title: Tc-99m-HL91 imaging in the early detection of neuronal injury in a neonatal rat model of hypoxic ischemia.
abstract: OBJECTIVE
  Hypoxic-ischemic insult in newborns results in progressive neuronal loss. For neuroprotective therapy to be effective, it is important to identify high-risk neonates soon after birth. 99mTc-labeled imaging agent, Tc-99m-HL91, developed as a putative hypoxic reagent, has been reported to demonstrate increased uptake in ischemic myocardium. We hypothesized that Tc-99m-HL91 is sensitive for the early identification of hypoxic-ischemic injury in neonatal rat brains.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Sprague-Dawley rat pups.
  
  
  METHODS
  Postnatal day-7 pups were divided into four groups: hypoxic-ischemia, hypoxia-only, ischemia-only, and controls. In the early (2 hrs), intermediate (20 hrs), and late (44 hrs) reoxygenation phases, Tc-99m-HL91 in vivo and ex vivo imaging and quantitative autoradiography were performed. Regions of interest were drawn to calculate the contrast ratio of Tc-99m-HL91 uptake between the ipsilateral and contralateral hemispheres. Pathology, cerebral blood flow, and blood-brain barrier damage were determined.
  
  
  RESULTS
  After hypoxic-ischemia, there were very few pyknotic neurons in the early phase, many pyknotic neurons in the intermediate phase, and extensive neuronal loss in the late phase postreoxygenation. Blood-brain barrier damage occurred in the early phase, progressed in the intermediate phase, and became extensive in the late phase. The hypoxia-only and ischemia-only pups showed no neuronal or blood-brain barrier damage and had higher cerebral blood flow postreoxygenation compared with the hypoxia-ischemia pups. Regions of interest analysis of in vivo and ex vivo images and autoradiography revealed significantly higher Tc-99m-HL91 contrast ratio at early and intermediate phases, not late phase of hypoxic-ischemic group. Hypoxic-ischemia group had significantly higher contrast ratio values in the early and intermediate phases than the hypoxia-only and ischemia-only groups. A contrast ratio value of 0.15 in the early phase on postnatal day 7 had a sensitivity of 0.95 and specificity of 0.89 in detecting significant hypoxic-ischemic lesions on postnatal day 21.
  
  
  CONCLUSIONS
  Tc-99m-HL91 uptake is sensitive for the early detection of hypoxic-ischemic injury in neonatal brains.
authors.affiliation: Department of Nuclear Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan.
authors.forename: Bi-Fang
authors.initials: BF
authors.lastname: Lee
authors.forename: Lan-Wan
authors.initials: LW
authors.lastname: Wang
authors.forename: Sheng-Hsiang
authors.initials: SH
authors.lastname: Lin
authors.forename: Ting-Jyun
authors.initials: TJ
authors.lastname: Jhuo
authors.forename: Nan-Tsing
authors.initials: NT
authors.lastname: Chiu
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Hsia
authors.forename: Lie-Hang
authors.initials: LH
authors.lastname: Shen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D042241:Early Diagnosis; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging*; D009474:Neurons / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds; D010091:Oximes; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime