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

磁共振引导聚焦超声介导脑肿瘤非热消融的实时监测和治疗评估

• 批准号: 10659248
• 负责人: Henrik Carl Axel Odeen
• 金额: $ 18.73万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10659248
• 关键词: Ablation; Acceleration; Acoustics; Acute; Aftercare; Animal Model; Biological Markers; Brain; Brain Neoplasms; Cancer Patient; Cause of Death; Central Nervous System Neoplasms; Cephalic; Clinic; Clinical; Clinical Trials; Data; Detection; Diagnosis; Diffusion; Emerging Technologies; Ensure; Erythrocytes; Evaluation; Extravasation; Focused Ultrasound; Focused Ultrasound Therapy; Goals; Histology; Histopathology; Hour; Image; Ischemic Stroke; Knowledge; Lesion; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Mediating; Methods; Microbubbles; Modality; Modeling; Monitor; Morbidity - disease rate; Movement Disorders; Operative Surgical Procedures; Patients; Persons; Phase; Physiologic pulse; Predisposition; Primary Brain Neoplasms; Process; Quality of life; Radiation Dose Unit; Radiation therapy; Rattus; Research; Scalp structure; Spinal Neoplasms; Structure; Survival Rate; System; Thermal Ablation Therapy; Thermometry; Time; Tissues; Toxic effect; Translations; Ultrasonics; United States; bone; brain tissue; chemotherapy; cost effective; cranium; imaging biomarker; imaging detection; imaging modality; improved; in vivo; innovation; interest; magnetic resonance imaging biomarker; nervous system disorder; novel; pre-clinical; pressure; psychologic; real time monitoring; side effect; tool; transmission process; treatment effect; tumor; ultrasound

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.

对于非侵入性、非电离和非化学毒性的药物存在明确而紧迫的未满足的临床需求 脑肿瘤患者的治疗选择。该提案的长期目标是发展非 使用相移微泡辅助磁共振引导聚焦的热消融 (NTA) 超声波（MRgFUS）成为一种新的非侵入性治疗选择，将为脑癌患者提供 提高存活率并减少副作用。该应用程序的总体目标是 (i) 开发 基于磁共振成像 (MRI) 的新颖方法，用于实时监测和指导非 热烧蚀工艺； (ii) 采用最近开发和验证的体素体内 MRI 来 组织病理学注册管道到大脑，并用它来开发和验证成像生物标志物，可以 敏锐地预测长期组织无活力。该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 全面了解非热诱导病变进展和长期组织预测 非存活对于促进非热 MRgFUS 脑消融的安全和及时转化是必要的 肿瘤到大型动物模型并最终进入临床。我们将通过两个具体目标来实现这一目标； 1） 开发基于 MRI 的创新方法，用于在非手术期间直接实时监测感兴趣的组织 热消融，并根据实时适用性和敏锐检测病变的灵敏度对其进行评估 大鼠脑肿瘤模型中的形成； 2) 使 MRI 适应组织病理学配准流程，并用它来 了解病变进展并开发用于急性预测的成像生物标志物 长期组织无活力。本申请提出的研究具有创新性，在申请人的 意见，因为它将开发实时监测病变进展的敏感方法 FUS 非热消融，并将使用 MRI 到组织学配准流程来加深理解 关于病变进展并开发成像生物标志物来预测组织无活力。最终，这部小说 非侵入性治疗方式有可能为数以万计的确诊患者提供治疗 每年都有一种安全有效的治疗方案来治疗脑肿瘤。