Abstract
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.
MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites.
RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = −.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = −2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = −.12, P = .36) alone.
CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.
ABBREVIATIONS:
- CC
- count based on the standard connected-components technique
- CG
- criterion standard count
- CP
- count based on the technique proposed in this study
- CV
- coefficient of variation
- EDSS
- Expanded Disability Status Scale
- EDDSavg
- average of the EDSS scores over all visits for each subject in the National Institute of Neurological Disorders and Stroke longitudinal study
- NAIMS
- North American Imaging in Multiple Sclerosis
- OASIS
- Automated Statistical Inference for Segmentation
Footnotes
A complete list of the NAIMS participants is provided in the acknowledgment section.
Disclosures: Jordan D. Dworkin—RELATED: Grant: National Institutes of Health.* Kristin A. Linn—UNRELATED: Payment for Development of Educational Presentations: Institute of Electrical and Electronics Engineers. Ipek Oguz—RELATED: Grant: National Institutes of Health.* Rohit Bakshi—UNRELATED: Consultancy: EMD Serono, Genentech, Sanofi Genzyme, Novartis; Grants/Grants Pending: Biogen, EMD Serono, Novartis, Sanofi Genzyme.* Peter A. Calabresi—UNRELATED: Consultancy: Biogen, Disarm Therapeutics; Grants/Grants Pending: Genzyme, Annexon Bio, MedImmune*; Royalties: Cambridge Press, Comments: book on optical coherence tomography. Roland G. Henry—UNRELATED: Consultancy: Roche, MedDay; Grants/Grants Pending: Roche, Genentech, MedDay*; Payment for Lectures Including Service on Speakers Bureaus: Sanofi-Genzyme. Daniel Pelletier—UNRELATED: Consultancy: Genzyme Sanofi, Biogen, Novartis, Actelion, Genentech. William Rooney—UNRELATED: Employment: Oregon Health & Science University; Grants/Grants Pending: National Institutes of Health*; Payment for Lectures Including Service on Speakers Bureaus: Teva Pharmaceutical Industries; Patents (Planned, Pending or Issued): Pending: US 20150141804 A1, US 20150087967 A1; Issued: US 7286867 B2, US 9619875 B2.* Nancy L. Sicotte—RELATED: Grant: Race to Erase MS.* Russell T. Shinohara—RELATED: Grant: National Institutes of Health*; UNRELATED: Board Membership: Genentech, Comments: Scientific Advisory Board member; Expert testimony: Roche, Comments: legal consulting; Payment for Lectures Including Service on Speakers Bureaus: National Institutes of Health, National Multiple Sclerosis Society.* *Money paid to the institution.
This work was supported in part by the National Institutes of Health grants R01 NS085211, R21 NS093349, R01 NS094456, and R01 NS060910 from the National Institute of Neurological Disorders and Stroke. The study was also supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke and the Race to Erase MS Foundation.
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
- © 2018 by American Journal of Neuroradiology
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