High-field (9.4T) MRI of brain dysmyelination by quantitative mapping of magnetic susceptibility

The multilayered myelin sheath wrapping around nerve axons is essential for proper functioning of the central nervous system. Abnormal myelination leads to a wide range of neurological diseases and developmental disorders. Non-invasive imaging of myelin content is of great clinical importance. The present work demonstrated that loss of myelin in the central nervous system of the shiverer mouse results in a dramatic reduction of magnetic susceptibility in white matter axons. The reduction resulted in a near extinction of susceptibility contrast between gray and white matter. Quantitative magnetic susceptibility imaging and diffusion tensor imaging were conducted on a group of control and shiverer mice at 9.4 T. We measured the resonance frequency distribution of the whole brain for each mouse. Magnetic susceptibility maps were computed and compared between the two groups. It was shown that the susceptibility contrast between gray and white matter was reduced by 96% in the shiverer compared to the controls. Diffusion measurements further confirmed intact fiber pathways in the shiverer mice, ruling out the possibility of axonal injury and its potential contribution to the altered susceptibility. As an autosomal recessive mutation, shiverer is characterized by an almost total lack of central nervous system myelin. Our data provide new evidences indicating that myelin is the predominant source of susceptibility differences between deep gray and white matter observed in magnetic resonance imaging. More importantly, the present study suggests that quantitative magnetic susceptibility is a potential endogenous biomarker for myelination.