Prediction of Gait Impairment in Toddlers Born Preterm From Near-Term Brain Microstructure Assessed With DTI, Using Exhaustive Feature Selection and Cross-Validation

AIM: To predict gait impairment in toddlers born preterm with very-low-birth-weight (VLBW), from near-term white-matter microstructure assessed with diffusion tensor imaging (DTI), using exhaustive feature selection, and cross-validation. METHODS: Near-term MRI and DTI of 48 bilateral and corpus callosum regions were assessed in 66 VLBW preterm infants; at 18–22 months adjusted-age, 52/66 participants completed follow-up gait assessment of velocity, step length, step width, single-limb support and the Toddle Temporal-spatial Deviation Index (TDI). Multiple linear models with exhaustive feature selection and leave-one-out cross-validation were employed in this prospective cohort study: linear and logistic regression identified three brain regions most correlated with gait outcome. RESULTS: Logistic regression of near-term DTI correctly classified infants high-risk for impaired gait velocity (93% sensitivity, 79% specificity), right and left step length (91% and 93% sensitivity, 85% and 76% specificity), single-limb support (100% and 100% sensitivity, 100% and 100% specificity), step width (85% sensitivity, 80% specificity), and Toddle TDI (85% sensitivity, 75% specificity). Linear regression of near-term brain DTI and toddler gait explained 32%–49% variance in gait temporal-spatial parameters. Traditional MRI methods did not predict gait in toddlers. INTERPRETATION: Near-term brain microstructure assessed with DTI and statistical learning methods predicted gait impairment, explaining substantial variance in toddler gait. Results indicate that at near term age, analysis of a set of brain regions using statistical learning methods may offer more accurate prediction of outcome at toddler age. Infants high risk for single-limb support impairment were most accurately predicted. As a fundamental element of biped gait, single-limb support may be a sensitive marker of gait impairment, influenced by early neural correlates that are evolutionarily and developmentally conserved. For infants born preterm, early prediction of gait impairment can help guide early, more effective intervention to improve quality of life. WHAT THIS PAPER ADDS: • Accurate prediction of toddler gait from near-term brain microstructure on DTI. • Use of machine learning analysis of neonatal neuroimaging to predict gait. • Early prediction of gait impairment to guide early treatment for children born preterm.