Assessment of Disease Activity in Multiple Sclerosis Phenotypes with Combined Gadolinium- and Superparamagnetic Iron Oxide–enhanced MR Imaging
Abstract
PURPOSE: 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. RESULTS: 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). CONCLUSION: 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.
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Iron oxide nanoparticles have a key advantage over gadolinium-based contrast agents in MS imaging: they visualize monocyte/macrophage infiltration, which correlates with ongoing demyelination and disease progression.
“In this context, a key advantage of using iron oxide nanoparticles over gadolinium-based contrast agents is the visualization of monocyte/macrophage infiltration by the former, which correlates with ongoing demyelination and is a hallmark of disease progression in MS [175–177].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [175]
Combining USPIO with gadolinium chelates in MS patients enables detection of additional active lesions compared to gadolinium alone.
“Thus, the use of USPIO in combination with gadolinium chelates in patients with MS enables detection of additional active lesions compared to gadolinium alone (Figure 4 B).”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [175]
Lesions appearing on both gadolinium- and USPIO-enhanced images are larger and more aggressive in tissue damage than lesions enhancing with only one agent.
“It has been shown that lesions which appear on both gadolinium- and USPIO-enhanced images are larger and more aggressive in terms of tissue damage than lesions which only show enhancement of one of the two agents.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [175]
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References 33 · Cited by 85
- Authors
- Tourdias, T., Roggerone, S., Filippi, M., Kanagaki, M., Rovaris, M., Miller, D. H., Petry, K. G., Brochet, B., Pruvo, J.-P., Radüe, E.-W., & Dousset, V.
- Affiliations
- Inserm (FR)
- IRCCS Ospedale San Raffaele (IT)
- Kyoto University (JP)
- Don Carlo Gnocchi Foundation (IT)
- UCL Queen Square Institute of Neurology (GB)
- Université de Bordeaux (FR)
- Hôpital Roger Salengro (FR)
- ORCID
- Venue
- Radiology
- Published
- 2012-07
- Volume
- 264
- Issue
- 1
- Pages
- 225-233
- ISSN
- 0033-8419 (ISSN-L)
- 1527-1315
- OpenAlex
- W1991392994
- Cited by
- 85
- References
- 33
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 7 · 2018: 5 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 3
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Radiology (publishedVersion)
- PubMed (publishedVersion)
- HAL (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Keywords
- multiple sclerosis, disease activity, gadolinium-based contrast agents, ultrasmall superparamagnetic iron oxide, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, lesion detection, lesion size, T1-weighted imaging, ring enhancement, longitudinal follow-up
- MeSH terms
- Adult, Contrast Media, Dextrans, Disability Evaluation, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Meglumine, Middle Aged, Multiple Sclerosis, Organometallic Compounds, Phenotype, Prospective Studies, Sensitivity and Specificity, Reproducibility of Results, Chi-Square Distribution, Statistics, Nonparametric, Magnetite Nanoparticles
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