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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>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\u2010based analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Type<\/jats:title><jats:p>Prospective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>A total of 42 neonates (24 males and 18 females).<\/jats:p><\/jats:sec><jats:sec><jats:title>Field Strength\/Sequence<\/jats:title><jats:p>3\u2010T, diffusion\u2010weighted echo\u2010planar imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Assessment<\/jats:title><jats:p>Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross\u2010section (FC), and fiber density and cross\u2010section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel\u2010based analysis was performed to assess group differences in individual fiber components within a voxel (fixel).<\/jats:p><\/jats:sec><jats:sec><jats:title>Statistical Tests<\/jats:title><jats:p>One\u2010way analysis of covariance (ANCOVA) to compare dMRI metrics among severe\/moderate\/mild HIE and control groups and general linear model for fixel\u2010wise group differences (age, sex, and body weight as covariates). Adjusted <jats:italic>P<\/jats:italic> value\u2009&lt;\u20090.05 was considered statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For severe HIE, ROI\u2010based 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\u2010based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto\u2010occipital 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\u2010posterior IFOF and ILF, and in the central\u2010to\u2010right part of SCC in moderate HIE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Conclusion<\/jats:title><jats:p>For severe HIE, extensive microstructural injury was identified. For moderate\u2013mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Level<\/jats:title><jats:p>1<\/jats:p><\/jats:sec><jats:sec><jats:title>Technical Efficacy<\/jats:title><jats:p>Stage 3<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmri.28366","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T12:38:53Z","timestamp":1658407133000},"page":"1131-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia\u2013Ischemia"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8119-6436","authenticated-orcid":false,"given":"Zuozhen","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education, Department of 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