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Published online before print November 26, 2008, 10.1148/radiol.2501080480

(Radiology 2009;250:506.)

A more recent version of this article appeared on February 1, 2009
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© RSNA, 2008

Neuroradiology

Subtraction MR Images in a Multiple Sclerosis Multicenter Clinical Trial Setting1

Bastiaan Moraal, MD, Dominik S. Meier, PhD, Peter A. Poppe, MD, Jeroen J. G. Geurts, PhD, Hugo Vrenken, PhD, William M. A. Jonker, Dirk L. Knol, PhD, Ronald A. van Schijndel, MSc, Petra J. W. Pouwels, PhD, Christoph Pohl, MD, Lars Bauer, MD, Rupert Sandbrink, MD, PhD, Charles R. G. Guttmann, MD, and Frederik Barkhof, MD, PhD

1 From the Departments of Radiology (B.M., P.A.P., J.J.G.G., H.V., W.M.A.J., F.B.), Pathology (J.J.G.G.), Physics and Medical Technology (H.V., P.J.W.P.), Clinical Epidemiology and Biostatistics (D.L.K.), and Informatics (R.A.v.S.), and MS Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Departments of Radiology and Neurology, Center for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (D.S.M., C.R.G.G.); Department of Specialized Therapeutics, Bayer Schering Pharma, Berlin, Germany (C.P., L.B., R.S.); Department of Neurology, University Hospital of Bonn, Bonn, Germany (C.P.); and Heinrich-Heine-University, Düsseldorf, Germany (R.S.). Received March 12, 2008; revision requested April 23; revision received June 27; accepted July 15; final version accepted August 8. Supported by Dutch MS Research Foundation (02-358b/c MS). Supported in part by U.S. National Multiple Sclerosis Society (RG 3574-A-1) and National Institutes of Health (R01 NS35142). Address correspondence to B.M. (e-mail: b.moraal{at}vumc.nl).

Purpose: To explore the applicability of subtraction magnetic resonance (MR) images to (a) detect active multiple sclerosis (MS) lesions, (b) directly quantify lesion load change, and (c) detect treatment effects (distinguish treatment arms) in a placebo-controlled multicenter clinical trial by comparing the subtraction scheme with a conventional pair-wise comparison of nonregistered MR images.

Materials and Methods: Forty-six pairs of MR studies in 40 patients (31 women; mean age, 31.9 years) from a multicenter clinical trial were used. The clinical trial was approved by local ethics review boards, and all subjects gave written informed consent. Active MS lesions were scored by two independent raters, and lesion load measurements were conducted by using semiautomated software. Lesion counts were evaluated by using the Wilcoxon signed rank test, interrater agreement was evaluated by using the intraclass correlation coefficient (ICC), and treatment (interferon beta-1b) effect was evaluated by using the Mann-Whitney U test.

Results: When subtraction images were used, there was a 1.7-fold increase in the detection of positive active lesions, as compared with native image pairs, and significantly greater interobserver agreement (ICC = 0.98 vs 0.91, P < .001). Subtraction images also allowed direct quantification of positive disease activity, a measure that provided sufficient power to distinguish treatment arms (P = .012) compared with the standard measurement of total lesion load change on native images (P = .455).

Conclusion: MR image subtraction enabled detection of higher numbers of active MS lesions with greater interobserver agreement and exhibited increased power to distinguish treatment arms, as compared with a conventional pair-wise comparison of nonregistered MR images.

© RSNA, 2008