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

描述（由申请人提供）：尽管最近在手术、放疗和化疗方面取得了进展，恶性胶质瘤仍然普遍致命，胶质母细胞瘤的中位生存期为12-15个月，间变性星形细胞瘤为2-5年。神经影像学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。酰胺质子转移（APT）成像是一种基于组织中内源性细胞蛋白质产生图像对比度的新型分子MRI技术。这个APT成像项目在第一个资助期（7/09-4/13）非常成功。我们开发了几种相对快速的3 T和7 T三维APT成像序列，并建立了几种有效的图像采集协议和图像处理方法，用于人脑肿瘤的成像。此外，我们证明了APT成像是一个非常有价值的除了MRI设备更具体的表征人类脑肿瘤。值得注意的是，我们在各种胶质瘤模型和大鼠辐射诱导坏死模型中的临床前研究清楚地表明，活动性胶质瘤（高信号）和辐射坏死（低信号或等信号）表现出相反的APT-MRI信号，因此可以容易地区分。这些临床前结果是令人兴奋的，如果用适当的动力进行验证， 在患者中进行的研究，对临床护理和实验治疗的影响将是巨大的。APT成像的最终目标是其在临床环境中在不同供应商的各种MRI系统上的标准使用。然而，临床APT-MRI实验通常受到扫描仪硬件约束（特别是放大器占空比和脉冲长度）和比吸收率（SAR）要求的限制。因此，目前的APT成像协议在不同的研究所之间差异很大，远远没有得到优化，并且从不同的研究中心获得的结果很难相互比较。这项更新申请的总体目标是将这种重要的基于蛋白质的分子MRI技术改进为一种灵敏、用户友好和临床可重复的方法，并证明其有助于解决脑癌治疗中几个诊断难题的潜力。基于前期的研究成果和该领域的最新进展，我们设计了以下三个具体目标：（1）实现并优化基于并行射频传输（pTX）的3 T APT-MRI技术;（2）评价APT-MRI在非Gd增强高级别胶质瘤中的临床应用价值;（3）量化APT-MRI在区分放化疗后GBM假进展和真进展中的准确性。如果APT研究的这一步是成功的，这项研究将提供优化的方法和关键的灵敏度和特异性数据，将这一重要的APT-MRI技术转化为临床。

DESCRIPTION (provided by applicant): Despite recent advances in surgery, radiation, and chemotherapy, malignant gliomas remain universally fatal, with a median survival of 12-15 months for glioblastoma and 2-5 years for anaplastic astrocytoma. Limitations in neuroimaging complicate the clinical management of patients with gliomas, and impede efficient testing of new therapeutics. Amide proton transfer (APT) imaging is a novel molecular MRI technique that generates image contrast based on the endogenous cellular proteins in tissue. This APT imaging project has been extremely successful during the first grant period (7/09-4/13). We developed several relatively fast three- dimensional APT imaging sequences at 3T and 7T and established several effective image acquisition protocols and image processing approaches for imaging of human brain tumors. In addition, we demonstrated that APT imaging is a highly valuable addition to the MRI armamentarium for the more specific characterization of human brain tumors. Notably, our preclinical study in various glioma models and models of radiation- induced necrosis in rats clearly showed that active glioma (hyperintense) and radiation necrosis (hypointense or isointense) exhibited opposite APT-MRI signals, and could thus readily be distinguished. These preclinical results are exciting, and, if validated with appropriately powered studies in patients, the implications for clinical care and experimental therapeutics will be enormous. The ultimate goal for APT imaging is its standard use in a clinical setting on a variety of MRI systems from different vendors. However, clinical APT-MRI experiments are often limited by scanner hardware constraints (particularly amplifier duty cycle and pulse length) and specific absorption rate (SAR) requirements. Therefore, current APT imaging protocols vary substantially among different institutes, far from being optimized, and the results acquired from different research centers are difficult to compare to one another. The overall goals of this renewal application are to refine this important protein-based molecular MRI technology into a sensitive, user-friendly, and clinically reproducible approach and to demonstrate its potential to help resolve several diagnostic dilemmas in brain cancer therapy. Based on the results obtained in the previous grant period and recent progress in the field, we have designed the following three specific aims: (1) implement and optimize the parallel RF transmission (pTX)-based APT-MRI technique at 3T; (2) evaluate the clinical value of APT-MRI in identifying non-Gd-enhancing high-grade gliomas; and (3) quantify the accuracy of APT-MRI in distinguishing pseudoprogression from true tumor progression in GBM treated with chemoradiation therapy. If this step of the APT investigation is successful, this research will provide the optimized approaches and critical sensitivity and specificity data required to translate this important APT-MRI technology into the clinic.