Blood Flow MRI for Monitoring of Renal Cell Carcinoma

描述(申请人提供)：肿瘤血流是判断肿瘤侵袭性和预后的重要指标。最近的研究强调，生成新血管以供应不断增长的肿瘤的能力，或血管生成，是肿瘤存活和扩张的根本决定因素。旨在阻断血管生成的新疗法在动物实验中取得了惊人的成功，在人体试验中也显示出了希望。在最初的人体研究中，对这类药物的反应的评估将大大有助于非侵入性测量其效果的技术的可用。由于抗血管生成的目标是阻断血供的扩张，因此肿瘤血流量的测量应该是早期和强有力的治疗反应指标。然而，目前在体内进行血流成像和测量的方法相当有限。我们建议进一步开发和测试一种用于血流成像的MRI方法。虽然这项技术在大脑成像方面已经发展得很好，但在体内成像方面还没有得到充分的优化和评估。我们建议充分优化和评估该方法用于腹部和骨盆的血流成像。首先，我们将优化单个切片中的血流测量，并确定必要的时间和信号参数，以获得可重复性和准确的结果。接下来，我们将实现在短时间内对腹部和骨盆的体积进行成像的方法。最后，我们将使用优化的方法测量肾癌患者的血流，评价血流测量的重复性和准确性，并测量肾血管扩张剂对肾脏血流的调节。这些研究将为在新的实验疗法研究中最好地使用MRI血流方法监测患者反应提供必要的经验和验证。这项研究将改进和测试一种使用核磁共振成像制作肿瘤血液流动图像的技术。许多治疗癌症的新疗法试图通过限制肿瘤的血液供应来阻止肿瘤的生长。如果开发得当，这种核磁共振技术可能有助于观察这些治疗对某些患者是否有效，并有助于尽早发现治疗失败，以便使用更有效的治疗方法。

DESCRIPTION (provided by applicant): Tumor blood flow is an important indicator of aggressiveness and prognosis. Recent research has emphasized that the ability to generate new blood vessels to supply a growing tumor, or angiogenesis, is a fundamental determinant of tumor viability and expansion. New therapies which aim to block angiogenesis have achieved startling success in animal studies and show promise in human trials. Evaluation of response to such agents in initial human studies would be greatly aided by the availability of techniques for noninvasive measurement of their effects. Since the target of antiangiogenesis is to block the expansion of blood supply, measurement of tumor blood flow should be an early and powerful indicator of response to therapy. Current methods for blood flow imaging and measurement in the body are quite limited, however. We propose to further develop and test an MRI method for imaging of blood flow. While more well-developed for imaging of the brain, the technique has not been fully optimized and evaluated for imaging within the body. We propose to fully optimize and evaluate this method for the imaging of blood flow in the abdomen and pelvis. First we will optimize blood flow measurement in a single slice and determine the timing and signal parameters necessary for reproducible and accurate results. Next we will implement methods to image a volume of the abdomen and pelvis in a short period of time. Finally, we will use the optimized method to measure blood flow in patients with renal cell carcinoma, to evaluate the reproducibility and accuracy of the blood flow measurement, and to measure modulations in kidney blood flow induced by a renal vasodilator. These studies will provide the necessary experience and validation to best use the MRI blood flow method for monitoring of patient response in studies of new experimental therapies. This research will improve and test a technique for making pictures of blood flow into tumors using MRI. Many new treatments for cancer try to stop tumor growth by restricting its blood supply. This MRI technique, if properly developed, may be useful for seeing whether these treatments are effective in some patients and for detecting failure of the treatment as early as possible so more effective treatments can be used.