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.
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