Feasibility of transcranial histotripsy for pediatric neuro-oncology applications using a hemispherical transducer

儿科患者对微创治疗有真实的且迫切的未满足的需求， 安全地治疗脑肿瘤，而不会产生明显的晚期效应。该提案的长期目标是 开发一种有效的非侵入性治疗方式，无任何晚期效应， 和小儿恶性脑肿瘤这将通过聚焦超声利用组织液化来完成 （FUS）诱导的组织破坏。本申请中的总体目标是（i）阐明高 声压和非线性冲击介导组织液化过程， 当使用半球形FUS换能器时，三种可能的组织摧毁机制可能发挥作用;以及（ii） 系统地研究了支持半球形机械液化的参数空间， 在FUS波束路径中使用儿科颅骨的离体和体内换能器。中心假设是， 可以进行精心设计的实验来了解组织背后的作用机制 使用低F数的液化（例如，半球形）换能器，且组织摧毁术可以是可行 至少在儿科人群的一个子集内完成。该项目的基本原理是， 使用现有的和监管批准的方法，了解组织液化的机制 半球形经颅FUS换能器，连同体内参数优化，可能提供 为小儿脑肿瘤组织摧毁治疗的可行性提供了强有力的科学支持。核心假设 将通过追求两个具体目标进行测试：1）进行精心设计的计算，台式和实验室， 体内实验以确定三种可能的组织破坏机制中的每一种对组织的贡献 液化过程;和2）研究支持机械液化的参数空间， 半球形传感器穿过儿童头骨本申请中提出的研究具有创新性， 申请人的意见，因为它建议确定组织破坏组织后的作用机制 液化使用低f数FUS换能器，以及优化FUS脉冲参数。的 拟议的研究意义重大，因为它有望为进一步研究提供强有力的科学依据。 儿科人群的经颅组织破坏研究。最终，这种新型的非侵入性治疗方法 这种方式有可能帮助大约4,300名被诊断患有脑肿瘤的儿童， 美国每年有30%的人在诊断后五年内无法存活， 选项.

Pediatric patients have a real and urgent unmet need for less invasive treatments which can efficiently and safely treat brain tumors without incurring significant late effects. The long-term goal of this proposal is to develop an efficient non-invasive treatment modality without any late effects for safe treatment of both benign and malignant pediatric brain tumors. This will be done utilizing tissue-liquification by focused ultrasound (FUS)-induced histotripsy. The overall objectives in this application are to (i) elucidate the degree to which high acoustic pressures and non-linear shocking mediate the tissue liquification process and what contribution each of three possible histotripsy mechanism may play when using a hemispherical FUS transducer; and (ii) systematically investigate the parameter space that supports mechanical liquification by hemispherical transducers both ex vivo and in vivo with pediatric skulls in the FUS beam path. The central hypothesis is that carefully designed experiments can be performed to understand the mechanism of action behind tissue liquification using low f-number (e.g., hemispherical) transducers, and that histotripsy can be feasibly accomplished within at least a subset of the pediatric population. The rationale for this project is that understanding the mechanism responsible for tissue liquification using existing and regulatory approved hemispherical transcranial FUS transducers, together with in vivo parameter optimization, is likely to offer strong scientific support for the feasibility of pediatric brain tumor histotripsy treatments. The central hypothesis will be tested by pursuing two specific aims: 1) conduct carefully designed computational, benchtop, and ex vivo experiments to determine the contribution each of three possible histotripsy mechanism have on the tissue liquification process; and 2) investigate the parameter space that supports mechanical liquification by hemispherical transducers through pediatric skulls. The research proposed in this application is innovative, in the applicant’s opinion, because it proposes to determine the mechanism of action behind histotripsy tissue liquification using low f-number FUS transducers, as well as optimize the FUS pulsing parameters. The proposed research is significant because it is expected to provide a strong scientific justification for further studies of transcranial histotripsy for the pediatric population. Ultimately, this novel non-invasive treatment modality has the potential to help the approximately 4,300 children who are diagnosed with brain tumors in the US every year, 30% of whom do not survive past five years after diagnosis, with a safe an efficient treatment option.