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However, to date, useful biomarkers which may be used to early predict neurodevelopmental impairment for proper commencement of hypothermia therapy is still lacking. This study aimed to determine whether the early neuroimaging characteristics and ultrastructural correlates were associated with different injury progressions and brain damage severity outcomes after neonatal hypoxic ischaemia. Longitudinal 7\u2009T MRI was performed within 6\u2009h, 24\u2009h and 7\u2009days after hypoxic ischaemia in rat pups. The brain damage outcome at 7\u2009days post-hypoxic ischaemia assessed using histopathology and MRI were classified as mild, moderate and severe. We found there was a spectrum of different brain damage severity outcomes after the same duration of hypoxic ischaemia. The severity of brain damage determined using MRI correlated well with that assessed by histopathology. Quantitative MRI characteristics denoting water diffusivity in the tissue showed significant differences in the apparent diffusion coefficient deficit volume and deficit ratios within 6\u2009h, at 24\u2009h and 7\u2009days after hypoxic ischaemia among the 3 different outcome groups. The susceptible brain areas to hypoxic ischaemia were revealed by the temporal changes in regional apparent diffusion coefficient values among three outcome groups. Within 6\u2009h post-hypoxic ischaemia, a larger apparent diffusion coefficient deficit volume and deficit ratios and lower apparent diffusion coefficient values were highly associated with adverse brain damage outcome. In the apparent diffusion coefficient deficit areas detected early after hypoxic ischaemia which were highly associated with severe damage outcome, transmission electron microscopy revealed fragmented nuclei; swollen rough endoplasmic reticulum and degenerating mitochondria in the cortex and prominent myelin loss and axon detraction in the white matter. Taken together, different apparent diffusion coefficient patterns obtained early after hypoxic ischaemia are highly associated with different injury progression leading to different brain damage severity outcomes, suggesting the apparent diffusion coefficient characteristics may be applicable to early identify the high-risk neonates for hypothermia therapy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab048","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T12:53:55Z","timestamp":1616676835000},"source":"Crossref","is-referenced-by-count":5,"title":["Early neuroimaging and ultrastructural correlates of injury outcome after neonatal hypoxic-ischaemia"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7416-759X","authenticated-orcid":false,"given":"Yu-Chieh Jill","family":"Kao","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seu-Hwa","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Feng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9379-4211","authenticated-orcid":false,"given":"Bao-Yu","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-4373","authenticated-orcid":false,"given":"Cheng-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Medical Imaging, Taipei Medical University Hospital, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70428, 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