Biology subjects

Vedula, V.

Publications and source records attributed to Vedula, V..

8 recordsLinked to original sources

bioRxiv2026

A Method for Image-Based Modeling of Uterine Passive Mechanics During Late Pregnancy

PurposeComputational models of the uterus during pregnancy enable analysis of electro-chemo-mechanical pathways to predict labor timing and guide treatment planning. We aim to develop a robust image-based modeling pipeline to investigate uterine passive mechanics during late pregnancy. MethodsA parametric model of the uterus and cervix was created using a patients MRI measurements at 38 weeks of gestation. Inspired by advances in cardiac mechanics models, we created Laplace-Dirichlet solutions to inform tissue domains, fiber structure within the uterus and cervix, and spatially varying Robin boundary conditions. Prior imaging and mechanical testing data were used to fit material parameters. Boundary condition parameters were tuned to match the displacements of a previously established approach that employed contact with surrounding tissue. The tissue mechanical response to a physiologic load was assessed across varying material properties and fiber architectures. ResultsDiscrepancies in nodal displacements between the current approach and the contact-based model were limited to 3.4 {+/-} 1.8 mm, yielding nearly 90 % computational savings. Uterine tensile strains were more sensitive to ground substance elastic modulus (E) compared to fiber properties. Reduced E and fiber stiffness increased cervical strains and compression. Fiber dispersion and architecture modulated the opening of the cervical internal ostium but had a reduced impact on compression. ConclusionWe developed a novel workflow for modeling passive uterine mechanics, informed by patient-specific measurements and in vitro mechanical tests. The robust workflow may prove useful for studying labor progression and conducting longitudinal studies to enhance our understanding of normal and pathological pregnancies.

bioengineering↗

bioRxiv2026

A Multiscale Computational Analysis of Myometrial Excitation during Late Pregnancy

The control of uterine activity during pregnancy is a complex process that involves regulating myometrial excitability across multiple scales. While numerous studies have investigated various regulatory mechanisms and established the contributions of ion channels and gap junctions, how these mechanisms interact to produce observed changes in uterine activity remains poorly understood. Pivotal to these efforts are computational models that effectively capture gestational changes in excitability across scales. In this study, we propose a multiscale computational modeling framework that can reproduce measured activity at the cellular and tissue scales at a given gestational stage. At the cellular level, we identify key ion currents underlying the observed electrophysiological properties based on a literature review of their regulation and a sensitivity analysis of the Tong 2011 uterine smooth muscle cell activation model. The conductances of these ion currents are then fit to reproduce characteristic resting membrane potentials and burst properties using Bayesian optimization. To extend to the tissue level, we employ an anisotropic monodomain model, parameterized by the resistivity of late pregnancy uterine muscle, to investigate electrical propagation in a two-dimensional section of uterine tissue. We then apply the multiscale model to study myometrial activation in late pregnancy and elucidate the contributions of ion channel and gap junction regulation in transitioning the uterus from a quiescent state to labor. Our resulting model successfully reproduces measured electrophysiological properties at the cellular level and characteristic single-spike and burst-propagation patterns at the tissue level across the three late-pregnant time points analyzed (days 16/17, 18/19, and 20/21) in a murine model. Furthermore, our results suggest that the regulation of the conductances of the voltage-dependent potassium current (IK1), L-type calcium current (ICaL), and sodium current (INa) is most important in determining preterm uterine excitability. The framework established here will promote the development of more gestationally relevant models to better understand labor progression and the factors involved in dysfunctional labor. Author SummaryPregnancy is marked by drastic changes in the electrical and contractile activity of the uterus. As improper regulation of uterine activity is associated with preterm and dysfunctional labor, it is crucial to understand the physiological mechanisms underlying these changes. Currently, the roles of ion channels in determining cellular dynamics, and gap junctions in cell-to-cell coupling, as well as tissue properties, have been well established. However, how their regulation interacts to produce observed changes in cellular and tissue excitability and, in turn, organ-level activity is far less understood. While existing computational models of uterine electrophysiology have provided a greater insight into these processes, these are formulated for a single time point and cannot interrogate their effects over gestation. In response to this need, we develop a framework to generate a computational model of uterine excitation at a given gestational stage. We apply this to investigate the role of ion channels and gap junctions in transitioning the uterus to labor during late pregnancy. We identify three major ion channels and demonstrate agreement with observed action potential and tissue propagation properties at the analyzed time points. We further highlight how our framework can be applied to investigate other stages, including labor and postpartum.

bioengineering↗

bioRxiv2026

Effects of Left Atrial Wall Thickness on Myocardial Mechanics and Blood Dynamics using Multiscale Modeling

PurposePatient-specific models of left atrial (LA) mechanics often assume uniform left atrial wall thickness (LAWT), but the effect of LAWT on the mechanics and hemodynamics remains less quantified. MethodsFour LA myocardium models were built from gated CTA images: a baseline variable thickness (VT#0), two reduced-dilation variants, and a 2mm uniform thickness model. Multi-scale mechanics and blood flow simulations were performed across all the thickness variants using model parameters personalized on the baseline model. Predicted displacements, wall stresses and strains, and hemodynamics were compared. ResultsAcross all LAWT variants, myocardial volume spanned 14.4-19.9mL (38%), while cavity volume remained mostly within 5% of image data throughout the cardiac cycle. Circulatory system output, myocardial displacements, and strains varied by 5-6% relative to the baseline model. Instantaneous stresses increased by up to 19% in the thinner variable thickness models and decreased by up to 16% in the uniformly thick case. Globally, the area under low time-averaged wall shear stress (TAWSS) varied between 23% and 30% across all thickness variants, while LA exposed to elevated oscillatory shear index (OSI) increased from nearly 6% to 19%. Over 90% of LAA was exposed to low shear, but the high-OSI area increased from 7% in VT#0 to over 30% in Uniform. ConclusionA personalized multiscale modeling framework was leveraged to demonstrate that the left atrial myocardial stresses and oscillatory shear had a greater sensitivity to local wall thickness representation compared to cavity volumes, tissue displacements, strains, and mean blood shear.

bioengineering↗

bioRxiv2026

Hemodynamic Analysis of a Repaired Ascending Aorta with Preserved Aortic Root

PurposeTo evaluate the hemodynamic impact of restoring a normal sino-tubular junction (STJ) following a novel Hegar dilator-based procedure in patients undergoing root-sparing ascending thoracic aortic aneurysm (ATAA) repair using computational modeling. MethodsWe retrospectively selected an ATAA patient who underwent pre- and postoperative gated computed tomography angiography (CTA). We developed a novel workflow to segment the lumen, thick-walled aorta, and aortic valve from CTA images for subsequent blood flow analysis using computational fluid dynamics (CFD) and fluid-structure interaction (FSI). Morphological and hemodynamic characteristics of the root were quantified and compared against those of a control subject, with no noted ascending aortic dilation. The models sensitivity to graft properties and leaflet material heterogeneity was analyzed. ResultsBoth CFD and FSI results showed that the postoperative geometry reconstructed with a normal STJ profile reintroduces sinus vortices during peak systole, similar to the control subject, but were absent pre-surgery. Accounting for aortic valve leaflets in FSI studies yielded qualitatively similar results to the CFD cases, albeit with locally elevated velocities, time-averaged wall shear stress (TAWSS), and energy dissipation, likely due to the dynamically changing orifice area and differing profiles of the left ventricular outflow tract (LVOT). ConclusionWe demonstrated that the novel Hegar dilator-based STJ reconstruction restores normal blood flow patterns, highlighting the importance of reprofiling the aortic sinuses and STJ. The study also highlights the models sensitivities, particularly the LVOT shape and leaflet morphology and mobility, and may assist planning STJ reconstruction to yield optimal hemodynamics before intervention.

bioengineering↗

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

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↗

bioRxiv2021

Fluid-structure interaction simulation of tissue degradation and its effects on intra-aneurysm hemodynamics

Tissue degradation plays a crucial role in vascular diseases such as atherosclerosis and aneurysms. Computational modeling of vascular hemodynamics incorporating both arterial wall mechanics and tissue degradation has been a challenging task. In this study, we propose a novel finite element method-based approach to model the microscopic degradation of arterial walls and its interaction with blood flow. The model is applied to study the combined effects of pulsatile flow and tissue degradation on the deformation and intra-aneurysm hemodynamics. Our computational analysis reveals that tissue degradation leads to a weakening of the aneurysmal wall, which manifests itself in a larger deformation and a smaller von Mises stress. Moreover, simulation results for different heart rates, blood pressures and aneurysm geometries indicate consistently that, upon tissue degradation, wall shear stress increases near the flow-impingement region and decreases away from it. These findings are discussed in the context of recent reports regarding the role of both high and low wall shear stress for the progression and rupture of aneurysms.

bioengineering↗

bioRxiv2021

Computational Simulation of 4-D Micro-Circular Network in Zebrafish Tail Amputation and Regeneration

Wall shear stress (WSS) in the micro-vasculature contributes to biomechanical cues that regulate mechanotransduction underlying vascular development, regeneration, and homeostasis. We hereby elucidate the interplay between hemodynamic shear forces and luminal remodeling in response to vascular injury and regeneration in the zebrafish model of tail amputation. Using the transgenic Tg(fli1:eGFP; Gata1:ds-red) line, we were able to track the enhanced green-fluorescent protein (eGFP)-labeled endothelial lining of the 3-D microvasculature for post-image segmentation and reconstruction of fluid domain for computational fluid dynamics (CFD) simulation. At 1 day post amputation (dpa), dorsal aorta (DA) and posterior cardinal vein (PCV) were severed, and vasoconstriction developed in the dorsal longitudinal anastomotic vessel (DLAV) with a concomitant increase in WSS in the segmental vessels (SV) proximal to the amputation site and a decrease in WSS in SVs distal to amputation. Simultaneously, we observed angiogenesis commencing at the tips of the amputated DLAV and PCV where WSS was minimal in the absence of blood flow. At 2 dpa, vasodilation occurred in a pair of SVs proximal to amputation, resulting in increased flow rate and WSS, whereas in the SVs distal to amputation, WSS normalized to the baseline. At 3 dpa, the flow rate in the arterial SV proximal to amputation continued to rise and merged with DLAV that formed a new loop with PCV. Thus, our CFD modeling uncovered a well-coordinated micro-vascular adaptation process following tail amputation, accompanied by the rise and fall of WSS and dynamic changes in flow rate during vascular regeneration.

bioengineering↗