Abstract
BACKGROUND AND PURPOSE: Cellular uptake of the manganese ion, when administered as a contrast agent for MR imaging, can noninvasively highlight cellular activity and disease processes in both animals and humans. The purpose of this study was to explore the enhancement profile of manganese in patients with multiple sclerosis.
MATERIALS AND METHODS: Mangafodipir is a manganese chelate that was clinically approved for MR imaging of liver lesions. We present a case series of 6 adults with multiple sclerosis who were scanned at baseline with gadolinium, then injected with mangafodipir, and followed at variable time points thereafter.
RESULTS: Fourteen new lesions formed during or shortly before the study, of which 10 demonstrated manganese enhancement of varying intensity, timing, and spatial pattern. One gadolinium-enhancing extra-axial mass, presumably a meningioma, also demonstrated enhancement with manganese. Most interesting, manganese enhancement was detected in lesions that formed in the days after mangafodipir injection, and this enhancement persisted for several weeks, consistent with contrast coming from intracellular uptake of manganese. Some lesions demonstrated a diffuse pattern of manganese enhancement in an area larger than that of both gadolinium enhancement and T2-FLAIR signal abnormality.
CONCLUSIONS: This work demonstrates the first use of a manganese-based contrast agent to enhance MS lesions on MR imaging. Multiple sclerosis lesions were enhanced with a temporal and spatial profile distinct from that of gadolinium. Further experiments are necessary to uncover the mechanism of manganese contrast enhancement as well as cell-specific uptake.
ABBREVIATION:
- RRMS
- relapsing-remitting MS
Footnotes
This study was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (Z01 NS003119).
Paper previously presented as an oral presentation at: Congress of the European Committee for Treatment and Research in Multiple Sclerosis, September 11–13, 2019; Stockholm, Sweden.
Disclosures: Daniel J. Suto—RELATED: Grant: National Institutes of Health Internal Funding, Comments: National Institute of Neurological Disorders and Stroke Z01 NS003119*; Support for Travel to Meetings for the Study or Other Purposes: Congress of the European Committee for Treatment and Research in Multiple Sclerosis; Provision of Writing Assistance, Medicines, Equipment, or Administrative Support: National Institute of Neurological Disorders and Stroke Z01 NS003119*; UNRELATED: Employment: National Institutes of Health, Comments: National Institutes of Health Postbaccalaureate Program.* Erin S. Beck—RELATED: Grant: National Multiple Sclerosis Society, Comments: fellowship grant to support my salary.* Henry McFarland—UNRELATED: Employment: Scientific Director of the Cummings Foundation, Comments: not-for-profit educational foundation; Royalties: daclizumab (Biogen through the National Institutes of Health), Comments: <$100 in 2019. Alan P. Koretsky—RELATED: Grant: I am an Intramural Investigator at the National Institute of Neurological Disorders and Stroke, National Institutes of Health; Congress allocated money to the National Institute of Neurological Disorders and Stroke that was used to support this work; however, we do not refer to this support as a grant; UNRELATED: Patents (Planned, Pending or Issued): The National Institute of Neurological Disorders and Stroke supports patents for intramural investigators. I do have some patents pending, but there is no money to me or the National Institutes of Health; these are not related in any way to the submitted work; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Typically, travel is reimbursed when Intramural Investigators give academic presentations at universities or relevant meetings. No money is paid to me or the National Institutes of Health for these presentations. In addition, I serve on a couple of advisory committees (no compensation to me or the National Institutes of Health), for which travel is paid. Daniel S. Reich—UNRELATED: Expert testimony: Leventhal and Puga LLC, Bounds Law Group LLC; Grants/Grants Pending: Vertex Pharmaceuticals.* *Money paid to the institution.
- © 2020 by American Journal of Neuroradiology
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