Use of Theranostic Strategies in Myocardial Cavitation-Enabled Therapy

Abstract

The accumulation of microlesions induced by ultrasound interaction with contrast microbubbles in the myocardium potentially represents a new method of tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5-MHz focused ultrasound pulses triggered once every four heartbeats from the electrocardiogram during infusion of microbubble contrast agent. Treatment was guided by an 8-MHz B-mode imaging transducer, which also was used to provide estimates of left ventricular echogenicity as a possible predictor of efficacy during treatment. Strategies to reduce prospective clinical treatment durations were tested, including pulse modulation to simulate a theranostic scanning strategy and an increased agent infusion rate over shorter durations. Sources of variability, including ultrasound path variation and venous catheter placement, also were investigated. Electrocardiographic premature complexes were monitored, and Evans-blue stained cardiomyocyte scores were obtained from frozen sections. Left ventricular echogenicity reflected variations in the infused microbubble concentration, but failed to predict efficacy. Comparison of suspensions of varied microbubble size revealed that left ventricular echogenicity was dominated by larger bubbles, whereas efficacy appeared to be dependent on smaller sizes. Simulated scanning was as effective as the normal fixed-beam treatment, and high agent infusion allowed reduced treatment duration. The success of these theranostic strategies may increase the prospects for realistic clinical translation of myocardial cavitation-enabled therapy.