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: 10390856
• 负责人: ALEXANDRA J GOLBY
• 金额: $ 73.08万
• 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 2027-05-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390856
• 关键词: Adult; Anisotropy; Area; Biopsy; Brain; Brain Neoplasms; Brain imaging; Cell Density; Cell Size; Cells; Clinical; Clinical Treatment; Data; Data Set; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Discrimination; Drug Delivery Systems; Environment; 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; Time; Tissue Sample; Tissues; Translating; Tumor Tissue; Uncertainty; Validation; Water; Work; base; brain parenchyma; brain tissue; chemotherapy; clinical application; clinical imaging; design; digital; human subject; imaging modality; improved; in vivo; meetings; mouse model; neoplastic cell; neuroimaging; 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.

抽象的 我们建议研究和验证新型 MRI 脉冲序列和用于绘图的定量测量 原发性脑肿瘤边缘和浸润。我们将重点关注胶质母细胞瘤（W.H.O. IV 级胶质瘤 (GBM)）， 成人中最常见和致命的原发性脑肿瘤。这些进行性脑肿瘤浸润到 脑实质并以弥漫性边缘生长。然而，当前的临床成像方式无法可靠地 确定神经胶质瘤浸润的程度，对患者护理产生负面影响。神经外科医生面临着不确定的问题 计划最佳切除术时应切除哪些组织，以及放射肿瘤学家 必须根据对肿瘤范围的不完全了解来设计放射野。因此，有一个 对患者特异性、个性化的肿瘤边缘绘图（包括放射学范围内的内容）的需求尚未得到满足 使用当前最先进的成像技术以及超越它的技术来明确定义边缘），以改善临床 通过手术、放射治疗或药物输送等方法治疗神经胶质瘤。满足这一未满足的需求 需要改进大脑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 MRI 测量不同方向之间水分子运动的相关性，改善组织绘图 和肿瘤微观结构。最近的工作还证明了定量 MRI（T2-relaxome- 尝试）用于检测神经胶质瘤瘤周区域的浸润性肿瘤生长。事实上，不同的联合分布 融合松弛措施可以提供独立获取的 T2-re- 中缺失的重要信息 单独的松弛测量或 QTI 数据。在这个项目中，我们计划开发、研究和验证 rQTI（一种新型组合） T2 松弛测量和 QTI 的国家）用于神经胶质瘤边缘和浸润标测的关键临床应用。 为了实现这一目标，首先我们将创建全面且独特的扩散弛豫（rQTI）和组织学 用于研究神经胶质瘤浸润和边缘的数据集。这项工作将利用小鼠模型，我们将在其中 植入从人类 GBM 获得的患者来源的异种移植物，以密切重现人类的关键特征 脑肿瘤的微观结构和浸润等。其次，我们将开发优化的临床采集 用于计算基于 rQTI 的微观结构测量，可预测组织学，在 10 分钟内进行 询问时间。第三，我们将在 30 名患者中针对组织病理学验证基于 rQTI 的微观结构测量 与GBM。将使用优化的 rQTI 序列对患者进行扫描，并通过以下方式获取组织样本： 临床指示的组织立体定向取样和/或立体定向活检。 总的来说，这项研究的成功结果有可能改善 GBM 的非侵入性绘图 边缘并揭示以前在成像中看不见的浸润。预计这将提供重要的 GBM 治疗计划的信息，有可能提高患者的生存率和生活质量。