MR Imaging Intensity Modeling of Damage and Repair In Multiple Sclerosis: Relationship of Short-Term Lesion Recovery to Progression and Disability
D.S. Meiera,
H.L. Weinerb and
C.R.G. Guttmanna
a Department of Radiology, Center for Neurological Imaging, Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston Mass
b Department of Neurology, Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston Mass
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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).
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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.
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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.
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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).
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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.
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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 Table 1).
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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  ) 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.
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