Manganese-Enhanced MRI in Patients with Multiple Sclerosis

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Mangafodipir is a manganese chelate that was clinically approved for MR imaging of liver lesions. The authors 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. 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. Manganese enhancement was detected in lesions that formed in the days after mangafodipir injection, and this enhancement persisted for several weeks. They conclude that multiple sclerosis lesions were enhanced with a temporal and spatial profile distinct from that of gadolinium.

Abstract

BACKGROUND AND PURPOSE

Mangafodipir enhancement of an active gadolinium-enhancing lesion (participant 1). At screening, this lesion enhanced with gadolinium on T1-SPACE (A) with caudal edema visible on T1 (F, yellow arrow). At the center of the lesion (green plane, A–E), faint manganese enhancement is noted at 62 minutes (C) and resolved 13 days after injection (D). Caudal to the lesion (blue plane, F–M), manganese enhancement was noted outside the lesion border at 13 days (I, blue arrow) and on subtraction images (L). This enhancement persisted at 27 days (J and M, blue arrow). Additionally, ventricular narrowing, which commonly fluctuates,16 was noted on day 13 postmangafodipir in reference to the baseline (L); this appeared to resolve by day 27 postmangafodipir.

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.

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