The objective of this study is to determine whether the quantitative parameters derived frommetabolic and physiologic imaging characteristics are predictive of the biologic behavior of recurrent lowgrade gliomas (LOG). This is an important clinical question because of the need to determine whetheresions have transformed to more malignant phenotypes and to treat patients with the therapy that is mostlikely 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 treatmenteffects. Results from the current SPORE have allowed us to define MR parameters that are characteristic ofnewly diagnosed gliomas of different grades and have underlined the differences between the spatial extentof anatomic, metabolic and physiologic lesions in these patients. The analysis of follow-up MR data frompatients with high grade gliomas has also cast further doubt on the validity of standard MRI for distinguishingbetween treatment effects and tumor recurrence. In this renewal project we will investigate whether the MRspectroscopic 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 LGGhave 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 inrecurrent LGG are predictive of transformation to higher histological grade and hence more aggressivebiological behavior; (2) that patients with recurrent LGG having such rCBV, ADC, Lac and Lip predictive oftransformation to higher grade will have shorter time to progression than those who do not;(3) thatintegration of these metabolic and physiological imaging techniques into the design of clinical trials forpatients with recurrent LGG will contribute in evaluating the effectiveness of the therapy and may contributeto 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 molecularmorphology of image guided tissue samples.
In Specific Aim 2 we will examine a broader population ofpatients with recurrent LGG to see whether either the initial MR parameters or the short-term changes thatoccur in response to therapy can predict subsequent biological behavior.
In Specific Aim 3 will integrate theresults that we have obtained into the interpretation of imaging data from a clinical trial of rapamycin forrecurrent LGG that is planned as one of the specific aims of Project 4 in this SPORE renewal.
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