Atherosclerosis accounts of 50% of the deaths in the western world leading to a plethora of diseases that include myocardial infarction, stroke, and peripheral artery disease. Currently available imaging modalities have inherent limitations, including ionizing radiation, lack of compositional information, and difficulty acquiring volumetric data that constrain their use in studying cardiovascular disease. Photoacoustic Tomography (PAT) has emerged as a promising modality that could address these limitations to improve the characterization and diagnosis of atherosclerosis-related conditions. Non-ionizing pulsed laser light is delivered to tissue leading to thermoelastic expansion followed by propagation of a pressure transient that can be detected with an ultrasound transducer. The magnitude of the ultrasonic PAT signal is proportional to the optical absorption at that location, revealing physiologically relevant compositional information of the tissue. The objective of this work is to therefore develop advanced volumetric imaging techniques to characterize disease progression in a murine model of atherosclerosis. The novelty of this work lies in the methodology and validation presented towards characterization of small animal vascular lipid accumulation with a high-resolution PAT system that utilizes the second near-infrared window (1100-1300nm). Additionally, we utilized <i>in situ </i>PAT to cross-sectionally assess lipid deposition and <i>in vivo</i>ultrasound to longitudinally assess hemodynamic, kinematic, and morphological changes during atherosclerosis progression. Together, this dissertation lays the foundation towards utilizing dual-modality PAT and ultrasound for various applications including understanding atherosclerosis pathophysiology, evaluation of novel therapeutics, and translation of clinically relevant techniques.

Coronary artery disease remains the leading cause of death in the United States with over 1 million acute coronary events predicted to take place in 2019 alone. Heart failure, a common and deadly sequela of myocardial infarction (MI), is attributed to adverse ventricular remodeling driven by cardiomyocyte death, inflammation, and mechanical factors. Despite strong evidence suggesting the importance of myocardial mechanics in driving cardiac remodeling, many <i>in vivo</i> MI studies still rely on 2D analyses to estimate global left ventricular (LV) function and approximate strain using a linear definition. These metrics, while valuable in evaluating the overall impact of ischemic injury on cardiac health, do not capture regional differences in myocardial contractility. The objective of this work is therefore to expand upon existing ultrasound studies by enabling regional analysis of 3D myocardial strain. By integrating our recently developed four-dimensional ultrasound (4DUS) imaging technique with a direct deformation estimation algorithm for 3D strain, we identified unique remodeling patterns and regional strain differences between two murine models of MI with different infarct severities. By constructing 3D strain maps of the remodeling LVs, we were able to capture strain heterogeneity and characterize a sigmoidal strain profile at infarct border zones. Finally, we demonstrated that the maximum principal component of the 3D Green-Lagrange strain tensor correlates with LV remodeling severity and is predictive of final infarct size. Taken together, the presented work provides a novel and thorough approach to quantify regional 3D strain, an important component when assessing post-MI remodeling.