Neurite orientation dispersion and density imaging for evaluating the severity of neonatal hypoxic-ischemic encephalopathy in rats

Purpose: To evaluate the utility of neurite orientation dispersion and density imaging (NODDI) for longitudinally assessing neonatal hypoxic-ischemic (HI) encephalopathy severity with 7.0 T magnetic resonance imaging. Methods: Thirteen 8-day-old Wistar rats underwent unilateral ligation of the left common carotid artery followed by mild (1 h; n = 6) or severe (2 h; n = 7) hypoxic exposure (8% O₂, 34 °C). Diffusion-weighted, T₂-weighted (T₂W), and flow-sensitive alternating inversion recovery images were obtained with a horizontal 7.0 T scanner at 1, 24, 72, and 168 h after HI insult. The fractional anisotropy (FA), apparent diffusion coefficient (ADC), intracellular volume fraction (ICVF), isotropic volume fraction (ISO), orientation dispersion index (ODI), and cerebral blood flow (CBF) values were calculated for each group (mild and severe) at each time point (1, 24, 72, and 168 h). ICVF, ISO, and ODI were the NODDI parameters. Results: Left hemisphere brain damage was identified as slight hyperintensity on T₂W images after 1 h in both groups. In the severe group only, the signal hyperintensity increased time-dependently over 168 h. The ADC and CBF were not significantly different between the groups within any region. The ICVF and ODI were significantly higher in the severe vs. mild group at various points between 1 and 168 h (cortex, striatum, or white matter), whereas the FA was significantly higher in the mild vs. severe group at 168 h (cortex and white matter). The ISO was higher in the severe vs. mild group at 72 h (striatum) and 168 h (all regions), while the ISO was significantly higher in the mild vs. severe group at 24 h (all regions). Conclusion: Here, ODI, a NODDI metric, identified early differences between mild and severe HI injuries. Our findings support the potential utility of NODDI for determining neonatal HI encephalopathy severity in rats.