Controlled ultrasound tissue erosion.

High intensity ultrasound has the ability to focus energy deep within the human body and generate clinically significant bioeffects at the target without damaging overlying tissue. We have developed a new technique to achieve tissue erosion (physical removal of tissue) at a tissue-fluid interface using high intensity pulsed ultrasound. This technique can be considered as a form of soft tissue lithotripsy, which we call histotripsy. The overall goal of this dissertation is to develop a noninvasive ultrasound procedure to perforate the atrial septum (i.e. the membrane separating the two atria) as the first step to treat neonates suffering Hypoplastic Left Heart Syndrome (HLHS). The feasibility of histotripsy to create the atrial septal perforation is demonstrated both in vitro and in vivo. Our results show that short (less than 10 acoustic cycles) high intensity pulses delivered at certain pulse repetition frequencies can achieve localized, sharp boundary perforations. The erosion process is highly dependent on acoustic parameters. Furthermore, real-time monitoring of erosion is developed using temporally changing acoustic backscatter. The initiation of variable acoustic backscatter is required to produce erosion and its appearance is an excellent indicator that the erosion process is progressing normally. The primary mechanism for the erosion process is believed to be acoustic cavitation in which microbubbles within the focused region are activated by the acoustic field. Vigorous microbubble activities at the tissue-fluid interface mechanically and systemically remove small tissue fragments. To understand the physical basis for the erosion process, and to form a rational basis for further optimization, direct optical observations combined with acoustic feedback are employed to monitor dynamics of the ultrasound generated bubble cloud. In summary, we show that high intensity ultrasound pulses have the ability to physically remove soft tissue in a highly localized manner. The histotripsy technique will be developed as a potentially effective non-invasive tool in the treatment of intact atrial septum in neonatal patients with HLHS, as well as many other clinical procedures where mechanical removal of soft tissue would be indicated.PhDApplied SciencesBiomedical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125548/2/3192822.pd