The impact of intensity variations in T1-hypointense lesions on clinical correlations in multiple sclerosis

Tam, Roger; Traboulsee, Anthony; Riddehough, Andrew; Sheikhzadeh, Fahime; Li, D K B

doi:10.1177/1352458511402113

Cited by 37 publications

(39 citation statements)

References 31 publications

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“…Gadolinium-enhancing (Gd+) lesion counts on T1-weighted images, and new or enlarging T2-hyperintense lesions, give an indication of recent inflammation and may predict relapse rate in the short term [2, 3]. T2-weighted images allow a quantitation of the accumulated extent, or overall burden, of focal white matter disease [1, 4], whereas chronic (unenhancing) T1-hypointense lesions have been more strongly associated with tissue destruction and axonal loss, and their persistence is associated with increased disability and permanent neurological deficit [5, 6]. Overall reduction in brain volume over time is considered to be a marker of neurodegeneration, and shows a relatively strong correlation with physical disability and cognitive impairment [7].…”

Section: Introductionmentioning

confidence: 99%

Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study

et al. 2014

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In the Phase 3 DEFINE study, delayed-release dimethyl fumarate (DMF) 240 mg twice (BID) and three times daily (TID) significantly reduced the mean number of new or enlarging T2-hyperintense lesions and gadolinium-enhancing (Gd+) lesion activity at 2 years in patients (MRI cohort; n = 540) with relapsing–remitting MS. The analyses described here expand on these results by considering additional MRI measures (number of T1-hypointense lesions; volume of T2-hyperintense, Gd+, and T1-hypointense lesions; brain atrophy), delineating the time course of the effects, and examining the generality of the effects across a diverse patient population. Reductions in lesion counts with delayed-release DMF BID and TID, respectively, vs. placebo were apparent by the first MRI assessment at 6 months [T2-hyperintense: 80 and 69 % reduction (both P < 0.0001); Gd+, 94 and 81 % reduction (both P < 0.0001); T1-hypointense: 58 % (P < 0.0001) and 48 % (P = 0.0005) reduction] and maintained at 1 and 2 years. Reductions in lesion volume were statistically significant beginning at 6 months for T2-hyperintense [P = 0.0002 (BID) and P = 0.0035 (TID)] and Gd+ lesions [P = 0.0059 (BID) and P = 0.0176 (TID)] and beginning at 1 year [P = 0.0126 (BID)] to 2 years [P = 0.0063 (TID)] for T1-hypointense lesions. Relative reductions in brain atrophy from baseline to 2 years (21 % reduction; P = 0.0449) and 6 months to 2 years (30 % reduction; P = 0.0214) were statistically significant for delayed-release DMF BID. The effect of delayed-release DMF on mean number of new or enlarging T2-hyperintense lesions and Gd+ lesion activity was consistent across pre-specified patient subpopulations. Collectively, these results suggest that delayed-release DMF favorably affects multiple aspects of MS pathophysiology.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-014-7412-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study

et al. 2014

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“…We perform comparisons between the unpaired and paired methods at nine different intensity thresholds. The motivation for analyzing BHs at different intensities comes from a recent small study (Tam et al, 2011) in which we observed that the cross-sectional correlation between BH volume and clinical disability can be strongly influenced by the intensity range used to define the BHs, and limiting the measurement to the darker regions can yield stronger correlations. In this study, we incorporate a similar analysis, but with a much larger data set and an added longitudinal dimension.…”

Section: Introductionmentioning

confidence: 99%

Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis

Tam

Traboulsee

Riddehough

et al. 2012

NeuroImage: Clinical

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The change in T1-hypointense lesion (“black hole”) volume is an important marker of pathological progression in multiple sclerosis (MS). Black hole boundaries often have low contrast and are difficult to determine accurately and most (semi‐)automated segmentation methods first compute the T2-hyperintense lesions, which are a superset of the black holes and are typically more distinct, to form a search space for the T1w lesions. Two main potential sources of measurement noise in longitudinal black hole volume computation are partial volume and variability in the T2w lesion segmentation. A paired analysis approach is proposed herein that uses registration to equalize partial volume and lesion mask processing to combine T2w lesion segmentations across time. The scans of 247 MS patients are used to compare a selected black hole computation method with an enhanced version incorporating paired analysis, using rank correlation to a clinical variable (MS functional composite) as the primary outcome measure. The comparison is done at nine different levels of intensity as a previous study suggests that darker black holes may yield stronger correlations. The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes.

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“…Myelitis is typically segmental. Persistent hypointensities (‘black holes’) on T 1 -weighted imaging and brain atrophy have been used as markers of axonal loss and neuronal destruction to measure disease activity [3,4,5,6]. Hypointense lesion load on T 1 -weighted imaging correlates well with clinical measures of disability.…”

Section: Introductionmentioning

confidence: 99%

“…Black holes are more common in patients with secondary progression than with relapsing-remitting MS and in aggressive than in benign MS. A black hole is defined as an area that is hypointense compared with white matter on T 1 -weighted sequence and is concordant with a hyperintense lesion on T 2 -weighted sequence. The range of hypointensity is variable, ranging from signal intensities resembling gray matter to signal intensities resembling CSF [4,6]. There is no maximum size limit defining black holes.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Radiological Characteristics in Multiple Sclerosis Patients with Large Cavitary Lesions

Renard

Brochet²,

Vukusic

et al. 2012

Eur Neurol

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Background: Large cavitary lesions are not typical for multiple sclerosis (MS). Cavitary white matter changes may be seen in megalencephalic leukoencephalopathy with subcortical cysts, Alexander disease, mitochondrial leukoencephalopathies, vanishing white matter disease, leukoencephalopathy with calcifications and cysts, cytomegalovirus infection, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Objective: To analyze clinical and radiological characteristics in MS patients with large cavitary lesions. Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), Mini Mental State (MMS), corpus callosum lesions, history of segmental myelitis, CSF oligoclonal bands (OCB), visual evoked potentials (VEP), vanishing white matter disease genetic analysis, and characteristics of the cavitary lesions were analyzed. Results: Nine patients were analyzed, 1 man and 8 women. Mean age of disease onset was 38.5 years. Mean disease duration was 9 years. Three patients had initial relapsing-remitting MS and 6 patients had primary-progressive MS. Mean EDSS was 4.5. Mean MMS was 20/30. Segmental myelitis was present in 6 cases. OCB were found in 6 patients. VEP was performed in 6 patients, and pathological in all but one. Vanishing white matter disease genetic analysis was performed and negative in 5 patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance. Conclusion: MS patients with large cavitary lesions seem to represent an MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction.

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The impact of intensity variations in T1-hypointense lesions on clinical correlations in multiple sclerosis

Abstract: Intensity variations can have a large impact on black hole-EDSS correlation. Restricting the measurement to a subset of the darkest voxels may yield stronger correlations.

Cited by 37 publications

References 31 publications

Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study

Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study

Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis

Clinical and Radiological Characteristics in Multiple Sclerosis Patients with Large Cavitary Lesions

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