Diffusion kurtosis imaging of gray matter in young adults with autism spectrum disorder

Abstract

Prior ex vivo histological postmortem studies of autism spectrum disorder (ASD) have shown gray matter microstructural abnormalities, however, in vivo examination of gray matter microstructure in ASD has remained scarce due to the relative lack of non-invasive methods to assess it. The aim of this work was to evaluate the feasibility of employing diffusional kurtosis imaging (DKI) to describe gray matter abnormalities in ASD in vivo. DKI data were examined for 16 male participants with a diagnosis of ASD and IQ>80 and 17 age- and IQ-matched male typically developing (TD) young adults 18-25 years old. Mean (MK), axial (AK), radial (RK) kurtosis and mean diffusivity (MD) metrics were calculated for lobar and sub-lobar regions of interest. Significantly decreased MK, RK, and MD were found in ASD compared to TD participants in the frontal and temporal lobes and several sub-lobar regions previously associated with ASD pathology. In ASD participants, decreased kurtosis in gray matter ROIs correlated with increased repetitive and restricted behaviors and poor social interaction symptoms. Decreased kurtosis in ASD may reflect a pathology associated with a less restrictive microstructural environment such as decreased neuronal density and size, atypically sized cortical columns, or limited dendritic arborizations.

Figure 1

Decreased MK and RK in the right and left temporal lobe GM, and decreased RK in the left frontal lobe GM are observed in autism spectrum disorder compared to the typically developing group. All results shown were significant after ANCOVA between-group tests controlling for age and correcting for multiple comparisons (q ≤ .05 BH FDR).

Figure 2

Brain areas with decreased diffusion metrics (MK, RK and MD) in young males with autism spectrum disorder compared to a typically developing group. The color reflects the significance level (p ≤ .05, uncorrected (light blue) and q ≤ .05 BH corrected (dark blue). Solid colors are used for outer brain surface areas with see-through regions depicted by transparent colors.

Figure 3

Brain areas with significant associations between performance on the 3 sub-categories of the ADI-R and mean kurtosis in the ASD group. A lower score on the ADI-R indicates less severe symptoms and is associated with increased MK in ASD. The strength of the correlation and the corresponding p value are listed for both Spearman’s and Pearson’s tests for each graph.

Figure 4

Surface map of radial kurtosis values in a typically developing versus an autism spectrum disorder participant from an inferior view of the temporal, frontal and cingulate areas. RK values are projected from a middle GM cortical layer depth. Dark blue indicates lower values, while bright green indicates higher values.

Figure 5

Example of directional diffusion tensors in a mid-brain slice of a typically developing versus autism spectrum disorder participant. Red lines indicate left to right diffusion, blue lines indicate up to down diffusion, and green lines indicate front to back diffusion in the brain. The primary direction of GM diffusion in both brains is largely seen as perpendicular to the cortical mantle (AK), and thus the secondary (radial) diffusion direction is parallel to the cortical mantle (RK).