Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism

Abstract

Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted imaging technique, was used to examine gray matter microstructure in 24 children with ASD (5 female) and 20 matched typically developing (TD) participants (2 female), ages 7-17 years. RSI extends the spherical deconvolution model to multiple length scales to characterize neurite density (ND) and organization. Measures were examined in 48 cortical regions of interest per hemisphere. To our knowledge, this is the first time that a multi-compartmental diffusion model has been applied to cortical gray matter in ASD. The ND measure detected robust age effects showing a significant positive relationship to age in all lobes except left temporal when groups were combined. Results were also suggestive of group differences (ASD<TD) in anterior cingulate, right superior temporal lobe and much of the parietal lobes, but these fell short of statistical significance. For MD, significant group differences (ASD>TD) in bilateral parietal regions as well as widespread age effects were detected. Our findings support the value of multi-shell diffusion imaging for assays of cortical gray matter. This approach has the potential to add to postmortem literature, examining intracortical organization, intracortical axonal content, myelination, or caliber. Robust age effects further support the validity of the ND metric for in vivo examination of gray matter microstructure in ASD and across development. While diffusion MRI does not approach the precision of histological studies, in vivo imaging measures of microstructure can complement postmortem studies, by allowing access to large sample sizes, a whole-brain field of view, longitudinal designs, and combination with behavioral and functional assays. This makes multi-shell diffusion imaging a promising technique for understanding the underlying cytoarchitecture of the disorder.

Keywords: DTI; MRI; autism; cerebral cortex; connectivity; diffusion; gray matter; neurite.

Figure 1

Effects of age on neurite density. Mean ND is shown as a function of subject age for: (A) left parietal lobe, (B) left occipital lobe, (C) left postcentral gyrus, (D) posterior division of left supramarginal gyrus. ASD indicated in red, TD indicated in blue. Neurite density standardized to a 0–1000 range. ^*p < 0.05, ^**p < 0.005.

Figure 2

Group differences in ND, MD, and FA. Group differences and 95% confidence intervals are shown for each cortical lobe. Positive values indicate ASD >TD. Neurite density standardized to a 0–1000 range.