Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)

经颅磁共振引导下组织学检查（tcMRgHt） 项目摘要 该提案的目标是开发第一个用于治疗的集成tcMRgHt系统 脑肿瘤大约256，000名新患者被诊断患有原发性脑肿瘤 每年全球范围内，有更多的患者被诊断患有脑转移瘤。当前 脑肿瘤的临床治疗是高度侵入性的手术。五年存活率只有 33%，许多幸存的患者患有认知缺陷。经颅磁 共振引导聚焦超声（tcMRgFUS）已被研究作为一种非侵入性的 大脑中的消融方法。然而，由于颅骨过热，tcMRgFUS不能 治疗脑内直径>1 cm的靶体积或距离颅骨表面2 cm以内的位置， 使得高达约90%的脑肿瘤经常驻留的皮质区域不可手术。我们 假设经颅磁共振引导组织活检术（tcMRgHt）可以克服 tcMRgFUS的治疗位置和体积限制， 消融技术，以改善脑肿瘤的治疗。使用微秒长度， 高振幅的超声波脉冲从颅骨外施加，空化可以精确地 用来破坏目标脑区的细胞头骨的热度 可以通过使用非常低的占空比（<0.1%）来避免对周围组织的损伤。我们的初步数据 显示通过切除的人类头骨应用的组织摧毁术被用于消融大范围的 位置和脑容量的头骨内，同时保持温度增加的头骨 在4°C下。虽然经颅组织摧毁术和MRI引导的可行性已经被证明 另外，开发和建立一个集成的tcMRgHt系统是一个重要的技术问题， 挑战.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RF脉冲序列， tcMRgHt. 3)验证tcMRgHt系统在离体脑体模中的性能， 人类尸体一个集成的tcMRgHt系统，可以非侵入性地治疗广泛的 在大脑中的位置和体积，并在人类尸体上验证，将是一个关键的 里程碑，以推动这一有前途的技术，为未来的临床翻译治疗 脑瘤

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.