White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social communication deficits and the presence of restricted interests and repetitive behaviors. We have previously reported significant improvements in behavior, including increased social functioning, improved communication abilities, and decreased clinical symptoms in children with ASD, following treatment with a single infusion of autologous cord blood in a phase I open-label trial. In the current study, we aimed to understand whether these improvements were associated with concurrent changes in brain structural connectivity. Twenty-five 2- to 6-year-old children with ASD participated in this trial. Clinical outcome measures included the Vineland Adaptive Behavior Scales-II Socialization Subscale, Expressive One-Word Picture Vocabulary Test-4, and the Clinical Global Impression-Improvement Scale. Structural connectivity was measured at baseline and at 6 months in a subset of 19 children with 25-direction diffusion tensor imaging and deterministic tractography. Behavioral improvements were associated with increased white matter connectivity in frontal, temporal, and subcortical regions (hippocampus and basal ganglia) that have been previously shown to show anatomical, connectivity, and functional abnormalities in ASD. The current results suggest that improvements in social communication skills and a reduction in symptoms in children with ASD following treatment with autologous cord blood infusion were associated with increased structural connectivity in brain networks supporting social, communication, and language abilities. Stem Cells Translational Medicine 2019;8:138&10.

Keywords: Autism spectrum disorder; Autologous umbilical cord blood; Diffusion tensor imaging; White matter connectivity.

Figure 1

Overview of structural connectome creation. (A): Left, diffusion image; right, T1. (B) T1 registered in diffusion space. (C) Warp parcellated dilated UNC pediatric atlas to diffusion image space using advanced normalization tools. (D) Parcellated ROIs used to label tractography results. (E) DTI and deterministic tractography using the Connectome Mapper. (F) Visualization of connectome for a representative participant. Abbreviation: ROI, region of interest.

Figure 2

Mutual connectivity maps. Associations between changes in frontal, temporal, and subcortical white matter connectivity and changes in behavior following treatment with umbilical cord blood. Spheres represent region of interest node pairs. Tubes between spheres represent increased connectivity in edges between the nodes that is correlated with at least two outcome measures. Abbreviations: CGI‐I, Clinical Global Impression Improvement Scale; EOWPVT, Expressive One‐Word Picture Vocabulary Test; VABS, Vineland Adaptive Behavior Scale R, right hemisphere; L, Left hemisphere.