Advanced MRI and staging of multiple sclerosis lesions

Abstract

Over the past few decades, MRI-based visualization of demyelinated CNS lesions has become pivotal to the diagnosis and monitoring of multiple sclerosis (MS). In this Review, we outline current efforts to correlate imaging findings with the pathology of lesion development in MS, and the pitfalls that are being encountered in this research. Multimodal imaging at high and ultra-high magnetic field strengths is yielding biologically relevant insights into the pathophysiology of blood–brain barrier dynamics and both active and chronic inflammation, as well as mechanisms of lesion healing and remyelination. Here, we parallel the results in humans with advances in imaging of a primate model of MS — experimental autoimmune encephalomyelitis (EAE) in the common marmoset — in which demyelinated lesions resemble their human counterparts far more closely than do EAE lesions in the rodent. This approach holds promise for the identification of innovative biological markers and next-generation clinical trials that will focus more on tissue protection and repair.

Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging

“…(4) Lesions with an iron rim on average expand very slowly, while non-rim lesions show a tendency to shrink. Although expansion of rim lesions has already been observed in individual MS lesions [2, 3], we have statistically proven this expansion for the first time in multiple MS patients and lesions. However, it is important to note that some non-rim lesions expanded and some rim lesions shrinked.…”

“…We then examined whether lesions encircled by a rim-shaped signal in SWI are more likely to expand over a period of 3.5 years than those without rims in a prospective longitudinal study in seven patients with MS using a fluid attenuated inversion recovery/SWI fusion sequence (FLAIR–SWI) at 7 Tesla (7 T) [2, 11, 17]. …”

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T

“…This may be attributed to axonal transection secondary to demyelination, and grossly to a total decrease in tissue microstructure. In MS 3, the increased ΔAPT around the border of the lesions may be indicative of chronic active lesions similar to the ones identified in MS brains , in which the activated microglia surrounding the lesion margins would show an increase in protein concentration driving the increased ΔAPT . It is unclear why a difference in NAWM of MS patients with an EDSS of 0 cannot as easily be detected, but we hypothesize that the disease course in these patients is different and perhaps too premature to allow distinguishing different tissue types.…”

Magnetic susceptibility increases as diamagnetic molecules breakdown: Myelin digestion during multiple sclerosis lesion formation contributes to increase on QSM

“…When a peptide bond is lost from proteolysis, the molar susceptibility of MBP will decrease by the molar susceptibility of a peptide bond. A peptide bond has the structure of glycine and molar susceptibility of cm/mol in CGS units or a volume susceptibility change in SI units of: where ρ = 1.35 g/cm 3 and M = 18,500 g/mol for the density and molar mass, respectively, of MBP . Inserting these values into Eq.…”

“…The formation of multiple sclerosis (MS) lesions involves migration of peripheral, activated leukocytes into the central nervous system (CNS) . This inflammatory infiltration is associated with breakdown of the blood–brain barrier (BBB), caused by changes in endothelial tight junctions and damage to the basement membrane and astrocyte end‐feet and imaged routinely in clinical practice using T 1 ‐weighted imaging post‐gadolinium (Gd) injection . Macrophages are the principal cells that mediate demyelination by phagocytosing and degrading myelin, and the presence of foamy macrophages within an MS lesion indicates that it has formed within days or weeks .…”