The overall goal of this project is to improve the interpretation of magnetic resonance spectroscopy (MRS) data from non-enhancing glioma of various histologic subtypes in an effort to improve the therapeutic planning for patients harboring such tumors. Non-enhancing glioma are most often diagnosed as Grade II, half of which progress to Grade III histology at recurrence. Previous studies by our group have shown MRS to be effective for directing biopsies to the most proliferative and cellular tumor regions that are most likely to contain Grade III foci. Additional studies by our group and others have shown that both the MR spectroscopic and molecular genetic features of purely astrocytic tumors are distinct from those of oligodendroglial tumors. The interesting aspect of such findings stems from the fact that patients with oligodendroglioma (OD) enjoy a more favorable outcome than patients with astrocytoma. The current proposal seeks to evaluate the effectiveness of MRS for post-surgical prediction of the behavior of residual tumor. Particular attention will be paid to tumors with mixed histology (oligoastrocytoma, OA), which may have genetic features and clinical course similar to AS or OD and, therefore, are particularly difficult to treat.
The aims of this project will test the following hypotheses: (1) reductions in the creatine+phosphocreatine peak and elevations in the peak corresponding to lactate are observed more often in Grade II OD and Grade astrocytoma (AA) than in Grade II astrocytoma (AS), (2) MRS markers that correlate with prognostic markers for astrocytoma will be different than those that correlate with prognostic markers for oligodendroglioma, and (3) the MRS signature of mixed OA can be used as a surrogate marker for the molecular characteristics of the tumor. We will test these hypotheses by acquiring 3D-MRS data from patients prior to surgical resection and comparing the levels of the aforementioned metabolites within the various histologic subtypes. To more precisely associate metabolic features with the underlying biology, we will also use HRMAS MRS to correlate the MRS parameters with molecular markers of malignant activity (eg MIB-1 and TUNEL) and genetic markers of tumor type (1p/19q chromosomal deletions) and malignant progression (9p and 10q deletions) in tissue biopsies extracted from the tumors of the patients. We will also attempt to classify the OA biopsies based on their molecular, genetic, and MRS features.
| McKnight, Tracy R; Smith, Kenneth J; Chu, Philip W et al. (2011) Choline metabolism, proliferation, and angiogenesis in nonenhancing grades 2 and 3 astrocytoma. J Magn Reson Imaging 33:808-16 |
| Chang, Susan M; Nelson, Sarah; Vandenberg, Scott et al. (2009) Integration of preoperative anatomic and metabolic physiologic imaging of newly diagnosed glioma. J Neurooncol 92:401-15 |
| Bian, Wei; Khayal, Inas S; Lupo, Janine M et al. (2009) Multiparametric characterization of grade 2 glioma subtypes using magnetic resonance spectroscopic, perfusion, and diffusion imaging. Transl Oncol 2:271-80 |
