Abstract Body (Do not enter title and authors here): Background:
Cardiopulmonary bypass (CPB) can trigger inflammatory and oxidative stresses in the developing brain. Clinical studies showed altered brain network structure in children after infant cardiac surgery. However, the impact of CPB on structural connectivity remains poorly understood. This study aims to determine the effects of CPB on structural connectivity and underlying cellular events using a juvenile porcine model.

Methods:
CPB (150 min total) was performed on 2-week-old Yorkshire piglets. High-resolution diffusion tensor imaging (DTI) and neurite orientation dispersion and density (NODDI) imaging were performed 4 weeks post-CPB in a total of 12 animals (Control; n=7, CPB; n=5). Structural connectivity assay together with histological analysis was conducted to assess the brain network organization.

Results:
Our network analysis (Image 1) revealed a CPB-induced reduction of structural connections in particular nodes, such as in the anterior prefrontal cortex (APC), primary somatosensory cortex, substantia nigra (SN), and globus pallidus (GP). In contrast, there was an increase in the premotor cortex (PreMC), primary motor cortex (PriMC), dorsal posterior cingulate cortex (DPCC), and somatosensory cortex (SAC). Three-dimensional images were generated based on these altered nodes, and tractography was generated to indicate changed fiber tracking (Image 2). We found reduced network connections between the basal ganglia and frontal cortex, and increased connections between the motor and posterior region. DTI and NODDI indicated that microstructures of the superior corona radiata (SCR), internal capsule (PLIC), and anterior prefrontal (AP-WM), motor (PreM-/PriM-WM), and somatosensory white matter (SA-WM) were significantly altered after CPB (Image 3). While Iba1+ microglia was activated across all brain regions after CPB (P<.05), CPB-induced oligodendrocyte immatureness was identified in the WMs involved in APC-SN and APC-GP pathways (P<.05). Notably, CPB increased the number of mature oligodendrocytes in motor and SA-WMs (P<.05) where structural connections were increased after CPB. In addition, we found SN dopaminergic neuron injury after CPB (P<.05).

Conclusion:
CPB altered structural network organization in the developing brain. Spatial differences in oligodendrocyte responses and susceptibility of specific subpopulations of neurons may contribute to the unique connectivity alterations observed after CPB.