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

使用半球形换能器进行经颅组织解剖用于儿科神经肿瘤学应用的可行性

• 批准号: 10570948
• 负责人: Henrik Carl Axel Odeen
• 金额: $ 19.6万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570948
• 关键词: Ablation; Acceleration; Acoustics; Adoption; Amplifiers; Animals; Benign; Brain; Brain Neoplasms; Cancer Etiology; Cells; Cephalic; Child; Childhood; Childhood Brain Neoplasm; Childhood Malignant Brain Tumor; Clinical; Clinical Research; Development; Diagnosis; Emerging Technologies; Experimental Designs; FDA approved; Family suidae; Focused Ultrasound; Gases; Goals; Grant; Heating; Human; Late Effects; Lesion; Literature; Mechanics; Mediating; Methods; Modality; Modeling; Morbidity - disease rate; National Institute of Biomedical Imaging and Bioengineering; Neurologic; Operative Surgical Procedures; Outcome; Physiologic pulse; Play; Population; Process; Quality of life; Radiation exposure; Radiation therapy; Research; Research Personnel; Risk; Safety; Scalp structure; Second Primary Cancers; Series; Shapes; Shock; Stress; System; Tadpoles; Testing; Therapeutic; Thermal Ablation Therapy; Tissue Therapy; Tissues; Transducers; Tremor; Ultrasonic Transducer; Ultrasonics; attenuation; chemotherapy; clinical translation; cost; cranium; design; experimental study; heart damage; high risk; in vivo; innovation; lung injury; millisecond; mortality; nervous system disorder; neuro-oncology; novel; pediatric patients; pressure; response; simulation; transmission process

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.

儿科患者对于微创治疗有着真实而紧迫的未满足需求，这种治疗可以有效且有效地进行。 安全地治疗脑肿瘤，不会产生明显的后期影响。该提案的长期目标是 开发一种有效的非侵入性治疗方式，无任何后期影响，以安全治疗良性和 和小儿恶性脑肿瘤。这将通过聚焦超声波进行组织液化来完成 （FUS）诱导的组织切片术。本申请的总体目标是 (i) 阐明高水平的程度 声压和非线性冲击介导组织液化过程以及各自的贡献 使用半球形 FUS 换能器时可能会发挥三种可能的组织解剖机制； (二) 系统地研究支持半球机械液化的参数空间 FUS 光束路径中的离体和体内儿童头骨传感器。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（例如半球形）换能器进行液化，并且可以可行地进行组织解剖 至少在儿科人群的一个子集内完成。该项目的理由是 了解使用现有的和监管批准的负责组织液化的机制 半球形经颅 FUS 传感器与体内参数优化一起，可能会提供 为小儿脑肿瘤组织解剖治疗的可行性提供了强有力的科学支持。中心假设 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、台式和扩展 体内实验以确定三种可能的组织解剖机制对组织的贡献 液化过程； 2）研究支持机械液化的参数空间 穿过儿童头骨的半球形传感器。本申请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解剖组织背后的作用机制 使用低 f 数 FUS 传感器进行液化，并优化 FUS 脉冲参数。这 拟议的研究意义重大，因为预计它将为进一步的研究提供强有力的科学依据 针对儿科人群的经颅组织解剖学研究。最终，这种新颖的非侵入性治疗 该疗法有可能帮助该地区约 4,300 名被诊断患有脑肿瘤的儿童 美国每年有 30% 的患者在诊断后无法存活超过五年，但接受安全有效的治疗 选项。