Anatomical, Functional, and Molecular Imaging of Left Ventricular Myocardial Infarction in Mice Using High Frequency Ultrasound

Echocardiography plays a vital role in the evaluation of patients with suspected cardiovascular disease. Heart disease is the leading cause of death worldwide, with myocardial infarction being the major contributing factor to the high morbidity and mortality rates. Preclinical research on heart attack and heart failure is frequently conducted in mouse models of myocardial ischemia. The mouse species is preferred due to its low-cost, short reproductive cycle, and its utility in studying the role of specific genes in the pathophysiology of myocardial ischemia via transgenic and knockout mice. High frequency ultrasound is well suited to in vivo imaging of the mouse heart due to its high spatial and temporal resolution, lack of ionizing radiation, versatility, low-cost, ease of use, and non-invasive nature.
To demonstrate the utility of high frequency ultrasound in small animal imaging, I explore several novel approaches to quantify cardiac function in mouse models of myocardial ischemia and infarction. In Chapters 2 and 3, reconstruction of 3D motion in the mouse left ventricle is demonstrated by combining orthogonal 2D displacement fields. A finely sampled matrix of 3D motion vectors is then used to build a kinematic model of the left ventricle using polynomial functions and by assuming that the myocardium is approximately incompressible. In Chapter 4, novel metrics for quantification of left ventricular dyssynchrony and infarct size using ultrasound displacement and strain data, respectively, are presented. Using these metrics, myocardial contractile dysfunction in inducible nitric oxide synthase knockout mice exhibits improved function after myocardial infarction compared to control, wild type mice. Finally, in Chapter 5, a method for identifying previously ischemic regions of the myocardium by using molecularly targeted ultrasound contrast agents is presented.