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

描述(申请人提供)：尽管最近在手术、放疗和化疗方面取得了进展，但恶性胶质瘤仍然普遍是致命的，胶质母细胞瘤的中位生存期为12-15个月，间变性星形细胞瘤的中位生存期为2-5年。神经成像的局限性使神经胶质瘤患者的临床治疗复杂化，并阻碍了新疗法的有效测试。酰胺质子转移成像(APT)是一种基于组织中内源性细胞蛋白产生图像对比度的新型分子磁共振成像技术。这个APT成像项目在第一个赠款期间(7/09-4/13)非常成功。我们开发了几种相对快速的3T和7T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，我们还证明了APT成像是MRI设备的一个非常有价值的补充，可以更具体地描述人脑肿瘤。值得注意的是，我们在不同的胶质瘤模型和辐射诱导的大鼠坏死模型上的临床前研究清楚地显示，活动性胶质瘤(高信号)和放射性坏死(低信号或等信号)显示相反的APT-MRI信号，因此很容易区分。这些临床前的结果是令人兴奋的，如果用适当的动力进行验证 在患者中的研究，对临床护理和实验疗法的影响将是巨大的。APT成像的最终目标是在临床环境中对不同供应商的各种MRI系统进行标准使用。然而，临床APT-MRI实验往往受到扫描仪硬件限制(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成像方案在不同的研究所之间差别很大，远远没有得到优化，而且从不同研究中心获得的结果很难相互比较。这一更新应用的总体目标是将这项重要的基于蛋白质的分子磁共振技术提炼成一种敏感、用户友好和临床可重复性的方法，并展示其帮助解决脑癌治疗中的几个诊断难题的潜力。根据前一批资助期的研究结果和该领域的最新进展，我们设计了以下三个具体目标：(1)在3T实现和优化基于并行射频传输(PTX)的APT-MRI技术；(2)评估APT-MRI在识别非Gd增强的高级别胶质瘤中的临床价值；(3)量化APT-MRI在区分放化疗治疗的GBM假性进展和真实进展方面的准确性。如果APT研究的这一步成功，这项研究将提供将这项重要的APT-MRI技术转化为临床所需的优化方法和关键的敏感性和特异性数据。

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.