Blood Flow MRI for Monitoring Glioma Angiogenesis

描述（由申请人提供）：阻断新的肿瘤血管生成或血管生成，通过限制血液中携带的营养物质的供应而使肿瘤饥饿。抗血管生成是一种很有前途的肿瘤学新方法，但临床试验表明，不同学科间的反应差异很大。胶质瘤是一种常见的侵袭性脑肿瘤，耐药血管生成和肿瘤细胞侵入血液供应正常的周围组织可能是导致抗血管生成治疗失败的原因。我们建议使用无创磁共振成像（MRI）技术检测血流，作为胶质瘤患者血管生成的有效标志。这种新的核磁共振成像技术使用磁场来改变信号，或标记流入动脉血液的磁性水旋转。这种动脉自旋标记（ASL）方法可以在几分钟内生成高质量的血流图，作为常规MRI检查的一部分。这项拟议的研究将提供必要的信息和发展，使动脉自旋标记（ASL）血流MRI在胶质瘤实验治疗的临床试验中使用。我们将通过将手术和/或放射治疗前肿瘤中测量的血流与活检标本中的微血管密度测量相关联来验证该技术作为血管生成的标志物。我们将评估磁共振光谱胆碱代谢物测量（一种建议的细胞增殖指标）与血流的数量和空间分布之间的关系。我们将通过测量该技术在肿瘤中的测试-重测试可靠性来确定检测肿瘤血液供应变化的灵敏度极限。最后，我们将使用核磁共振成像来监测手术和放疗后脑肿瘤内部和附近的血流变化。这将为未来的临床试验提供对照数据，并确定检测肿瘤复发或进展的最敏感的方法组合。这些研究将推进我们的两个长期目标，即改进胶质瘤新疗法的测试和改进胶质瘤和其他癌症的治疗。这项研究将确定一种测量进入脑肿瘤的血流量的新方法是否可以用于量化新疗法的效果，特别是那些针对肿瘤血管的疗法。如果成功，这种方法也可以成为规划和监测治疗的重要临床工具。

DESCRIPTION (provided by applicant): Blocking of new tumor blood vessel creation, or angiogenesis, starves the tumor by restricting the supply of nutrients carried by blood flow. Anti-angiogenesis is a promisiing new approach to oncology, but clinical trials have shown large intersubject variation in response. In glioma, a common and aggressive brain tumor, both drug resistant angiogenesis and invasion of tumor cells into surrounding tissue with a functioning blood supply may play a role in failure of antiangiogenic therapy. We propose the use of a noninvasive Magnetic Resonance Imaging (MRI) technique for blood flow as a marker for effective angiogenesis in patients with glioma. This new MRI technique uses magnetic fields to change the signal, or label, the magnetic water spins of inflowing arterial blood. This arterial spin labeling (ASL) approach can generate high quality maps of blood flow in just a few minutes as part of a routine MRI exam. This proposed study will provide the needed information and developments to enable the use of arterial spin labeling (ASL) blood flow MRI in clinical trials of experimental therapies for glioma. We will validate the technique as a marker for angiogenesis by correlating measured blood flow in tumors before surgical and/or radiation therapy with microvascular density measurements in biopsy specimens. We will assess the relationship between a Magnetic Resonance Spectroscopy choline metabolite measure (a suggested indicator of cellular proliferation) and the amount and spatial distribution of blood flow. We will determine the sensitivity limits for detecting changes in blood supply to a tumor by measuring the test-retest reliability of the technique in tumors. Finally, we will use MRI to monitor blood flow changes in and near brain tumors following surgical and radiation therapy. This will provide control data for future clinical trials and also determine the most sensitive combination of methods for detecting reccurence or progression of tumors. These studies will advance our two long term goals of improved testing of new therapies for glioma and improved treatment of glioma and other cancers. This research will determine if a new method for measuring blood flow into brain tumors could be useful for quantifying the effects of new treatments, especially those that target tumor blood vessels. If successful, this method could also become an important clinical tool for planning and monitoring therapy.