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Brain Tumor Heterogeneity: Voxel-wise Correlational Study of MR Perfusion and 2D MR Spectroscopic Imaging

Annette Förschler, Katharina Schwede, Mirjam Ines Schubert, Claus Zimmer and Dirk Winkler

An accurate characterization of glioma heterogeneity is essential when determining tumor grade and the most appropriate therapy target. Non-invasive imaging modalities such as MR perfusion imaging (PWI) and 2D proton MR spectroscopic imaging (MRSI) can provide functional and metabolic information about the tumor to assist in this task. Using a voxel-wise correlation we aimed at investigating whether both MRSI and PWI characterize brain tumor heterogeneity similarly, and, whether the regions of their most pathologic values coincide. In 31 patients with different primary brain tumors rCBV and rCBF were correlated to the metabolites Cho, Cr and NAA and the metabolite ratios Cho/Cr, NAA/Cr and Cho/NAA on a voxel-wise basis. Intraindividually, we tested for significant relationships and we recorded the reliability and the direction of these relationships by calculating the inter individual variance of Kendall's correlation coefficient τb. Additionally, the locations of the most pathologic values of PWI and MRSI were compared. Across all tumors we found no reliable relationship between perfusion and spectroscopic measures apart from a positive correlation of rCBV and rCBF with Cr, mainly based on a positive correlation in II° gliomas and glioblastomas but not in III° gliomas or lymphomas. The separate analysis of the tumor groups revealed consistent correlations of additional value pairs in II° gliomas and glioblastomas, but not in III° gliomas or lymphomas. The overall spatial concordance rate between the maximum perfusion values and the most pathological metabolite values was 34%. Our results suggest that brain tumors display heterogenous correlation pattern of the perfusion markers of malignancy to the spectroscopy-derived malignancy markers. As the single modality methods may display different kinds of tumor hot spots, PWI and MRSI should be fused to allow for more specific therapy planning of brain tumors.