Histological-MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis

Purpose: To establish the relationship between ALS histopathology and quantitative MRI metrics. Materials and Methods: ALS patients (N = 8) in advanced stages of the disease were enrolled and, immediately after death, the brain of each patient was removed. Freshly excised ALS tissue was imaged at 3.0 Tesla with T₁and T₂ mapping protocols and subsequently stained with astrocyte, myelin, and neuronal markers. Measures of ALS histological stains were compared with the internal control (primary visual cortex) and longitudinal parametric maps. Results: Post-mortem T₁-weighted images demonstrate diminished contrast between gray and white matter and alterations in T₁ relaxation within the primary motor cortex. An increase in astrocyte number and reactivity as well as evident neuronal loss, a decrease in axonal density, and unraveling of the myelin sheaths in subcortical white matter were found in the ALS primary motor cortex exhibiting significant T₁ relaxation and contrast changes. Conclusion: This study provides a histopathological basis for differences in MR T₁ contrast and relaxation seen in the ALS brain.