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

描述(申请人提供)：尽管进行了最大限度的手术治疗、放射治疗和化疗，但恶性脑瘤仍然是最致命的癌症形式之一。神经成像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基于磁化转移的磁共振成像技术，称为酰胺质子转移(APT)成像，它可以检测内源可移动蛋白和肽的各种酰胺质子，例如细胞质中的那些。我们的临床前研究和使用单层切片采集的初步临床数据表明，APT可能提供关于脑肿瘤存在和分级的独特信息，其基础是MRI引导的蛋白质组学和活体磁共振波谱揭示的细胞内蛋白质和多肽含量的增加。然而，在这项技术能够可靠地应用于临床全脑成像之前，还有许多技术问题需要解决。这项建议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APT与标准MRI序列相比提供关于胶质瘤不同部位的独特视觉数据的能力。为了实现这一目标，我们组建了一个由基础科学家和临床医生组成的多学科团队，在国家脑癌计划的框架内，他们将各自贡献他们在物理学、生物统计学、肿瘤学、神经外科、病理学和神经放射学领域的独特专业知识。我们的具体目标是：(1)开发一种及时有效的3T全脑APT成像技术用于临床应用；(2)通过区分肿瘤核心与瘤周水肿以及低级别与高级别胶质瘤，确定APT成像在评估异质性脑肿瘤中的敏感性和特异性；(3)利用APT图像引导下的活检来探索脑肿瘤APT对比度的来源，以便进行组织学验证；(4)探讨7T APT成像的可行性和最佳质量。这项工作有可能产生一种临床适用的新MRI技术，这种技术在蛋白质和多肽水平上对组织进行成像的能力是独特的。这可能会提高脑MRI对恶性胶质瘤以及潜在的其他脑部疾病的诊断准确性，因此具有巨大的临床重要性。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多肽的磁共振成像技术，称为酰胺质子转移(APT)成像，并确定APT成像检测脑肿瘤的敏感性和特异性。APT-MRI可提高恶性胶质瘤的诊断和手术准确性。

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.