Development and Evaluation of Advanced Non-Contrast Perfusion MRI for Monitoring Treatment Response in Brain Metastases

项目摘要 脑转移瘤(BM)是最常见的中枢神经系统肿瘤类型，更多 比原发的颅内肿瘤更常见。在过去的几年里，各种疗法的进展都在加快。 十年来，通过正在进行的临床试验，BM患者的历史预后一直很差 明显改善。常规应用对比剂增强的T1加权MRI来描述大小为 增强病变用于评估治疗反应。血脑损伤所致的病变强化 屏障在脑肿瘤的功能中是相当非特异性的。研究最多的磁共振灌注成像方法 测量是动态磁化率对比灌注加权成像(DSC-PWI)，它测量 脑血流量(CBF)和脑血容量(CBV)。CBV是被广泛采用的血流灌注测量方法 肿瘤血管的敏感标记物。然而，它在骨髓研究中的临床适用性因其缺乏而受到阻碍。 绝对量化、对比度泄漏效应和频繁的敏感性伪影。动脉自旋标记 (ASL)是经常对肿瘤血管进行无创纵向监测的理想选择。标准化的空间 用于CBF定位的选择性ASL技术是使用单个后处理的伪连续ASL(PCASL)方法. 标记延迟，这可能会由于动脉血流缓慢导致的传输时间延迟而低估CBF 这在老年患者中很常见。为了消除时延敏感性，提出了速度选择性ASL(VSASL)。 我们的团队实现了第一个基于速度选择反演(VSI)的3D分段VSASL 与常规ASL方法相比，GRAS对灌注信号具有更高的敏感性。 此外，我们的团队首先通过消除标记延迟开发了基于VSASL的CBV映射，这提供了 比基于ASL的CBF标测的信噪比高得多。此外，我们的初步数据显示，VSASL 使用基于3D螺旋堆叠的闪光采集，可提供更好的灌注图像质量和更少的伪影 与使用GRASE相比，高时间分辨率可能允许足够的回溯运动校正。 本研究的目的是：目标1，对基于VSASL的CBF和CBV进行进一步的技术开发 使用加速采集的映射协议；目标2，评估两个优化的VSASL的敏感性 放射治疗后一个月内脑血流量和脑血流量变化的方案，并评估其早期预测 目的3，比较VSASL衍生的CBF和CBV值在 转移复发与辐射诱发效应的区别；目标4，以确保高重复性 不同厂商和场强的多台扫描仪之间的VSASL协议。通过填写 提出的AIMS、基于VSASL的CBF和CBV映射方法有望得到验证 监测BM治疗反应的重要价值，将随时可用于大规模临床研究， 并有助于对体内所有原发和转移肿瘤的研究。

Project Abstract Brain metastases (BM) are the most commonly diagnosed type of central nervous system tumor, more frequent than primary intracranial neoplasms. Progress on various therapies have accelerated over the past decade through ongoing clinical trials, and the historically poor outcomes for patients with BM have been markedly improved. Contrast-enhanced T1-weighted MRI is routinely applied to depict BM with the size of the enhanced lesions for assessing treatment response. Lesion enhancement due to the disruption of blood-brain barrier is rather nonspecific of the functions of brain tumors. The most studied MRI methodology for perfusion measurement is dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), which measures cerebral blood flow (CBF) and cerebral blood volume (CBV). CBV is the widely adopted perfusion measure as a sensitive marker of tumor vascularity. However, its clinical applicability in BM studies is hampered by its lack of absolute quantification, the contrast-leakage effect, and frequent susceptibility artifacts. Arterial spin labeling (ASL) is ideal for frequent non-invasive longitudinal monitoring of tumor vascularity. The standardized spatially selective ASL technique for CBF mapping is the pseudo-continuous ASL (PCASL) method using a single post- labeling delay, which may render underestimation of CBF due to transit time delay caused by slow arterial flow typical in elderly patients. Velocity-selective ASL (VSASL) was proposed to remove the time-delay sensitivity. Our group has implemented the first velocity-selective inversion (VSI) based VSASL with 3D segmented GRASE acquisition and demonstrated its higher sensitivity to perfusion signal over conventional ASL methods. Additionally, our group first developed VSASL based CBV mapping by removing labeling delay, which delivered much higher SNR than ASL based CBF mapping. Furthermore, our preliminary data showed that VSASL with 3D stack-of-spiral based FLASH acquisition delivered better perfusion image quality with less artifacts than using GRASE, and high temporal resolution potentially allowing adequate retrospective motion correction. The purpose of this study is: Aim 1, to conduct further technical developments for VSASL based CBF and CBV mapping protocols with accelerated acquisitions; Aim 2, to evaluate the sensitivity of the two optimized VSASL protocols to CBF and CBV changes within a month after the radiation therapy, and assess their early prediction to treatment outcomes; Aim 3, to compare the specificity of VSASL derived CBF and CBV values in the distinction of metastatic recurrence from radiation-induced effects; Aim 4, to ensure high reproducibility of the VSASL protocols between multiple scanners with different vendors and field strength. By completing the proposed aims, the advanced VSASL based CBF and CBV mapping methods are expected to demonstrate important values for monitoring treatment response in BM, will be readily available for large-scale clinical studies, and can benefit for studies of all primary and metastatic tumors in the body.