Neuropathologically informed imaging of cortical grey matter lesions in MS - A pilot study.

Multiple sclerosis (MS) is frequently misdiagnosed based on MRI abnormalities detected in the brain white matter. Cortical lesions have been well described neuropathologically, but remain challenging to detect in clinical practice. Therefore, the ability to detect cortical lesions offers real potential to reduce misdiagnosis. Cortical lesions have been shown to have a predilection for regions with CSF stasis - such as the insula and cingulate gyrus. This pathological observation forms the basis of our current pilot MR imaging study, which successfully uses high spatial resolution imaging of these two anatomical regions to clearly identify cortical lesions in MS.

Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation. METHODS: We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression. RESULTS: 113 people were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (ß=0.33, p<0.01) and cord area (ß=-0.45, p<0.01) were independently associated with EDSS (R(2)=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (ß=-0.33, p<0.01) and timed walk (ß=-0.20, p=0.04). CONCLUSIONS: The study findings suggest that pathological involvement of the spinal cord GM contributes significantly to physical disability in relapse-onset MS and SPMS in particular.

A pilot MRI study of white and grey matter involvement by multiple sclerosis spinal cord lesions.

OBJECTIVES: Spinal cord pathology is a major cause of disability in multiple sclerosis (MS) and pathology studies show multifocal demyelinating lesions in white matter (WM) tracts and central grey matter (GM). Better localisation of cord lesions by in vivo MRI may help to understand the structural-functional effects of spinal cord pathology in MS. METHODS: Three-Tesla MRI was performed on upper cervical cord in 15 MS patients and one clinically isolated syndrome. Axial 3D gradient-echo fast field echo (3D-FFE) and phase sensitive inversion recovery sequences (3D-PSIR) were acquired. Two readers reviewed images to detect and classify lesions: WM-only, mixed WM-GM or GM-only. Location of the WM component was classified: anterior (AC), lateral (LC) or posterior (PC) column. RESULTS: Fifty one lesions were identified: 32 (63%) mixed WM-GM, 19 (37%) WM-only, no GM-only. Most were in LC (n=30, 59%), followed by PC (n=18, 35%) and AC (n=3, 6%). Mean lesion areas: AC 4.3mm(2), LC 8.5mm(2), PC 11.3mm(2), corresponding to 6.1%, 12% and 16.1% of mean cord area, respectively. Mean lesion lengths: 18.3mm in AC, LC 17.6mm and PC 24.8mm. CONCLUSIONS: While there was good depiction of WM tract involvement by cord lesions, involvement of central grey matter was not as clear. Noting the important effects of spinal cord pathology in MS, further work to better depict cord lesions by in vivo imaging is warranted.

Feasibility of grey matter and white matter segmentation of the upper cervical cord in vivo: a pilot study with application to magnetisation transfer measurements.

Spinal cord pathology can be functionally very important in neurological disease. Pathological studies have demonstrated the involvement of spinal cord grey matter (GM) and white matter (WM) in several diseases, although the clinical relevance of abnormalities detected histopathologically is difficult to assess without a reliable way to assess cord GM and WM in vivo. In this study, the feasibility of GM and WM segmentation was investigated in the upper cervical spinal cord of 10 healthy subjects, using high-resolution images acquired with a commercially available 3D gradient-echo pulse sequence at 3T. For each healthy subject, tissue-specific (i.e. WM and GM) cross-sectional areas were segmented and total volumes calculated from a 15 mm section acquired at the level of C2-3 intervertebral disc and magnetisation transfer ratio (MTR) values within the extracted volumes were also determined, as an example of GM and WM quantitative measurements in the cervical cord. Mean (± SD) total cord cross-sectional area (TCA) and total cord volume (TCV) of the section studied across 10 healthy subjects were 86.9 (± 7.7) mm(2) and 1302.8 (± 115) mm(3), respectively; mean (±SD) total GM cross-sectional area (TGMA) and total GM volume (TGMV) were 14.6 (± 1.1) mm(2) and 218.3 (± 16.8) mm(3), respectively; mean (± SD) GM volume fraction (GMVF) was 0.17 (± 0.01); mean (± SD) MTR of the total WM volume (WM-MTR) was 51.4 (± 1.5) and mean (± SD) MTR of the total GM volume (GM-MTR) was 49.7 (± 1.6). The mean scan-rescan, intra- and inter-observer % coefficient of variation for measuring the TCA were 0.7%, 0.5% and 0.5% and for measuring the TGMA were 6.5%, 5.4% and 12.7%. The difference between WM-MTR and GM-MTR was found to be statistically significant (p=0.00006). This study has shown that GM and WM segmentation in the cervical cord is possible and the MR imaging protocol and analysis method presented here in healthy controls can be potentially extended to study the cervical cord in disease states, with the option to explore further quantitative measurements alongside MTR.