The objective of this study is to determine whether the quantitative parameters derived from metabolic and physiologic imaging characteristics are predictive of the biologic behavior of recurrent low grade gliomas (LOG). This is an important clinical question because of the need to determine whether esions have transformed to more malignant phenotypes and to treat patients with the therapy that is most likely to be effective for their particular lesion. Although it is used for clinical evaluation of recurrent LGG, standard Magnetic Resonance (MR) provides ambiguous findings with respect to tumor grade and treatment effects. Results from the current SPORE have allowed us to define MR parameters that are characteristic of newly diagnosed gliomas of different grades and have underlined the differences between the spatial extent of anatomic, metabolic and physiologic lesions in these patients. The analysis of follow-up MR data from patients with high grade gliomas has also cast further doubt on the validity of standard MRI for distinguishing between treatment effects and tumor recurrence. In this renewal project we will investigate whether the MR spectroscopic imaging (MRSI), perfusion weighted imaging (PWI)and diffusion weighted imaging(DWI) techniques that we have developed for monitoring brain tumors are able to determine whether recurrent LGG have transformed to higher grade and predict subsequent response to therapy. Our hypotheses are (1) that the existence of regions with elevated relative cerebral blood volume (rCBV), decreased apparent diffusion coefficient (ADC), elevated lactate (Lac) and elevated lipid (Lip) resonances in recurrent LGG are predictive of transformation to higher histological grade and hence more aggressive biological behavior;(2) that patients with recurrent LGG having such rCBV, ADC, Lac and Lip predictive of transformation to higher grade will have shorter time to progression than those who do not;(3) that integration of these metabolic and physiological imaging techniques into the design of clinical trials for patients with recurrent LGG will contribute in evaluating the effectiveness of the therapy and may contribute to selecting therapies that are tailored to specific patients.
Specific Aim 1 of our study will examine the sub- population of patients who are receiving surgery and will compare the MR parameters with the molecular morphology of image guided tissue samples.
In Specific Aim 2 we will examine a broader population of patients with recurrent LGG to see whether either the initial MR parameters or the short-term changes that occur in response to therapy can predict subsequent biological behavior.
In Specific Aim 3 will integrate the results that we have obtained into the interpretation of imaging data from a clinical trial of rapamycin for recurrent LGG that is planned as one of the specific aims of Project 4 in this SPORE renewal.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-RPRB-7)
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University of California San Francisco
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