High and ultra-high field MRI in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the upper and lower motor neurons. In ALS, pathologic changes in the primary motor cortex (M1) include Betz cell depletion and the presence of reactive iron-loaded microglia. Differently from the lower motor neuron impairment that can be carefully investigated with electrophysiologic tests, the evaluation of upper motor neuron (UMN) burden is mainly clinical and is partially confounded by signs related to lower motor neuron degeneration. Therefore, this study was focused on searching for qualitative and quantitative MRI markers of UMN impairment in ALS patients using both 7T and 3T MR systems. 7T MRI allows detailed depiction of the normal radiological anatomy of M1 and offers the possibility to reveal morphological changes in ALS patients, namely the thinning and T2* hypointensity of the deep layers of the primary motor cortex. These MR features are detectable also using clinical 3T MR systems, although with less accuracy than at 7T, and are assessable at the level of individual subjects. Both thinning and T2* hypointensity of M1 can have a not homogeneous distribution among patients. Indeed, they can affect the cortical ribbon with a variable length and target specific sub-regions of the motor cortex. Areas of the motor homunculus with radiological abnormalities correspond to the body regions affected by UMN impairment, and the degree of MR alterations is associated with the magnitude of clinical UMN burden. Indeed, both MR abnormalities of M1 correlate with the clinical UMN impairment and seem to correspond to pathological hallmarks of ALS. More in detail, the cortical thinning can represent the result of the upper motor neurons loss, whereas the T2* hypointensity can be related to the intracortical accumulation of activated iron-load microglia. The amount of intracortical iron, then the degree of neuroinflammation, can be estimated using a quantitative method (QSM) at both 7T and 3T. QSM allows the objective evaluation of the cortex and the monitoring of iron deposits over time. Interestingly, the magnetic susceptibility of each sub-region of the motor homunculus correlates with the clinical UMN impairment of the corresponding limb, supporting the link among neuroinflammation, loss of Betz cells and clinical UMN impairment.