Correlation between Magnetic Resonance Spectroscopy Imaging and Image-guided Biopsies: Semiquantitative and Qualitative Histopathological Analyses of Patients with Untreated Glioma

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Abstract
Since intratumoral heterogeneity of gliomas is not adequately reflected in conventional magnetic resonance imaging (MRI), we sought to determine a correlation between different proton magnetic resonance spectroscopic imaging (1H MRSI) metabolic ratios and the degree of tumor infiltration in diffusely infiltrating gliomas. In this report, we describe the microscopic anatomy of gliomas on imaging. Image-guided biopsies with semiquantitative and qualitative histopathological analyses from a series of 31 untreated patients with low- and high-grade gliomas were correlated with multivoxel 1H MRSI referenced to the same spatial coordinates. This series yielded 247 tissue samples and 307 observations. Choline-containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetylaspartate appear to correlate best with the degree of tumor infiltration. Similar correlations were present within each grade after stratification. Despite the interpatient overlap of metabolic ratios between normal tissue and mild tumor infiltration, preliminary analyses revealed that 1H MRSI appears more accurate than conventional MRI in defining the tumor boundary and quantifying the degree of tumor infiltration. This is the first study showing histopathological validation of tumor boundaries using 1H MRSI. These results support the conclusion that 1H MRSI accurately reflects the extent of the disease in patients with gliomas. This has important diagnostic and therapeutic implications for more accurately assessing the burden of disease as well as for planning and assessing response to therapy.