Intraluminal thrombus (ILT) is present in over 75% of all abdominal aortic aneurysms (AAAs) and probably contributes to the complex biomechanics and pathobiology of these lesions. A reliable predictor of thrombus formation in enlarging lesions could thereby aid clinicians in treatment planning. The primary goal of this work was to identify a new phenomenological metric having clinical utility that is motivated by the hypothesis that two basic haemodynamic features must coincide spatially and temporally to promote the formation of a thrombus on an intact endothelium-platelets must be activated within a shear flow and then be presented to a susceptible endothelium. Towards this end, we propose a new thrombus formation potential (TFP) that combines information on the flow-induced shear history experienced by blood-borne particles that come in close proximity to the endothelium with information on both the time-averaged wall shear stress (WSS) and the oscillatory shear index (OSI) that locally affect the endothelial mechanobiology. To illustrate the possible utility of this new metric, we show computational results for 10 carotid
Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.
Many vascular disorders, including aortic aneurysms and dissections, are characterized by localized changes in wall composition and structure. Notwithstanding the importance of histopathologic changes that occur at the microstructural level, macroscopic manifestations ultimately dictate the mechanical functionality and structural integrity of the aortic wall. Understanding structure-function relationships locally is thus critical for gaining increased insight into conditions that render a vessel susceptible to disease or failure. Given the scarcity of human data, mouse models are increasingly useful in this regard. In this paper, we present a novel inverse characterization of regional, nonlinear, anisotropic properties of the murine aorta. Full-field biaxial data are collected using a panoramic-digital image correlation (p-DIC) system. An inverse method, based on the principle of virtual power (PVP), is used to estimate values of material parameters regionally for a microstructurally motivated constitutive relation. We validate our experimental-computational approach by comparing results to those from standard biaxial testing. The results for the nondiseased suprarenal abdominal aorta from apolipoprotein-E null mice reveal material heterogeneities, with significant differences between dorsal and ventral as well as between proximal and distal locations, which may arise in part due to differential perivascular support and localized branches. Overall results were validated for both a membrane and a thick-wall model that delineated medial and adventitial properties. Whereas full-field characterization can be useful in the study of normal arteries, we submit that it will be particularly useful for studying complex lesions such as aneurysms, which can now be pursued with confidence given the present validation.
Background: Artificial intelligence (AI)-enabled analysis of 12-lead electrocardiograms (ECGs) may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful and generalizable improvement in predictive accuracy beyond clinical risk factors for AF. Methods: We trained a convolutional neural network ("ECG-AI") to infer 5-year incident AF risk using 12-lead ECGs in patients receiving longitudinal primary care at Massachusetts General Hospital (MGH). We then fit three Cox proportional hazards models, each composed of: a) ECG-AI 5-year AF probability, b) the Cohorts for Heart and Aging in Genomic Epidemiology AF (CHARGE-AF) clinical risk score, and c) terms for both ECG-AI and CHARGE-AF ("CH-AI"). We assessed model performance by calculating discrimination (area under the receiver operating characteristic curve, AUROC) and calibration in an internal test set and two external test sets (Brigham and Women's Hospital and UK Biobank). Models were recalibrated to estimate 2-year AF risk in the UK Biobank given limited available follow-up. We used saliency mapping to identify ECG features most influential on ECG-AI risk predictions and assessed correlation between ECG-AI and CHARGE-AF linear predictors. Results: The training set comprised 45,770 individuals (age 55±17 years, 53% women, 2,171 AF events), and the test sets comprised 83,162 individuals (age 59±13 years, 56% women, 2,424 AF events). AUROC was comparable using CHARGE-AF (MGH 0.802, 95% CI 0.767-0.836; BWH 0.752, 95% CI 0.741-0.763; UK Biobank 0.732, 95% CI 0.704-0.759) and ECG-AI (MGH 0.823, 95% CI 0.790-0.856; BWH 0.747, 95% CI 0.736-0.759; UK Biobank 0.705, 95% CI 0.673-0.737). AUROC was highest using CH-AI: MGH 0.838, 95% CI 0.807-0.869; BWH 0.777, 95% CI 0.766-0.788; UK Biobank 0.746, 95% CI 0.716-0.776). Calibration error was low using ECG-AI (MGH 0.0212; BWH 0.0129; UK Biobank 0.0035) and CH-AI (MGH 0.012; BWH 0.0108; UK Biobank 0.0001). In saliency analyses, the ECG P-wave had the greatest influence on AI model predictions. ECG-AI and CHARGE-AF linear predictors were correlated (Pearson r MGH 0.61, BWH 0.66, UK Biobank 0.41). Conclusions: AI-based analysis of 12-lead ECGs has similar predictive utility to a clinical risk factor model for incident AF and both approaches are complementary. ECG-AI may enable efficient quantification of future AF risk.
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