MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium

Abstract

Background and purpose: Inflammatory multiple sclerosis (MS) lesions are characterized by microglia activation and infiltration of T cells, B cells, and macrophages across the blood-brain barrier (BBB). In the experimental autoimmune encephalomyelitis (EAE) rat model of MS, previous MR imaging investigations with a new contrast agent ultra-small-particle iron oxide (USPIO) that accumulates in phagocytic cells revealed in vivo the presence of macrophage brain infiltration. The goal of this study was to characterize MS lesions with the use of this contrast agent.

Methods: A prospective MR imaging study of 10 patients with MS in acute relapses was achieved by using USPIO and gadolinium.

Results: Twenty-four hours after USPIO injection, 33 acute MS lesions in 9 patients showed USPIO uptake. Lesions were seen as high signal intensities on T1-weighted images and low signal intensities on T2-weighted images. Gadolinium enhancement was seen in 31 of these lesions in 7 patients. These 7 patients presented 24 gadolinium-enhanced lesions that did not enhance with USPIO. Two patients showed USPIO-enhanced lesions but no gadolinium-enhanced lesions.

Conclusion: Taken together with earlier findings obtained in experimental models or in human stroke, the visualization of macrophage activity in vivo with USPIO characterize a distinct cellular and inflammatory event of the dynamic process of MS lesion formation. The macrophage activity information obtained with USPIO is distinct and complementary to the increased BBB permeability seen with gadolinium.

Fig 1.

Ultra-small-particle iron oxide (USPIO)- and gadolinium-enhanced multiple sclerosis (MS) lesions on several MR imaging sequences. MR imaging 1 performed with fluid-attenuated inversion recovery (FLAIR) (A), T2-weighted (B), T2*-weighted (C), and magnetization transfer T1-weighted postgadolinium images (D). Some MS lesions were enhanced by gadolinium. MR imaging 2, performed 24 hours after USPIO injection, shows an uptake of USPIO in 1 lesion on FLAIR (E), turbo spin echo (TSE) T2-weighted (F), T2*-weighted (G), and T1-weighted (H) images (short arrows). Veins are clearly seen as dark signal intensity on T2*-weighted images (G) (long arrow).

Fig 2.

Mismatch of contrast agents uptake in an ultra-small-particle iron oxide (USPIO)-enhanced acute multiple sclerosis (MS) plaque. MR imaging 1 T2-weighted (A) and T1-weighted postgadolinium images (B) shows a large MS lesion that was not enhanced by gadolinium. MR imaging 2 shows the USPIO uptake at the periphery of the lesion (arrows), seen as a decreased signal intensity on T2-weighted images (C) and a high signal intensity on T1-weighted images (D). According to histologic observations (Lucchinetti et al, 2000), the number of macrophages at the center of acute MS lesions is usually minor.

Fig 3.

Mismatch of contrast agent uptake in gadolinium-enhanced acute multiple sclerosis (MS) plaques. MR imaging 1 T1-weighted image (A) revealing the presence of 3 gadolinium-enhanced MS lesions (arrows). MR imaging 2 T1-weighted image (B) reveals USPIO enhancement in only one small lesion (arrow).