Subtraction MR images in a multiple sclerosis multicenter clinical trial setting.

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.

Interobserver agreement on the radiological criteria of the International Panel on the diagnosis of multiple sclerosis.

We assessed the interobserver agreement on the radiological part of the International Panel (IP) criteria for the diagnosis of multiple sclerosis (MS), comprising the assessment of dissemination in space (DIS) and time (DIT) based exclusively on MRI. Four radiologists trained and four radiologists naive in the application of the IP criteria scored the fulfillment for DIS (i.e., > or =3 periventricular, > or =1 infratentorial, > or =1 juxtacortical, > or = 1 enhancing lesion or a total of > or =9 T2-weighted lesions) and DIT (presence of new or enhancing lesions at follow-up) in baseline and two follow-up scans from 20 patients suspected for having MS. The IP-trained radiologists agreed at least moderately on all assessments (kappa>0.40), whereas the IP-naive radiologists showed fair agreement (kappa<0.40) on five of 16 assessments. In the final conclusion on DIS and DIT, the IP-trained radiologists agreed substantially on both items (kappa=0.62 and kappa=0.60, respectively) compared with a fair agreement on DIS (kappa=0.29) and moderate agreement on DIT (kappa=0.52) among the IP-naive radiologists. Given the poor interobserver agreement among IP-naive observers, the new IP criteria for MS require additional training and should perhaps be simplified.