Quantitative T₂ MRI is predictive of neurodegeneration following organophosphate exposure in a rat model

Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative T₂ MRI could be used as a biomarker of neurodegeneration. Quantitative T₂ MRI was performed using a 9.4 T MRI on rats prior to and following soman exposure. T₂ images were taken at least 24 h prior, 1 h and 18-24 h after soman exposure. Rats were pre- and post-treated with HI-6 dimethanesulfonate and atropine methyl nitrate. A multicomponent T₂ acquisition and analysis was performed. Brains were stained with Fluoro-Jade C to assess neurodegeneration. Rats exposed to soman developed behavioral expression of electrographic seizures. At 18-24 h after soman exposure, significant increases in T₂, a possible marker of edema, were found in multiple regions. The largest changes were in the piriform cortex (before: 47.7 ± 1.4 ms; 18-24 h: 82.3 ± 13.4 ms). Fluoro-Jade C staining showed significant neurodegeneration 18-24 h post exposure. The piriform cortex had the strongest correlation between the change in relaxation rate and percent neurodegeneration (r = 0.96, p < 0.001). These findings indicate there is regionally specific neurodegeneration 24 h after exposure to soman. The high correlation between T₂ relaxivity and histopathology supports the use of T₂ as a marker of injury.