# Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial Trabeculation and Function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $491,732

## Abstract

ABSTRACT
Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial
Trabeculation and Function
Non-compaction cardiomyopathy (NCC) is a disease of endomyocardial trabeculation or known as
spongy myocardium. NCC carries a high risk of malignant arrhythmias, thromboembolic events, and
ventricular dysfunction in association with congenital heart defects or skeletal myopathy. Studies have
linked left ventricular non-compaction with autosomal dominant inherited disorders, and mutations in
Notch pathways are implicated in defective trabeculation and ventricular NCC. Biomechanical force is
intimately connected with mechanotransduction and cardiac morphogenesis. During development, the
myocardium differentiates into an outer compact zone and an inner trabeculated zone. Notch receptor-
ligand interaction induces EphrinB2-Nrg-ErbB2 signaling to initiate trabecular formation. Our in silico
analysis (Alison Marsden, Stanford) revealed elevated oscillatory shear index (OSI) in trabecular
ridges, leading to increased viscous dissipation, which was associated with changes in ventricular
contractile function and remodeling. However, uncoupling myocardial contraction from intracardiac flow
dynamics to elucidate Notch-mediated trabecular organization and subsequent associated changes in
local hemodynamics remains an unmet biomechanical challenge. In this context, we hypothesize that
hemodynamic shear and myocardial contractile forces coordinate trabecular organization needed to
preserve the ventricular structure and contractile efficiency. In combination of laser light-sheet and light-
field for super resolution and volumetric imaging, we simultaneously captured myocardial contraction
and intracardiac flow dynamics. In collaboration with Stanford Cardiac Mechanics, we integrated fluid
structure interaction (FSI) with super resolution imaging to demonstrate 4-D endocardial shear stress in
the trabecular ridges and grooves as possible developmental modulator. To test our hypothesis, we
propose three specific aims. In Aim 1, we will demonstrate that intracardiac shear stress activates
endocardial Delta-Notch signaling to promote trabecular ridge formation. In Aim 2, we will
demonstrate that ventricular contraction activates myocardial Jagged-Notch signaling to organize
trabecular groove formation. In Aim 3, we will demonstrate that the combination of trabecular ridge
and groove formation leads to optimal local hemodynamics and ventricular energetics. The
integration of advanced imaging, fluid structure interaction, and zebrafish genetics is uniquely suitable
to unveil trabecular organization in relation to kinetic energy dissipation. Our multi-disciplinary approach
provides new biomechanical insights into non-compaction cardiomyopathy with pathophysiological
significance to ventricular remodeling and function.

## Key facts

- **NIH application ID:** 10458052
- **Project number:** 5R01HL159970-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tzung K Hsiai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $491,732
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458052

## Citation

> US National Institutes of Health, RePORTER application 10458052, Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial Trabeculation and Function (5R01HL159970-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458052. Licensed CC0.

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