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AJNR Am J Neuroradiol. 2018 Apr;39(4):618-625. doi: 10.3174/ajnr.A5542. Epub 2018 Feb 8.

Iron-Insensitive Quantitative Assessment of Subcortical Gray Matter Demyelination in Multiple Sclerosis Using the Macromolecular Proton Fraction.

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From the Department of Radiology (V.L.Y.), University of Washington, Seattle, Washington
Research Institute of Biology and Biophysics (E.P.K., G.A., V.L.Y.), Tomsk State University, Tomsk, Russian Federation.
Multiple Sclerosis Center (P.R., A.M., P.Q., L.K.J.H., B.G., J.D.B.), Swedish Neuroscience Institute, Seattle, Washington.
Piedmont Henry Hospital (L.K.J.H.), Stockbridge, Georgia.



Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping.


Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data.


The macromolecular proton fraction in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to patients with relapsing-remitting MS and from those with relapsing-remitting MS to patients with secondary-progressive MS. The macromolecular proton fraction in all subcortical structures significantly correlated with the Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range of 0.4-0.6. Significant correlations (r = -0.4 to -0.6) were also identified between the macromolecular proton fraction and the 9-Hole Peg Test, indicating a potential relationship with nigrostriatal pathway damage. Among T2* values, weak significant correlations with clinical variables were found only in the putamen. The macromolecular proton fraction did not correlate with T2* in any of the studied anatomic structures.


The macromolecular proton fraction provides an iron-insensitive measure of demyelination. Myelin loss in subcortical GM structures in MS is unrelated to excess iron deposition. Subcortical GM demyelination is more closely associated with the disease phenotype and disability than iron overload.

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