Atlas-based Multi-Parametric Quantitative Brain MRI Analysis of Children with Neurofibromatosis Type 1.
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PURPOSE: Neurofibromatosis type 1 (NF1) is a multisystem disorder with wide-ranging clinical presentations. Patients with NF1 may manifest with macrocephaly, strokes, and cognitive deficits, abnormal neural development, and other neurologic symptoms. This study used an atlas-based approach to quantitatively examine structural and physiologic changes of the brain in children with NF1. METHODS: Children evaluated for NF1 over a 9-year period at a children's hospital were retrospectively reviewed (n = 34). Children with intracranial tumors or prior strokes were excluded. Patients received diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging on a 3T MRI scanner. Using an atlas-based approach, quantitative assessment of regional brain volumes, median apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) was performed for the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brainstem, and cerebral white matter. Differences were tested between NF1 patients and 100 typically developing controls. RESULTS: Compared to controls, children with NF1 demonstrated significantly increased volume measurements in all brain regions (p < 0.001), significantly higher median ADC values in all structures except for the putamen and nucleus accumbens (p < 0.001), and significantly lower median CBF most notable in the cerebral white matter (p < 0.001), globus pallidus (p < 0.001), hippocampus (p < 0.001), amygdala (p < 0.001), and brainstem (p = 0.001). CONCLUSION: This study measured microstructural and physiologic brain changes in children with NF1 compared to typically developing children. Further studies are needed to elucidate the cellular and molecular basis for these differences. With further refinement, atlas-based quantitative MRI brain signatures may serve as useful biomarkers of neural development, cognitive dysfunction, and risks for vasculopathy-related strokes in children with NF1.