Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization

Individuals with a constitutional chromosome abnormality consisting of a deletion of a portion of the long arm of chromosome 18 (18q-) have a high incidence (∼95%) of dysmyelination. Neuroradiologic findings in affected children report a smaller corpus callosum, but this finding has not been quantified. This is in part due to the large intersubject variability of the corpus callosum size and shape and the small number of subjects with 18q-, which leads to low statistical power for comparison with typically developing children. An analysis method called targetless spatial normalization (TSN) was used to improve the sensitivity of statistical testing. TSN converges all images in a group into what is referred as group common space. The group common space conserves common shape, size, and orientation while reducing intragroup variability. TSN in conjunction with a Witelson vertical partitioning scheme was used to assess differences in corpus callosum size between 12 children with 18q- and 12 age-matched normal controls. Significant global and regional differences in corpus callosum size were seen. The 18q- group showed an overall smaller (25%) corpus callosum (P < 10⁷), even after correction for differences in brain size. Regionally, the posterior portions of corpus callosum (posterior midbody, isthmus, and splenium), which contain heavily myelinated fibers, were found to be 25% smaller in the population with 18q-.