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，非离子化和非化学毒性，有明确而紧迫的未满足的临床需求 脑肿瘤患者的治疗选择。该提议的长期目标是发展非 使用相移微泡磁共振引导聚焦的热消融（NTA） 超声（MRGFU）成一种新的非侵入性治疗选择，该选择将为脑癌患者提供 增加存活率和副作用增加。该应用程序的总体目的是（i）开发 基于新型磁共振成像（MRI）的方法，用于实时监测和非 - 热消融过程； （ii）在体内MRI中调整最近开发和验证的体素的验证 组织病理学的注册管道向大脑，并使用它来开发和验证成像生物标志物可以 急性预测长期组织不可变性。该项目的理由是一种无创的手段 实时监控，直接对治疗对感兴趣组织的影响进行成像，一起 了解非热感应的病变进展和长期组织的预测 对于促进非热MRGFU大脑消融的安全和及时翻译是必要的 大型动物模型的肿瘤，最终到诊所。我们将以两个具体的目标来实现这一目标。 1） 开发创新的基于MRI的方法，用于直接对非 - 非 - 热消融，并根据实时适用性和对急性检测病变的敏感性进行评估 大鼠脑肿瘤模型中的形成； 2）将MRI调整到组织病理学注册管道中，并将其使用 了解病变进展并开发成像生物标志物，以急性预测 长期组织不可变性。本申请中提出的研究是创新的，在申请人的 意见，因为它将开发敏感方法，以实时监测病变的进展 FUS非热消融，并将使用MRI到历史的注册管道来发展理解 关于病变进展和发展成像生物标志物以预测组织不可变性。最终，这本小说 非侵入性治疗方式有可能提供数以万计的患者 每年都有一个安全的治疗选择。