Spatial Coherence of Oriented White Matter Microstructure: Applications to White Matter Regions Associated with Genetic Similarity
This work addresses the need for more precise methods to study heritable influences in brain white matter, offering a domain-specific advancement over previous undirected approaches.
The researchers tackled the problem of identifying white matter regions associated with genetic similarity by analyzing diffusion MRI scans of twins and siblings, finding that 3.7% of white matter showed significant genetic associations with 75% clustering into 22 contiguous regions. They demonstrated that orientation similarity in these regions generalizes to non-twin siblings, who were as similar as dizygotic twins.
We present a method to discover differences between populations with respect to the spatial coherence of their oriented white matter microstructure in arbitrarily shaped white matter regions. This method is applied to diffusion MRI scans of a subset of the Human Connectome Project dataset: 57 pairs of monozygotic and 52 pairs of dizygotic twins. After controlling for morphological similarity between twins, we identify 3.7% of all white matter as being associated with genetic similarity (35.1k voxels, $p < 10^{-4}$, false discovery rate 1.5%), 75% of which spatially clusters into twenty-two contiguous white matter regions. Furthermore, we show that the orientation similarity within these regions generalizes to a subset of 47 pairs of non-twin siblings, and show that these siblings are on average as similar as dizygotic twins. The regions are located in deep white matter including the superior longitudinal fasciculus, the optic radiations, the middle cerebellar peduncle, the corticospinal tract, and within the anterior temporal lobe, as well as the cerebellum, brain stem, and amygdalae. These results extend previous work using undirected fractional anisotrophy for measuring putative heritable influences in white matter. Our multidirectional extension better accounts for crossing fiber connections within voxels. This bottom up approach has at its basis a novel measurement of coherence within neighboring voxel dyads between subjects, and avoids some of the fundamental ambiguities encountered with tractographic approaches to white matter analysis that estimate global connectivity.