Fixel-based evidence for preserved white matter asymmetry in human situs inversus totalis

Situs inversus totalis (SIT), a rare condition involving the complete reversal of thoracic and abdominal organ placement, provides a unique model for investigating potential relationships between visceral and cerebral asymmetries. In this study, we examined whether white matter asymmetries are altered in a group of 21 SIT participants compared with 21 matched situs solitus (SO) controls. This sample represents the largest cohort of SIT individuals studied to date. Using fixel-based analysis, an advanced diffusion magnetic resonance imaging framework, we compared micro- and macrostructural white matter asymmetries across the whole brain between the two groups, specifically assessing fiber density and cross-section (FDC). Both groups showed extensive yet comparable patterns of white matter asymmetry, with no significant group differences. These asymmetry patterns were consistent with those reported in previous fixel-based studies. These results suggest that white matter lateralization is preserved despite complete visceral reversal. The observed divergence between brain and visceral asymmetry patterns suggests that symmetry breaking in visceral laterality relies on distinct mechanisms.