Histotripsy for Pediatric Cardiac Applications.

Abstract

Medicine continues to move towards less invasive techniques for many cardiac conditions, especially for high-risk patients that may not tolerate the alternative, more invasive approach. For instance, patients born with the congenital heart defect hypoplastic left heart syndrome often require emergent creation of a perforation through the atrial septum for survival prior to palliative surgery. However, most approaches are catheter based, still invasive, and continue to have significant challenges, limitations, and complications. A completely non-invasive technique such as histotripsy may provide the same result in a faster, safer, and more efficient manner. Using high-pressure ultrasound pulses applied outside the body and focused to the targeted tissue, histotripsy generates a cluster of cavitating micro-bubbles that fractionate the target tissue. The goal of this work is to investigate the safety and efficacy of histotripsy for neonatal cardiac applications. To aid in this goal, therapy guidance and monitoring techniques are developed, and an integrated histotripsy therapy system, optimized for the human neonate with congenital heart disease, was designed and constructed. In this dissertation, histotripsy is first demonstrated to be capable of generating targeted intra-cardiac communications when positioned outside the body in an intact neonatal animal model with minimal collateral damage or systemic side-effects. Second, to mitigate the possibility of unintended injury due to heart motion, real-time motion correction using ultrasound imaging is developed and integrated into a histotripsy therapy system. The performance of the motion correction is quantified in vitro and a validated in a single in vivo experiment. Third, to maximize therapy efficacy, novel bubble-induced color Doppler feedback to monitor the degree of tissue damage during histotripsy treatment is developed and validated in vitro. Finally, a histotripsy therapy transducer with appropriate physical dimensions and acoustic parameters to precisely ablate cardiac tissue non-invasively in a human neonate is developed and integrated into an ultrasound guided histotripsy therapy system. The data and the integrated system accomplished from this dissertation form the essential foundation to a pioneering clinical trial for histotripsy cardiac therapy in infants, which will position histotripsy for application on a broad range of cardiac disorders in patients of all ages.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108732/1/millerrm_1.pd