Purpose To determine the feasibility of radiomic (computer extracted texture) features in differentiating radiation necrosis (RN) from recurrent brain tumors on routine MRI (Gadolinium (Gd)-T1w, T2w, FLAIR). Methods A retrospective study of brain tumor MRI obtained after 9-months (or later) post-radio-chemotherapy was collected from two institutions. In total, 58 patient studies were analyzed, consisting of a training (N = 43) cohort from one institution and an independent test (N = 15) cohort from another, with surgical histologic findings confirmed by an experienced neuropathologist at the respective institutions. Brain lesions on MRI were manually annotated by an expert neuro-radiologist. A set of radiomic features was extracted for every lesion on each MRI sequence: Gd-T1w, T2w, FLAIR. Feature selection was employed to identify the top 5 most discriminating features for every MRI sequence on the training cohort. These features were then evaluated on the test cohort via a support vector machine (SVM) classifier. The classification performance was compared against diagnostic reads by two expert neuro-radiologists, who had access to the same MRI sequences (Gd-T1w, T2w, and FLAIR) as the classifier. Results On the training cohort, the area under the receiver operating characteristic curve (AUC) was highest for FLAIR with 0.79, 95% CI [0.77, 0.81] for primary (N =22), and 0.79, 95% CI [0.75, 0.83], for metastatic subgroups (N = 21). Of the 15 studies in the holdout cohort, the SVM classifier identified 12 of 15 studies correctly, while neuro-radiologist 1 diagnosed 7 of 15, and neuro-radiologist 2 diagnosed 8 of 15 studies correctly, respectively. Discussion Our preliminary results appear to suggest that radiomic features may provide complementary diagnostic information on routine MRI sequences that may improve distinction of RN from recurrence, both for primary and metastatic brain tumors.

Nayate A, Moore SA, Weiss R, Taktakishvili OM, Lin L.-H., Talman WT. Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 296: R272-R279, 2009. First published November 19, 2008 doi:10.1152/ajpregu.00080.2008.-Humans with central lesions that augment sympathetic nerve activity are predisposed to cardiac arrhythmias, myocardial lesions, and sudden death. Previously, we showed that selectively killing neurons with neurokinin-1 receptors in the nucleus tractus solitarii (NTS) of rats attenuated the baroreflex and, in some animals, led to sudden unexplained death within ϳ2 wk. Interruption of arterial baroreflexes is known to increase sympathetic activity. Here we tested the hypothesis that lesions in the NTS lead to fatal cardiac arrhythmias and myocardial lesions. We studied electrocardiograms, echocardiograms, blood pressure, and heart rate in 14 adult male rats after bilateral microinjection into the NTS of stabilized substance P conjugated to the toxin saporin and compared the variables in five sham control rats and in five animals with toxin injected outside the NTS. Only injection of toxin into the NTS led to increased lability of arterial blood pressure, a sign of baroreflex interruption. Two animals treated with toxin died suddenly. All animals engaged in normal activity until, in two, rapid development of asystole and death over 6 -8 min. Cardiac function when examined by echocardiography was normal, but pathologic examination of the heart revealed diffuse microscopic areas of acute coagulation necrosis in the myocardium in five animals, focal subacute necrosis in two animals, and both changes in one animal. This study supports the hypothesis that NTS lesions interrupting the baroreflex may induce cardiac arrhythmias and myocardial changes similar to those seen in humans with central lesions and may lead to sudden cardiac death. baroreflex; cardiac arrhythmia; heart injuries; sudden death; sympathetic nervous system PREVIOUS STUDIES HAVE SUGGESTED that substance P, acting at neurons that express neurokinin-1 (NK1) receptors, may participate in transmission of arterial baroreflexes at the level of the nucleus tractus solitarii (NTS) (17,23,26). In an earlier study, we injected into NTS a toxin that selectively targeted neurons with NK1 receptors (24), and we showed that the ensuing lesion attenuated baroreflex responses (24). The altered baroreflex transmission was associated with sudden, unexpected, death in 33% of the experimental animals. Death in these animals was reminiscent of that seen in humans who have sustained central lesions (30). While subarachnoid hemorrhage is a most common cause, other central lesions that lead to enhanced sympathetic nerve activity also predispose an individual to the fatal outcome (30). In fact, sympathetic nerve activity and excessive circulating catecholamines alone may lead to cardiac arrhythmias and death (12,33). Sudden death in humans with central lesions correlates with cardiac arrhythmias, but the lesions also may l...

Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

BACKGROUND AND PURPOSE:Fluorine-18 florbetapir is a recently developed ␤-amyloid plaque positron-emission tomography imaging agent with high sensitivity, specificity, and accuracy in the detection of moderate-to-frequent cerebral cortical ␤-amyloid plaque. However, the FDA has expressed concerns about the consistency of interpretation of [18 F] florbetapir PET brain scans. We hypothesized

Subtle tissue deformations caused by mass-effect in Glioblastoma (GBM) are often not visually evident, and may cause neurological deficits, impacting survival. Radiomic features provide sub-visual quantitative measures to uncover disease characteristics. We present a new radiomic feature to capture mass effect-induced deformations in the brain on Gadolinium-contrast (Gd-C) T1w-MRI, and their impact on survival. Our rationale is that larger variations in deformation within functionally eloquent areas of the contralateral hemisphere are likely related to decreased survival. Displacements in the cortical and subcortical structures were measured by aligning the Gd-C T1w-MRI to a healthy atlas. The variance of deformation magnitudes was measured and defined as Mass Effect Deformation Heterogeneity (MEDH) within the brain structures. MEDH values were then correlated with overall-survival of 89 subjects on the discovery cohort, with tumors on the right (n = 41) and left (n = 48) cerebral hemispheres, and evaluated on a hold-out cohort (n = 49 subjects). On both cohorts, decreased survival time was found to be associated with increased MEDH in areas of language comprehension, social cognition, visual perception, emotion, somato-sensory, cognitive and motor-control functions, particularly in the memory areas in the left-hemisphere. Our results suggest that higher MEDH in functionally eloquent areas of the left-hemisphere due to GBM in the right-hemisphere may be associated with poor-survival.