title: Long-term effects of neonatal hypoxia-ischemia on structural and physiological integrity of the eye and visual pathway by multimodal MRI.
abstract: OBJECTIVE
  Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brain's visual pathways.
  
  
  METHODS
  Eight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner.
  
  
  RESULTS
  Within the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres.
  
  
  CONCLUSIONS
  High-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brain's visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury.
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Chan
authors.affiliation: UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Swarupa
authors.initials: S
authors.lastname: Kancherla
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Fan
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005123:Eye / Q000098:blood supply*; D005500:Follow-Up Studies; D000860:Hypoxia / Q000175:diagnosis* / Q000503:physiopathology; D007511:Ischemia / Q000175:diagnosis* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014793:Visual Cortex / Q000473:pathology* / Q000503:physiopathology; D014795:Visual Pathways / Q000473:pathology* / Q000503:physiopathology
keywords: contrast-enhanced MRI; diffusion tensor imaging; neonatal hypoxia-ischemia; ocular tissue permeability; visual pathway integrity