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The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis.Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group.Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p ≤ 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p ≤ 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM.Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics.