Background and Purpose Fast macromolecular proton fraction (MPF) mapping is a recent quantitative MRI method for myelin assessment. The objectives of this study were to evaluate MPF as a measure demyelination in subcortical gray matter (GM) structures in multiple sclerosis (MS) and asses a potential relationship between demyelination and excess iron deposition using MPF and T2* mapping. Materials and Methods MPF and T2* maps were obtained from 12 healthy controls, 18 relapsing-remitting MS (RRMS), and 12 secondary-progressive MS (SPMS) patients using 3T MRI. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data. RESULTS: MPF in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to RRMS and from RRMS to SPMS. MPF in all subcortical structures significantly correlated with Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range 0.4-0.6. Significant correlations (r=-0.4--0.6) were also identified between MPF 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. MPF did not correlate with T2* in any of the studied anatomic structures. Conclusions MPF 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.

Abstract. Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. Key words: multiple sclerosis, macromolecular proton fraction, demyelination, magnetic resonance imaging, subcortical gray matter. IntroductionMultiple sclerosis was used to determine as white matter disease because plaques, main marker of MS, were clearly visualized [1]. At present it was obvious that gray matter damage which was poorly detectable using conventional MRI method occurred at the first stage of MS and correlated with clinical symptoms (both motor and cognitive) [2]-[4] Subcortical gray matter involvement in MS pathology was also observed [2], [5]but still need to be studied. In our research, basal ganglia demyelination in MS patients was evaluated using fast mapping of macromolecular proton fraction (MPF). The method of fast MPF mapping was developed by Yarnykh [6] and based on the magnetization transfer effect. Of note, relaxation-based MRI methods [7]-[9] are highly sensitive to paramagnetic ions and hardly appropriate for the assessment of demyelination in structures with high iron content, such as basal ganglia In contrast, MPF mapping is a highly-accurate quantitative method insensitive to iron and, therefore, very suitable for studying demyelination in gray matter in MS.We present the results of secondary analysis of earlier published data [4] aimed to identify the effect of demyelination on MPF in subcortical gray matter structures in MS.