Quantitative Glioblastoma Margin and Infiltration Mapping with advanced diffusion-relaxation MRI

使用先进的扩散弛豫 MRI 定量胶质母细胞瘤边缘和浸润图

• 批准号: 10677545
• 负责人: ALEXANDRA J GOLBY
• 金额: $ 73.07万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677545
• 关键词: Adult; Anisotropy; Area; Biopsy; Brain; Brain Neoplasms; Brain imaging; Cell Density; Cell Size; Cells; Chemotherapy and/or radiation; Clinical; Clinical Treatment; Data; Data Set; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Discrimination; Drug Delivery Systems; Excision; Glioblastoma; Glioma; Goals; Histologic; Histology; Histopathology; Human; Image; Implant; Infiltration; Joints; Magnetic Resonance Imaging; Maps; Measures; Methods; Microscopic; Modeling; Motion; Mus; Neurosurgeon; Operative Surgical Procedures; Outcome Study; Patient Care; Patients; Phenotype; Physiologic pulse; Price; Primary Brain Neoplasms; Quality of life; Radiation; Radiation Oncologist; Radiation therapy; Radiology Specialty; Relaxation; Scanning; Shapes; Structure; Time; Tissue Sample; Tissues; Translating; Tumor Tissue; Uncertainty; Validation; Water; Work; brain parenchyma; brain tissue; chemotherapy; clinical application; clinical imaging; design; digital; human subject; imaging modality; improved; in vivo; meetings; mouse model; neoplastic cell; neuroimaging; neurosurgery; novel; patient derived xenograft model; pre-clinical; success; tissue mapping; treatment planning; tumor; tumor growth

Abstract We propose to investigate and validate novel MRI pulse sequences and quantitative measures for mapping primary brain tumor margins and infiltration. We will focus on glioblastomas (W.H.O. grade IV gliomas (GBM)), the most prevalent and deadly primary brain tumor in adults. These progressive brain tumors infiltrate into the brain parenchyma and grow with diffuse margins. However, current clinical imaging modalities fail to reliably define the extent of glioma infiltration, negatively impacting patient care. Neurosurgeons are faced with uncer- tainty about what tissue should be removed when planning an optimal resection, and radiation oncologists must design radiation fields based on an incomplete understanding of the tumor's extent. Therefore, there is an unmet need for patient-specific, personalized mapping of tumor margins (including what is within the radiologi- cally defined margin using current state-of-the-art imaging and what is beyond it) in order to improve clinical treatment of gliomas via methods such as surgery, radiation therapy, or drug delivery. Meeting this unmet need requires improved imaging of brain and tumor tissue microstructure. We recently proposed q-space trajectory imaging (QTI), which goes beyond conventional diffusion MRI to measure the correlation of water molecule motion between different directions, improving mapping of tissue and tumor microstructure. Recent work has also demonstrated the potential of quantitative MRI (T2-relaxome- try) for detecting infiltrative tumor growth in the peritumoral area of gliomas. In fact, the joint distribution of dif- fusion-relaxation measures can provide important information that is missing in independently acquired T2-re- laxometry or QTI data alone. In this project, we plan to develop, investigate, and validate rQTI (a novel combi- nation of T2-relaxometry and QTI) for the critical clinical application of glioma margin and infiltration mapping. To reach this goal, first we will create a comprehensive and unique diffusion-relaxation (rQTI) and histology dataset for the study of glioma infiltration and margins. This work will leverage a mouse model in which we will implant patient-derived xenografts obtained from human GBMs to closely recapitulate key features of human brain tumors such as microstructure and infiltration. Second, we will develop an optimized clinical acquisition for computing rQTI-based microstructure measures that are predictive of histology, in under 10 minutes of ac- quisition time. Third, we will validate rQTI-based microstructure measures against histopathology in 30 patients with GBM. Patients will be scanned with the optimized rQTI sequence and tissue samples will be obtained us- ing clinically indicated stereotactic sampling of tissue and/or stereotactic biopsy. Overall, the successful outcome of this study has the potential to improve non-invasive mapping of GBM margins and to reveal infiltration that was previously invisible on imaging. This is expected to provide important information for GBM treatment planning, with the potential of improving patient survival and quality of life.

摘要 我们建议研究和验证新的MRI脉冲序列和用于标测的定量方法 原发性脑肿瘤的边缘和浸润性。我们将重点关注胶质母细胞瘤(WHO IV级胶质瘤(GBM))， 成人中最常见和最致命的原发脑瘤。这些进行性脑瘤渗入到 脑实质，并随着弥漫边缘生长。然而，目前的临床成像方式不能可靠地 明确胶质瘤的浸润性程度，对患者的护理产生负面影响。神经外科医生正面临着无法- 计划最佳切除时应切除哪些组织的污点，以及放射肿瘤学家 必须基于对肿瘤范围的不完全了解来设计辐射场。因此，有一个 尚未满足的特定于患者的个性化肿瘤边缘测绘需求(包括放射学范围内的内容) 使用当前最先进的成像技术和超越它的技术来计算定义的边缘)，以改善临床 通过手术、放射治疗或药物输送等方法治疗胶质瘤。满足这一未得到满足的需求 需要改进脑部和肿瘤组织微观结构的成像。 我们最近提出了q空间轨迹成像(Qti)，它超越了传统的扩散磁共振成像。 测量水分子在不同方向之间运动的相关性，改进组织图谱 和肿瘤的微观结构。最近的工作也证明了定量MRI(T2-松弛-核磁共振)的潜力 Try)用于检测胶质瘤瘤周区域的浸润性肿瘤生长。事实上，DIF的联合分布-- 融合松弛措施可以提供独立获得的T2-Re序列中缺失的重要信息。 松弛计量法或QTI数据。在这个项目中，我们计划开发、调查和验证rQTI(一种新的组合--RQTI)。 国家T2-松弛计量学和QTI)的关键临床应用胶质瘤边缘和浸润图。 为了达到这一目标，首先我们将创建一个全面和独特的扩散-松弛(RQTI)和组织学 用于研究胶质瘤浸润性和边缘的数据集。这项工作将利用一个老鼠模型，在这个模型中，我们将 从人的基底膜中植入患者来源的异种移植物，以准确概括人类的关键特征 脑肿瘤等微结构和浸润性改变。第二，我们将开发优化的临床采购 用于计算可预测组织学的基于rQTI的微结构测量，在不到10分钟的Ac. 问答时间到了。第三，我们将在30名患者中验证基于rQTI的微结构测量与组织病理学的对照。 使用GBM。患者将用优化的rQTI序列进行扫描，并将获得组织样本。 ING临床指征为立体定向组织取样和/或立体定向活检。 总体而言，这项研究的成功结果有可能改进GBM的非侵入性标测 边缘和揭示以前在成像上看不见的渗透。预计这将提供重要的 为GBM治疗计划提供信息，具有改善患者生存和生活质量的潜力。