Abstract

Abstract INTRODUCTION The T2-FLAIR mismatch (T2FM) sign on anatomical MRI is highly specific for isocitrate dehydrogenase (IDH)-mutant 1p/19q-intact gliomas (astrocytomas) and is characterized by relative hypointense FLAIR signal within the T2 hyperintense lesion. However, studies on T2FM sign have mostly utilized qualitative visual assessment. This study explored quantitative subtraction maps of T2-w and FLAIR MRI in human non-enhancing gliomas to quantify the extent of T2FM and assess T2FM subregion volumetric and diffusion MRI differences. METHODS Seventy-two newly-diagnosed, non-enhancing gliomas with known IDH- and 1p/19q-status from The Cancer Imaging Archive (TCIA) were studied. An institutional cohort (n= 36) was analyzed for validation. T2-FLAIR subtraction maps were generated from voxel-wise subtraction of co-registered, normalized T2-w and FLAIR MRI scans. Tumor volumes of interest (VOIs) were segmented on the T2 hyperintensity excluding macroscopic cysts. Tumor VOIs were split into mismatched and non-mismatched subregions using consistent T2-FLAIR subtraction map thresholds. Tumor subregion volumes and normalized apparent diffusion coefficient (nADC) values were obtained, and tumor T2FM percentage was calculated. RESULTS In the TCIA cohort, a threshold of > 16% T2FM had 92.3% specificity and 34.8% sensitivity and a threshold of > 42% T2FM had 100% specificity and 21.7% sensitivity for classifying IDH-mutant astrocytomas (AUC= 0.704, P= 0.004). IDH-mutant astrocytomas with > 16% T2FM had higher nADC in mismatched compared to non-mismatched subregions (mean difference= 0.51; P< 0.0001). Using the same T2FM thresholds, these findings were validated in the institutional cohort for glioma classification (AUC= 0.918, P< 0.0001; > 16% T2FM: 100% specificity, 66.7% sensitivity, PPV= 100%, NPV= 65.2%; > 42% T2FM: 100% specificity, 23.8% sensitivity, PPV= 100%, NPV= 48.3%) and subregion nADC differences (mean difference= 0.56, P< 0.0001). CONCLUSIONS T2-FLAIR subtraction maps may be a useful, automated tool for classifying non-enhancing gliomas and exploring T2FM subregion differences. Elevated nADC in mismatched subregions may reflect microcystic changes.

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