Renal denervation guided and ablated by noninvasive ultrasound in canines

Abstract

This study aimed to explore the application and efficacy of a novel stimulation-guided, targeting ablation, and efficacy verification technique based on dual-frequency extracorporeal focused ultrasound interference for renal denervation (RDN) in treating resistant hypertension. Existing RDN techniques are often invasive or lack clear intervention targets and efficacy endpoints, limiting their effectiveness and safety. To address these limitations, we developed a technique using dual-frequency extracorporeal focused ultrasound interference, which modulates acoustic radiation force to stimulate renal nerves for targeted RDN. Initial validation in C57 mice sciatic nerves demonstrated that differential-frequency stimulation (Δf = 40 kHz) achieved effective neuromuscular activation (leg twitching with recorded action potentials) at 0.25 W acoustic power, whereas same-frequency stimulation required significantly higher power (1.25 W) to elicit responses (P < 0.001 for action potential amplitude comparison).In old beagles, acoustic stimulation (with stimulation parameters set at 50 W acoustic power and a Δf = 10 kHz,) was applied across multiple cross-sectional quadrants of the main renal artery to identify and selectively ablate significant blood pressure response sites (≥5 mmHg). Further RDN was achieved through re-stimulation verification and supplementary ablation. Our findings reveal a predominant distribution of positive reaction sites in the proximal segment of the renal artery and that nearly one-third of the response sites still reacted to stimulation after ablation, necessitating additional ablation. When compared to anatomic landmark RDN method, the stimulate-guided RDN demonstrated notably superior reductions in systolic BP (14.4 ± 3.1 vs 9.6 ± 4.4 mmHg, P = 0.026) on day 28. Notably, the implementation of this method did not result in any serious complications. Our study suggests that nerve acoustic stimulation guidance has the potential to be further explored as a non-invasive RDN strategy for targeted ablation and efficacy validation in clinical settings.