Assessment and Control of a Cavitation-Enabled Therapy for Minimally Invasive Myocardial Reduction

Cavitation induced microlesions;Cavitation therapy;Hypertrophic cardiomyopathy (HCM);myocardial reduction;therapeutic ultrasound;tissue shrinkage;Biomedical Engineering;Engineering;Biomedical Engineering

Zhu, YiyingMiller, Douglas L ;

University of Michigan

关键词: Cavitation induced microlesions;    Cavitation therapy;    Hypertrophic cardiomyopathy (HCM);    myocardial reduction;    therapeutic ultrasound;    tissue shrinkage;    Biomedical Engineering;    Engineering;    Biomedical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/136970/zhuyiy_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Hypertrophic cardiomyopathy (HCM), which occurs in 1/500 individuals globally can lead to sudden death in adults without prior symptoms. Echocardiography is commonly used to diagnose hypertrophic cardiomyopathy. Current treatment involves invasive and high-risk procedures such as surgery or catheter-based ablation of spetum to potentially prevent left ventricular outflow tract obstruction. A novel technique, called Myocardial Cavitation-Enabled Therapy (MCET), has been proposed as a means to achieve minimally invasive myocardial reduction, i.e. heart tissue ablation. MCET aims to target hypertrophic heart muscle over time without substantial tissue scarring. The treatment employs contrast echocardiography at higher than diagnostic pressure amplitudes to produce scattered microlesions (clusters of dead cells) by cavitating contrast agent microbubbles. The assessment and control of MCET is explored in three different contexts as follows:A computer-aided 3-D quantitative evaluation scheme, for acute studies, is developed to characterize macrolesions (targeted region for treatment) based on histology sections, including lesion size and lesion density. The characterization is based on brightfield and fluorescence histological images as available in acute preclinical studies. The radially symmetric model employed to characterize macrolesion density is feasible for the study using a single focused beam to perform treatment. This methodology provides a volume-oriented, quantity- sensitive therapy evaluation. Results from parametric studies of MCET demonstrate that the quantitative scoring scheme reduces visual scoring ambiguity, overcomes the limitation of traditional visual scoring and works for cases with a large histologically identified lesion count, i.e. has an appropriate dynamic range for evaluating therapeutic applications. The presented results presented here have shown that MCET-induced macrolesions grow radially as the acoustic pressure amplitude increases. Using a swept beam as a new method seems to be able to shorten treatment time.MCET shows great potential as a minimally-invasive myocardial tissue reduction therapy after long-term healing. Chronic studies of 6-week show the maturation of MCET induced microlesions with quantitative results of the fibrotic tissue fraction. And the tissue reduction in a HCM rat model is demonstrated by showing and heart muscle wall shrinkage by about 16%, which is a therapeutically useful magnitude. MCET method can be improved by addition of adjuvant treatment with steroids and hypertension medication to help fibrosis reduction. Further development and refinement in larger animals of MCET treatment for HCM should fill the need for a new clinical treatment option.Feasibility of detection, quantification and localization for microbubble cavitation is investigated for treatment monitoring and controls. A passive cavitation imaging algorithm and variations of this algorithm provide spatial information on the extent of cavitation events. Cavitation sites can be localized with reasonable spatial resolution. The described passive imaging algorithm applies to both systems: Verasonics (an ultrasound research platform) alone transmitting high intensity focused ultrasound (HIFU) and receiving signals with cavitation signatures, and Verasonics only for passive receiving with another HIFU system for therapeutic exposure. The overall therapy-monitoring scheme is able to adequately delineate the spatial location of triggered microbubble dynamics for real-time monitoring of monitoring of microlesion accumulation.