Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)

经颅磁共振引导组织解剖 (tcMRgHt)

• 批准号: 10396108
• 负责人: Zhen Xu
• 金额: $ 63.16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396108
• 关键词: Ablation; Acoustics; Aftercare; Algorithms; Anatomy; Blood; Brain; Brain Neoplasms; Brain region; Cadaver; Caliber; Cattle; Cells; Cerebrum; Clinical; Clinical Treatment; Cognitive deficits; Craniotomy; Data; Diagnosis; Disease; Edema; Essential Tremor; Excision; FDA approved; Family suidae; Focused Ultrasound; Fractionation; Future; Goals; Heating; Human; Image; Injury; Length; Location; Magnetic Resonance; Magnetic Resonance Imaging; Metastatic malignant neoplasm to brain; Methods; Modeling; Monitor; Morbidity - disease rate; Necrosis; Neoplasm Metastasis; Neuraxis; Operative Surgical Procedures; Patients; Performance; Pharmaceutical Preparations; Physiologic pulse; Positioning Attribute; Primary Brain Neoplasms; Primary Neoplasm; Radiation Dose Unit; Radiation necrosis; Radiation therapy; Rodent; Safety; Secondary to; Sonication; Speed; Structure; Surface; Survival Rate; System; Techniques; Technology; Temperature; Thermometry; Time; Tissues; Trauma; base; brain tissue; brain volume; clinical translation; cranium; design and construction; effective therapy; image guided; improved; in vivo; invention; millimeter; preclinical study; prevent; radiation risk; skull base; tool; tumor; ultrasound

Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt) Project Summary The goal of this proposal is to develop the first integrated tcMRgHt system for treatment of brain tumors. Approximately 256,000 new patients are diagnosed with primary brain tumor annually worldwide, and many more patients are diagnosed with brain metastases. The current clinical treatment for brain tumors is a highly invasive surgery. The five-year survival rate is only 33% with many surviving patients suffering from cognitive deficits. Transcranial magnetic resonance guided focused ultrasound (tcMRgFUS) has been investigated as a noninvasive ablation method in the brain. However, due to the overheating of the skull, tcMRgFUS cannot treat a target volume >1 cm diameter in the brain or locations within 2 cm from the skull surface, rendering inoperable up to ~90% of the cortex regions where brain tumors often reside. We hypothesize that transcranial MR guided histotripsy (tcMRgHt) can overcome the treatment location and volume limitations of tcMRgFUS and provide a non-invasive ablation technique to improve the treatment of brain tumors. Using microsecond-length, high-amplitude ultrasound pulses applied from outside the skull, cavitation can be precisely generated to disrupt cells within the targeted brain region. The heating to the skull and surrounding tissue can be avoided by using a very low duty cycle (<0.1%). Our preliminary data show that histotripsy applied through excised human skulls was used to ablate a wide range of locations and brain volumes inside the skull, while keeping the temperature increase in the skull under 4°C. Although the feasibility of transcranial histotripsy and MRI guidance has been shown separately, developing and building an integrated tcMRgHt system is a substantial technical challenge. We propose the following three specific aims. 1) Design and construct an integrated tcMRgHt system. 2) Develop and optimize specialized RF pulse sequences for MRI guidance of tcMRgHt. 3) Validate the performance of the tcMRgHt system in ex vivo brain phantom and human cadaver. An integrated tcMRgHt system that can noninvasively treat a wide range of locations and volumes in the brain and validated in human cadavers would be a critical milestone to advance this promising technology for future clinical translation for treatment of brain tumors.

经颅磁共振引导组织解剖 (tcMRgHt) 项目概要 该提案的目标是开发第一个用于治疗的集成 tcMRgHt 系统 约 256,000 名新患者被诊断患有原发性脑肿瘤。 每年全世界都有更多的患者被诊断出患有脑转移。 脑肿瘤的临床治疗是一种高侵入性的手术，五年生存率仅有。 33% 的许多幸存患者患有认知缺陷。 共振引导聚焦超声 (tcMRgFUS) 已被作为一种非侵入性研究 然而，由于颅骨过热，tcMRgFUS 无法进行。 治疗大脑中直径 >1 厘米的目标体积或距颅骨表面 2 厘米以内的位置， 导致脑肿瘤常驻留的约 90% 的皮层区域无法手术。 其次，经颅 MR 引导组织解剖 (tcMRgHt) 可以克服 tcMRgFUS 的治疗位置和体积限制，并提供非侵入性 使用微秒长度的消融技术来改善脑肿瘤的治疗。 从颅骨外部施加高振幅超声波脉冲，可以精确地产生空化作用 产生的热量会破坏目标大脑区域内的细胞和 我们的初步数据可以通过使用非常低的占空比（<0.1%）来避免。 表明通过切除的人类头骨进行组织解剖可用于消融大范围的 颅骨内的位置和脑容量，同时保持颅骨温度升高 尽管经颅组织解剖和 MRI 引导的可行性已被证明。 单独开发和构建集成的 tcMRgHt 系统是一项重大技术 我们提出以下三个具体目标： 1）设计和构建一个集成的。 tcMRgHt 系统 2) 开发和优化用于 MRI 引导的专用射频脉冲序列。 tcMRgHt 3) 验证 tcMRgHt 系统在离体脑模型中的性能 人体尸体的综合 tcMRgHt 系统，可以无创地治疗多种疾病。 大脑中的位置和体积并在人体尸体中得到验证将是一个关键 推进这项有前途的技术在未来临床转化治疗中的里程碑 脑肿瘤。

项目成果

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

经颅磁共振引导脑外科组织解剖：临床前研究。

• 发表时间: 2022-01
• 影响因子: 2.9
• 作者: Lu, Ning;Gupta, Dinank;Daou, Badih J;Fox, Adam;Choi, Dave;Sukovich, Jonathan R;Hall, Timothy L;Camelo;Chaudhary, Neeraj;Snell, John;Pandey, Aditya S;Noll, Douglas C;Xu, Zhen
• 通讯作者: Xu, Zhen

Stereotactic Transcranial Focused Ultrasound Targeting System for Murine Brain Models.

用于鼠脑模型的立体定向经颅聚焦超声靶向系统。

• 发表时间: 2021-01
• 作者: Choi, Sang Won;Gerhardson, Tyler I;Duclos, Sarah E;Surowiec, Rachel K;Scheven, Ulrich M;Galban, Stefanie;Lee, Fred T;Greve, Joan M;Balter, James M;Hall, Timothy L;Xu, Zhen
• 通讯作者: Xu, Zhen

Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model.

猪脑出血模型中的组织解剖学凝块液化。

• 发表时间: 2020-03-01
• 影响因子: 4.8
• 作者: Gerhardson, Tyler;Sukovich, Jonathan R;Chaudhary, Neeraj;Chenevert, Thomas L;Ives, Kim;Hall, Timothy L;Camelo;Xu, Zhen;Pandey, Aditya S
• 通讯作者: Pandey, Aditya S