Focal ultrasound-mediated nonthermal ablation of brain tumors

项目摘要 多形性胶质母细胞瘤（GBM）是最常见和最具侵袭性的原发性人脑肿瘤， 总是致命的标准治疗包括肿瘤减积，通常通过手术;然而，并非所有 GBM肿瘤或患者有资格接受该手术。消融术是外科手术的有效替代方法 切除，并可以进行非侵入性经颅聚焦超声。拟议 项目中，经颅聚焦超声将与新型相移纳米乳液（PSNE）相结合 用于GBM肿瘤的局灶性非热消融。PSNE可以用超声脉冲蒸发， 由此产生的气泡会产生强烈的机械力， 组织.在已建立的GBM肿瘤中选择性地蒸发纳米乳液将使得能够高度地 局部非热消融颅内肿瘤，同时保留周围的健康脑组织。测试 在此前提下，我们将评估损伤程度和对消融的免疫反应（即免疫细胞 浸润）作为声压和PSNE的函数 浓度.我们还将分析消融区域神经酰胺的表达，神经酰胺是一种凋亡启动子， 据报道，它将放射治疗的效果提高了10倍以上。最后，我们将评估 非热局部消融对荷瘤大鼠存活率的影响。总的来说，我们的目标是阐明 促进安全有效的原发性脑超声介导非热消融的参数 肿瘤的

PROJECT SUMMARY Glioblastoma multiforme (GBM) is the most common and aggressive primary human brain tumor and is invariably fatal. Standard of care includes debulking of tumor, normally through surgery; however, not all GBM tumors or patients are eligible for the procedure. Ablation is an effective alternative to surgical resection, and can be performed noninvasively with transcranial focused ultrasound. In the proposed project, transcranial focused ultrasound will be combined with a novel phase-shift nanoemulsion (PSNE) for focal nonthermal ablation of GBM tumors. PSNE can be vaporized with ultrasound pulses and the resultant bubbles can generate intense mechanical forces that can collapse blood vessels or fractionate tissue. Vaporization of the nanoemulsions selectively in established GBM tumors will enable highly localized nonthermal ablation of intracranial tumors while sparing surrounding healthy brain tissue. To test this premise, we will evaluate the extent of damage and immune response to ablation (i.e. immune cell infiltration) within and adjacent to sonicated brain tumors as a function of acoustic pressure and PSNE concentration. We will also analyze ablated regions for expression of ceramide, an apoptotic promoter that reportedly enhances the efficacy of radiotherapy by more than 10-fold. Lastly, we will assess the impact of nonthermal focal ablation on the survival of tumor-burdened rats. Overall, we aim to elucidate the parameters that facilitate safe and effective ultrasound-mediated nonthermal ablation of primary brain tumors.