Early trajectory of white matter development in nonsyndromic craniosynostosis compared with neurotypical infants: a 3-site diffusion tensor imaging study

OBJECTIVE: Nonsyndromic craniosynostosis (NSC) might disrupt normal white matter maturation, and infant surgical intervention remains the standard of care. The aim of this multisite study was to assess baseline differences in white matter tract development and compare white matter tract development following surgical correction in NSC patients relative to normally developing controls using diffusion tensor imaging (DTI). METHODS: Pre- and postoperative DTI was obtained at three centers (Arkansas, Vanderbilt, and Yale) in children who underwent surgical correction for NSC (n = 16), and age-matched control scans (n = 47) were obtained from the Lifespan Baby Connectome Project. Analysis of diffusion parameters was performed for 48 white matter tracts defined by the Johns Hopkins University white matter tractography atlas. Descriptive analyses were used to compare diffusion parameters between the NSC and control cohorts at pre- and postoperative time points. Linear mixed-effects models were fit to assess whether tract development between pre- and postoperative scans differed between patients and controls. RESULTS: Patients with NSC showed greater global mean, axial, and radial diffusivity at the preoperative time point compared with age-matched controls. Following surgical correction, the NSC cohort had greater decreases in mean, axial, and radial diffusivity across multiple association, commissural, and projection tracts (e.g., the inferior and superior longitudinal fasciculi, corpus callosum, corona radiata, cingulum, and internal and external capsules) between pre- and postoperative time points compared with controls. Changes in fractional anisotropy were comparable between patients and controls. CONCLUSIONS: Patients with NSC exhibited greater decreases in diffusivity across major white matter tracts following surgery compared with normally developing controls. These decreases might represent accelerated maturation/normalization of white matter following surgical correction of NSC.