Histotripsy for Benign Prostatic Hyperplasia

描述(由申请人提供)： 这项应用的直接目标是开发和改进组织电切术(一种产生非热机械组织破坏的新型非侵入性超声波疗法)，作为良性前列腺增生症(BPH)的治疗方法。组织破坏的机制是由空化所介导的，这种现象是从压缩到稀疏的快速循环导致组织内形成微泡。随后这些微泡的振荡和猛烈的坍塌会机械地分解细胞和亚细胞结构，留下一堆不能存活的碎片。 此应用程序旨在通过与Charles Cain博士(生物医学工程)和Brian Fowlkes博士(放射学和生物医学工程)建立合作关系，促进研究人员作为内科科学家的发展。职业发展计划结合了声学物理的教学培训，实验方法的指导，以及来自一个有凝聚力、经验丰富的研究团队的周到指导。概述了最初的组织和急性活体犬实验，以评估不同组织类型和解剖结构对组织摩擦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去瘤治疗策略提供洞察力，而不会造成附带损害。使用活体慢性犬模型，描述了确定前列腺组织组织电切术后局部和全身反应的研究。 与公共卫生相关：随着男性年龄的增长，前列腺肥大是一种常见的发现，并导致排尿困难。移除多余组织和改善尿液排出的现有治疗方法需要侵入性手术。使用热能杀死多余的前列腺组织的侵入性更小的替代品已经被开发出来，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摩擦的新技术，这种技术使用超声波能量机械地分离前列腺组织，并将其转化为可随尿排出的液体。我们相信这将在不需要侵入性手术的情况下拓宽尿路并改善尿路功能。

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.