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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：
10433621
负责人：
Henrik Carl Axel Odeen
金额：
$ 20.06万
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/10433621
关键词：
Ablation Acoustics Adoption Amplifiers Animals Benign Brain Brain Neoplasms Cancer Etiology Cells Child Childhood Childhood Brain Neoplasm Childhood Malignant Brain Tumor Clinical Clinical Research Development Diagnosis Emerging Technologies 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 Shock Stress System Tadpoles Testing 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

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.

儿科患者有一个真实的和迫切的未满足的需求，需要更少的侵入性治疗，可以有效和