Tc-99m-HL91 imaging in the early detection of neuronal injury in a neonatal rat model of hypoxic ischemia

Bi Fang Lee, Lan Wan Wang, Sheng Hsiang Lin, Ting Jyun Jhuo, Nan Tsing Chiu, Chao Ching Huang, Chien Chung Hsia, Lie Hang Shen

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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. Tc-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. Design: Laboratory investigation. Setting: University research laboratory. Subjects: Sprague-Dawley rat pups. Interventions: 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. Measurements and Main 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. Conclusion: Tc-99m-HL91 uptake is sensitive for the early detection of hypoxic-ischemic injury in neonatal brains.

Original languageEnglish
Pages (from-to)1930-1938
Number of pages9
JournalCritical care medicine
Issue number6
Publication statusPublished - 2012 Jun

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine


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