Deep learning-based grading of white matter hyperintensities enables identification of potential markers in multi-sequence MRI data

White matter hyperintensities (WMHs) are widely-seen in the aging population, which are associated with cerebrovascular risk factors and age-related cognitive decline. At present, structural atrophy and functional alterations coexisted with WMHs lacks comprehensive investigation. This study developed a WMHs risk prediction model to evaluate WHMs according to Fazekas scales, and to locate potential regions with high risks across the entire brain.We developed a WMHs risk prediction model, which consisted of the following steps: T2 fluid attenuated inversion recovery (T2-FLAIR) image of each participant was firstly segmented into 1000 tiles with the size of 32 × 32 × 1, features from the tiles were extracted using the ResNet18-based feature extractor, and then a 1D convolutional neural network (CNN) was used to score all tiles based on the extracted features. Finally, a multi-layer perceptron (MLP) was constructed to predict the Fazekas scales based on the tile scores. The proposed model was trained using T2-FLAIR images, we selected tiles with abnormal scores in the test set after prediction, and evaluated their corresponding gray matter (GM) volume, white matter (WM) volume, fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF) via longitudinal and multi-sequence Magnetic Resonance Imaging (MRI) data analysis.The proposed WMHs risk prediction model could accurately predict the Fazekas ratings based on the tile scores from T2-FLAIR MRI images with accuracy of 0.656, 0.621 in training data set and test set, respectively. The longitudinal MRI validation revealed that most of the high-risk tiles predicted by the WMHs risk prediction model in the baseline images had WMHs in the corresponding positions in the longitudinal images. The validation on multi-sequence MRI demonstrated that WMHs were associated with GM and WM atrophies, WM micro-structural and perfusion alterations in high-risk tiles, and multi-modal MRI measures of most high-risk tiles showed significant associations with Mini Mental State Examination (MMSE) score.Our proposed WMHs risk prediction model can not only accurately evaluate WMH severities according to Fazekas scales, but can also uncover potential markers of WMHs across modalities. The WMHs risk prediction model has the potential to be used for the early detection of WMH-related alterations in the entire brain and WMH-induced cognitive decline.