Amide Proton Transfer (APT) MRI of Brain Tumors at 3T and 7T

描述（由申请人提供）：恶性脑肿瘤仍然是最致命的癌症形式之一，尽管最大的手术干预，放射治疗和化疗。神经影像学技术的局限性使神经胶质瘤患者的临床管理复杂化，并阻碍了新疗法的有效测试。最近，我们设计了一种新的磁化转移为基础的MRI技术，被称为酰胺质子转移（APT）成像，检测各种内源性移动的蛋白质和肽，如那些在细胞质中的酰胺质子。我们的临床前研究和试点临床数据，使用单层采集表明，APT可以提供独特的信息，脑肿瘤的存在和等级的基础上增加细胞的蛋白质和肽的含量，如MRI引导的蛋白质组学和体内MR光谱。然而，许多技术问题必须解决之前，这项技术可以可靠地应用于全脑成像在临床设置。本提案的总体目标是开发一种用于临床的快速全脑APT方法，并评估与标准MRI序列相比，APT提供有关胶质瘤异质部分的独特视觉数据的能力。为了实现这一目标，我们在国家脑癌计划的框架内组建了一个由基础科学家和临床医生组成的多学科团队，每个人都将在物理学，生物统计学，肿瘤学，神经外科学，病理学和神经放射学领域贡献自己的专业知识。我们的具体目标是：（1）开发用于临床应用的3 T下的时间有效的全脑APT成像技术，（2）通过区分肿瘤核心与瘤周水肿和低级别与高级别胶质瘤来确定3 T下的APT成像在评估异质性脑肿瘤中的灵敏度和特异性，（3）使用APT图像引导的活检来探索脑肿瘤的APT对比度的来源以允许组织学验证，（4）探讨7 T APT成像的可行性和最佳成像质量。这项工作有可能产生一种临床适用的新MRI技术，该技术在蛋白质和肽水平上成像组织的能力是独一无二的。这可能会提高脑MRI对恶性胶质瘤的诊断准确性，并可能提高其他脑疾病的诊断准确性，因此具有巨大的临床意义。公共卫生相关性：该项目的目标是开发一种新的基于蛋白质和肽的MRI技术，称为酰胺质子转移（APT）成像，并确定APT成像检测脑肿瘤的灵敏度和特异性。APT-MRI可提高恶性胶质瘤的诊断和手术治疗的准确性。

DESCRIPTION (provided by applicant): Malignant brain tumors remain one of the deadliest forms of cancer despite maximal surgical intervention, radiation therapy and chemotherapy. Limitations in neuroimaging technology complicate the clinical management of patients with gliomas and impede efficient testing of new therapeutics. Recently, we have designed a new magnetization transfer-based MRI technique, dubbed amide proton transfer (APT) imaging, that detects a variety of amide protons of endogenous mobile proteins and peptides, such as those in the cytoplasm. Our preclinical studies and pilot clinical data using single-slice acquisition suggest that APT may provide unique information about the presence and grade of brain tumors based on increased cellular content of proteins and peptides, as revealed by MRI-guided proteomics and in vivo MR spectroscopy. However, many technical problems have to be resolved before this technique can be applied reliably for whole-brain imaging in a clinical setting. The overall goals of this proposal are to develop a fast whole-brain APT methodology for use in the clinic and to assess the capability for APT to provide unique visual data about heterogeneous portions of gliomas when compared to standard MRI sequences. To achieve this goal, we have assembled a multidisciplinary team of basic scientists and clinicians, within the framework of a national brain cancer program, who will each contribute their particular expertise in the fields of physics, biostatistics, oncology, neurosurgery, pathology, and neuroradiology. Our specific aims are: (1) Develop a time-efficient whole-brain APT imaging technique at 3T for clinical application, (2) Determine the sensitivity and specificity of APT imaging at 3T in evaluating heterogeneous brain tumors by distinguishing tumor core from peritumoral edema and low- from high-grade gliomas, (3) Explore the origin of the APT contrast for brain tumors using APT-image guided biopsy to allow histologic validation, and (4) explore the feasibility and optimal quality of APT imaging at 7T. This work has the potential to yield a clinically applicable new MRI technique that is unique in its ability to image tissue at the protein and peptide level. This may improve the diagnostic accuracy of brain MRI for malignant gliomas and, potentially, other diseases of the brain and, hence, is of enormous clinical importance. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a novel protein and peptide-based MRI technique, called amide proton transfer (APT) imaging, and to determine the sensitivity and specificity of APT imaging for the detection of brain tumors. APT-MRI may improve the diagnostic and surgical accuracy in treating malignant gliomas.