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

儿科患者对侵入性更小的治疗有着真实而迫切的需求，这种治疗可以有效和 安全治疗脑瘤，不会招致明显的后遗症。这项提议的长期目标是 开发一种有效的非侵入性治疗方法，安全地治疗这两种良性疾病 和儿童恶性脑瘤。这将通过聚焦超声进行组织液化来完成。 (FUS)诱导的组织学检查。本申请的总体目标是：(I)阐明高 声压和非线性冲击在组织液化过程中的中介作用及其各自的贡献 当使用半球FUS换能器时，三种可能的组织摩擦机制可能起作用；和(Ii) 系统地研究了半球面支持机械液化的参数空间 在体外和体内的换能器，在FUS束路径上有儿科头骨。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(例如，半球)换能器的液化，并且该组织摩擦检查是可行的 至少在儿科人群的一个子集内完成。这个项目的基本原理是 了解使用现有的和法规批准的组织液化的机制 半球经颅fus换能器，加上活体参数优化，可能会提供 为儿童脑肿瘤组织学治疗的可行性提供了有力的科学支持。中心假说 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、台式计算机和 活体实验，以确定三种可能的组织摩擦机制对组织的贡献 液化过程；以及2)研究支持机械液化的参数空间 通过儿童头骨的半球换能器。本申请中提出的研究具有创新性，在 申请人的意见，因为它提议确定组织摩擦组织背后的作用机制 使用低f数FUS换能器进行液化，以及优化FUS脉冲参数。这个 拟议的研究具有重要意义，因为它有望为进一步的 儿童人群经颅组织学检查的研究。最终，这种新的非侵入性治疗 这种模式有可能帮助大约4300名被诊断为脑瘤的儿童 美国每年有30%的人在确诊后五年内不能存活，采用安全有效的治疗方法 选择。

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.