Manganese‐enhanced MRI detection of neurodegeneration in neonatal hypoxic‐ischemic cerebral injury

Abstract

In this study, we investigated the Mn‐enhanced MRI (MEMRI) for detecting neurodegenerative processes in neonatal hypoxic‐ischemic (H‐I) cerebral injury. Seven‐day‐old rats were induced with H‐I injury, and scanned for T₁‐weighted image (T₁WI) and T₂‐weighted image (T₂WI) with and without systemic MnCl₂ administration. Serial histological analysis was performed for Mn‐superoxide dismutase (Mn‐SOD) and glutamine synthetase (GS), which are Mn‐binding enzymes against the oxidative stress and glutamate excitotoxicity in neurodegeneration. In the acute phase (first 2 days), the ipsilateral lesion exhibited no Mn enhancement in T₁WIs, with histology showing no Mn‐SOD and GS production. In the mid‐phase (from day 3), Mn enhancement was found in the cortex, basal ganglia, and hippocampus, correlating with local Mn‐SOD and GS increase. In the late phase, the enhancement became more localized to the pericyst basal ganglia and cortex, and then gradually diminished. In T₂WIs, a signal decrease was observed from day 3 in the corresponding regions. Hypointense voids gradually formed in the late phase, correlating with the local iron accumulation. H‐I rats without Mn²⁺ administration exhibited similar but weak changes in T₁WIs and T₂WIs from days 14 and 7, respectively. These results indicate that Mn²⁺ may be a useful in vivo probe for monitoring Mn‐SOD and GS enzymatic activities. Magn Reson Med, 2008.