Patient-specific modeling of the heart to predict outcomes in heart failure
Anatomical and structural alterations of the heart under pathological conditions are key predictors of heart failure (HF). Traditional measures such as ventricular dilation, wall thinning/hypertrophy, or scar size used to characterize the heart remodeling fall short as precise predictors of HF prognosis. New tools integrating computational techniques with imaging technologies are needed to non-invasively reveal detailed description of cardiac remodeling, predict short-term and long-terms outcomes of interventions, and accordingly individualize treatments.
The overall objective of this project is to develop and use novel image-based computational cardiac models to understand and predict fiber-, tissue- and organ-level remodeling of the heart in HF patients. We further use the models to study the correlations between mechanical biomarkers and drug targets to develop computational tools for personalized pharmaceutical interventions.
Understanding concerted multiscale remodeling of the RV in PAH
Pulmonary arterial hypertension (PAH) imposes a pressure overload on the right ventricle (RV) leading to myofiber hypertrophy and remodeling of the collagen fiber network. While the macroscopic behavior of healthy and post-PAH right ventricle free wall tissue has been studied previously, alterations in the individual mechanical contribution and the degree of remodeling of myofibers and the extracellular matrix (ECM) remains largely unexplored.
Investigation of these fundamental remodeling events could lead to an improved understanding of the role of individual mechanisms (hypertrophy and fibrosis) in cardiac adaptation to PAH.
Despite significant progress in in-silico cardiac modeling, there is a need to develop realistic cell-to-organ models to allow for the study of fiber-specific structural remodeling and to link alterations at the cell level with organ level adaptation in response to heart disease. In this project, we are developing a high-fidelity computational model of the myocardium microstructure from confocal imaging data. This model will allow us to study the interaction between sub-cellular events and cardiac function across multiple length scales.
Characterizing region-specific remodeling of left ventricular myocardium in MI
Myocardial infarction (MI) results in cardiac myocyte death and the formation of a fibrotic scar in the left ventricular free wall (LVFW). In the days and weeks that follow an acute MI, left ventricular (LV) remodeling, which consists of several alterations in the structure and properties of cellular and extracellular components of the LVFW, becomes an important predictor of clinical outcomes. The normal function of a heart is strongly influenced by the passive biomechanical behavior of the LVFW, and progressive myocardial structural remodeling can have a detrimental effect on both diastolic and systolic function of the LV leading to heart failure.
In this project, we study the LVFW remodeling in the rodent model of MI induced by ligation. Our goal is to develop a methodology to (1) integrate the biomechanical and structural remodeling within a rat-specific computational model of the LVFW, and (2) study the regional specificity in the analysis of strain in the LVFW. Ultimately, the delineation of subject-specific LV remodeling, with a focus on regional biomechanical changes throughout LV, will replace the traditional measures of LV and infarct dimensions that often lead to gross and limited information on cardiac performance and MI prognosis.