Development and application of optical imaging techniques in diagnosing cardiovascular disease
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Atherosclerosis and specifically rupture of vulnerable plaques account for 23% of all deaths worldwide, far surpassing both infectious diseases and cancer. Plaque-based macrophages, often associated with lipid deposits, contribute to atherogenesis from initiation through progression, plaque rupture and ultimately, thrombosis. Therefore, the macrophage is an important early cellular marker related to vulnerability of atherosclerotic plaques. The objective of my research is to assess the ability of multiple optical imaging modalities to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanoparticles as a contrast agent) and lipid deposits in atherosclerotic plaques. Tissue phantoms and macrophage cell cultures were used to investigate the capability of nanorose as an imaging contrast agent to target macrophages. Ex vivo aorta segments from a rabbit model of atherosclerosis after intravenous nanorose injection were imaged by optical coherence tomography (OCT), photothermal imaging (PTW) and two-photon luminescence microscopy (TPLM), respectively. OCT images depicted detailed surface structure of atherosclerotic plaques. PTW images identified nanorose-loaded macrophages (confirmed by co-registration of a TPLM image and corresponding RAM-11 stain on a histological section) associated with lipid deposits at multiple depths. TPLM images showed three-dimensional distribution of nanorose-loaded macrophages with a high spatial resolution. Imaging results suggest that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques at the edges of lipid deposits. Combination of OCT with PTW or TPLM can simultaneously reveal plaque structure and composition, permitting assessment of plaque vulnerability during cardiovascular interventions.