TI-relaxation time changes over five years in relapsing-remitting multiple sclerosis

Abstract

The pathological effects of multiple sclerosis are not confined to lesions; tissues that appear normal on conventional magnetic resonance imaging scans are also affected, albeit subtly. One imaging technique that has proven sensitive to such effects is T1-relaxation time measurement, with previous work demonstrating abnormalities in normal-appearing white matter and grey matter. In this work we investigated the evolution of T1-relaxation time changes in normal-appearing white matter and grey matter in relapsing-remitting multiple sclerosis. Three- and five-year follow-up data from 35 people with clinically early (a mean of 1.6 years from first clinical event) relapsing-remitting multiple sclerosis and 15 healthy controls were analysed. T1-relaxation time histograms were extracted from normal-appearing white matter and grey matter, and mean, peak height and peak location values were estimated. T1-relaxation time peak height declined in the multiple sclerosis normal-appearing white matter and grey matter, but not the control group (rate difference p = 0.024 in normal-appearing white matter, in normal-appearing grey matter p = 0.038); other T1-relaxation time changes were not significantly different between groups. Changes in T1-relaxation time measures did not correlate with increases in brain T2-weighted lesion loads or Expanded Disability Status Scale scores. These results suggest that the processes underlying changes in normal-appearing white matter and grey matter T1-relaxation times are not immediately linked to white matter lesion formation, and may represent more diffuse but progressive sub-clinical pathology in relapsing-remitting multiple sclerosis.

Short-term stability of T 1 and T 2 relaxation measures in multiple sclerosis normal appearing white matter

“…Therefore, we did 3 Normalized histograms of NAWM for two subjects (solid line and dashed line) at months 0 (black) and 6 (grey) for T 1 and T 2 relxation-derived metrics: a T 1 , b MWF and c GMT 2 . No statistically significant change was observed over time; however, clear intersubject variability exists not observe the larger changes seen by other T 1 -relaxation studies that have shown peak height to decrease from a range of 1.6-7% per year [26,27,41,42]. In particular, previous longitudinal studies of RRMS subjects have found similarly small longitudinal changes in NAWM T 1 mean and peak location.…”

“…They did find weak evidence for a decline over time in NAWM T 1 peak height but rejected such findings due to lack of significant difference between patient-control rate of change. In contrast, Parry et al [26] and Papadopoulos et al [27] both found significant decrease in T 1 peak height over 14-22 months in 9 RRMS and 5 secondary progressive MS subjects and 3-5 years in 35 RRMS subjects, respectively. The discrepancy between Parry's findings and Davies as well as ours may be due to the addition of secondary progressive MS (SPMS) subjects in their study.…”

“…No correlation was found between MR measurements and disease disability. As previous studies have observed changes in NAWM T 1 over a longer period of time (14-22 months [26]; 3 and 5 years [23,24,27]), it is probable that a change in NAWM T 1 would also be expected with an extended follow-up period for our subjects. While the longitudinal evolution of geometric mean T 2 and myelin water fraction in NAWM is still unknown, because loss of myelin has been observed to varying degrees in MS NAWM [23,24,46], it is reasonable to hypothesize that diffuse progressive myelin loss will also occur given a longer follow-up period.…”

“…Longitudinal studies, with follow-up periods ranging from 1-5 years [26,27], have found increases in NAWM T 1 over time, suggesting that T 1 alterations occur within the timescale of years. However, given the observation of progressive structural deficits of white matter volume within the first 12 months of illness [28], it may be possible to detect a change in NAWM T 1 , MWF or GMT 2 histogram metrics in as short as 6 months.…”

Quantitative MR Imaging of Brain Tissue and Brain Pathologies

“…However, with relaxation times of different pathologies overlapping considerably [3][4][5], more complex tissue characterization came into focus, for example, those based on water diffusion, magnetization transfer, and perfusion. It became obvious that the strengths of quantitative or semi-quantitative MR parameter maps lie in the detection of diffuse changes in brain tissues that appeared normal in conventional MRI [6][7][8], best demonstrated in multiple sclerosis patients [2,7,[9][10][11][12][13][14].…”