Investigating White Matter Abnormalities in Autism Using Voxel Based Morphometry and Voxel Based Relaxometry

Background: Although there is strong evidence that autism is associated with abnormal brain development, the anatomical extent and timing of any neurobiological differences are unknown. Findings of volumetric studies in children with autism often implicate increased white matter volumes, with more recent studies focusing on evaluating regional contributions to an overall white matter volume increase. One method to examine tissue abnormalities in vivo is quantitative transverse relaxation time (T2) imaging. T2 is influenced by the molecular environment and tissue properties. We have reported an increase in overall white matter T2 in children and adolescents with autism, with follow-up studies finding disproportionally localized increases in the frontal and parietal lobes, as well as radiate and bridging white matter. This pattern of increased T2 parallels that of increased white matter volume of some volumetric studies in autism.

Objectives: The purpose of this study was to further investigate any possible relationship between white matter volumes and T2 differences in patients with autism with a voxel-wise multimodal image analysis mapping method known as biological parametric mapping (BPM).

Methods: Twenty-one male patients with autism between the ages of 6 and 16 and 20 male controls in the same age range participated in this study. The diagnosis was made according to DSM-IV-TR criteria using the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Schedule. All patients had non-verbal IQ greater than 70. Control subjects were drawn from the local community and were assessed to rule out any psychiatric disorders. The groups did not differ significantly in age, sex, race, full-scale IQ, or non-verbal intelligence. 10 patients were medication-naïve at the time of their scan, while 3 others had discontinued their medication prior to the scan. 16 patients required sedation with oral midazolam in order to complete the scan.

Results: Data have been collected and preprocessed and results are pending BPM analyses. Both an ANCOVA will be performed using T2 data as the principal modality and white matter VBM data as the imaging regressor. Given the changes in T2 described in childhood, the statistical analysis will be covaried for age. Furthermore, a correlation analysis between these two datasets will be performed on a voxel-by-voxel basis using BPM's correlation model.

Conclusions: Conclusions are pending analyses