Non-Invasive Quantitative In Vivo Imaging of Atherosclerosis

Current means of measuring disease in preclinical models of atherosclerosis include ex vivo assessment of disease tissues post-mortem and non-invasive imaging primarily of structural and anatomic features of lesions, in vivo. A non-invasive, quantitative means of imaging known biologic profiles associated with atherosclerotic disease, in vivo, would enable a robust additional understanding and analysis of disease progression and therapeutic response in research and drug development. We report the utility of the near infrared (NIR) protease-sensing, ProSense® 750 Fluorescent Pre-clinical Imaging Agent, in combination with the FMT® 2500 Quantitative Pre-clinical Imaging System for the noninvasive quantitative measurement of atherosclerotic disease biology and related response to therapy in apolipoprotein (apo) E-deficient mice in vivo. FMT (Fluorescence Molecular Tomography) imaging measured significant increases in aortic region protease activity with a range of values that were comparable to the range seen in the ex vivo aortic arches assessed by fluorescence reflectance imaging (FRI). Significant disease was detected by FRI in apoE-/aortic tissue as early as 20 weeks with animals on high cholesterol diet, and with a steady increase in disease progression at 25 and 30 weeks. Non-invasive FMT imaging showed a similar progression of disease over time with an excellent correlation to tissue FRI. Atorvastatin treatment showed an anticipated modest decrease in plasma cholesterol and a more dramatic Pre-clinical Imaging A P P L I C A T I O N N O T E