Quantitative 7-Tesla Imaging of Cortical Myelin Changes in Early Multiple Sclerosis

Abstract

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS. A combined myelin estimation (CME) cortical map was obtained from quantitative 7-Tesla (7T) T2* and T1 acquisitions in 25 patients with early MS and 19 healthy volunteers. Cortical lesions in MS patients were classified based on their myelin content by comparison with CME values in healthy controls as demyelinated, partially demyelinated, or non-demyelinated. At follow-up, we registered changes in cortical lesions as increased, decreased, or stable CME. Vertex-wise analysis compared cortical CME in the normal-appearing cortex in 25 MS patients vs. 19 healthy controls at baseline and investigated longitudinal changes at 1 year in 10 MS patients. Measurements from the neurite orientation dispersion and density imaging (NODDI) diffusion model were obtained to account for cortical neurite/dendrite loss at baseline and follow-up. Finally, CME maps were correlated with clinical metrics. CME was overall low in cortical lesions (p = 0.03) and several normal-appearing cortical areas (p < 0.05) in the absence of NODDI abnormalities. Individual cortical lesion analysis revealed, however, heterogeneous CME patterns from extensive to partial or absent demyelination. At follow-up, CME overall decreased in cortical lesions and non-lesioned cortex, with few areas showing an increase (p < 0.05). Cortical CME maps correlated with processing speed in several areas across the cortex. In conclusion, CME allows detection of cortical microstructural changes related to coexisting demyelination and remyelination since the early phases of MS, and shows to be more sensitive than NODDI and relates to cognitive performance.

Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review

“…Similar to what was seen in WM assessments, ODI highlighted inconsistent results. In included studies, this measure was decreased in cortical and GM lesions 28,35 and unchanged in cortical lesions 24,30 when compared with NAGM and NGM. In comparison to NGM of HC, one study showed elevated ODI of NAGM, 25 two showed null results of ODI changes in NA cortex, 24,26 and three reported decreased ODI in NA cortex and NAGM 28,35,36 .…”

“…In included studies, this measure was decreased in cortical and GM lesions 28,35 and unchanged in cortical lesions 24,30 when compared with NAGM and NGM. In comparison to NGM of HC, one study showed elevated ODI of NAGM, 25 two showed null results of ODI changes in NA cortex, 24,26 and three reported decreased ODI in NA cortex and NAGM 28,35,36 . All the studies assessing ISOVF demonstrated no alterations in cortical lesions 30 and NA cortex 30,37 in affected people.…”

“…Among the 24 studies, 18 studies had high quality (7–9 NOS scores), six studies had intermediate quality (4–6 NOS scores), and none were low‐quality studies (Table S1). Participants were age‐matched in four studies, 24,28,37,39 sex‐matched in one study 36 . Meanwhile, 15 studies controlled for both age and gender 16,18,23,26,27,29–31,33–35,40–43 …”

Imaging cortical lesions in multiple sclerosis

“…Interestingly CME abnormalities were not coupled by changes in neurite orientation dispersion and density imaging (NODDI) [42], a measure of neurite/dendrite loss, supporting the hypothesis that CME changes were mostly driven by demyelination. At the same time, areas of increased CME could imply elevated arborization of the dendrites in repairing lesions [43 ▪▪ ]. In a larger MS cohort, NODDI modeling demonstrated that overall, cortical lesions identified at 3 T present a significant reduction of neurite density and orientation dispersion index, possibly due to a simplification of neurite complexity [44 ▪▪ ].…”

Seeing is believing: ultra-high field magnetic resonance imaging in vascular and neurodegeneration research

“…The perivenous lesion development or central vein sign in multiple sclerosis (MS) has been revealed in vivo for the first time, 2 which has proved useful for a differential diagnosis of MS. 3 Seven teslas MRI showed improved detection of cortical MS lesions that are consistent with histopathological patterns of cortical demyelinating lesions regarding their cortical layer involvement that are not seen on 3 T MRI. 4 The visibility of small venous architecture, including small cortical and medullary veins, has an important implication for tissue oxygen utilization and neuronal degeneration. 5 By introducing an ultrasmall-superparamagnetic-iron-oxide (USPIO) contrast agent (e.g., ferumoxytol), the small arterioles can also be seen on 7 T SWI, which allows the detection of small arterial tortuosity in the elderly, likely the major cause of small vessel disease.…”