Diffusion tensor imaging of post mortem multiple sclerosis brain

Abstract

Magnetic resonance imaging (MRI) is being used to probe the central nervous system (CNS) of patients with multiple sclerosis (MS), a chronic demyelinating disease. Conventional T2-weighted MRI (cMRI) largely fails to predict the degree of patients' disability. This shortcoming may be due to poor specificity of cMRI for clinically relevant pathology. Diffusion tensor imaging (DTI) has shown promise to be more specific for MS pathology. In this study we investigated the association between histological indices of myelin content, axonal count and gliosis, and two measures of DTI (mean diffusivity [MD] and fractional anisotropy [FA]), in unfixed post mortem MS brain using a 1.5-T MR system. Both MD and FA were significantly lower in post mortem MS brain compared to published data acquired in vivo. However, the differences of MD and FA described in vivo between white matter lesions (WMLs) and normal-appearing white matter (NAWM) were retained in this study of post mortem brain: average MD in WMLs was 0.35 × 10− 3 mm2/s (SD, 0.09) versus 0.22 (0.04) in NAWM; FA was 0.22 (0.06) in WMLs versus 0.38 (0.13) in NAWM. Correlations were detected between myelin content (Trmyelin) and (i) FA (r = − 0.79, p < 0.001), (ii) MD (r = 0.68, p < 0.001), and (iii) axonal count (r = − 0.81, p < 0.001). Multiple regression suggested that these correlations largely explain the apparent association of axonal count with (i) FA (r = 0.70, p < 0.001) and (ii) MD (r = − 0.66, p < 0.001). In conclusion, this study suggests that FA and MD are affected by myelin content and – to a lesser degree – axonal count in post mortem MS brain.

Heterogeneity in age-related white matter changes

“…They concluded that both techniques are sufficiently suited to detect microstructural tissue alterations at least in the white matter of the murine brain. Postmortem histological analyses assessing myelin content, axonal density, and gliosis revealed similar correlations in brains of patients with Alzheimer's disease [29] or multiple sclerosis [71][72][73].…”

In VivoDiffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy

“…The correlations between the diffusion tensor and histological parameters of human white matter had hitherto only been addressed in the postmortem state. In multiple sclerosis, DTI was demonstrated to correlate with axon counts and myelin (Schmierer et al, 2007(Schmierer et al, , 2008. Recently, it has been shown that postmortem diffusion anisotropy correlates with myelin basic protein in the developing human cerebellum of freshly aborted human fetuses (Saksena et al, 2008).…”

“…Correlations between DTI and myelin content and to a lesser extent axon count have been shown in humans, but were based on DTI acquired on postmortem brains of patients with multiple sclerosis (Schmierer et al, 2007). While brains are rapidly fixed in animal studies, this process is typically delayed in human cadavers.…”

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

“…Multiple sclerosis is a central nervous system disease characterized by a complex pathophysiology,1 the fundamental features of which have been derived from the analysis of post mortem tissue 2, 3, 4, 5. Spinal cord pathology is an important determinant of permanent neurological disability with cardinal characteristics being inflammatory demyelination, synaptic, neuronal and axonal loss 6, 7, 8, 9, 10, 11.…”