Abstract 14673: The Effect of Increasing the Ultrasound Pulse Length on Sonoreperfusion Therapy

Abstract

Background: In recent years, long and short pulse ultrasound (US)-targeted microbubble cavitation (UTMC) has been shown to increase perfusion in healthy and ischemic skeletal muscle, in pre-clinical animal models of microvascular obstruction, and in the myocardium of patients presenting with acute myocardial infarction, and microvascular vasodilation played an important role in its efficacy. Our prior preliminary data suggested that long pulse US confers enhanced sonoreperfusion efficacy compared to short pulse US. Objective: In this study, we sought to definitively compare acoustic energy matched, long (5000 cycles) and short pulse (500 х 10 cycles, separated by 100 μs intervals) US (pressure of 1.5 MPa with an equivalent total number of acoustical cycles and at the same frequency (1 MHz)), in a rodent hindlimb model, with and without microvascular obstruction (MVO). Results: By quantifying perfusion using burst replenishment contrast enhanced US imaging, we found that: (1) long and short pulses result in different vasodilation kinetics in an intact hindlimb model. The long pulse causes an initial reduction in flow due to microvascular spasm that spontaneously resolved at 4-min, followed by sustained higher flow rates (~2-folds) compared to baseline, starting 10 min after therapy ( p <0.05). The short pulse caused a short-lived ~2-fold increase in flow rate that peaked at 4-min ( p <0.05), but without the initial microvascular spasm; (2) the sustained increase in perfusion during long pulse is not simply reactive hyperemia; and (3) both pulses are effective in reperfusion of MVO in our hindlimb model by restoring blood volume, but only the long pulse caused an increase in flow rate after treatment 2, compared to MVO ( p <0.05). Histological analysis post UTMC with either pulse configuration indicates no evidence of tissue damage or hemorrhage. Conclusions: Our findings demonstrate that the microbubble oscillation induces vasodilation and therapeutic efficacy for the treatment of MVO can be tuned by varying pulse length; relative to short pulse US, longer pulses drive greater microbubble cavitation and more rapid microvascular flow rate restoration after MVO, warranting further optimization of the pulse length for sonoreperfusion therapy.