National Institute of Neurological Disorders and Stroke
Translational Neuroradiology Section

Author Of 1 Presentation

Imaging Oral Presentation

PS11.05 - Inclusion of small ovoid lesions in central vein sign assessment improves sensitivity for multiple sclerosis

Speakers
Presentation Number
PS11.05
Presentation Topic
Imaging
Lecture Time
10:09 - 10:21

Abstract

Background

The ‘central vein sign’ (CVS) is increasingly recognized as a valuable biomarker with high specificity and sensitivity for multiple sclerosis (MS) MRI lesions. Current consensus North American Imaging in Multiple Sclerosis (NAIMS) guidelines recommend excluding lesions <3mm in diameter in any plane for CVS assessment. However, different lesion-size exclusion cut-offs for CVS have not been systematically evaluated.

Objectives

To evaluate the impact of different lesion size cut-offs and exclusion methodologies on CVS analysis and select3* criteria for MS diagnosis.

Methods

MS patients and non-MS controls were recruited as part of the National Institute of Neurological Disorders and Stroke MS natural history study and underwent 3T MRI on either Siemens Skyra or Philips Achieva scanners. MS lesions were segmented using a deep learning-based method and manually corrected by a single rater. Individual lesions were extracted as clusters of connected voxels, and their principal axes lengths (calculated as the lengths of the major axes of an ellipsoid with the same normalized second central moments) were used to measure lesion size in 3 dimensions. Ground truth CVS assessment was conducted by two raters on all lesions regardless of size. Two paradigms of lesion exclusion were compared: (1) excluding lesions if any dimension was less than threshold (ExcAny), or (2) if all dimensions were less than threshold (ExcAll).

Results

A total of 3920 lesions from 71 subjects (8 healthy controls, 36 RRMS, 12 SPMS, 14 PPMS, 1 CIS) were included in the analysis. CVS+ lesions were more likely to be ovoid and less spherical compared to their CVS- counterparts, as measured by the fractional anisotropy of lesion dimensions (mean difference 0.02, p=0.001). Of the 1679 CVS+ lesions in the cohort, 82% met the ExcAny criteria to be excluded at a 3mm cut-off, which was reduced to 29% when ExcAll criteria were used (McNemar test, p < 0.001). At the subject-level, an increase in the sensitivity of select3* CVS criteria for MS diagnosis was noted at 3mm using the less strict ExcAll (95%) compared to the more conservative ExcAny criteria (61%), without impacting specificity (100% for both methods). There was a reduction in specificity for both ExcAny and ExcAll criteria when size cut-offs less than or equal to 2mm were used (88% for both).

Conclusions

Compared to the current NAIMS guidelines, ExcAll criteria for CVS lesion analysis allow the inclusion of a larger proportion of CVS+ lesions and improve the sensitivity of select3* criteria for MS diagnosis. These findings improve the applicability of the CVS as a diagnostic marker for MS in clinical practice and provide evidence for future modifications of CVS lesion exclusion guidelines.

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Author Of 1 Presentation

Imaging Poster Presentation

P0612 - New cortical lesions are rare in an MS cohort with stable white matter lesions: a 7T multicontrast longitudinal study (ID 1866)

Speakers
Presentation Number
P0612
Presentation Topic
Imaging

Abstract

Background

Cortical lesions are common and often extensive in MS, and have been associated with worse disability and progressive disease. There is limited evidence that cortical lesions continue to form in progressive phases of the disease, when new white matter lesion formation is minimal, perhaps offering an explanation for worsening disability in progressive MS.

Objectives

We longitudinally characterized cortical lesions in an MS cohort with stable white matter lesion burden in the year prior to enrollment to determine whether new cortical lesions are more frequent in people with worsening disability.

Methods

45 adults with MS (30 relapsing remitting (RR), 13 secondary progressive (SP), and 2 primary progressive (PP)), underwent 7T brain MRI (T2*w and MP2RAGE, each with 0.5mm isometric resolution), 3T brain and spine MRI, and clinical evaluation annually for 1 year. Cortical lesions were segmented manually on 7T images and categorized as leukocortical, intracortical, or subpial. White matter and spinal cord lesion burden were also determined.

Results

At baseline, 93% of individuals (42/45) had at least 1 cortical lesion. Median cortical lesion number was higher in progressive MS (median 55, interquartile range (IQR) 96, range 2–177) than RRMS (median 15, IQR 21, range 0–108; p<0.01). Cortical lesion volume correlated with physical and cognitive measures of disability. There was only a weak correlation between subpial and white matter lesion volume (r=0.35, p<0.05). During 1 year of follow-up, 6 people (4 RR, 2 SP) developed 1 new cortical lesion each. 4 of the 6 new cortical lesions were leukocortical, 1 was intracortical, and 1 was subpial. 5 people developed new white matter lesions, none of whom developed a new cortical lesion. In 2 people, we observed white matter lesions expand into the cortex. 3/6 people with new cortical lesions were on highly effective disease-modifying therapy during the follow up period. There was no difference in new cortical lesion or new white matter lesion number in people with stable vs worsening disability.

Conclusions

Using sensitive 7T MRI techniques, cortical lesions are detected in almost all MS cases. Cortical lesions are associated with worse and progressive disability and may form independently from white matter lesions. New cortical lesions appear to form infrequently in people with stable white matter lesions, however current disease-modifying therapies may not be completely effective at stopping cortical lesion formation.

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Presenter Of 1 Presentation

Imaging Poster Presentation

P0612 - New cortical lesions are rare in an MS cohort with stable white matter lesions: a 7T multicontrast longitudinal study (ID 1866)

Speakers
Presentation Number
P0612
Presentation Topic
Imaging

Abstract

Background

Cortical lesions are common and often extensive in MS, and have been associated with worse disability and progressive disease. There is limited evidence that cortical lesions continue to form in progressive phases of the disease, when new white matter lesion formation is minimal, perhaps offering an explanation for worsening disability in progressive MS.

Objectives

We longitudinally characterized cortical lesions in an MS cohort with stable white matter lesion burden in the year prior to enrollment to determine whether new cortical lesions are more frequent in people with worsening disability.

Methods

45 adults with MS (30 relapsing remitting (RR), 13 secondary progressive (SP), and 2 primary progressive (PP)), underwent 7T brain MRI (T2*w and MP2RAGE, each with 0.5mm isometric resolution), 3T brain and spine MRI, and clinical evaluation annually for 1 year. Cortical lesions were segmented manually on 7T images and categorized as leukocortical, intracortical, or subpial. White matter and spinal cord lesion burden were also determined.

Results

At baseline, 93% of individuals (42/45) had at least 1 cortical lesion. Median cortical lesion number was higher in progressive MS (median 55, interquartile range (IQR) 96, range 2–177) than RRMS (median 15, IQR 21, range 0–108; p<0.01). Cortical lesion volume correlated with physical and cognitive measures of disability. There was only a weak correlation between subpial and white matter lesion volume (r=0.35, p<0.05). During 1 year of follow-up, 6 people (4 RR, 2 SP) developed 1 new cortical lesion each. 4 of the 6 new cortical lesions were leukocortical, 1 was intracortical, and 1 was subpial. 5 people developed new white matter lesions, none of whom developed a new cortical lesion. In 2 people, we observed white matter lesions expand into the cortex. 3/6 people with new cortical lesions were on highly effective disease-modifying therapy during the follow up period. There was no difference in new cortical lesion or new white matter lesion number in people with stable vs worsening disability.

Conclusions

Using sensitive 7T MRI techniques, cortical lesions are detected in almost all MS cases. Cortical lesions are associated with worse and progressive disability and may form independently from white matter lesions. New cortical lesions appear to form infrequently in people with stable white matter lesions, however current disease-modifying therapies may not be completely effective at stopping cortical lesion formation.

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