Real-time monitoring and treatment evaluation of MR guided focal ultrasound-mediated non-thermal ablation of brain tumors

临床上对非侵入性、非电离性和非化学毒性的需求明显而迫切，尚未得到满足。 脑瘤患者的治疗选择。这项提议的长期目标是发展非 相移微泡辅助磁共振引导聚焦热消融 超声(MRgFUS)成为一种新的非侵入性治疗选择，将为脑癌患者提供 提高存活率，减少副作用。此应用程序的总体目标是(I)开发 基于磁共振成像(MRI)的非脑血管疾病实时监测和引导新方法 热消融过程；以及(Ii)使最近开发和验证的体内体素磁共振成像 组织病理学注册管道到大脑，并使用它来开发和验证成像生物标记物，可以 敏锐地预测组织长期无法存活。这个项目的基本原理是一种非侵入性的手段 实时监测，直接成像治疗对感兴趣组织的影响，以及 深入了解非热损伤的进展和对长期组织的预测 无生存能力是促进安全和及时的非热MRgFUS脑消融术的必要条件 肿瘤到大型动物模型，最终到临床。我们将通过两个具体目标实现这一目标：1) 开发基于MRI的创新方法，用于在非 热消融，并根据实时适用性和敏感度对其进行评估 在大鼠脑瘤模型中形成；2)使MRI适应组织病理学配准管道并使用它 了解病变进展并开发用于急性预测的成像生物标记物 组织长期无法存活。这项申请中提出的研究是创新的，在申请人的 意见，因为它将开发敏感的方法，实时监测病变进展 FUS非热消融，并将使用MRI到组织学的注册管道来发展理解 关于病变进展，并开发成像生物标记物来预测组织死亡。最终，这部小说 非侵入性治疗方式有可能为数以万计的患者提供诊断 与脑瘤每年都有一个安全有效的治疗选择。

There is a clear and urgent unmet clinical need for non-invasive, non-ionizing and non-chemo-toxic treatment options for patients with brain tumors. The long-term goal of this proposal is to develop non- thermal ablation (NTA) using phase shift microbubble-aided Magnetic Resonance guided Focused Ultrasound (MRgFUS) into a new non-invasive treatment option that will provide brain cancer patients with increased survival rates and decreased side effects. The overall objective of this application is to (i) develop novel Magnetic Resonance Imaging (MRI) based methods for real-time monitoring and guidance of the non- thermal ablation process; and (ii) adapt a recently developed and validated voxel-wise in vivo MRI to histopathology registration pipeline to brains, and use it to develop and verify imaging biomarkers which can acutely predict long-term tissue non-viability. The rationale for this project is that a means for non-invasive real-time monitoring which directly image the effect of the treatment on the tissue of interest, together with a thorough understanding of non-thermally induced lesion progression and prediction of long-term tissue nonviability are necessary to facilitate safe and timely translation of non-thermal MRgFUS ablation of brain tumors to large animal models and ultimately to the clinic. We will achieve this in two specific aims; 1) Develop innovative MRI-based approaches for direct real-time monitoring of tissue of interest during non- thermal ablation, and evaluate them based on real-time applicability and sensitivity to acutely detect lesion formation in a rat brain tumor model; 2) Adapt an MRI to histopathology registration pipeline and use it to gain understanding about lesion progression and to develop imaging biomarkers for acute prediction of long-term tissue non-viability. The research proposed in this application is innovative, in the applicant’s opinion, because it will develop sensitive approaches for real-time monitoring of the lesion progression of FUS non-thermal ablation, and will use a MRI-to-histology registration pipeline to develop understanding about lesion progression and develop imaging biomarkers to predict tissue nonviability. Ultimately, this novel non-invasive treatment modality has the potential to provide the tens of thousands of patients diagnosed with brain tumors each year with a safe an efficient treatment option.