Biology subjects

Lindsey, S. E.

Publications and source records attributed to Lindsey, S. E..

5 recordsLinked to original sources

bioRxiv2026

Modeling steady state thermoregulation of near-term human fetus

Maternal thermal strain is associated with adverse pregnancy outcomes, yet fetal temperatures cannot currently be directly measured, limiting quantification of fetal thermal strain. Here, we develop two steady-state models for estimating internal temperatures in a near-term fetus. First, we improve the only previously published human fetal thermoregulation model, deriving a closed-form solution within its simplified uniform-cylinder representation. Second, we introduce a multilayer, anatomically segmented model that resolves tissue-specific temperatures. Both couple the fetal body to central blood pool and amniotic fluid compartments and incorporate a new placenta-umbilical cord heat-exchanger representation. Predictions agree with available intrauterine scalp measurements, with fetal core and head-center temperatures approximately 0.5{degrees}C and 0.8{degrees}C above maternal core, respectively. Physiologically plausible changes in umbilical cord heat-exchanger effectiveness or blood flow increased fetal temperatures by approximately 0.3{degrees}C. These models enable estimation of otherwise inaccessible temperatures, while the multilayer formulation lays a foundation for transient, coupled maternal-fetal thermoregulation modeling.

biophysics↗

bioRxiv2026

3D vascular quantitation with application to computational modeling: a pre-clinical light sheet microscopy, high resolution ultrasound, nano-computed tomography comparison study

It is increasingly necessary to both study biology in 3D and obtain quantitative measurements. Not all 3D-reconstructions are created equal, particularly when using the anatomical model as a basis for force calculations, i.e. computational modeling. Here, we compare 3D anatomical reconstructions from two emerging imaging modalities: 4D ultrasound (4DUS) and light sheet fluorescent microscopy (LSFM) against our previous nano-computed tomography (nanoCT) cohort data, using the tortuous highly intricate pharyngeal arch artery system of the chick embryo as a test bed. We highlight modality-specific morphological image acquisition discrepancies and their influence on subsequent computational fluid dynamics results. Overall, LSFM accurately captured quantitative volumetric measurements of small rapidly-changing vascular morphologies while 4DUS systematically inflated small tortuous vessels. Differences in image-based morphology changes led to significant changes in computationally-obtained force magnitudes and flow patterns linked to vessel angle and tortuosity. This validates LSFM as a comparative preclinical vascular quantitative imaging tool and suggests that 4DUS needs extensive 3D anatomical validation for non cardiac chamber vessels.

bioengineering↗

bioRxiv2026

Altered Cardiac Neural Crest Migration Patterning in a Left Atrial Ligation Model of Hypoplastic Left Heart Syndrome

Cardiac neural crest cells (CNCCs) contribute to key cardiac structures during embryonic development. Disruption of CNCC patterning or function can lead to congenital heart defects. Here, we investigate whether hemodynamic perturbation alters CNCC behavior in chick embryos. We use the left atrial ligation model to modify intracardiac blood flow in the early common-atrium, common-ventricle heart and track retrovirally labelled CNCCs for lineage tracing and single-cell transcriptomic analysis. Results revealed a significant reduction of CNCC derivatives in major cardiac regions, including the pharyngeal arch arteries and myocardium, in flow-perturbed embryos compared with controls. Notably, despite reduced CNCC numbers in the PAAs, their relative proportion increased, suggesting retention within the PAAs and delayed differentiation. Transcriptional analysis shows the expression of CNCC post-migratory markers (HAND1, FOXC2, GATA6, and TBX2) were consistently downregulated at 4, 24, and 48 hours after LAL. Together, these findings indicate that hemodynamic perturbation impairs CNCC migration and differentiation while preserving their capacity to contribute to mature cardiac structures.

developmental biology↗

bioRxiv2022

High-Resolution Ultrasound and Speckle Tracking: a non-invasive approach to assess in vivo gastrointestinal motility during development

Gastrointestinal motor activity has been extensively studied in adults, conversely only few studies have investigated fetal motor skills. When the gastrointestinal tract starts to contract during the embryonic period and how this function evolves during development are not known. Here, we adapted a non-invasive high-resolution echography technique combined with speckle tracking analysis to examine the gastrointestinal tract motor activity dynamics during chick embryo development. We provided the first recordings of fetal gastrointestinal motility in living embryos. We found that although gastrointestinal contractions appear very early during development, they become synchronized only at the end of the fetal period. To validate this approach, we used various pharmacological inhibitors and BAPX1 gene overexpression in vivo. We found that the enteric nervous system determinates the onset of the synchronized contractions in the stomach. Moreover, alteration of smooth muscle fiber organization led to an impairment of this functional activity. Altogether, our findings show that non-invasive high-resolution echography and speckle tracking analysis allow visualizing and quantifying gastrointestinal motility during development and highlight the progressive acquisition of functional and coordinated gastrointestinal motility before birth.

developmental biology↗

bioRxiv2020

Experimental-based Computational Modeling Distinguishes Early Cardiac Outflow Tract Compensation Mechanisms

Mechanical forces are essential for proper growth and remodeling of the primitive pharyngeal arch arteries (PAAs) into the great vessels of the heart. Despite general acknowledgement of a link between abnormal hemodynamics and cardiac malformations, the direct correlation between hemodynamics and pharyngeal arch artery morphogenesis remains poorly understood. The elusiveness behind understanding hemodynamic-malformation links is largely due to the difficulty of performing isolated hemodynamic perturbations and quantifying key hemodynamic indices in-vivo. To overcome this issue, minimally invasive occlusion experiments were combined with three-dimensional anatomical models of development and in-silico testing of experimental phenomenon. This combined experimental-computational approach led to a mechanistic understanding of physiological compensation mechanisms in abnormal cardiac morphogenesis. Using our experimental-based framework, we detail morphological and hemodynamic changes twenty-four hours post vessel occlusion. To gain mechanistic insights into the dynamic vessel adaptation process, we perform in-silico occlusions which allow for quantification of instantaneous changes in mechanical loading. We follow the propagation of small defects in a single embryo Hamburger Hamilton (HH) Stage 18 embryo to a more serious defect in an HH29 embryo. Results demonstrate that abnormal PAA hemodynamics can precipitate abnormal cardiac function given the correct timing and location of injury. Following vessel occlusion, morphology changes along the arches are no longer a simple flow-mediated response but rather work to maintain a range of wall shear stress values. Occlusion of the presumptive aortic arch overrides natural growth mechanisms and prevents it from becoming the dominant arch of the aorta. Author SummaryThe developing great vessels transport flow from the heart to the rest of the body. Proper spatial temporal morphogenesis of the primitive paired vessels into the definitive outflow tract of the heart is critical for normal cardiac function. Malpatterning of the great vessels is highly prevalent in congenital heart defects and occurs in conjunction with other intracardiac malformations, such as impaired ventricle and valve development. In this work, we combine experimental-based computational modeling with theoretical adaptation principles. Our combined experimental-computational framework allows for the delineation of immediate and longer-term vascular remodeling as well as the physical mechanisms behind such changes. We show that a small flow obstruction originating within the developing vessels can propagate into structurally serious malformations with impaired functionality.

developmental biology↗