Ultrasound molecular imaging with modulated Acoustic Radiation Force-based beam sequence in mouse abdominal aorta: A feasibility study

Ultrasound-based molecular imaging has been implemented in pre-clinical studies of cancer and cardiovascular diseases. Unfortunately, existing methods face substantial challenges in large blood vessel environments. We hypothesized that a clinically translatable method, the modulated Acoustic Radiation Force (ARF)-based imaging, is capable of rapid detection of inflammation in the abdominal aorta of a murine model. Mice stimulated with tumor necrosis factor (TNF)-α were used as an inflammation model (M_Inflammation). Age-matched normal mice were used as controls (M_Normal). P-selectin-targeted (MB_P-selectin), and isotype control (MB_Control) microbubbles were synthesized by conjugating anti-P-selectin, and isotype control antibodies to the shell of microbubbles, respectively. The abdominal aorta of mice were imaged for 180 s during a constant infusion of microbubbles. The parameter produced from the new imaging sequence, residual-to-saturation ratio (RSR), was used to assess P-selectin expression. For the inflammation model, RSR of the M_Inflammation + MB_P-selectin group was 40.9%, significantly higher (p <; 0.0005) than other groups. Feasibility was demonstrated to achieve rapid and statistically significant assessment of P-selectin in a mouse abdominal aorta for the first time. The proposed technique closes the gap toward rapid targeted molecular imaging in large blood vessels, and thus has the potential for early diagnosis and treatment selection of atherosclerosis via ultrasound molecular imaging.