MR imaging depicts oxidative stress induced by methemoglobin

To correlate the effect of red blood cell hemoglobin on signal generation during magnetic resonance (MR) imaging and local oxidation of low-density lipoprotein (LDL).

Informed consent was obtained from all volunteers participating in this study, which was approved by the research ethics board. T1 relaxometry of blood samples from six volunteers was performed. Lipid peroxidation was assayed by using thiobarbituric acid reactive species (TBARS) and fluorescence quenching of cis-parinaric acid. Two-tailed Student t tests were used to detect differences between means. A Pearson correlation coefficient was calculated to determine the linearity of the data.

Lipid oxidation was significantly enhanced after addition of blood, according to results of the TBARS assay; greater oxidation occurred with ferric than with ferrous blood. The cis-parinaric acid assay demonstrated increased oxidative stress caused by extracellular as compared with intracellular ferric hemoglobin. MR imaging measures showed a T1 relaxivity that was 10 times higher for ferric than for ferrous forms of hemoglobin.

Extracellular ferric hemoglobin is significantly more pro-oxidant and has higher T1 relaxivity than its ferrous counterparts. These results support the hypothesis that ferric methemoglobin-generated T1 high signal intensity reflects a pro-oxidant environment that, in the setting of vessel wall disease, might be proatherogenic.