Ratio of T1-Weighted to T2-Weighted Signal Intensity as a Measure of Tissue Integrity: Comparison with Magnetization Transfer Ratio in Patients with Multiple Sclerosis

DISCUSSION

This exploratory study compares the distribution in T1/T2 and MTR in a relatively small group of patients with relapsing-remitting MS. Healthy controls were not included in this study because the main goal was to investigate the correspondence between MTR and T1/T2 in damaged tissue. Comparisons were performed across subjects for NAGM, NAWM, and lesion masks and also across individual lesions in each subject. Several factors may have affected the lesion-by-lesion correlations, such as small coregistration errors between MTR and T1/T2, which may have displaced the lesion masks, as well as patient movement during acquisition.

The correlations ranged from moderate to strong, suggesting that most probably, the 2 methods are not sensitive to the same pathologic substrate. In addition, T1/T2 was associated with the EDSS and disease duration, while MTR was only associated with EDSS. The concept that T1/T2 is a proxy for myelin in gray matter has been derived from studies performed in healthy individuals,^1,2 in whom neither myelin nor axonal loss nor inflammation is present. In MS, T1/T2 in gray matter has been related to dendrite density rather than myelin⁵ in a study performed ex vivo in tissue blocks from brain donors; and, again in an ex vivo study, T1/T2 has shown a moderate correlation with MTR in gray matter.⁴ However, it is expected that T1/T2 will also be affected by edema and iron content, because T1WI and T2WI separately are affected.³ MTR has been mainly related to both myelin and axonal damage and, to a lesser degree, to inflammation and gliosis in MS.⁶ In this context, it is likely that compared with MTR, T1/T2 is more dependent on additional pathologic substrates and not just on myelin integrity, though new studies in vivo are needed to confirm the source of the signal in the T1/T2 approach. The main advantage of T1/T2 is that it provides a wider range of values than those given by MTR, as was seen in postmortem studies.⁴ Thus, an intermediate degree of tissue destruction would be more likely to be captured with T1/T2 than MTR. Nevertheless, these results could not be extrapolated to any T1WI, T2WI, or MTR sequence because T1/T2 and MTR contrast and, consequently, the correlation between them, depends on the acquisition parameters.⁷ Further longitudinal studies with larger sample sizes as well as further in-depth assessment of lesional tissue (including black holes and new lesions) are warranted to assess the validity of T1/T2 as a biomarker of tissue damage and lesion recovery in MS.