A Comprehensive Corpus Callosum Segmentation Tool for Detecting Callosal Abnormalities and Genetic Associations from Multi Contrast MRIs

Structural alterations of the midsagittal corpus callosum (midCC) have been associated with a wide range of brain disorders. The midCC is visible on most MRI contrasts and in many acquisitions with a limited field-of-view. Here, we present an automated tool for segmenting and assessing the shape of the midCC from T1w, T2w, and FLAIR images. We train a UNet on images from multiple public datasets to obtain midCC segmentations. A quality control algorithm is also built-in, trained on the midCC shape features. We calculate intraclass correlations (ICC) and average Dice scores in a test-retest dataset to assess segmentation reliability. We test our segmentation on poor quality and partial brain scans. We highlight the biological significance of our extracted features using data from over 40,000 individuals from the UK Biobank; we classify clinically defined shape abnormalities and perform genetic analyses

Genetic map of regional sulcal morphology in the human brain from UK biobank data.

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease