measurements of SUVmax of carotid arteries and mean SUV of superior vena cava (SVC). Results: SUVA-V, SUVA-V_high, and SUVA-V_low were significantly higher in the active group than in the inactive group, but neither SUVA/V, SUVA/V_high, nor SUVA/V_low showed significant differences between the active and inactive groups. The difference in rank between groups of SUVA/V_high and SUVA/V_low was greater than the difference in rank between groups of SUVA-V_high and SUVA-V_low. The CVE incidence differed between SUVA/V_high and SUVA/V_low of high carotid FDG uptake, but the CVE incidence did not differ between SUVA-V_high and SUVA-V_low of high carotid FDG uptake. Conclusion: SUVA-V may be a more rational solution than SUVA/V for evaluating atherosclerotic plaque inflammation on 18F-FDG PET/CT.

miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease.

BACKGROUND: Alzheimer's dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. METHODS: We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N = 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N = 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification. RESULTS: Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and APOE ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs. CONCLUSIONS: Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.