Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children
Authors: Elisabeth Burnor, Dora Cserbik, Devyn L. Cotter, Clare E. Palmer, Hedyeh Ahmadi, Sandrah P. Eckel, Kiros Berhane, Rob McConnell, Jiu-Chiuan Chen, Joel Schwartz, Raymond Jackson, Megan M. Herting
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Outdoor particulate matter 2.5 μm or less in diameter (PM<sub>2.5</sub>) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM<sub>2.5</sub>and white matter connectivity. <h3>Objectives</h3> To assess associations between annual residential PM<sub>2.5</sub>exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes. <h3>Design, Setting, and Participants</h3> This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021. <h3>Exposures</h3> Annual mean PM<sub>2.5</sub>exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline. <h3>Main Outcomes and Measures</h3> Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM<sub>2.5</sub>exposure and DWI. <h3>Results</h3> In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM<sub>2.5</sub>and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM<sub>2.5</sub>exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM<sub>2.5</sub>increase from 8 to 12 μg/m<sup>3</sup>was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM<sub>2.5</sub>and mean diffusivity. <h3>Conclusions and Relevance</h3> The findings of this cross-sectional study suggest that annual mean PM<sub>2.5</sub>exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.