Katrina Burson

Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

Objective To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants. Methods A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities. Results Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum. Conclusions Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments.

Automatically Quantified Diffuse Excessive High Signal Intensity on MRI Predicts Cognitive Development in Preterm Infants

BACKGROUND Cognitive and language impairments constitute the majority of disabilities observed in preterm infants. It remains unclear if diffuse excessive high signal intensity on magnetic resonance imaging at term represents delayed white matter maturation or pathology. METHODS We hypothesized that diffusion tensor imaging-based objectively quantified diffuse excessive high signal intensity measures at term will be strong predictors of cognitive and language development at 2 years in a cohort of 41 extremely low birth weight (≤1000 g) infants. Using an automated probabilistic atlas, mean diffusivity maps were used to objectively segment and quantify diffuse excessive high signal intensity volume and mean, axial, and radial diffusivity measures. Standardized neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant Development, third edition. RESULTS Thirty-six of the 41 infants (88%) had complete developmental data at follow-up. Objectively quantified diffuse excessive high signal intensity volume correlated significantly with cognitive and language scores at 2 years (P < 0.001 for both). The sum values of the three diffusivity measures in detected diffuse excessive high signal intensity regions also correlated significantly with the Bayley scores (r(2) 34.7%; P < 0.001 for each). Infants in the highest quartile for diffuse excessive high signal intensity volumes had scores between 19 and 24 points lower than infants in the lowest quartile (P < 0.01). When diagnosed subjectively by neuroradiologists however, Bayley scores were not significantly lower in infants with extensive diffuse excessive high signal intensity. CONCLUSIONS These findings lend further evidence that diffuse excessive high signal intensity is pathologic and that objectively quantified diffusion-based diffuse excessive high signal intensity volume at term is associated with cognitive and language impairments. Our approach could be used for risk stratification and early intervention for such high-risk extremely preterm infants.