Amide Proton Transfer (APT) MRI of Brain Tumors at 3T

3T 脑肿瘤酰胺质子转移 (APT) MRI

• 批准号: 10063492
• 负责人: JINYUAN ZHOU
• 金额: $ 38.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063492
• 关键词: 3-Dimensional; Amides; Area; Biological; Biopsy; Blood - brain barrier anatomy; Brain Neoplasms; Cellularity; Central Nervous System Neoplasms; Classification; Clinical; Clinical Data; Complex; Contralateral; Development; Diagnosis; Diagnostic radiologic examination; Disease; Excision; Exhibits; FDA approved; Funding; Gadolinium; Genetic; Genetic Markers; Glioblastoma; Glioma; Goals; Heterogeneity; Histology; Image; Imaging Techniques; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Methodology; Methods; Molecular; Molecular Diagnosis; Mutation; Neuraxis; Neurosurgical Procedures; Operative Surgical Procedures; Patients; Primary Brain Neoplasms; Prognosis; Proteins; Protocols documentation; Protons; Radiation therapy; Recurrence; Reproducibility; Research; Research Methodology; Retrospective Studies; Sampling; Signal Transduction; Technology; Therapeutic; Time; Tumor Burden; Variant; base; brain tissue; cancer diagnosis; cancer therapy; chemotherapy; clinical application; design; high risk; image guided; imaging biomarker; molecular marker; molecular phenotype; mutant; mutational status; neuro-oncology; neuroimaging; neurosurgery; novel therapeutics; tumor; tumorigenesis; user-friendly

ABSTRACT Gliomas, the most common primary brain tumors, are biologically complex and exhibit substantial molecular and phenotypic spatial variation. A major obstacle in both the daily management of patients with gliomas, and in the development of new therapies for these cancers, is the inability of neuroimaging to accurately define the tumor burden. Specifically, gadolinium (Gd) enhancement reveals focal areas of malignant gliomas where the blood-brain barrier (BBB) is disrupted, but it does not show large high-risk areas of infiltrating tumor with a high cellularity. The recent breakthrough in the understanding of genetic features in gliomas, such as isocitrate dehydrogenase (IDH) mutations, has resulted in a prompt reappraisal of the molecular oncogenesis of this group of diseases. Notably, the most recent 2016 WHO classification of CNS tumors uses molecular parameters, in addition to histology, to define tumor entities. The 2016 CNS WHO represents an unmet radiographic need, namely, the identification of genetic biomarkers preoperatively, with non-invasive methods such as MRI. This project has been very successful during the 2nd funding period (9/13- 7/17) in developing an important protein-based molecular MRI technology, called amide proton transfer- weighted (APTw) imaging, into a sensitive, user-friendly, and reproducible approach for routine clinical use. Numerous early clinical data have demonstrated that APTw imaging adds important value to the standard clinical MRI sequences in brain cancer diagnosis. Compared to the contralateral normal-appearing brain tissue, the conspicuous, highly reproducible APTw hyperintensity can always be visualized in high-grade gliomas (including those without Gd enhancement). Thus, APTw imaging allowed accurate identification of high-grade regions within heterogeneous gliomas—a core need during neurosurgical procedures. Notably, we have recently found that the APTw signal could be a valuable imaging biomarker by which to identify IDH mutation status in low-grade gliomas. These early findings are very exciting. However, all currently used imaging protocols are essentially not quantitative, and the images obtained are often called APT-weighted images because of other contributions. The overall goals of this renewal application are to develop highly sensitive, fast, and quantitative APT-MRI methodologies on 3T clinical MRI scanners and to evaluate the potential of these methodologies in brain cancer molecular diagnosis. We have designed the following specific aims: (i) develop quantitative APT-MRI methodologies using compressed sensing at 3T; (ii) determine the capability of APT-MRI for the prediction of IDH mutation status in grade-II gliomas; and (iii) determine the accuracy of APT-MRI for the identification of high-risk regions of tumor outside Gd-enhancing masses in patients with glioblastomas. If successful, our results will significantly push, to a whole new level, the APT-MRI methodology research and clinical applications for brain tumors.

抽象的 神经胶质瘤是最常见的原发性脑肿瘤，其生物学结构复杂，并且表现出大量的 分子和表型空间变异。成为患者日常管理的主要障碍 神经胶质瘤以及这些癌症的新疗法的开发中，神经影像学无法 准确定义肿瘤负荷。具体来说，钆 (Gd) 增强揭示了 血脑屏障 (BBB) 被破坏的恶性胶质瘤，但未显示大的高风险区域 具有高细胞结构的浸润性肿瘤。最近对基因特征的理解取得了突破 神经胶质瘤，例如异柠檬酸脱氢酶（IDH）突变，导致了对神经胶质瘤的迅速重新评估 这组疾病的分子肿瘤发生。值得注意的是，最新的 2016 年 WHO 中枢神经系统分类 除了组织学之外，肿瘤还使用分子参数来定义肿瘤实体。 2016年中枢神经系统世界卫生组织 代表了未满足的放射照相需求，即术前识别遗传生物标志物， 非侵入性方法，例如 MRI。该项目在第二期资助期间（9/13- 7/17）开发一种重要的基于蛋白质的分子 MRI 技术，称为酰胺质子转移 - 加权 (APTw) 成像，成为一种敏感、用户友好且可重复的常规临床使用方法。 大量早期临床数据表明 APTw 成像为标准增加了重要价值 脑癌诊断中的临床 MRI 序列。与对侧正常的大脑相比 在组织中，显着的、高度可重复的 APTw 高信号始终可以在高等级中显现出来。 神经胶质瘤（包括那些没有 Gd 增强的神经胶质瘤）。因此，APTw 成像可以准确识别 异质胶质瘤内的高级别区域——神经外科手术过程中的核心需求。值得注意的是，我们 最近发现 APTw 信号可能是一种有价值的成像生物标志物，可用于识别 IDH 低级别胶质瘤的突变状态。这些早期发现非常令人兴奋。然而目前使用的都是 成像协议本质上不是定量的，获得的图像通常称为 APT 加权 由于其他贡献而产生的图像。此更新应用程序的总体目标是开发高度 在 3T 临床 MRI 扫描仪上建立灵敏、快速、定量的 APT-MRI 方法，并评估 这些方法在脑癌分子诊断中的潜力。我们具体设计了如下 目标：(i) 使用 3T 压缩感知开发定量 APT-MRI 方法； (ii) 确定 APT-MRI 预测 II 级胶质瘤 IDH 突变状态的能力； (iii) 确定 APT-MRI 识别 Gd 增强肿块外肿瘤高风险区域的准确性 胶质母细胞瘤患者。如果成功，我们的结果将显着将 APT-MRI 推向一个全新的水平 脑肿瘤的方法学研究和临床应用。