Magnetic resonance imaging reveals neuronal degeneration in the brainstem of the superoxide dismutase 1 transgenic mouse model of amyotrophic lateral sclerosis.

Magnetic resonance imaging (MRI) is becoming the preferred neuroimaging modality for the diagnosis of human amyotrophic lateral sclerosis (ALS). A useful animal model of ALS is the superoxide dismutase 1G93A G1H transgenic mouse, which shows many of the clinico-pathological features of the human condition. We have employed a 4.7-Tesla MRI instrument to determine whether a noninvasive imaging approach can reveal pathological changes in the nervous system of this animal model. Our T2-weighted MRI revealed consistent changes in brain and brainstem of these mice. Hyperintensities, indicative of neuropathology, were observed in several areas including the nucleus ambiguus, facial nucleus, trigeminal motor nucleus, rostroventrolateral reticular nucleus, lateral paragigantocellular nucleus and the substantia nigra. Histology analysis including neuronal counts of the imaged brains confirmed the T2-weighted MRI findings. Enlarged ventricles and hypointense striations, indicative of global atrophy, were also observed in the brain and cerebellum. This atrophy was confirmed by fresh brain weight data. The extensive global degeneration involving multiple structures suggests a multisystem disease that is similar to human ALS.