A key factor in the treatment of patients with low-grade gliomas (LGGs) is the characterization of the extent and proliferative rate of active tumor. More than half of all tumors diagnosed as low grade contain anaplastic foci and once treated, 30-90 percent transform to a higher grade by the time symptoms recur or death occurs. The degree of hypercellularity and proliferation are two of the histological features that are used to distinguish malignant tumor (grade 3) from low-grade (grade 2) lesions. Typically, biopsies are obtained from locations that appear bright on contrast-enhanced MRIs. However, most LGGs and 30 percent of grade 3 tumors do not enhance, making it difficult to distinguish one from the other pre-operatively. We have developed a 3D MR spectroscopic imaging (3D- MRSI) method that provides a spatial map of metabolite levels in brain. We have also developed a diffusion tensor MRI method for mapping the apparent diffusion coefficient (ADC) in brain. Preliminary studies have shown that the size of the peaks in the spectral region corresponding to choline-containing compounds (Cho) varies in LGGs. The Cho peak in 3D-MRSI arises from compounds associated with the synthesis and degradation of cell membranes. An elevated Cho peak is a common feature of tumor spectra and is thought to reflect the higher cell density and proliferative activity of tumors. In this proposal, we will investigate the hypothesis that combined 3D-MRS and diffusion tensor imaging can be used to assess cellular proliferation and hypercellularity and, as such, can help to identify malignant foci and/or evaluate the potential for malignant transformation in specific regions of LGGs. We describe methods for testing the hypothesis through the use of high resolution (HR) MRS and molecular analyses of 3D-MRSI-directed biopsies obtained from Grades 2 and 3 newly diagnosed gliomas. The HR MRS studies will be performed on the intact tissue samples using a magic-angle spinning NMR technique that should reveal the specific compounds that contribute to the Cho peak in in vivo 3D-MRSI data. We expect phosphocholine, which is associated with the synthesis of cell membranes, will predominate in the malignant biopsies. After the non- destructive HR MRS analysis, the proliferative activity within each biopsy will be determined with an immunohistochemical MIB-1 assay. We expect that these studies will: (1) further the understanding of the cellular mechanisms that give rise to the metabolic and physiologic features that are observed in in vivo MR studies of gliomas; and (2) result in new MR methods for identifying malignant and pre-malignant regions in LGGs. Such information would be of great value for performing targeted biopsies and tailoring treatments of patients with these lesions.
| McKnight, Tracy R; Lamborn, Kathleen R; Love, Tonya D et al. (2007) Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas. J Neurosurg 106:660-6 |
| Laprie, Anne; Pirzkall, Andrea; Haas-Kogan, Daphne A et al. (2005) Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy. Int J Radiat Oncol Biol Phys 62:20-31 |
| McKnight, Tracy Richmond (2004) Proton magnetic resonance spectroscopic evaluation of brain tumor metabolism. Semin Oncol 31:605-17 |
