A multi-reader comparison of normal-appearing white matter normalization techniques for perfusion and diffusion MRI in brain tumors

PURPOSE: There remains no consensus normal-appearing white matter (NAWM) normalization method to compute normalized relative cerebral blood volume (nrCBV) and apparent diffusion coefficient (nADC) in brain tumors. This reader study explored nrCBV and nADC differences using different NAWM normalization methods. METHODS: Thirty-five newly diagnosed glioma patients were studied. For each patient, two readers created four NAWM regions of interests: (1) a single plane in the centrum semiovale (CSOp), (2) 3 spheres in the centrum semiovale (CSOs), (3) a single plane in the slice of the tumor center (TUMp), and (4) 3 spheres in the slice of the tumor center (TUMs). Readers repeated NAWM segmentations 1 month later. Differences in nrCBV and nADC of the FLAIR hyperintense tumor, inter-/intra-reader variability, and time to segment NAWM were assessed. As a validation step, the diagnostic performance of each method for IDH-status prediction was evaluated. RESULTS: Both readers obtained significantly different nrCBV (P < .001), nADC (P < .001), and time to segment NAWM (P < .001) between the four normalization methods. nrCBV and nADC were significantly different between CSO and TUM methods, but not between planar and spherical methods in the same NAWM region. Broadly, CSO methods were quicker than TUM methods, and spherical methods were quicker than planar methods. For all normalization techniques, inter-reader reproducibility and intra-reader repeatability were excellent (intraclass correlation coefficient > 0.9), and the IDH-status predictive performance remained similar. CONCLUSION: The selected NAWM region significantly impacts nrCBV and nADC values. CSO methods, particularly CSOs, may be preferred because of time reduction, similar reader variability, and similar diagnostic performance compared to TUM methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00234-022-03072-y.