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

摘要 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存在， 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。 神经影像学的局限性使胶质瘤患者的临床治疗复杂化， 新疗法的测试。酰胺质子转移（APT）成像是一种新的分子MRI技术， 基于组织中的内源性细胞蛋白生成图像对比度。这个APT成像项目 在第一次赠款期间（7/09-4/13）取得了极大的成功。我们开发了几个比较快的三- 在3 T和7 T的三维APT成像序列，并建立了几个有效的图像采集 用于人脑肿瘤成像的协议和图像处理方法。此外，我们还展示了 APT成像是MRI设备的一个非常有价值的补充，用于更具体的表征 人类脑肿瘤。值得注意的是，我们在各种胶质瘤模型和放射模型中的临床前研究- 大鼠的诱导坏死清楚地显示，活动性胶质瘤（高信号）和放射性坏死（低信号 或等强度）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，如果在患者中进行适当的研究， 护理和实验性治疗将是巨大的。APT成像的最终目标是其标准用途， 来自不同供应商的各种MRI系统的临床设置。然而，临床APT-MRI实验 通常受到扫描器硬件约束（特别是放大器占空比和脉冲长度）的限制， 比吸收率（SAR）要求。因此，当前的APT成像协议差异很大 不同研究所之间，远未优化，以及从不同研究中心获得的结果 很难相互比较。此更新应用程序的总体目标是完善这一重要的 将基于蛋白质的分子MRI技术转化为灵敏、用户友好和临床可重复的方法 并展示其帮助解决脑癌治疗中几个诊断难题的潜力。基于 根据上一个资助期取得的成果和该领域的最新进展，我们设计了 实现并优化基于并行射频传输（pTX）的APT-MRI （2）评价APT-MRI对非Gd强化的高级别MRI的临床应用价值 定量分析APT-MRI在鉴别假进展和真肿瘤中的准确性 放化疗治疗GBM的进展。如果APT调查的这一步成功， 研究将提供翻译所需的优化方法和关键的灵敏度和特异性数据， 这一重要的APT-MRI技术应用于临床。

ABSTRACT 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.