Abstract 13031: Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta With Modulated Acoustic Radiation Force

Abstract

Introduction: Ultrasound molecular imaging has demonstrated the ability to detect the molecular signature of early vascular inflammation. Consequently, it may enable more timely detection of atherosclerosis. Unfortunately, existing methods face substantial challenges in large blood vessels. Recently, a new modulated acoustic radiation force (ARF)-based imaging method has demonstrated rapid and quantitative measurements of biomarkers in large vessels. Hypothesis: We hypothesized that a clinically translatable method could be tested pre-clinically for non-invasive rapid detection of vascular cell adhesion molecule (VCAM)-1 in the mouse abdominal aorta. Methods: C57BL/6 mice fed with a high-fat diet were used as a diet-induced obesity model (M DIO ). Normal mice were used as controls (M Normal ). Anti-VCAM-1 and isotype control antibodies were conjugated to microbubbles to form the VCAM-1 targeted (MB VCAM-1 ) and control (MB Control ) microbubbles, respectively. Constant infusions of microbubbles were performed, during imaging, for 180 s ( A ). A parameter, residual-to-saturation ratio (RSR), was extracted and used to assess VCAM-1 expression. Four groups of mice were studied (5 mice per group): M Normal + MB Control , M DIO + MB Control , M Normal + MB VCAM-1 , and M DIO + MB VCAM-1 . Results: RSR of the M DIO + MB VCAM-1 group was 56.0%, significantly higher ( p < 0.0005) than that of any other group (-94.9% for M Normal + MB Control , -13.9% for M DIO + MB Control , and -37.4% for M Normal + MB VCAM-1 ) ( B ). Immunohistochemistry confirmed M Normal exhibited minimal VCAM-1 staining while M DIO exhibited VCAM-1 staining localized to the endothelium ( C ). Conclusions: In conclusion, a statistically significant assessment of VCAM-1 in mouse abdominal aorta was achieved using the modulated ARF-based method. This technique yields progress towards rapid targeted molecular imaging in large blood vessels, and thus has long-term potential for early diagnosis of atherosclerosis.