Focal ultrasound-mediated nonthermal ablation of brain tumors

项目总结 多形性胶质母细胞瘤(GBM)是人类最常见和最具侵袭性的原发脑肿瘤。 总是致命的。护理的标准包括通常通过手术切除肿瘤；然而，并不是所有的 GBM肿瘤或患者有资格接受该手术。消融是外科手术的有效替代方法 可以通过经颅聚焦超声无创地进行切除。在建议的 项目中，经颅聚焦超声将与一种新型相移纳米乳剂(PSNE)相结合 用于基底膜肿瘤的局部非热消融。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，使血管崩溃或碎裂。 组织。在已建立的GBM肿瘤中选择性地汽化纳米乳剂将使 局部非热消融颅内肿瘤，同时保留周围健康脑组织。为了测试 在此前提下，我们将评估消融的损伤程度和免疫反应(即免疫细胞 浸润性)作为声压和PSNE的函数 集中精神。我们还将分析神经酰胺的消融区域，神经酰胺是一种凋亡促进剂， 据报道，将放射治疗的疗效提高了10倍以上。最后，我们将评估 非热聚焦消融对荷瘤大鼠存活率的影响。总体而言，我们的目标是澄清 促进安全有效的超声介导性非热脑消融的参数 肿瘤。

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.