Timing of high-intensity pulses for myocardial cavitation-enabled therapy

BACKGROUND: High-intensity ultrasound pulses intermittently triggered from an ECG signal can interact with circulating contrast agent microbubbles to produce myocardial cavitation microlesions of potential therapeutic value. In this study, the timing of therapy pulses relative to the ECG R wave was investigated to identify the optimal time point for tissue reduction therapy with regard to both the physiological cardiac response and microlesion production. METHODS: Rats were anesthetized, prepared for ultrasound, placed in a heated water bath, and treated with 1.5 MHz focused ultrasound pulses targeted to the left ventricular myocardium with an 8 MHz imaging transducer. Initially, the rats were treated for 1 min at each of six different time points in the ECG while monitoring blood pressure responses to assess cardiac functional effects. Next, groups of rats were treated at three different time points: end diastole, end systole, and mid-diastole to assess the impact of timing on microlesion creation. These rats were pretreated with Evans blue injections and were allowed to recover for 1 day until hearts were harvested for scoring of injured cardiomyocytes. RESULTS: The initial results showed a wide range of cardiac premature complexes in the ECG, which corresponded with blood pressure pulses for ultrasound pulses triggered during diastole. However, the microlesion experiment did not reveal any statistically significant variations in cardiomyocyte injury. CONCLUSION: The end of systole (R + RR/3) was identified as an optimal trigger time point which produced identifiable ECG complexes and substantial cardiomyocyte injury but minimal cardiac functional disruption during treatment.