UCLA

The complex, but highly organized arrangement of myocytes within the left ventricle (LV) underlies the anisotropic mechanical and electrical function of the heart. Whole heart surveys of microstructural remodeling are critical to our basic science understanding of cardiac pathophysiology. Recently, diffusion tensor magnetic resonance imaging (DT-MRI) has emerged as a means for quantifying global and regional microstructural remodeling.

Previous observations of myocardial microstructure have predominantly relied on histological methods, which are tedious and difficult to spatially register in three-dimensions (3D). DT-MRI enables the 3D evaluation of whole heart microstructure. Each diffusion tensor can be decomposed into a system of eigenvectors and eigenvalues. The eigenvectors of the diffusion tensor contain the diffusion orientation information within the tissue microstructure and have established correspondence with the myofiber (primary eigenvector) and myolaminar sheet orientations (secondary and tertiary eigenvectors). Meanwhile, the eigenvalues quantify the magnitude of diffusion along each eigenvector and characterize the overall shape of diffusion. DT invariants (e.g. trace, fractional anisotropy, or mode), which are functions of the eigenvalues alone, saliently characterize specific attributes of tensor shape and can be used to evaluate specific attributes of microstructural remodeling.

Chapter 1 of this dissertation provides an understanding of myocardial microstructure in health and disease. Chapter 2 provides an understanding of DT-MRI, and its capabilities in evaluating soft tissue microstructure. In Chapter 3 we used an ovine model to establish the correspondence between both the secondary and tertiary eigenvectors of the local diffusion tensor and the dual sheet orientations observed in local histology. In Chapter 4 we quantified microstructural remodeling in a porcine model of myocardial infarction and its border zone using DT-MRI and revealed that the border zone significantly remodeled compared to both infarct and remote myocardium, providing a unique microstructural environment. In Chapter 5 we revealed significant microstructural remodeling in a rabbit mode of pacing induced heart failure using DT-MRI within transmural regions as well as transmural heterogeneity of microstructure within both normal and heart failure myocardium. Chapters 6 and 7 describe the conclusions of this work and provide an outlook for continued research based on this work's achievements.