NFB-11. White Matter Differences in Children With Nf1 Compared to Controls

Abstract

INTRODUCTION Neurofibromatosis type 1 (NF1) is a genetic condition in which children develop learning challenges and glioma. White matter tracts (WMT) are implicated in these cognitive functions, while oligodendroglial precursor cells are implicated in both gliomagenesis and white-matter development. Specific WMTs have not been well characterized in NF1. METHODS Twenty NF1 patients aged 1.4–17.6 years (M = 9.5 years, 24 male) and 20 age-and-sex-matched controls underwent dMRI at 3T (25 directions, b=1000 s/mm2). Automated segmentation of WMTs extracted fractional anisotropy (FA) and mean diffusivity (MD) of 18 major WMTs. Covariance analysis examined the effect of group (NF1/controls) on FA/MD after controlling for intracranial volume. Regression analyses for WMTs determined the interaction of FA/MD with age for NF1 patients compared to controls. Significance was set at p<0.05 after correcting for multiple comparisons using false discovery rate. RESULTS Compared to controls, children with NF1 had significantly decreased FA in 8 and increased MD in 12/18 tracts. Differences held after controlling for intracranial volume. The interaction between group and age accounted for a significant proportion of the variance in FA in 9 and in MD in 16/18 tracts. FA and MD differences between children with NF1 and controls were greater at younger than older ages. CONCLUSION Microstructural differences were observed in WMTs in children with NF1 compared to controls. These differences were not explained by intracranial volume and were most pronounced in younger children with NF1 compared to controls. These findings have implications for understanding neurocognitive deficits and gliomagenesis observed in children with NF1.

Elucidating microstructural alterations in neurodevelopmental disorders: application of advanced diffusion-weighted imaging in children with Rasopathies

“…Prior diffusion tensor imaging studies on children with NF1 and NS found widespread reduced fractional anisotropy and increased mean diffusivity in both conditions (8, 23,25). Fractional anisotropy and mean diffusivity are sensitive to disruptions in microstructural integrity; however, they are also non-speci c measures and di cult to interpret in voxels with complex microstructural properties (e.g., crossing bers) (28, 29).…”

“…These ROIs comprise grey and white matter, whereas the tracts are predominantly white matter. ROIs and white matter tracts were selected based on prior diffusion tensor imaging studies where signi cant alterations to parameters such as fractional anisotropy and mean diffusivity were found in NF1 and NS (8, [23][24][25]. TRActs Constrained by UnderLying Anatomy (TRACULA) delineated 42 major white matter tracts using probabilistic tractography (26).…”