Clinically feasible MTR is sensitive to cortical demyelination in MS

Abstract

Objective: Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS.Methods: MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MM ctx ), mostly demyelinated (MD ctx ), or intermediately demyelinated (ID ctx ). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. Conclusions: This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS. Neurology â 2013;80:246-252 GLOSSARY CL 5 cortical demyelinated lesions; HSD 5 honestly significant difference; ID ctx 5 intermediately demyelinated; LSM 5 least-squares mean; MD ctx 5 mostly demyelinated; MM ctx 5 mostly myelinated; MR 5 magnetic resonance; MS 5 multiple sclerosis; MTR 5 magnetization transfer ratio; MTR ctx 5 mean cortical magnetization transfer ratio; normMTR ctx 5 normalized cortical magnetization transfer ratio; PLP 5 proteolipid protein; TE 5 echo time; TR 5 repetition time; T1W 5 T1-weighted; WM 5 white matter.Cortical demyelinated lesions (CL) have been detected in patients with multiple sclerosis (MS) for more than 5 decades.1,2 Postmortem studies have raised the possibility that CL may be more prevalent than white matter (WM) demyelination 3 and that intracortical and mixed cortical/ WM lesions together may account for .50% of all MS brain lesions. 4 Despite their detection on postmortem tissue, most CL are invisible on conventional MRI. 4,5 The double inversion recovery sequence improves detection but does not reveal most CL. 5,6 While nonquantitative imaging features low sensitivity to CL, the sensitivity of semiquantitative and quantitative MRI is unclear. Although one ex vivo imaging study performed at 1.5 T revealed that T1 and T2 relaxation rates (not magnetization transfer ratio [MTR]) are sensitive to CL, 7 a separate study performed at 9.4 T found MTR and T2 relaxation rate (not T1) to be most sensitive.

Hippocampal volume is related to cognitive decline and fornicial diffusion measures in multiple sclerosis

“…Recent work has found that MTR is sensitive to cortical demyelination in patients with MS [38], and changes have been found in GM MTR and in the fornix specifically [39-41]. We did find modest positive correlations between MTR and performance on cognitive tasks, consistent with other studies that found associations between MTR and overall cognitive impairment [41-43].…”

Multivariate combination of magnetization transfer, T 2 * and B0 orientation to study the myelo-architecture of the in vivo human cortex

“…For example, MT ratio (MTR) was shown to correlate well with myelin content in the white matter (Schmierer et al, 2004). Recently, MTR was shown to be sensitive to cortical demyelination in multiple sclerosis patients (Chen et al, 2013; Derakhshan et al, 2014). However, MTR is only a semi-quantitative metric and has several confounds.…”

“…MTR is an index calculated using images with and without MT saturation pulse and was shown to correlate with myelin content (Henkelman et al, 2001; Schmierer et al, 2004). Recently, MTR was mapped in the cortex of MS patients (Chen et al, 2013; Derakhshan et al, 2014) and showed similarities between myelinated regions and high MTR values. However, MTR is only a semi-quantitative metric as it depends on sequence parameters, B1 profile and T1 relaxation (Berry et al, 1999; Pike Bruce, 1996).…”

Characteristics of lesional and extra-lesional cortical grey matter in relapsing–remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study

“…To achieve this, we used a combination of MRI techniques: PSIR to detect cortical lesions, 15 high-resolution MTR (sensitive to GM demyelination), 16 and DTI to assess tissue structural integrity. To avoid contamination of GM lesion measures by WM, we confined our analysis to intracortical GM lesions.…”