Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia–Ischemia

Abstract

Background Diffusion MRI (dMRI) is known to be sensitive to hypoxic–ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. Purpose To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel‐based analyses. Study Type Prospective. Population A total of 42 neonates (24 males and 18 females). Field Strength/Sequence 3‐T, diffusion‐weighted echo‐planar imaging. Assessment Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross‐section (FC), and fiber density and cross‐section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel‐based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). Statistical Tests One‐way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel‐wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. Results For severe HIE, ROI‐based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract‐based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto‐occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle‐posterior IFOF and ILF, and in the central‐to‐right part of SCC in moderate HIE. Data Conclusion For severe HIE, extensive microstructural injury was identified. For moderate–mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. Evidence Level 1 Technical Efficacy Stage 3

Quantification of Diffusion Magnetic Resonance Imaging for Prognostic Prediction of Neonatal Hypoxic-Ischemic Encephalopathy

“…ABA performed with diffusion MRI showed that severe HIE neonates scanned at approximately 1 week of age [[94]] showed an extensive reduction in FA, while moderate HIE neonates showed a reduction in FA only in the inferior association fibers (inferior longitudinal fasciculus and inferior fronto-occipital fasciculus). In addition, diffusion MRI measurements obtained by non-tensor modeling, such as fiber density, fiber cross-section, and fiber density and cross-section obtained by pixel-based analysis, demonstrate the potential for highly sensitive detection of anatomical changes seen in mild-to-moderate HIE newborns [[94]]. The topic of non-tensor modeling is discussed in the section “Remaining Challenges and Future Directions.”…”

Editorial for “Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia‐Ischemia”

“…In this issue of JMRI, Cao et al 8 present a systematic evaluation of microstructural changes of tissues due to mild to severe HIE at ROI, tract, and fixel levels. The ROI analysis was based on the JHU Neonatal Atlas and consisted of 40 ROIs bilaterally in the white matter and deep gray matter nuclei.…”