Assessment of Disease Activity in Multiple Sclerosis Phenotypes with Combined Gadolinium- and Superparamagnetic Iron Oxide–enhanced MR Imaging

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This study underpins the potential advantages of using both a gadolinium-based contrast agent and ultrasmall superparamagnetic iron oxide in patients with multiple sclerosis to increase the sensitivity of MR imaging in the detection of disease activity, even in progressive forms, and suggests that lesions that enhance with both contrast agents represent a subgroup with more severe features.


To compare magnetic resonance (MR) imaging features of multiple sclerosis (MS) lesions after the administration of a gadolinium-based contrast agent and ultrasmall superparamagnetic iron oxide (USPIO) particles among the clinical phenotypes of MS and over time.

Materials and Methods

This study was approved by the local ethics committee, and written informed consent was obtained from all patients. Twenty-four patients with MS (10 with relapsing and 14 with progressive forms) underwent clinical and gadolinium- and USPIO-enhanced MR examinations at baseline and 6-month follow-up. The number of lesions that enhanced with gadolinium alone, USPIO alone, or both was compared with the Pearson χ2 or Fisher exact test, and lesion sizes were compared with the Wilcoxon Mann-Whitney U test. At 6-month follow-up, the lesion signal intensity on precontrast T1-weighted images and the enhancement after repeat injection of the contrast agent were compared with the baseline postcontrast imaging features by using the McNemar test.


Fifty-six lesions were considered active owing to contrast enhancement at baseline; 37 lesions (66%) in 10 patients enhanced with gadolinium. The use of USPIO helped detect 19 additional lesions (34%), and two additional patients were classified as having active disease. Thus, the use of both agents enabled detection of 51% (19 of 37 lesions) more lesions than with gadolinium alone. Enhanced lesions were more frequently observed in the relapsing compared with the progressive forms of MS (P < .0001). USPIO enhancement, in the form of ringlike patterns, could also be observed on T1-weighted images in patients with progressive MS, enabling the detection of five lesions in addition to the five detected with gadolinium in this phenotype. Lesions that enhanced with both contrast agents at baseline were larger (mean size, 6.5 mm ± 3.8; P = .001) and were more likely to persistently enhance at 6-month follow-up (seven of 27 lesions, P < .0001) compared with those that enhanced only with gadolinium (mean size, 4.9 mm ± 2.2; one of nine lesions) or USPIO (mean size, 3.5 mm ± 1.5; 0 of 17 lesions).


The combination of gadolinium and USPIO in patients with MS can help identify additional active lesions compared with the current standard, the gadolinium-only approach, even in progressive forms of MS. Lesions that enhance with both agents may exhibit a more aggressive evolution than those that enhance with only one contrast agent.

© RSNA, 2012

Supplemental material:


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Article History

Received July 6, 2011; revision requested September 12; revision received November 17; accepted December 13; final version accepted February 21, 2012.
Published online: July 2012
Published in print: July 2012