MRI of structured-based ventricular mechanics

The relation between myocardial kinematics and underlying architectural components is the key to understanding the functional design of the ventricular myocardium. This thesis develops a completely noninvasive method, registered diffusion and strain MRI, to acquire information about myocardial architecture and myocardial strain under identical in-vivo conditions. This noninvasive methodology solves important limitations of existing methods all of which require myocardial dissection. It provides metrically correct data of myocardial structure and myocardial function without postmortem distortion. Further, it can be applied to living humans and allows examinations of multiple time horizons, essential to the study of normal development and disease. To provide a valid MR methodology to study myocardial structure and structure-function relations in living humans, we focus on the three steps most essential to achieving this goal: 1) validate the correspondence between diffusion MRI and myocardial architecture, particularly the fiber and sheet organizations; 2) develop a practical method of measuring myocardial diffusion in vivo; 3) show that data obtained by registered diffusion and strain MRI can be employed to address important questions about myocardial structure-function relations. To validate the ability of diffusion MRI to map myocardial architecture, we show, with a novel printing technique, that the deviation of sheet orientations is within MR noise from those in the cow heart specimens. The correspondence between directions of greatest diffusivity and fiber orientations is also verified by the consistency of architectural patterns in MRI of the cadaver heart with those reported in histology. To measure myocardial diffusion in vivo, a robust MR method is developed. In the normal heart that has the synchronous contraction, we show that the strain effect is negligibly small at time points relative to which the mean strain over one cardiac cycle equals zero: "sweet spots." Using this fact, we localize the sweet spots and show that the depicted myocardial fiber architecture agrees with the ex-vivo results. Using registered diffusion and strain MRI, we obtain first quantitative maps of fiber and sheet dynamics in human hearts. Anatomically, MRI shows the classic pattern of fiber helix angles, namely a smooth transmural variation from a left-handed helix at the epicardium to a right-handed helix at the endocardium. It also shows a septum-versus-free-wall polarization of sheet orientations, a pattern recently documented in canine hearts. Analysis of conjoint data of diffusion and strain gives a clear picture of myocardial structure-function relations: 1) systolic fiber shortening, 11±3% relative to end-diastole, is exceptionally uniform across the wall; 2) cross-fiber shortening has a steep transmural slope; it is produced by a linear variation of angles between fibers and directions of principal shortening against wall depth (from 0 at the epicardium to 900 at the endocardium). Moreover, MRI shows two new findings: 1) there is no difference in fiber shortening between trabecular and compact myocardium; 2) sheet orientations are optimized to maximize sheet shear. In conclusion, registered diffusion and strain MRI can map myocardial structure and structurefunction relations practically and reliably in living human subjects. The noninvasive and spatially resolved characteristics of this methodology will facilitate investigation of myocardial mechanics in human disease. Thesis Supervisor: Van J. Wedeen, M.D. Title: Assistant Professor of Radiology at Harvard Medical School