Stéphanie E. Lindsey

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.

Abstract 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.

In small animal models of cardiovascular development and diseases, subject-specific computational simulations of blood flow enable quantitative assessments of hemodynamic metrics that are difficult to measure experimentally. Computational fluid dynamic simulations shed light on the critical roles of mechanics in cardiovascular function and disease progression. Acquiring high-quality volumetric images of the vessels of interest is central to the accuracy and reproducibility of morphological measurement and flow quantitation results. This study proposes a rapid, cost-effective, and accessible method for whole-mount high-resolution imaging of small animal vasculature using light-sheet fluorescence microscopy. The modified iDISCO+ (immunolabeling-enabled three-dimensional imaging of solvent-cleared organs) light-sheet sample preparation protocol involves (1) labeling vasculature with a fluorescent agent, (2) preserving the sample, and (3) rendering the sample transparent. Unlike classical iDISCO+, which uses immunohistochemical staining, the authors label vascular endothelium with FITC-tagged poly-L-lysine, an affordable non-specific fluorescent dye that is highly resistant to photo-bleaching, in a process termed "endo-painting." The rapid labeling reduces sample preparation time from approximately four weeks to less than 3 days. Furthermore, the use of minimally hazardous solvent ethyl cinnamate (ECi) as the clearing agent and imaging solution makes the samples safer to handle and compliant with a wider range of imaging facilities. The proposed protocol is applied to obtain highly resolved light-sheet fluorescence microscopy image stacks of the cardiovascular system in chick embryos ranging from day 3 (HH18) to day 8 (HH34). This study further demonstrates the suitability of this method for vascular quantitation through 3D reconstruction and computational hemodynamic modeling of a day 5 (HH 26) chick embryo.

We implement full, three-dimensional constrained mixture theory for vascular growth and remodeling into a finite element fluid-structure interaction (FSI) solver. The resulting "fluid-solid-growth" (FSG) solver allows long term, patient-specific predictions of changing hemodynamics, vessel wall morphology, tissue composition, and material properties. This extension from short term (FSI) to long term (FSG) simulations increases clinical relevance by enabling mechanobioloigcally-dependent studies of disease progression in complex domains.

We implement full, three-dimensional constrained mixture theory for vascular growth and remodeling into a finite element fluid-structure interaction (FSI) solver. The resulting "fluid-solid-growth" (FSG) solver allows long term, patient-specific predictions of changing hemodynamics, vessel wall morphology, tissue composition, and material properties. This extension from short term (FSI) to long term (FSG) simulations increases clinical relevance by enabling mechanobioloigcally-dependent studies of disease progression in complex domains.

Computational hemodynamic simulations are becoming increasingly important for cardiovascular research and clinical practice, yet incorporating numerical simulations of human fetal circulation is relatively underutilized and underdeveloped. The fetus possesses unique vascular shunts to appropriately distribute oxygen and nutrients acquired from the placenta, adding complexity and adaptability to blood flow patterns within the fetal vascular network. Perturbations to fetal circulation compromise fetal growth and trigger the abnormal cardiovascular remodeling that underlies congenital heart defects. Computational modeling can be used to elucidate complex blood flow patterns in the fetal circulatory system for normal versus abnormal development. We present an overview of fetal cardiovascular physiology and its evolution from being investigated with invasive experiments and primitive imaging techniques to advanced imaging (4D MRI and ultrasound) and computational modeling. We introduce the theoretical backgrounds of both lumped-parameter networks and three-dimensional computational fluid dynamic simulations of the cardiovascular system. We subsequently summarize existing modeling studies of human fetal circulation along with their limitations and challenges. Finally, we highlight opportunities for improved fetal circulation models.

YALES2BIO est un solveur multiphysique pour décrire les écoulements sanguins aux échelles micro- et macroscopiques, basé sur la méthode des volumes finis. Différents cas d'école ont été traités : rupture de jet turbulent, étirement de globule rouge par pince optique, organisation de globules rouges en écoulement, mais aussi des applications industrielles (déviateur de débit, cœur artificiel, etc.).