Batch Effect Correction for Neuroimaging Data with Heterogeneous Spatial Correlations

Abstract

Magnetic resonance imaging scans are effective tools for unveiling brain structures and understanding pathology for complex neurodevelopmental and aging processes. The spatial correlations among various brain regions reveal critical information and insights into the mechanisms of brain functions and their associations with cognitive abilities. Large-scale neuroimaging studies that acquire or aggregate imaging scans from multiple sites have become increasingly popular. Doing so enhances the diversity of study samples and robustness of study findings, and increases the statistical power of any analysis conducted for the biological hypotheses of interest. However, collecting images across different sites introduces non-biological variability attributed to differences in imaging protocol and configurations, known as batch effects. While there are methods to perform this batch effect correction, there are limited methods that directly account for the spatial patterns found in images of the brain. We develop Covariance-Aware Multivariate (CAM) ComBat that accounts for such spatial correlation across high-dimensional features, which could be heterogeneous across batches. We also propose a computationally efficient alternative of CAM-ComBat, Spatially-Informed Iterative Block (SIB) ComBat, that is scalable for very high dimension of features. We show that these methods outperform existing batch effect correction methods through simulation studies and an application to real neuroimaging data.