Serial Molecular-Microstructural Multimodal Intravascular Imaging of Atherosclerotic Plaques in Mice

Murine models are essential for cardiovascular translational research for developing new therapies to reduce the risk of heart attacks. However, assessment of murine atherosclerotic plaques by traditional histological methods fails to capture the entirety of plaque development across the length of a blood vessel over time. Here, the authors have developed and validated the first longitudinal molecular and microstructural intravascular imaging approach to study murine atherosclerosis. This approach combines a unique murine surgical model and a miniaturized multimodal intravascular imaging device with optical coherence tomography (OCT) and fluorescence imaging capabilities able to detect infused indocyanine green (ICG), a marker of macrophages. This multimodal device could identify important plaque features and their changes over multiple time points across the length of vessels containing atherosclerosis in high-cholesterol diet-fed apolipoprotein E knockout mice. It is found that OCT-derived plaque lipid measures correlate closely with histologically assessed plaque lipid (Oil Red O) in co-registered sections. Plaque ICG fluorescence also correlates with CD68+ macrophages, measured by immunofluorescence in co-registered sections. This novel approach maximizes data acquisition of plaque evolution dynamics within individual vessels. It represents a paradigm shift over the current need to compare disparate atherosclerosis plaques histologically across multiple timepoints and in multiple animals.