Tawfik M. Hussein
BME PhD Proposal Presentation
Date: 2024-08-26
Time: 10:00 AM - 12:00 PM
Location / Meeting Link: HSRB 2 N100 (in-person); https://emory.zoom.us/j/99237541681?pwd=7fhbXP184IjpeHvNrqna7Q9b8IweH6.1 (virtual)
Committee Members:
John N. Oshinski, PhD (advisor); W. Robert Taylor, MD, PhD; Rudolph L. Gleason, PhD; Alessandro Veneziani, PhD; Lucas Timmins, PhD
Title: A Multiscale Computational Model of the Myocardium for Patient-specific Diagnosis of Heart Failure with a Preserved Ejection Fraction (HFpEF)
Abstract:
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome in which patients have normal or near normal ejection fraction (EF) but show classic signs of heart failure. The etiologic basis of these symptoms is poor filling and limited relaxation of the cardiac ventricular chambers, often due to pathological stiffening of the myocardium. Diagnosing HFpEF is challenging, as myocardial changes that can be imaged using traditional techniques (e.g., ultrasound (US), magnetic resonance imaging (MRI), etc.) do not always correlate with stiffening. While direct measurement of myocardial stiffness could be of great value, a technique is lacking, resulting in a significant unmet clinical need in diagnosing HFpEF using direct estimation of myocardial stiffness. The central hypothesis is that myocardial stiffness, characterized by passive material properties, can be derived from patient-specific modeling based on non-invasively measured myocardial strains, providing a novel approach to diagnose and predict the progression of HFpEF. Hence, the overarching goal of this project is to measure three-dimensional (3D) myocardial stiffness non-invasively in patients with HFpEF using MRI and the Criscione-Hussein model, a novel model that can estimate stiffness in the form of material stiffness parameters non-invasively from MRI-derived strains as well as represent the passive biomechanical properties of the myocardium better than currently used models. Towards that end, two groups will be recruited for this study, a patient group that has HFpEF with diastolic dysfunction (n=16), and an age-matched control group of healthy subjects (n=16). Aim 1 will seek to implement a 3D Displacement Encoding with Stimulated Echoes (DENSE) sequence to measure patient-specific 3D myocardial strain in both groups. Aim 2 will seek to calculate regionally the distributed myocardial material stiffness parameters to quantify 3D stiffness using the Criscione-Hussein model and the strains from aim 1. Aim 3 will assess the measured stiffness by comparing the reproducibility, sensitivity, and specificity of the MRI-derived material stiffness parameters with that of clinical indices of HFpEF. These material stiffness parameters will prove superior to currently used global metrics in both diagnosing HFpEF and providing key insights into stiffness heterogeneity as well as assessing the extent of stiffness on a patient-specific basis, thus serving for risk-stratification and optimizing treatment planning. The long-term objective of this proposal is to elucidate deeper insights into how HFpEF changes the biomechanical properties of the myocardium and leverage such insights towards predicting and managing HFpEF early in its course, ultimately improving clinical outcomes and patients living longer, healthier lives.
