Seven‐tesla phase imaging of acute multiple sclerosis lesions: A new window into the inflammatory process

Abstract

Objectives In multiple sclerosis (MS), accurate, in vivo characterization of dynamic inflammatory pathological changes occurring in newly forming lesions could have major implications for understanding disease pathogenesis and mechanisms of tissue destruction. Here, we investigated the potential of ultrahigh-field MRI (7T), particularly phase imaging combined with dynamic contrast enhancement, to provide new insights in acute MS lesions. Methods Sixteen active MS patients were studied at 7T. Noncontrast, high-resolution T2* magnitude and phase scans, T1 scans before/after gadolinium contrast injection, and dynamic contrast-enhanced (DCE) T1 scans were acquired. T2*/phase features and DCE pattern were determined for acute and chronic lesions. When possible, one-year follow-up 7T MRI was performed. Results Of 49 contrast-enhancing lesions, 44 could be analyzed. Centrifugal DCE lesions appeared isointense or hypointense on phase images, whereas centripetal DCE lesions showed thin, hypointense phase rims that clearly colocalized with the initial site of contrast enhancement. This pattern generally disappeared once enhancement resolved. On the other hand, in 43 chronic lesions also selected for the presence of hypointense phase rims, the findings were stable over time, and the rims were typically thicker and darker. These considerations suggest different underlying pathological processes in the two lesion types. Interpretation Ultrahigh-field MRI and, especially, phase contrast, are highly sensitive to tissue changes in acute MS lesions, which differ from the patterns seen in chronic lesions. In acute lesions, the hypointense phase rim reflects the expanding inflammatory edge and may directly correspond to inflammatory byproducts and sequelae of blood-brain barrier opening.

Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis

“…However, the relationship between the efficiency of remyelination, age, and disease duration is still controversial, and our results contribute to an ongoing debate regarding the key question of whether the remyelination potential remains constant throughout life or is modified by aging and disease stage 37, 41. The majority of voxels dynamically changing their myelin content in either direction during the follow‐up were localized in the peripheral lesional area in accordance to both neuropathological and ultra‐high‐field MRI studies demonstrating that the lesion edge corresponds to the expanding inflammation where new demyelination takes place and to the privileged lesional area where active remyelination occurs 37, 42…”

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

“…A novel radiological finding in a subset of chronic lesions, the peripheral paramagnetic rim (12)(13)(14)(15)(16)(17) that can be seen on magnetic resonance susceptibility imaging (T2*-weighted magnitude and susceptibility-weighted phase images), has been suggested to be a potential marker of chronic active lesions (12). However, against this hypothesis, a few short-term longitudinal MRI studies (~1-2 years) failed to demonstrate that chronic rim lesions expand over time into the surrounding normal tissue (16,18), although MRI studies with longer follow-up are still needed.…”

“…However, against this hypothesis, a few short-term longitudinal MRI studies (~1-2 years) failed to demonstrate that chronic rim lesions expand over time into the surrounding normal tissue (16,18), although MRI studies with longer follow-up are still needed. Furthermore, existing radiological-pathological correlation studies have not resulted in a clear consensus on the extent to which the magnetic susceptibility-related MRI signal change in the lesion rim is caused only by iron deposition (iron-laden macrophages, ferritin, and/ or hemosiderin deposits) (13,14,19,20) or by other MS-relevant comprehensive biological model of lesion development, are necessary to elucidate the rim's pathophysiological significance and potential relationship with mechanisms of lesion repair.…”

Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset

“…Recent data on newly forming lesions in MS (Gaitan et al, 2011;Absinta et al, 2013) have shown how the dynamic pattern of contrast enhancement can give specific information about the age of a lesion, a parameter that in human MS autopsy studies it is difficult to directly establish. Indeed the time frame between the first appearance of a lesion (potentially detectable with in vivo brain imaging) and the death of the patient is usually determined only indirectly, by the quality of myelin degradation products present within macrophages' and/or the expression of macrophage activation markers (Bruck et al, 1995).…”