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. |