Influence of Paramagnetic Changes in Cytochrome c on T2-Weighted MRI of G93A-SOD1 Transgenic ALS Mice

Karunakaran Chandran¹, Xiping Liu¹, Donna McAllister¹, Vinai Roopchansingh¹, B. Douglas Ward¹, William E. Antholine¹, Joy Joseph¹, Shi-Jiang Li¹, B. Kalyanaraman¹

The role of mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS) is well established. In this study we have combined the EPR and MRI techniques to better understand the changes in the MR signal intensity detected in a preclinical ALS mouse model. Low-temperature EPR data indicate that cytochrome c release from mitochondria during ALS progression correlates with the observed T2 increase in brain stem of ALS mice. The T2 hyperintensity may be attributed to increased spin conversion from a low spin iron (S=1/2) to a high spin iron (S=5/2) of cytochrome c in ALS brain stem tissues.