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

摘要 胶质瘤是最常见的脑部原发肿瘤，其生物学特性复杂，表现为实质性的肿瘤。 分子和表型的空间变异。这是患者日常管理的一个主要障碍 神经胶质瘤，以及对这些癌症的新疗法的开发，是神经成像无法 准确界定肿瘤负担。特别是，Gd(Gd)增强显示了 恶性胶质瘤，血脑屏障(BBB)被破坏，但没有显示大片高危区域 高细胞性的浸润性肿瘤。中国人对遗传特征认识的最新突破 胶质瘤，如异柠檬酸脱氢酶(IDH)突变，已导致迅速重新评估 这类疾病的分子致癌作用。值得注意的是，2016年世卫组织对中枢神经系统的最新分类 除组织学外，肿瘤还使用分子参数来定义肿瘤实体。2016年世界卫生组织CNS 代表未得到满足的放射学需求，即术前识别遗传生物标记物， 核磁共振等非侵入性方法。该项目在第二个资助期内非常成功(9/13- 7/17)在开发一种重要的基于蛋白质的分子磁共振技术，称为酰胺质子转移- 将加权(APTw)成像转变为一种灵敏、用户友好且可重复性的常规临床使用方法。 大量的早期临床数据表明，APTw成像增加了标准的重要价值。 临床MRI序列在脑癌诊断中的应用与对侧外观正常的大脑相比 组织，明显的，高度可重复性的APTw高信号总是可以在高级别 胶质瘤(包括无Gd增强的)。因此，APTw成像可以准确地识别 异质性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信号可能是识别IDH的一个有价值的成像生物标记物 低级别胶质瘤的突变状态。这些早期的发现非常令人兴奋。然而，目前使用的所有 成像方案本质上不是定量的，所获得的图像通常被称为APT加权 图像，因为其他贡献。本次续订申请的总体目标是高度发展 灵敏、快速、定量的APT-MRI方法在3T临床MRI扫描仪上的应用 这些方法在脑癌分子诊断中的潜力。我们设计了以下具体的 目标：(I)利用3T压缩传感技术开发定量APT-MRI方法；(Ii)确定 APT-MRI预测II级胶质瘤IDH突变状态的能力；以及(Iii)确定 APT-MRI对Gd增强肿块外肿瘤高危区域识别的准确性 胶质母细胞瘤患者。如果成功，我们的结果将把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。

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.