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

• Published in: Critical care medicine Vol. 40; no. 6; p. 1930
• Main Authors: Lee, Bi-Fang, Wang, Lan-Wan, Lin, Sheng-Hsiang, Jhuo, Ting-Jyun, Chiu, Nan-Tsing, Huang, Chao-Ching, Hsia, Chien-Chung, Shen, Lie-Hang
• Format: Journal Article
• Language: English
• Published: United States 01.06.2012
• Subjects: Animals; Animals, Newborn; Disease Models, Animal; Early Diagnosis; Hypoxia-Ischemia, Brain - diagnostic imaging; Neurons - diagnostic imaging; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0b013e31824e1883

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. Laboratory investigation. University research laboratory. Sprague-Dawley rat pups. 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. 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. Tc-99m-HL91 uptake is sensitive for the early detection of hypoxic-ischemic injury in neonatal brains.