Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy

Abstract

Cardiovascular diseases such as ischemic heart attack and stroke are the leading cause of morbidity and mortality, which accounted for 37% of all death in the U.S in 2003. The direct and indirect treatment cost for cardiovascular diseases was projected to exceed $400 billion in 2006.¹ Atherosclerosis is the major underlying process leading to cardiovascular diseases.² Like other complex human diseases, atherosclerosis progressively develops over time. Its initiation is characterized by the deposition of low-density lipoprotein (LDL), infiltration of monocytes, and maturation of monocytes into LDL-engulfing macrophages in the subendothelial layer of the intima. The lesions progress into plaques when smooth muscle cells infiltrate the intima, and collagen fibrils, and lipid particles deposit in the extracellular space. In advanced stages, lipid-rich necrotic cores, calcium deposits, and intimal thickening are often observed.^{2, 3} Although the most obvious impact of advanced atherosclerotic lesions is stenosis, clinical complications generally come from plaque rupture and thrombosis, leading to myocardial infarction and stroke.^{4, 5} It has been shown that pathological behaviors of plaques depend not only on their sizes but also on their compositions of collagen fibrils, lipid droplet deposits, and lipid-rich cells.^{3, 6}