Biology subjects

Chen, I. Y.

Publications and source records attributed to Chen, I. Y..

7 recordsLinked to original sources

bioRxiv2025

Personalized biventricular mechanics and sensitivity to model morphology

AO_SCPLOWBSTRACTC_SCPLOWWe present a computational framework for constructing patient-specific models of cardiac mechanics based on standard clinical data, including electrocardiogram (ECG), cuff blood pressure, and electrocardiography-gated computed tomography angiography (CTA) imaging. The model is coupled to a closed-loop lumped parameter network (LPN) circulatory model and incorporates rule-based fiber architecture, as well as spatially varying epicardial boundary conditions to approximate surrounding tissue support. Model parameters are personalized through a multistep procedure that sequentially tunes circulatory dynamics, passive mechanics, and active contraction. The resulting personalized BiV model closely matches clinical pressure and volume measurements and reasonably agrees with image-based myocardial deformation. To assess the impact of anatomical model choice, we compare the BiV model to two commonly-used simplifications: a truncated BiV (t-BiV) model cut at the basal plane and a left ventricle-only (LV) model. For these models, we also evaluate their sensitivity to plausible variations in boundary conditions and contractile strength. With all other inputs held fixed, the LV model exhibits similar global pressure/volume behavior, despite moderate differences in regional deformation. In contrast, the t-BiV model produces substantial differences in both global function and local myocardial mechanics. These results suggest that while LV-only models may be sufficient for biomechanical studies, truncation at the basal plane strongly impacts model outputs and should be used with caution.

bioengineering↗

bioRxiv2025

Intrinsic Phenotypic Differences, Not Hemodynamic Shear, Associate with Cusp-Specific Remodeling in Aortic Valve Disease

Aortic valve disease (AVD) is asymmetric. Various clinical reports indicate that the non- coronary cusp (NCC) is disproportionally burdened by pathological remodeling like inflammation, fibrosis, and calcification. This has long been attributed to the resulting differences in hemodynamic load that arise from the presence, or lack thereof, of coronary ostia in respective sinuses. However, there is little to no empirical evidence to suggest that these differences in hemodynamic shear alone are enough to drive the difference in pathological remodeling that is observed. C57BL/6J mice exhibit a high variance in right coronary ostium (RCO) positioning with respect to the right coronary cusp (RCC). Through computational fluid dynamics (CFD) simulations of a mouse aortic valve (AoV) during end diastolic loading, we show negligible differences in wall shear stress (WSS) between a high RCO on the RCC and no ostium on the NCC. Also, though CFD analyses depict at least an order of magnitude difference in WSS through physiologically relevant ostia positions within the sinuses, ostium position does not correlate with calcification burden in a CKD mouse model of calcific AVD. Cusp dependent extracellular matrix (ECM) abundance analysis reveals asymmetric collagen and elastin content in healthy adult mice, but this does not follow the same trend as pathological remodeling. Instead, asymmetric abundance of elastin (P=0.034) and collagen (P=0.018) was mainly driven by an increase of these ECM proteins in the left coronary cusp (LCC) with no differences in leaflet thickness. Cusp dependent transcriptomic (spatial and bulk RNA sequencing) analyses reveal asymmetric phenotypic profiles between the three cusps in healthy adult mice. Of note, genes associated with vascular smooth muscle cell contraction and known modulators of AoV remodeling were upregulated in the NCC and downregulated in both the RCC and LCC. Together, these data suggest that the differences in shear resulting from the coronary ostia are not sufficient to explain the asymmetric onset of calcific AVD.

physiology↗

bioRxiv2025

Personalized Multiscale Modeling of Left Atrial Mechanics and Blood Flow

We present a personalized multiscale mechanics model of the left atrium (LA) to simulate its deformation throughout the cardiac cycle and drive blood flow. Our patient data-driven model tightly integrates 3D structural mechanics of the LA myocardium, incorporating both passive and active components, with a 0D closed-loop lumped parameter network (LPN)-based circulatory system model. A finite element (FE) model of LA tissue is constructed from the patients images, assuming uniform thickness and employing rule-based fiber directions, a structurally based constitutive model for the passive mechanics, and a phenomenological contraction model while applying physiologically relevant boundary conditions. We then adopted a multi-step personalization approach, in which the LPN parameters with a surrogate LA model are first optimized to match cuff-based blood pressures and cardiac lumen volumes derived from time-resolved 3D gated computed tomography angiography (CTA) images. The surrogate LA pressure during passive expansion is used to estimate myocardial passive mechanics parameters and the reference unloaded configuration using an inverse finite element analysis (iFEA) framework. Finally, a robust multiscale coupling is applied between the iFEA-optimized FE model and the tuned 0D LPN model to characterize LA contraction. This effectively captures the 8-shaped pressure-volume curve and reasonably aligns with the image-based cavity volumes and deformation. The resulting simulation-predicted deformation is imposed as a moving-wall boundary condition to model atrial hemodynamics. Overall, this comprehensive digital twinning platform could be applied to study LA biomechanics in health and disease and assist in devising personalized treatment plans.

bioengineering↗

bioRxiv2024

Immunosuppression Drugs Exhibit Differential Effects on Endothelial Cell Function

Immunosuppressive medications are widely used to treat patients with neoplasms, autoimmune conditions, and solid organ transplants. Prior studies indicate that immunosuppression drugs can cause adverse vascular remodeling. Given the systemic effects of the drugs, elucidating cell-type specific drug-effects has been challenging. We utilized induced pluripotent stem-cell derived endothelial cells to investigate the role of widely used immunosuppression drugs on endothelial function. We found that among immunosuppression agents, sirolimus reduced basic endothelial cell functions including cell migration, proliferation, acetylated LDL uptake, and angiogenesis properties; while tacrolimus only reduced nitric oxide release. This model allows for investigation of differential effect of immunosuppression drugs on endothelial function that can elucidate mechanisms contributing to adverse vascular profiles observed clinically.

cell biology↗

bioRxiv2024

Engagement in moderate-intensity physical activity supports overnight emotional memory retention in older adults

ImportancePreserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior work suggests that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. ObjectiveTo investigate associations between engagement in physical activity (PA) and overnight emotional memory retention and examine whether theoretically replacing 30-minutes of lower-intensity activity with MPA is associated with better consolidation. Design, Setting, and ParticipantsA cross-sectional study of 40 community-dwelling older adults free of neurological and psychiatric disorders. Data were collected from May 2018 to July 2022 and analyzed from January to July 2024. ExposuresParticipants completed an overnight polysomnography (PSG) with emotional memory tested before and after sleep and a self-report questionnaire assessing habitual PA. Main Outcome(s) and Measures(s)Emotional memory performance was assessed via recognition memory or mnemonic discrimination performance. Overnight memory retention was calculated by subtracting immediate test from delayed test performance for both recognition memory and mnemonic discrimination, with more negative scores indicating lower memory retention. Frequency and duration of MPA, light-intensity PA, non-exertive activity, and sedentary behavior were calculated from the Community Health Activities Model Program for Seniors (CHAMPS) Activities Questionnaire for Older Adults. Isotemporal substitution modelling evaluated whether statistically reallocating time spent in sedentary and lower-intensity activity to MPA was associated with better overnight memory retention. ResultsData from 40 participants were analyzed ({square}age=72.3{+/-}5.8, 26 female). Better overnight emotional recognition memory retention was associated with the frequency ({beta}=0.663, SE=0.212, p=0.003) and duration ({beta}=0.214, SE=0.101, p=0.042) of MPA. No relationships were found with mnemonic discrimination or neutral recognition memory. Statistically modelling the replacement of 30 minutes of lower-intensity activity with MPA was associated with better overnight retention of emotional memories ({beta}=0.108, SE=0.048, p=0.030), but not neutral ({beta}=-0.029, SE=0.069, p=0.679). Conclusions and RelevanceMPA may enhance sleep-dependent consolidation of emotional memories in older adults. Modest increases in MPA may yield significant benefits for sleep-dependent emotional memory retention. These findings may guide interventions to preserve memory function and inform public health recommendations by demonstrating that substituting even short durations of low-intensity activity for MPA could produce significant cognitive gains relevant for maintaining quality of life in older adulthood.

neuroscience↗

bioRxiv2024

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimers disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

neuroscience↗

bioRxiv2023

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality--graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes--map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

neuroscience↗