Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta.

Abstract

The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta. Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively. C57BL/6 mice, not exposed to tumor necrosis factor α or DIO, were used as controls (MNormal). P-selectin-targeted (MBP-selectin), vascular cell adhesion molecule (VCAM)-1-targeted (MBVCAM-1), and isotype control (MBControl) microbubbles were synthesized by conjugating anti-P-selectin, anti-VCAM-1, and isotype control antibodies to microbubbles, respectively. The abdominal aortas were imaged for 180 seconds during a constant infusion of microbubbles. A parameter, residual-to-saturation ratio (RSR), was used to assess P-selectin and VCAM-1. Statistical analysis was performed with the Student t test. For the inflammation model, RSR of the MInflammation + MBP-selectin group was significantly higher (40.9%, P < 0.0005) than other groups. For the DIO model, RSR of the MDIO + MBVCAM-1 group was significantly higher (60.0%, P < 0.0005) than other groups. Immunohistochemistry staining of the abdominal aorta confirmed the expression of P-selectin and VCAM-1. A statistically significant assessment of P-selectin and VCAM-1 in mouse abdominal aorta was achieved. This technique yields progress toward rapid targeted molecular imaging in large blood vessels and thus has the potential for early diagnosis, treatment selection, and risk stratification of atherosclerosis.