Cohort discovery and risk stratification for Alzheimer’s disease: an electronic health record‐based approach

BackgroundWe sought to leverage data routinely collected in electronic health records (EHRs), with the goal of developing patient risk stratification tools for predicting risk of developing Alzheimer’s disease (AD).MethodUsing EHR data from the University of Michigan (UM) hospitals and consensus‐based diagnoses from the Michigan Alzheimer’s Disease Research Center, we developed and validated a cohort discovery tool for identifying patients with AD. Applied to all UM patients, these labels were used to train an EHR‐based machine learning model for predicting AD onset within 10 years.ResultsApplied to a test cohort of 1697 UM patients, the model achieved an area under the receiver operating characteristics curve of 0.70 (95% confidence interval = 0.63‐0.77). Important predictive factors included cardiovascular factors and laboratory blood testing.ConclusionRoutinely collected EHR data can be used to predict AD onset with modest accuracy. Mining routinely collected data could shed light on early indicators of AD appearance and progression.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155901/1/trc212035-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155901/2/trc212035_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155901/3/trc212035.pd

Image-based Quantification of 3D Morphology for Bifurcations in the Left Coronary Artery: Application to Stent Design

Background Improved strategies for stent‐based treatment of coronary artery disease at bifurcations require a greater understanding of artery morphology. Objective We developed a workflow to quantify morphology in the left main coronary (LMCA), left anterior descending (LAD), and left circumflex (LCX) artery bifurcations. Methods Computational models of each bifurcation were created for 55 patients using computed tomography images in 3D segmentation software. Metrics including cross‐sectional area, length, eccentricity, taper, curvature, planarity, branching law parameters, and bifurcation angles were assessed using open‐sources software and custom applications. Geometric characterization was performed by comparison of means, correlation, and linear discriminant analysis (LDA). Results Differences between metrics suggest dedicated or multistent approaches should be tailored for each bifurcation. For example, the side branch of the LCX (i.e., obtuse marginal; OM) was longer than that of the LMCA (i.e., LCXprox) and LAD (i.e., first diagonal; D1). Bifurcation metrics for some locations (e.g., LMCA Finet ratio) provide results and confidence intervals agreeing with prior findings, while revised metric values are presented for others (e.g., LAD and LCX). LDA revealed several metrics that differentiate between artery locations (e.g., LMCA vs. D1, LMCA vs. OM, LADprox vs. D1, and LCXprox vs. D1). Conclusions These results provide a foundation for elucidating common parameters from healthy coronary arteries and could be leveraged in the future for treating diseased arteries. Collectively the current results may ultimately be used for design iterations that improve outcomes following implantation of future dedicated bifurcation stents

Immersive Visualization for Enhanced Computational Fluid Dynamics Analysis

Modern biomedical computer simulations produce spatiotemporal results that are often viewed at a single point in time on standard 2D displays. An immersive visualization environment (IVE) with 3D stereoscopic capability can mitigate some shortcomings of 2D displays via improved depth cues and active movement to further appreciate the spatial localization of imaging data with temporal computational fluid dynamics (CFD) results. We present a semi-automatic workflow for the import, processing, rendering, and stereoscopic visualization of high resolution, patient-specific imaging data, and CFD results in an IVE. Versatility of the workflow is highlighted with current clinical sequelae known to be influenced by adverse hemodynamics to illustrate potential clinical utility

Myocardial dysfunction in the periinfarct and remote regions following anterior infarction in rats quantified by 2D radial strain echocardiography: An observational cohort study

<p>Abstract</p> <p>Background</p> <p>Heart failure from adverse ventricular remodeling follows myocardial infarction, but the contribution of periinfarct and remote myocardium to the development of cardiomyopathy remains poorly defined. 2D strain echocardiography (2DSE) is a novel and sensitive tool to measure regional myocardial mechanics. The aim is to quantify radial strain in infarcted (I), periinfarct (PI) and remote (R) myocardial regions acutely and chronically following anterior infarction in rats.</p> <p>Methods</p> <p>The left anterior coronary artery of male Sprague-Dawley rats (270–370 g) were occluded for 20–30 minutes and 2DSE was performed in the acute setting (n = 10; baseline and 60 minutes post-reperfusion) and in the chronic setting (n = 14; baseline, 1, 3 and 6 weeks). Using software, radial strain was measured in the mid-ventricle in short axis view. The ventricle was divided into 3 regions: I (anteroseptum, anterior and anterolateral), PI – (inferoseptum and inferolateral) and R – (inferior). Infarct size was measured using triphenyl tetrazolium chloride in the acute group.</p> <p>Results</p> <p>Following infarct, adverse remodeling occurred with progressive increase in left ventricular size, mass and reduced fractional shortening within 6 weeks. Radial strain decreased not only in the infarct but also in the periinfarct and remote regions acutely and chronically (I, PI, R, change vs. baseline, 60 minutes -32.7 ± 8.7, -17.4 ± 9.4, -13.5 ± 11.6%; 6 weeks -24.4 ± 8.2, -17.7 ± 8.3, -15.2 ± 8.4% respectively, all p < 0.05). Reduced radial strain in periinfarct and remote regions occurred despite minimal or absent necrosis (area of necrosis I, PI, R: 48.8 ± 23, 5.1 ± 6.6, 0 ± 0%, p < 0.001 vs. I).</p> <p>Conclusion</p> <p>Following left anterior coronary occlusion, radial strain decreased at 60 minutes and up to 6 weeks in the periinfarct and remote regions, similar to the reduction in the infarct region. This demonstrates early and chronic myopathic process in periinfarct and remote regions following myocardial infarction that may be an under recognized but important contributor to adverse left ventricular remodeling and progression to ischemic cardiomyopathy.</p

Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance: comparison with ultrasound intima media thickness

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) allows volumetric carotid plaque measurement that has advantage over 2-dimensional ultrasound (US) intima-media thickness (IMT) in evaluating treatment response. We tested the hypothesis that 6-month statin treatment in patients with carotid plaque will lead to plaque regression when measured by 3 Tesla CMR but not by IMT.</p> <p>Methods</p> <p>Twenty-six subjects (67 ± 2 years, 7 females) with known carotid plaque (> 1.1 mm) and coronary or cerebrovascular atherosclerotic disease underwent 3T CMR (T1, T2, proton density and time of flight sequences) and US at baseline and following 6 months of statin therapy (6 had initiation, 7 had increase and 13 had maintenance of statin dosing). CMR plaque volume (PV) was measured in the region 12 mm below and up to 12 mm above carotid flow divider using software. Mean posterior IMT in the same region was measured. Baseline and 6-month CMR PV and US IMT were compared. Change in lipid rich/necrotic core (LR/NC) and calcification plaque components from CMR were related to change in PV.</p> <p>Results</p> <p>Low-density lipoprotein cholesterol decreased (86 ± 6 to 74 ± 4 mg/dL, p = 0.046). CMR PV decreased 5.8 ± 2% (1036 ± 59 to 976 ± 65 mm³, p = 0.018). Mean IMT was unchanged (1.12 ± 0.06 vs. 1.14 ± 0.06 mm, p = NS). Patients with initiation or increase of statins had -8.8 ± 2.8% PV change (p = 0.001) while patients with maintenance of statin dosing had -2.7 ± 3% change in PV (p = NS). There was circumferential heterogeneity in CMR plaque thickness with greatest thickness in the posterior carotid artery, in the region opposite the flow divider. Similarly there was circumferential regional difference in <it>change </it>of plaque thickness with significant plaque regression in the anterior carotid region in region of the flow divider. Change in LR/NC (R = 0.62, p = 0.006) and calcification (R = 0.45, p = 0.03) correlated with PV change.</p> <p>Conclusions</p> <p>Six month statin therapy in patients with carotid plaque led to reduced plaque volume by 3T CMR, but ultrasound posterior IMT did not show any change. The heterogeneous spatial distribution of plaque and regional differences in magnitude of plaque regression may explain the difference in findings and support volumetric measurement of plaque. 3T CMR has potential advantage over ultrasound IMT to assess treatment response in individuals and may allow reduced sample size, duration and cost of clinical trials of plaque regression.</p

Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>Light chain amyloidosis (AL) is a rare but often fatal disease due to intractable heart failure. Amyloid deposition leads to diastolic dysfunction and often preserved ejection fraction. We hypothesize that AL is associated with regional systolic dyssynchrony. The aim is to compare left ventricular (LV) regional synchrony in AL subjects versus healthy controls using 16-segment dyssynchrony index measured from 3-dimension-al (3D) echocardiography.</p> <p>Methods</p> <p>Cardiac 3D echocardiography full volumes were acquired in 10 biopsy-proven AL subjects (60 ± 3 years, 5 females) and 10 healthy controls (52 ± 1 years, 5 females). The LV was subdivided into 16 segments and the time from end-diastole to the minimal systolic volume for each of the 16 segments was expressed as a percent of the cycle length. The standard deviations of these times provided a 16-segment dyssynchrony index (16-SD%). 16-SD% was compared between healthy and AL subjects.</p> <p>Results</p> <p>Left ventricular ejection fraction was comparable (control vs. AL: 62.4 ± 0.6 vs. 58.6 ± 2.8%, p = NS). 16-SD% was significantly higher in AL versus healthy subjects (5.93 ± 4.4 vs. 1.67 ± 0.87%, p = 0.003). 16-SD% correlated with left ventricular mass index (R 0.45, p = 0.04) but not to left ventricular ejection fraction.</p> <p>Conclusion</p> <p>Light chain amyloidosis is associated with left ventricular regional systolic dyssynchrony. Regional dyssynchrony may be an unrecognized mechanism of heart failure in AL subjects.</p