Perivenular brain lesions in a primate multiple sclerosis model at 7-tesla magnetic resonance imaging

Abstract

Background Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time – a perspective not obtainable with postmortem histopathology. Relapsing-remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter lesions similar to those observed in MS. Methods Brain lesion development and evolution were studied in vivo and postmortem in 4 marmosets with EAE through serial T2- and T2*-weighted scans at 7 tesla. Supratentorial white matter lesions were identified and characterized. Results Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles. Conclusion As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.

“Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine

“…This perivenous configuration of MS lesions has been recently demonstrated using T2*‐weighted ultrahigh‐field 7T MRI,13, 15 and in studies that have included non‐MS populations, the quantification of CVs has predicted a diagnosis of MS 12, 14, 17, 27, 28, 29. Several studies reported detection of CVs in lesions of MS patients more frequently than other populations, including patients with Susac syndrome29 and neuromyelitis optica spectrum disorder,17 and controls with high risk for vascular disease 28.…”

“…One such method may be detection of the “central vessel sign” (CVS) 10. It has been known from histopathological studies at autopsy that most MS lesions are centered around veins,11 and only recently have a variety of imaging techniques using susceptibility‐weighted imaging on ultrahigh‐field 7‐tesla (T) research magnets demonstrated this relationship in vivo 12, 13, 14, 15, 16, 17. A small number of studies have also evaluated the ability of 3T scanners, which are used routinely in clinical practice, to detect a “central vessel” (CV) in MS lesions 18, 19, 20, 21.…”

Advanced MRI and staging of multiple sclerosis lesions

“…EAE lesions in the marmoset brain present with similar features to MS lesions, including distribution throughout the CNS with a preferred location in the subcortical white matter 3,34,35 , uptake of gadolinium contrast agent 3,36 , and perivenular topography 37 (Figure 1). Interestingly, the veins around which most of the lesions form are already visible on scans prior to disease induction, supporting the notion that the inflammation associated with EAE affects previously normal veins.…”

Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset

“…The same techniques can be applied to the marmoset EAE at various magnetic field strengths (1.5 T, 3 T and 7 T) (Jordan et al, 1999;Gaitan et al, 2013;Maggi et al, 2014a;Blezer et al, 2007;Helms et al, 2013). Similarly to MS, new WM lesions in the marmoset EAE appear hyperintense on T2w and PDw and hypointense on T1w sequences.…”

“…Two main marmoset EAE models have been developed so far. The first model, originally described by Massacesi et al, is induced with white matter (WM) homogenate (WMH) giving perivenular brain and spinal cord WM lesions (t Hart and Massacesi, 2009;Gaitan et al, 2013) pathologically resembling the lesions observed in MS autopsies. The second model, induced with recombinant human myelin oligodendrocite glycoprotein (rhMOG) gives generally fewer but larger demyelinated lesions.…”