ORIGINAL RESEARCH PEDIATRICS A Prospective Longitudinal BrainMorphometry Study of Children

BACKGROUND AND PURPOSE: Age-related changes in brain morphology are crucial to understanding the neurobiology of sickle cell disease. We hypothesized that the growth trajectories for total GM volume, total WM volume, and regional GM volumes are altered in children with sickle cell disease compared with controls. MATERIALS ANDMETHODS: We analyzed T1-weighted images of the brains of 28 children with sickle cell disease (mean baseline age, 98 months; female/male ratio, 15:13) and 28 healthy age- and sex-matched controls (mean baseline age, 99 months; female/male ratio, 16:12). The total number ofMR imaging examinations was 141 (2–4 for each subject with sickle cell disease, 2–3 for each control subject). Total GM volume, total WM volume, and regional GM volumes were measured by using an automated method. We used the multilevel-model-for-change approach to model growth trajectories. RESULTS: Total GM volume in subjects with sickle cell disease decreased linearly at a rate of 411 mm3 per month. For controls, the trajectory of total GM volumewas quadratic; we did not observe a significant linear decline. For subjects with sickle cell disease, we found 35 brain structures that demonstrated age-related GM volume reduction. Total WM volume in subjects with sickle cell disease increased at a rate of 452 mm3 per month, while the trajectory of controls was quadratic. CONCLUSIONS: There was a significant age-related decrease in total GM volume in children with sickle cell disease. The GM volume reduction was spatially distributed widely across the brain, primarily in the frontal, parietal, and occipital lobes. Total WM volume i