Ultrasound contrast agent enhanced focused ultrasound ablation of brain tumors

尽管在许多领域取得了进展，但脑瘤仍然是一个非同寻常的挑战。由于固有的 手术切除和放射治疗相关的风险，许多中枢神经系统肿瘤的侵袭性，以及 抗癌药物脑内转运困难对多种脑肿瘤患者预后的影响 MORS的形势依然严峻。这一挑战对于关键结构附近的肿瘤来说尤其严峻，例如 头骨底部。虽然神经外科领域取得了非凡的进步，但手术过程漫长，令人伤脑筋。 马季奇，并对患者构成重大风险。放射外科是一种非侵入性选择，但它也有局限性。 而复发也是一个重大挑战。现有手术的新的、侵入性较小的替代方案是DES- 非常需要。这项研究将测试经颅磁共振成像引导的组合 聚焦超声(TcMRgFUS)消融及微泡造影剂(USCA)治疗 脑肿瘤的消融术。USCA的添加将超声效应直接定向到微血管- 并能够在不加热的情况下对组织进行消融，从而大大降低了超声诊断率。 当然了。这种方法能够在不损害周围结构的情况下对肿瘤进行消融，即使在 具有挑战性的区域，如颅底。我们正在开发方法，使这种消融方法 在不损伤邻近神经的情况下，以受控方式应用于切除颅底的组织体积 结构。我们将优化曝光水平，以尽可能低的能量传输产生消融 在不同的肿瘤模型中。我们还将使用临床TcMRgFUS系统在非人类灵长类动物身上进行测试- TEM旨在确定在大脑动物身上使用超声波刺激脑深部结构的安全性。目标将被锁定- 直接与视束相邻，因此我们可以证实，在没有胶合的情况下，可以实现消融- 邻近神经结构的外周损伤。同时，我们将开发一种被动超声成像方法。 适用于经颅实时监测空化暴露情况。这种类型的消融只有 开始被研究。拟议的工作将获得所需的翻译数据，以证明fo- 超声是临床上可行的脑肿瘤消融方法，即使在具有挑战性的区域，如 头骨底部。 相关性(请参阅说明)： 以头骨为基础的肿瘤是一个非同寻常的挑战，需要新的、侵入性较小的技术。在这 在这项工作中，我们将测试磁共振成像引导的聚焦超声和一种微型 泡沫剂，它使我们能够非侵入性地消融组织体积，紧随其后的是具有挑战性的脑损伤 像头盖骨底部这样的区域。 项目/绩效网站(S)(如果需要额外空间，请使用

Despite progress made in many areas, brain tumors remain an extraordinary challenge. Due to the inherent risks associated with surgical resection and radiotherapy, the aggressiveness of many CNS tumors, and the difficulty in delivering anticancer drugs to the brain, the prognosis for patients with many types of brain tu- mors remains grim. This challenge is particularly stark for tumors near critical structures, such as those near the skull base. While extraordinary advances have occurred in neurosurgery, the procedures are long, trau- matic, and pose significant risk to the patient. Radiosurgery is a noninvasive option, but it also has limitations and recurrence is also a major challenge. New and less invasive alternatives to existing procedures are des- perately needed. This study will test the combination of Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound (TcMRgFUS) ablation and a microbubble-based ultrasound contrast agent (USCA) for ablation of brain tumors. The addition of the USCA targets the ultrasound effects directly to the microvascu- lature and enables ablation of tissue without bulk heating, which allows dramatically lower ultrasound expo- sure levels. This approach enables the ablation of tumors without damage to surrounding structures even in challenging areas, such as the skull base. We are developing methods that allow this ablation method to be applied in a controlled manner to ablate tissue volumes at the skull base without damaging adjacent nerve structures. We will optimize the exposure levels to produce ablation with the lowest possible energy delivery in different tumor models. We will also perform tests in nonhuman primates using a clinical TcMRgFUS sys- tem to establish the safety of sonicating deep brain structures in a large-brained animal. Targets will be se- lected directly adjacent to the optic tract, so we can confirm that the ablation can be achieved without collat- eral damage to adjacent nerve structures. In parallel, we will develop a passive ultrasound imaging method suitable for transcranial use to monitor the cavitation exposures in real time. This type of ablation has only begun to be studied. The proposed work will obtain the translational data needed to demonstrate that fo- cused ultrasound is clinically feasible approach to brain tumor ablation, even in challenging areas such as the skull base. RELEVANCE (See Instructions): Skull-based tumors are an extraordinary challenge, and new, less-invasive technologies are needed. In this work, we will test the combination of Magnetic Resonance Imaging-guided focused ultrasound and a micro- bubble-based agent, which enables us to noninvasively ablate tissue volumes next to challenging brain re gions such as the skull base. PROJECT/PERFORIWANCE SITE(S) (if additional space is needed, use