Real-Time Contrast Ultrasound Muscle Perfusion Imaging with Intermediate-Power Imaging Coupled with Acoustically Durable Microbubbles

Abstract

There is growing interest in limb contrast-enhanced ultrasound (CEU) perfusion imaging for the evaluation of peripheral artery disease. Because of low resting microvascular blood flow in skeletal muscle, signal enhancement during limb CEU is prohibitively low for real-time imaging. The aim of this study was to test the hypothesis that this obstacle can be overcome by intermediate- rather than low-power CEU when performed with an acoustically resilient microbubble agent. Viscoelastic properties of Definity and Sonazoid were assessed by measuring bulk modulus during incremental increases in ambient pressure to 200mm Hg. Comparison of invivo microbubble destruction and signal enhancement at a mechanical index (MI) of 0.1 to 0.4 was performed by sequential reduction in pulsing interval from 10 to 0.05 sec during limb CEU at 7MHz in mice and 1.8MHz in dogs. Destruction was also assessed by broadband signal generation during passive cavitation detection. Real-time CEU perfusion imaging with destruction-replenishment was then performed at 1.8MHz in dogs using an MI of 0.1, 0.2, or 0.3. Sonazoid had a higher bulk modulus than Definity (66±12 vs 29±2kPa, P=.02) and exhibited less inertial cavitation (destruction) at MIs≥0.2. On invivo CEU, maximal signal intensity increased incrementally with MI for both agents and was equivalent between agents except at an MI of 0.1 (60% and 85% lower for Sonazoid at 7 and 1.8MHz, respectively, P<.05). However, on progressive shortening of the pulsing interval, Definity was nearly completely destroyed at MIs≥0.2 at 1.8 and 7MHz, whereas Sonazoid was destroyed only at 1.8MHz at MIs≥0.3. As a result, real-time CEU perfusion imaging demonstrated approximately fourfold greater enhancement for Sonazoid at an MI of 0.3 to 0.4. Robust signal enhancement during real-time CEU perfusion imaging of the limb is possible when using intermediate-power imaging coupled with a durable microbubble contrast agent.