MR imaging intensity modeling of damage and repair in multiple sclerosis: Relationship of short-term lesion recovery to progression and disability

41Citations
Citations of this article
68Readers
Mendeley users who have this article in their library.

Abstract

BACKGROUND AND PURPOSE: Formation of lesions in multiple sclerosis (MS) shows pronounced short-term fluctuation of MR imaging hyperintensity and size, a qualitatively known but poorly characterized phenomenon. With the use of time-series modeling of MR imaging intensity, our study relates the short-term dynamics of new T2 lesion formation to those of contrast enhancement and markers of long-term progression of disease. MATERIALS AND METHODS: We analyzed 915 examinations from weekly to monthly MR imaging in 40 patients with MS using a time-series model, emulating 2 opposing processes of T2 prolongation and shortening, respectively. Patterns of activity, duration, and residual hyperintensity within new T2 lesions were measured and evaluated for relationships to disability, atrophy, and clinical phenotype in long-term follow-up. RESULTS: Significant T2 activity was observed for 8 to 10 weeks beyond contrast enhancement, which suggests that T2 MR imaging is sensitive to noninflammatory processes such as degeneration and repair. Larger lesions showed longer subacute phases but disproportionally more recovery. Patients with smaller average peak lesion size showed trends toward greater disability and proportional residual damage. Higher rates of disability or atrophy were associated with subjects whose lesions showed greater residual hyperintensity. CONCLUSION: Smaller lesions appeared disproportionally more damaging than larger lesions, with lesions in progressive MS smaller and of shorter activity than in relapsing-remitting MS. Associations of lesion dynamics with rates of atrophy and disability and clinical subtype suggest that changes in lesion dynamics may represent a shift from inflammatory toward degenerative disease activity and greater proximity to a progressive stage, possibly allowing staging of the progression of MS earlier, before atrophy or disability develops.

Figures

  • Fig 1. New lesion detection via intensity change maps. The top row shows the registered and normalized PD-weighted image series of time points t7 to t9, with the formation of 2 new lesions (red and orange arrows). The bottom row shows coefficient of variation (COV SD/mean) maps, created from a sliding window of 3 adjacent time points. The COV maps very reliably identified areas of change, which were then manually boxed (red and orange rectangles) around the area of maximal size or change (same lesion as Fig. 2).
  • Fig 2. Time-series modeling method applied to extract lesion dynamics: a mathematical model is fit to the time series of each lesion pixel. The model emulates 2 opposing processes (I1-I2) driving the T2 signal intensity toward hyperintensity and isointensity, respectively. A, Example of a new lesion, marked by a 3D bounding box, and the time series of this lesion showing its appearance in week 6, reaching peak around week 9, and end of activity around week 21. B, Example profiles extracted at 3 points within the lesion, and the resulting model fit. C, Mathematical model and the extracted characteristics: peak hyperintensity (relative to baseline) residual hyperintensity (relative to peak), and the duration of activity (split into an acute, subacute and chronic phase). These characteristics are then shown for each lesion pixel in color maps (D), revealing spatial patterns of lesion dynamics.
  • Fig 3. Comparison of T2 activity (blue) with contrast enhancement (T1-GdDTPA, red). A, Example time profiles of a single-lesion pixel followed for 1 year. T2 activity lasts twice as long as contrast activity at this location. B, Duration distributions for contrast-enhancing lesions (red, dashed) and new T2 lesions (blue, solid), showing how many lesions (%) were active for how long (only new lesions during the first 6 weeks, as in20). Dominant duration for contrast enhancement was 1 to 2 weeks (data from20), whereas subacute T2 activity ranges from 3 to more than 20 weeks. The 2 populations differ significantly (P 10 10). Excluding subjects in the progressive group from the distribution (cyan, dashed) did not significantly affect the result. This determines that temporal changes in T2-weighted MR imaging are present long after Gd-enhancement subsides, underlining the characterization of new T2 lesion formation into acute, subacute, and chronic phases.
  • Fig 4. Patterns of lesion formation, comparing acute and subacute durations of activity. Examples of 3 lesions of different sizes, with columns showing different sections from superior to inferior (left to right). Lesion 1 was small extending only over 2 sections; lesion 3 was much larger and was visible on 9 sections (section thickness, 3 mm). Lesions are shown at individual scale (see size bar for each lesion). Rows show duration in weeks of acute (A) and subacute phases (B), as defined in Fig. 2. Analogous concentric patterns and a faster recovery at the periphery of the lesion are apparent. Note that the duration of the acute phase is far shorter (4 weeks or less) than that of the subacute phase (up to 20 weeks).
  • Fig 5. Patterns of lesion formation, comparing peak and residual hyperintensity, for the same 3 lesions as shown in Fig. 4. Peak (a) and residual hyperintensities (b) are shown in rows. Concentric patterns and a correlation between higher levels of intensity and greater residual are apparent (ie, residual damage [b] tends to occur in areas of maximal hyperintensity. Also, note how the proportions of residual damage are disproportionally smaller for larger lesions.
  • Fig 6. Effect of “average lesion volume” (total new lesion volume/total new lesion number) on residual damage (B) and clinical disability (C). Although total lesion burden (A) is not different, both the volume percentage of residual damage (B) and clinical disability (C) are significantly greater for the “small lesion” group. As a per-patient measure, the 2 groups can be interpreted as “many small lesions” versus “few large lesions.” The significantly greater proportions of residual damage and disability are suggestive of a more destructive nature for smaller lesions. Boxes and P values in green show analysis with the progressive group excluded (as a result of the unbalanced design with regard to Expanded Disability Status Scale [EDSS]; see on-line
  • Fig 7. Short-term lesion recovery related to progression of atrophy and disability. A, Significant progression of both atrophy (change in BPF) and disability (change in EDSS) during the observation period was observed, for both subjects with relapsing (blue ) and progressive (green ƒ) disease. B, Lesions with higher residual hyperintensity (lower recovery) were associated with faster rates of atrophy progression as well as greater disability. Boxes and P values in green show t test analysis with progressive patients excluded.

References Powered by Scopus

Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)

13545Citations
N/AReaders
Get full text

Axonal transection in the lesions of multiple sclerosis

3631Citations
N/AReaders
Get full text

Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination

2854Citations
N/AReaders
Get full text

Cited by Powered by Scopus

MRI in multiple sclerosis: current status and future prospects

283Citations
N/AReaders
Get full text

Longitudinal multiple sclerosis lesion segmentation: Resource and challenge

251Citations
N/AReaders
Get full text

Magnetic resonance monitoring of lesion evolution in multiple sclerosis

104Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Meier, D. S., Weiner, H. L., & Guttmann, C. R. G. (2007). MR imaging intensity modeling of damage and repair in multiple sclerosis: Relationship of short-term lesion recovery to progression and disability. American Journal of Neuroradiology, 28(10), 1956–1963. https://doi.org/10.3174/ajnr.A0701

Readers over time

‘09‘10‘11‘12‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24036912

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 20

42%

Researcher 17

35%

Professor / Associate Prof. 10

21%

Lecturer / Post doc 1

2%

Readers' Discipline

Tooltip

Medicine and Dentistry 26

50%

Neuroscience 12

23%

Agricultural and Biological Sciences 9

17%

Engineering 5

10%

Save time finding and organizing research with Mendeley

Sign up for free
0