Histotripsy for Benign Prostatic Hyperplasia

描述（由申请人提供）： 本申请的直接目标是开发和完善组织摧毁术（一种新型的非侵入性超声治疗，可产生非热机械组织破坏）作为良性前列腺增生（BPH）的治疗方法。组织破坏的机制是由空化介导的，空化是一种从压缩到稀疏的快速循环导致组织内形成微泡的现象。这些微泡随后的振荡和剧烈坍塌机械地破坏细胞和亚细胞结构，留下不可存活的碎片浆。 本申请旨在通过与Charles Cain博士建立合作关系，促进研究者作为医生科学家的发展。（生物医学工程）和Brian Fowlkes博士（放射学和生物医学工程）。职业发展计划结合了声学物理学的教学培训，实验方法的指导，以及来自有凝聚力，经验丰富的研究团队的周到指导。概述了初始组织和急性体内犬实验，以评估不同组织类型和解剖结构对组织破坏诱导的生物效应的敏感性。这将为开发精确的前列腺组织分离和减积治疗策略提供见解，而不会造成附带损害。使用体内慢性犬模型，描述了研究，以确定前列腺组织的组织破坏消融后的局部和全身反应。 公共卫生相关性：随着年龄的增长，前列腺肿大是男性常见的发现，并导致排尿困难。现有的治疗方法，以消除这种多余的组织和改善尿液引流需要侵入性手术。已经开发了使用热量杀死多余前列腺组织的侵入性较小的替代方案，但效果不佳，可能是因为被破坏的组织实际上并没有被移除。我们建议开发和测试一种名为组织摧毁术的新技术，该技术使用超声波能量机械地分解前列腺组织，并将其转化为可以通过排尿的液体。我们相信这将导致尿道的拓宽和泌尿功能的改善，而不需要侵入性手术。

DESCRIPTION (provided by applicant): The immediate objective of this application is to develop and refine histotripsy (a novel, non-invasive ultrasound therapy that produces non-thermal mechanical tissue destruction) as a therapy for benign prostatic hyperplasia (BPH). The mechanism of tissue destruction is mediated by cavitation, a phenomenon where rapid cycling from compression to rarefaction results in formation of microbubbles within the tissue. The subsequent oscillation and violent collapse of these microbubbles mechanically breaks apart cellular and subcellular structures leaving a nonviable slurry of debris. This application seeks to foster the development of the investigator as a physician scientist by building upon established collaborations with Charles Cain, Ph.D. (Biomedical Engineering) and Brian Fowlkes, Ph.D. (Radiology and Biomedical Engineering). The career development plan combines didactic training in acoustical physics, guidance in experimental methods, and thoughtful mentorship from a cohesive, experienced researcher team. Initial tissue and acute in-vivo canine experiments are outlined to assess the susceptibility of different tissue types and anatomic structures to histotripsy induced bio-effects. This will provide insight into development of precise treatment strategies for prostate tissue fractionation and debulking without collateral damage. Using an in-vivo chronic canine model, studies are described to define the local and systemic response following histotripsy ablation of prostate tissue. PUBLIC HEALTH RELEVANCE: Prostate enlargement is a common finding in men as they age and causes difficulty with urination. Established treatments to remove this excess tissue and improve urinary drainage require invasive surgery. Less invasive alternatives that use heat to kill the excess prostate tissue have been developed but are not as effective, probably because the destroyed tissue is not actually removed. We propose to develop and test a novel technology called histotripsy, which uses ultrasound energy to mechanically break apart prostate tissue and converts it into a liquid that can be passed with urination. We believe this will result in widening of the urinary channel and improved urinary function without requiring invasive surgery.