Synthetic MRI demonstrates prolonged regional relaxation times in the brain of preterm born neonates with severe postnatal morbidity

BACKGROUND: To identify preterm infants at risk for neurodevelopment impairment that might benefit from early neurorehabilitation, early prognostic biomarkers of future outcomes are needed.

OBJECTIVE: To determine whether synthetic MRI is sensitive to age-related changes in regional tissue relaxation times in the brain of preterm born neonates when scanned at term equivalent age (TEA, 37-42 weeks), and to investigate whether severe postnatal morbidity results in prolonged regional tissue relaxation times.

MATERIALS AND METHODS: This retrospective study included 70 very preterm born infants scanned with conventional and synthetic MRI between January 2017 and June 2019 at TEA. Infants with severe postnatal morbidity were allocated to a high-risk group (n = 22). All other neonates were allocated to a low-risk group (n = 48). Linear regression analysis was performed to determine the relationship between relaxation times and postmenstrual age (PMA) at scan. Analysis of covariance was used to evaluate the impact of severe postnatal morbidity in the high-risk group on T1 and T2 relaxation times. Receiver operating characteristic (ROC) curves were plotted and analysed with area under the ROC curve (AUC) to evaluate the accuracy of classifying high-risk patients based on regional relaxation times.

RESULTS: A linear age-related decrease of T1 and T2 relaxation times correlating with PMA at scan (between 37 and 42 weeks) was found in the deep gray matter, the cerebellum, the cortex, and the posterior limb of the internal capsule (PLIC) (p < .005 each), but not in the global, frontal, parietal, or central white matter. Analysis of covariance for both risk groups, adjusted for PMA, revealed significantly prolonged regional tissue relaxation times in neonates with severe postnatal morbidity, which was best illustrated in the central white matter of the centrum semiovale (T1 Δ = 11.5%, T2 Δ = 13.4%, p < .001) and in the PLIC (T1 Δ = 9.2%, T2 Δ = 6.9%, p < .001). The relaxation times in the PLIC and the central white matter predicted high-risk status with excellent accuracy (AUC range 0.82-0.86).

CONCLUSION: Synthetic MRI-based relaxometry in the brain of preterm born neonates is sensitive to age-related maturational changes close to TEA. Severe postnatal morbidity correlated with a significant delay in tissue relaxation. Synthetic MRI may provide early prognostic biomarkers for neurodevelopment impairment.