Introduction: White matter hyperintensity volume (WMHv) is an important and highly heritable cerebrovascular phenotype; however, manual or semi-automated approaches to clinically acquired MRI analysis hinder large-scale studies in acute ischemic stroke (AIS). In this work, we develop a high-throughput, fully automated WMHv analysis pipeline for clinical fluid-attenuated inversion recovery (FLAIR) images to facilitate rapid genetic discovery in AIS.
Methods: Automated WMHv extraction from multiple subjects relies on significant pre-processing of medical scans, including co-registration of the images. To reduce the effects of anisotropic voxel sizes, each FLAIR image is upsampled using bi-cubic interpolation. Brain extraction is performed using RObust Brain EXtraction (ROBEX). Images are then registered to an in-house FLAIR template using Advanced Normalization Tools (ANTs). The spatial covariation of WMH is learned through principal component analysis (PCA) of manual outlines from 100 subjects. Areas of leukoaraiosis are identified and separated from other lesions using the PCA modes. Volumes are then computed using non-interpolated slices for each subject. Standard deviation (SD) in WMHv (9 subjects; 6 raters each) is calculated as a measure of variability. Good agreement between automated and manual outlines is assessed in 358 subjects (automated WMHv within 3SD of manual WMHv).
Results: As part of the MRI-Genetics Interface Exploration (MRI-GENIE) study, WMHv were calculated on a set of 2703 FLAIR images of patients from 12 independent AIS cohorts (sites). Results are shown in Figure 1. Comparing manual and automated WMHv shows that 88% of the automated WMHv fall within 3 SD from the manual WMHv, suggesting good agreement.
Conclusion: WMHv segmentation using a fully-automated pipeline for analysis of clinical MRIs is both feasible and accurate. Ongoing analysis of the extracted WMHv is expected to advance current knowledge of risks and outcomes in AIS.