Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle (LV).  Despite the prevalence of this disease, it remains difficult to diagnose, mainly due to inherent compensatory mechanisms and a limited physical understanding of the filling process.  LV filling can be non-invasively imaged using color m-mode echocardiography which provides a spatio-temporal map of inflow velocity.  These filling patterns, or waves, are conventionally used to qualitatively assess the filling pattern, however, this work aims to physically quantify the filling waves to improve understanding of diastole and develop robust, reliable, and quantitative parameters. This work reveals that LV filling waves in a normal ventricle act as dispersive waves and not only propagate along the length of the LV but also spread and disperse in the direction of the apex.  In certain diseased ventricles, this dispersion is limited due to changes in LV geometry and wall motion.  This improved understanding could aid LVDD diagnostics not only for determining health and disease, but also for distinguishing between progressing disease states. This work also identifies a limitation in a current LVDD parameter, intra ventricular pressure difference (IVPD), and presents a new methodology to address this limitation.  This methodology is also capable of synthesizing velocity information from a series of heartbeats to generating one representative heartbeat, addressing inaccuracies due to beat-to-beat variations.  This single beat gives a comprehensive picture of that specific patient's filling pattern.  Together, these methods improve the clinical utility of IVPD, making it more robust and limiting the chance for a misdiagnosis. / Master of Science

Numerous studies have shown that cardiac diastolic dysfunction and diastolic filling play a critical role in dictating overall cardiac health and demonstrated that the filling wave propagation speed is a significant index of the severity of diastolic dysfunction. However, the governing flow physics underlying the relationship between propagation speed and diastolic dysfunction are poorly understood. More importantly, currently there is no reliable metric to allow clinicians the ability to diagnose cardiac dysfunction. There is a greater need than ever for more accurate and robust diagnostic tools with the increasing number of deaths caused by this disease. Color M-mode (CMM) echocardiography is a technique that is commonly used in the diagnosis of Left Ventricular Diastolic Dysfunction (LVDD) and is used as the image modality in this work. The motivation for the current work is a hypothesized change in the mechanism driving early diastolic filling. The early filling wave of a healthy patient is driven by a rapid early diastolic relaxation creating a pressure difference within the left ventricle despite the fact the left ventricular volume is increasing. As diastolic dysfunction progresses, the left ventricular relaxation declines and it is hypothesized that the left atrial pressure rises to create the favorable pressure difference needed to drive early diastole. This changes the mechanism driving early diastolic filling from a pulling mechanism primary driven by left ventricular relaxation to a pushing mechanism primarily driven by high left atrial pressure. Within this study, CMM echocardiography images from 125 patients spanning healthy and the three stages of LVDD are analyzed using a newly developed automated algorithm. For the first time, a series of isovelocity contours is utilized to estimate the conventional propagation velocity. A critical point within the early filling wave is quantified as the point of early filling velocity deceleration. The clinically used propagation velocity is compared to a novel critical point propagation velocity calculated as a weighted average of the propagation velocities before and after the critical point showing an increase in the correlation between decreasing diastolic dysfunction stage and decreasing propagation velocity. For the first time the spatial pressure distributions calculated as the pressure relative to the mitral valve pressure at each location from the mitral valve to the ventricular apex, are quantified and analyzed at the instant of peak mitral to apical pressure difference for patients with varying stages of LVDD. The analysis of the spatial pressure distribution revealed three filling regions present in all patients. The pressure filling regions were used to calculate a useful filling efficiency with healthy patients having a useful filling efficiency of 64.8 ± 12.7% and severely diseased filling patients having an efficiency of 37.1 ± 12.1%. The newly introduced parameters and analysis of the CMM echocardiography data supports the hypothesis of a change in the mechanism driving early diastolic efficiency by displaying a decline in the early diastolic propagation velocity earlier into the left ventricle for severely diseased patients than for healthy filling patients and a premature breakup of the progressive pressure gradient fueling early diastolic filling in severely diseased patients. / Master of Science