Preliminary Evidence of Altered Gray and White Matter Microstructural Development in the Frontal Lobe of Adolescents With Attention-Deficit Hyperactivity Disorder: A Diffusional Kurtosis Imaging Study

Purpose: To investigate non-Gaussian water diffusion using diffusional kurtosis imaging (DKI) to assess age effects on gray matter (GM) and white matter (WM) microstructural changes in the prefrontal cortex (PFC) of adolescents with attention-deficit hyperactivity disorder (ADHD) compared to typically developing controls (TDC). Materials and Methods: In this preliminary cross-sectional study. T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) and DKI images were acquired at 3T from TDC (n = 13) and adolescents with ADHD (n = 12). Regression analysis of the PFC region of interest (ROI) was conducted. Results: TDC show a significant kurtosis increase of WM microstructural complexity from 12 to 18 years of age, particularly in the radial direction, whereas WM microstructure in ADHD is stagnant in both the axial and radial directions. In ADHD, GM microstructure also lacked a significant age-related increase in complexity as seen in TDC; only kurtosis measures were able to detect this difference. Conclusion: These findings support the prevailing theory that ADHD is a disorder affecting frontostriatal WM. Our study is the first to directly quantify an aberrant age-related trajectory in ADHD within GM microstructure, suggesting that the assessment of non-Gaussian directional diffusion using DKI provides more sensitive and complementary information about tissue microstructural changes than conventional diffusion imaging methods.