Axonal Integrity of Brain White Matter Tracts in 22q11del Syndrome Subjects: A Diffusion Tensor Imaging StudyT. Ballinger, Z. Kikinis, T. Asami, C. Finn, R. Kucherlapati, M. Kubicki, M. E. Shenton
Mysell Harvard Research Day, Psychiatry Annual Meeting
Background:Subjects with 22q11del syndrome are at high risk to develop schizophrenia; their incidence rate for developing the disease in adulthood is 30 Subjects with schizophrenia have been widely found to have reduced white matter fractional anisotropy (FA)(Assaf2008). Other anisotropic measures such as radial and axial diffusivity have been shown to correspond to specific types of white matter damage in animal model. The VCFS subjects examined in this study have also been found to have reduced white matter FA in the cerebellum on both sides and in the deep white matter of theparietal lobe in the left hemisphere.Here we are analyzing the same subjects for the anisotropic measures radial and axial diffusivity.
Materials and Methods:1.5T diffusion weighted scans were acquired from 9 patients with reconfirmed chromosomal deletion of region 22q11 and from 9 healthy subjects matche on age, sex, and parental socioeconomic status. Voxel-wise statistical analysis of various anisotropic diffusion measures was carried out using TBSS (Tract-Based Spatial Statistics) (Smith2006). First,brain-masked tensor map images were produced and anisotropic measures calculated with Slicer3, an open source software program ( http://www.slicer3.org). All subjects' FA images were then nonlinearly aligned into a common space.Next,the mean FA image was created and thinned to create a mean FA skeleton which represents the centers of all tracts common to the group.At this point each subject's anisotropic data could be projected on to this common skeleton, and voxel-wise comparisons of th evarious anisotropic measures performed. The permutation-based inference tool Randomize was used and a two sample t-test was conducted for all voxel-wise group comparisons using a threshold-free cluster enhancement method. The number of permutations was set at 500,and the significance level was set at Family-WiseError (FWE) corrected p<0.05. The tracts of the regions of reduction were identified by using John Hopkins University White-Matter Tractography Atlas.
Results:Significant reduction in axial diffusivity was found in the 22q11del syndrome group.Previous FA results showed an area of deep white matter in the parietal lobe in the left hemisphere for statistically significant reductions of FA in the 22q11del group (a,b,and d show three views of this region). The location of these white matter differences corresponds very closely to the reductions in axial diffusivity in the 22q11del group (c), a region of the parietal lobe which has several white matter tracts: the posterior thalamic radiation,inferior frontal occipital fasciculus(IFOF) and inferior longitudinal fasciculus (ILF). However,no similar difference in axial diffusivity was found to correspond with the FA differences in the cerebellum on both sides (not visible from the views shown in a,b,and d). No significant differencesbetween the groups were found in the other anisotropic diffusion measure studied radial diffusivity.
Discussion:Demyelination has been shown to result in increases in radial diffusivity in animal models (Kim2006), while decreases in axial diffusivity are likely due to axonal damage (Song2002). Our results suggest that axonal damage may be partially responsible for the reduced FA in these locations among the 22q11del group. Since radial diffusivity did not significantly increase, evidence of demyelization is not observed, and thus likely not involved in the white matter pathology of this disorder.