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

基本信息

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
项目类别：
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

项目摘要

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.

小儿患者对减少侵入性治疗的真正迫切需求可以有效，并且安全治疗脑肿瘤而不会产生明显的晚期作用。该提议的长期目标是开发有效的非侵入性治疗方式，没有任何延迟效果以安全治疗两种良性和恶性小儿脑肿瘤。这将通过聚焦超声使用组织液化来完成（FUS）诱导的组织疗法。本应用程序中的总体目标是（i）阐明高度的程度声压力和非线性震动介导组织清算过程以及每个贡献使用半球形螺丝式传感器时，可能会发挥三种可能的组织疗法机制。（ii）系统地研究支持半球机械清算的参数空间在FUS束路径中带有小儿头骨的体内和体内传感器。中心假设是可以进行精心设计的实验以了解组织后面的作用机理使用低F数（例如半球形）换能器进行清算，并且该组织疗法是可行的至少在小儿人群的一部分内完成。这个项目的理由是了解使用现有和法规批准的组织清算的机制半球形经颅FUS传感器以及体内参数优化，可能会提供对小儿脑肿瘤组织疗法的可行性的强烈科学支持。中心假设将通过追求两个具体目标来测试：1）进行精心设计的计算，台式和EX 体内实验以确定三种可能的组织练习机制中的每一个对组织的贡献清算过程； 2）研究支持机械清算的参数空间通过小儿头骨的半球传感器。本应用程序中提出的研究具有创新性申请人的意见，因为它提议确定组织疗法组织背后的作用机理使用低F-number Fus传感器的液化，并优化FUS脉动参数。这拟议的研究很重要，因为预计它将提供强大的科学理由以进一步针对小儿种群的thrancranial组织疗法研究。最终，这种新颖的非侵入性治疗模态有可能帮助大约4,300名被诊断出患有脑肿瘤的儿童美国每年，诊断后五年中的30％无法生存，并有一个安全的治疗选项。