Dual-modality Photoacoustic and Ultrasound Imaging for Murine Atherosclerosis Characterization

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 in situ PAT to cross-sectionally assess lipid deposition and in vivoultrasound 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.