A magnetization transfer histogram study of normal-appearing brain tissue in MS

Objective: To evaluate 1) the ability of magnetization transfer ratio (MTR) histogram analysis to detect the extent of changes occurring outside MS lesions seen on conventional scans, 2) whether such changes vary in the different MS clinical phenotypes, 3) whether the changes are associated with the extent and severity of the macroscopic lesion load, and 4) the contribution to brain atrophy. Methods: Dual-echo, T1-weighted, and MT scans of the brain were obtained from 77 patients with varying MS courses and 20 age- and sex-matched control subjects. To create MT histograms of the normal-appearing cerebral tissue, MS lesions were segmented from dual-echo scans, superimposed automatically, and nulled out from the coregistered and scalp-stripped MTR maps. Average MTR, peak height, and peak position were considered. T2 and T1 lesion loads, average lesion MTR, and brain volume were also measured. Results: Average histogram MTR. (p < 0.0001) and peak position (p ( 0.0001) from patients with relapsing-remitting MS (RMMS) were lower than those from control subjects. Patients with primary progressive MS (PPMS) had lower average histogram MTR (p = 0.002) and histogram peak height (p = 0.01) than control subjects. Patients with secondary progressive MS (SPMS) had a lower peak height (p = 0.05) than those with RRMS. Average lesion MTR (p < 0.0001) correlated highly with the histogram MTR. Average histogram MTR (p < 0.0001) and T2 lesion load (p = 0.001) correlated highly with brain volume. Conclusions: The amount of microscopic changes account for an important fraction of the lesion load in MS. They may contribute to the development of brain atrophy and tend to be more evident in patients with secondary progressive MS.