Various magnetic resonance (MR) techniques are used to study the pathological evolution of demyelinating diseases, such as multiple sclerosis (MS). However, few studies have validated MR derived measurements with histopathology. Here, we determine the correlation of myelin water imaging, an MR measure of myelin content, with quantitative histopathologic measures of myelin density. The multi-component T2 distribution of water was determined from 25 formalin-fixed MS brain samples using a multi-echo T2 relaxation MR experiment. The myelin water fraction (MWF), defined as T2 signal below 30 milliseconds divided by the total signal, was determined for various regions of interest and compared to Luxol fast blue (myelin stain) mean optical density (OD) for each sample. MWF had a strong correlation with myelin stain [mean (range) R2 = 0.67 (0.45-0.92)], validating MWF as a measure of myelin density. This quantitative technique has many practical applications for the in vivo monitoring of demyelination and remyelination in a variety of disorders of myelin.

NAWM in MS has a higher water content and lower myelin water fraction than control white matter. The cause of the myelin water fraction decrease in NAWM could potentially be due to either diffuse edema, inflammation, demyelination or any combination of these features. We present a simple model which suggests that myelin loss is the dominant feature of NAWM pathology.

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The ability to measure myelin in vivo has great consequences for furthering our knowledge of normal development, as well as for understanding a wide range of neurological disorders. The following review summarizes the current state of myelin imaging using MR. We consider five MR techniques that have been used to study myelin: 1) conventional MR, 2) MR spectroscopy, 3) diffusion, 4) magnetization transfer, and 5) T2 relaxation. Fundamental studies involving peripheral nerve and MR/histology comparisons have aided in the interpretation and validation of MR data. We highlight a number of important findings related to myelin development, damage, and repair, and we conclude with a critical summary of the current techniques available and their potential to image myelin in vivo.