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Objectives:  To evaluate white matter hyperintensities (WMH) quantification reproducibility from multiple aspects of view and examine the effects of scan–rescan procedure, types of scanner, imaging protocols, scanner software upgrade, and automatic segmentation tools on WMH quantification results using magnetic resonance imaging (MRI).   Methods:  Six post-stroke subjects (4 males; mean age = 62.8, range = 58–72 years) were scanned and rescanned with both 3D T1-weighted, 2D and 3D T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) MRI across four different MRI scanners within 12 h. Two automated WMH segmentation and quantification tools were used to measure WMH volume based on each MR scan. Robustness was assessed using the coefficient of variation (CV), Dice similarity coefficient (DSC), and intra-class correlation (ICC).   Results:  Experimental results show that the best reproducibility was achieved by using 3D T2-FLAIR MRI under intra-scanner setting with CV ranging from 2.69 to 2.97%, while the largest variability resulted from comparing WMH volumes measured based on 2D T2-FLAIR MRI with those of 3D T2-FLAIR MRI, with CV values in the range of 15.62%–29.33%. The WMH quantification variability based on 2D MRIs is larger than 3D MRIs due to their large slice thickness. The DSC of WMH segmentation labels between intra-scanner MRIs ranges from 0.63 to 0.77, while that for inter-scanner MRIs is in the range of 0.63–0.65. In addition to image acquisition, the choice of automatic WMH segmentation tool also has a large impact on WMH quantification.   Conclusion:  WMH reproducibility is one of the primary issues to be considered in multicenter and longitudinal studies. The study provides solid guidance in assisting multicenter and longitudinal study design to achieve meaningful results with enough power.

Intra-Scanner and Inter-Scanner Reproducibility of Automatic White Matter Hyperintensities Quantification