Ultrasound contrast agent enhanced focused ultrasound ablation of brain tumors

尽管在许多领域取得了进展，但脑肿瘤仍然是一个巨大的挑战。由于固有的 与手术切除和放射治疗相关的风险，许多CNS肿瘤的侵袭性， 抗癌药物难以输送到大脑，许多类型脑肿瘤患者的预后， 莫尔斯仍然很冷酷。这种挑战对于靠近关键结构的肿瘤尤其严峻，例如那些靠近 头骨底部虽然神经外科取得了非凡的进步，但手术时间长，创伤大， 这对患者来说是一个巨大的风险。放射外科是一种非侵入性的选择，但它也有局限性 复发也是一大挑战。新的和侵入性较小的替代现有的程序是des- 非常需要。本研究将测试经颅磁共振成像引导 聚焦超声（TcMRgFUS）消融和基于微泡的超声造影剂（USCA）用于 切除脑肿瘤USCA的加入将超声效应直接靶向微血管， 它可以在不产生大量热量的情况下消融组织，从而显著降低超声暴露。 确定水平。这种方法能够在不损伤周围结构的情况下消融肿瘤， 具有挑战性的区域，例如颅底。我们正在开发的方法，使这种消融方法， 以受控的方式施加以消融颅底处的组织体积而不损伤邻近神经 结构.我们将优化暴露水平，以尽可能低的能量输送进行消融 在不同的肿瘤模型中。我们还将使用临床TcMRgFUS系统在非人灵长类动物中进行测试， tem以确定在大脑动物中超声处理脑深部结构的安全性。目标将被- 选择直接邻近视束，因此我们可以确认消融可以在没有准直的情况下实现， 对邻近神经结构的损伤。同时，我们将开发一种被动超声成像方法， 适合于经颅使用以真实的实时监测空化暴露。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， 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领域， 头骨底部 相关性（见说明）： 基于颅骨的肿瘤是一个非凡的挑战，需要新的、侵入性较小的技术。在这 工作，我们将测试磁共振成像引导的聚焦超声和微 基于气泡的药剂，使我们能够非侵入性地消融组织体积旁边的挑战性的脑再灌注损伤。 像颅底这样的区域。 项目/施工现场（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