DFC-Igloo: A dynamic functional connectome learning framework for identifying neurodevelopmental biomarkers in very preterm infants

Background and objective: Very preterm infants are susceptible to neurodevelopmental impairments, necessitating early detection of prognostic biomarkers for timely intervention. The study aims to explore possible functional biomarkers for very preterm infants at born that relate to their future cognitive and motor development using resting-state fMRI. Prior studies are limited by the sample size and suffer from efficient functional connectome (FC) construction algorithms that can handle the noisy data contained in neonatal time series, leading to equivocal findings. Therefore, we first propose an enhanced functional connectome construction algorithm as a prerequisite step. We then apply the new FC construction algorithm to our large prospective very preterm cohort to explore multi-level neurodevelopmental biomarkers.

Methods: There exists an intrinsic relationship between the structural connectome (SC) and FC, with a notable coupling between the two. This observation implies a putative property of graph signal smoothness on the SC as well. Yet, this property has not been fully exploited for constructing intrinsic dFC. In this study, we proposed an advanced dynamic FC (dFC) learning model, dFC-Igloo, which leveraged SC information to iteratively refine dFC estimations by applying graph signal smoothness to both FC and SC. The model was evaluated on artificial small-world graphs and simulated graph signals.

Results: The proposed model achieved the best and most robust recovery of the ground truth graph across different noise levels and simulated SC pairs from the simulation. The model was further applied to a cohort of very preterm infants from five Neonatal Intensive Care Units, where an enhanced dFC was obtained for each infant. Based on the improved dFC, we identified neurodevelopmental biomarkers for neonates across connectome-wide, regional, and subnetwork scales.

Conclusion: The identified markers correlate with cognitive and motor developmental outcomes, offering insights into early brain development and potential neurodevelopmental challenges.