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

Abstract

Background Cognitive and language impairments constitute the majority of disabilities observed in preterm infants. It remains unclear if diffuse excessive high signal intensity (DEHSI) on MRI at term represents delayed white matter maturation or pathology. Methods We hypothesized that diffusion tensor imaging-based objectively quantified DEHSI measures at term will be strong predictors of cognitive and language development at 2 years in a cohort of 41 extremely low birth weight (ELBW; ≤1000g) infants. Using an automated probabilistic atlas, mean diffusivity maps were used to objectively segment and quantify DEHSI 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 DEHSI 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 DEHSI regions also correlated significantly with the Bayley scores (R2 34.7%; P<0.001 for each). Infants in the highest quartile for DEHSI volumes had scores between 19–24 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 DEHSI. Conclusions These findings lend further evidence that DEHSI is pathologic and that objectively quantified diffusion-based DEHSI volume at term is associated with cognitive and language impairments. Our approach could be utilized for risk stratification and early intervention for such high-risk extremely preterm infants.

Early Conventional MRI for Prediction of Neurodevelopmental Impairment in Extremely-Low-Birth-Weight Infants

“…These findings suggest that we must exercise caution in relying on MRI as a key predictor of NDI[23, 24]. In our cohort, the inability of WM abnormalities to predict outcomes other than CP was true irrespective of the scoring system we employed.…”

“…We speculate that defining the presence, type, and degree of WM abnormality on qualitative MRI is subjective and this contributes to our inability to predict cognitive or language outcomes. Furthermore, conventional MRI is less sensitive in diagnosing delayed/aberrant brain development and microstructural abnormalities that are likely common contributors to cognitive and language development[24]. Beyond conventional MRI data, advanced applications of MRI may prove to be more helpful in predicting outcomes, along with other forms of neurologic assessment.…”

Advanced neuroimaging and its role in predicting neurodevelopmental outcomes in very preterm infants

“…Both studies found a strong association between volume of DEHSI and cognitive and language scores on the Bayley-III at 2 years of age. 41,65 …”

“…41,65 Four additional studies that examined the centrum semiovale also found a significant correlation between diffusion metrics or brain NAA/Choline and cognitive and language scores at 18–24 months CA. 35,50,54,60 This finding is in distinct contrast to studies that have qualitatively evaluated DEHSI and found no association with outcomes.…”

Brain functional network connectivity development in very preterm infants: The first six months

“…While connectivity for such long-range networks is expected to be lower, subtle and diffuse brain abnormalities such as diffuse excessive high signal intensity abnormalities may also be contributing to the lower connectivity observed in these regions. Such abnormalities are observed in up to 75-80% of very preterm infants and appear to be associated with cognitive and language deficits [47,48]. It is not yet known if infants with diffuse excessive high signal intensity abnormalities exhibit early maturational delays in executive and frontoparietal networks.…”