Heart failure and associated structural and functional remodeling: assessment employing various magnetic resonance imaging methodologies.

Abstract

Cardiovascular magnetic resonance imaging (MRI), or cardiac MR, is currently considered the "gold" standard for noninvasively characterizing cardiac function and viability, having 3D capabilities and a high spatial and temporal resolution. More recently, the capabilities of MRI have been extended to study tissue microstrucure and fiber orientation in both the brain and the heart through specially designed pulse sequences which are sensitive to diffusion. In this specialized imaging method, known as diffusion tensor magnetic resonance imaging (DTMRI), myofiber orientation can be probed in high resolution and this technique has been successfully utilized to study the helical arrangement of muscle fibers within the myocardium. As such, the counter-wound helical structure of the myocardium is considered to be responsible for the torsional or wringing motion of the left ventricle and serves three main mechanical functions: (1) equalizing myofiber strain and workload; (2) optimizing the volume of blood ejected during systole (stroke volume); and/or (3) storing torsional energy in the intracellular and extracellular matrices and, when released, increasing ventricular filling during diastole. Therefore, cardiac fiber orientation can also be considered as a primary determinant of ventricular pump function, and is of great clinical interest in the study of structure and function within either the normal or diseased heart. To date, the primary focus of cardiac DTMRI has been to characterize myofiber orientation in healthy animal hearts, with little progress in the study of myofiber arrangement in the diseased heart. As such, due to the long scan times required for in vivo DTMRI, and the limited availability of freshly excised human hearts for ex vivo imaging, data are limited in the characterization of fiber orientation in both healthy and diseased human hearts. Therefore, in my thesis research, the primary objective was to investigate myofiber orientation in both healthy and diseased hearts using DTMRI. Specifically, changes in myofiber orientation were investigated in a high rate pacing model of dilated cardiomyopathy in swine, and also in excised healthy and diseased human hearts obtained from the Bequest Anatomy program at the University of Minnesota, and LifeSource (the Upper Midwest, a non-profit organ procurement organization). In addition, the mechanical activation due to cardiac pacing from the right ventricular apex was uniquely characterized in a case study of an isolated human heart using MRI, as cardiac pacing from the right ventricular apex is known to chronically result in deleterious changes in fiber orientation and cardiac function. My thesis was divided into several chapters, in the first it was considered paramount to gain a thorough understanding of cardiac MRI. As such, a review of cardiovascular MRI is provided in Chapter 1. The goal of this chapter was to familiarize the reader with cardiac MR and nomenclature, review current techniques to quantify cardiac function with MRI, and to introduce the reader to cardiac diffusion tensor magnetic resonance imaging (DTMRI), which is used in the present work to quantify fiber orientation in the heart. In Chapter 2, a literature review of cardiac fiber orientation and relevant changes resulting from disease is presented, and the measurement of fiber orientation using DTMRI is further discussed. The intent of this chapter is to familiarize the reader with diffusion imaging and the associated parameters used to characterize fiber orientation and tissue integrity. In addition, the methodologies and computational tools developed to measure fiber orientation using a 3 tesla Siemens MRI clinical scanner are described. Chapters 3-5 describe novel investigations in the assessment of fiber orientation using DTMRI. In chapter 3, the effects of decomposition on the diffusion properties of the myocardium were studied in freshly excised human hearts recovered at varying post mortem intervals. From this study, the time frame for the recovery of a human heart was determined to be 3 days, such that the tissue still remains viable for the measurement of fiber orientation using DTMRI. In Chapter 4, a swine model of dilated cardiomyaphy was used to assess in vivo functional and anatomical changes resulting from severe dilation of both the right and left ventricle. Following in vivo functional imaging, ex vivo DTMRI was used to investigate the resultant fiber orientation. Chapter 5 provides a preliminary comparison of fiber orientation in healthy and diseased human hearts, collected within a post-mortem interval of 3 days. Furthermore, in Chapter 6, the mechanical activation during pacing from the right ventricular apex was studied in an isolated human heart. Since pacing from the right ventricular apex is known to cause deleterious changes in fiber orientation, it was of great interest to characterize myocardial strain and motion during RVA pacing as part of my thesis work. In general, this research project has advanced our overall knowledge as to our understanding of ex vivo DTMRI, and the remodeling of the myocardial architecture in heart failure. This described work is not an exhaustive list of the changes in fiber orientation that occur in every type of cardiomyopathy, but provides novel insights into fiber reorganization which occurs in swine due congestive heart failure, and in human hearts excised from patients with a history of heart failure. Additionally, with the development of methodologies and computational tools presented here, and the study of post mortem intervals on the diffusion properties of the myocardium, the framework has been laid for the future analysis of fiber orientation in other cardiomyopathies presented in human cadaveric hearts.