The objective of this project is to integrate metabolic and physiologic MR imaging data into the clinicalmanagement of patients with newly diagnosed glioblastoma multiforme (GBM). Our current studies haveprovided strong evidence that Magnetic Resonance Spectroscopic Imaging (MRSI), Perfusion Weightedimaging (PWI) and Diffusion Weighted Imaging (DWI) produce information concerning the biologicalbehavior of such lesions that is likely to be valuable for clinical decision making. We propose to explore theclinical impact of these imaging methods with respect to improving and evaluating treatment with ConvectionEnhanced Delivery (CED) of biologically active agents. The first area that is of interest is to more reliablyidentify the location of residual disease after surgery so that it will ultimately be possible to direct therapy toto foci of residual disease. The second area of interest is in defining metabolic and physiologic imagingparameters that predict whether the patient is likely to benefit from treatment that uses CED. The third areais in evaluating short-term changes that occur as a result of combining CED with subsequent radiation andchemotherapy. Previous studies of such focal treatments have not utilized state of the art metabolic andphysiologic imaging methods to select patients, to identify microscopic disease and heterogeneity or toevaluate response to therapy. We believe that it is critical to determine whether this approach is feasible withregard to CED and to obtain evidence that would help in deciding how to best integrate such information intofuture clinical trials.
Specific Aim 1 will provide direct correlation between specific imaging and tissue characteristics byimmunohistochemical and ex-vivo NMR spectroscopy of image guided surgical samples from patients withnewly diagnosed GBM. This will establish the link between in vivo MR parameters and biological behavior asdefined by molecular morphology.
Specific Aim 2 will address the characteristics of patients who areparticipating in a Phase II clinical trial of GBM patients receiving CED. It will examine the relationshipbetween pre-CED MR parameters and subsequent imaging change, as well as comparing these findingswith a population of patients with similar characteristics who have not been treated with CED.
Specific Aim 3 will perform a Phase I clinical trial in patients with GBM that integrates the metabolic and physiologic imagingparameters that have been shown relevant with results obtained in Project 3 with regard to improving theCED process to more accurately target regions of interest. While the focus in these initial clinical trials is onpatients who have received a gross total resection based on conventional MR imaging, the knowledge thatwill be gained has broad implications for selecting and targeting many other types of focal therapy and islikely to change the definition of tumor burden and response to therapy for patients with GBM
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