Quantitative spinal cord MRI in MOG-antibody disease, neuromyelitis optica and multiple sclerosis

Abstract Spinal cord involvement is a hallmark feature of multiple sclerosis, neuromyelitis optica with AQP4 antibodies and MOG-antibody disease. In this cross-sectional study we use quantitative spinal cord MRI to better understand these conditions, differentiate them and associate with relevant clinical outcomes. Eighty participants (20 in each disease group and 20 matched healthy volunteers) underwent spinal cord MRI (cervical cord: 3D T1, 3D T2, diffusion tensor imaging and magnetization transfer ratio; thoracic cord: 3D T2), together with disability, pain and fatigue scoring. All participants had documented spinal cord involvement and were at least 6 months post an acute event. MRI scans were analysed using publicly available software. Those with AQP4-antibody disease showed a significant reduction in cervical cord cross-sectional area (P = 0.038), thoracic cord cross-sectional area (P = 0.043), cervical cord grey matter (P = 0.011), magnetization transfer ratio (P ≤ 0.001), fractional anisotropy (P = 0.004) and increased mean diffusivity (P = 0.008). Those with multiple sclerosis showed significantly increased mean diffusivity (P = 0.001) and reduced fractional anisotropy (P = 0.013), grey matter volume (P = 0.002) and magnetization transfer ratio (P = 0.011). In AQP4-antibody disease the damage was localized to areas of the cord involved in the acute attack. In multiple sclerosis this relationship with lesions was absent. MOG-antibody disease did not show significant differences to healthy volunteers in any modality. However, when considering only areas involved at the time of the acute attack, a reduction in grey matter volume was found (P = 0.023). This suggests a predominant central grey matter component to MOG-antibody myelitis, which we hypothesize could be partially responsible for the significant residual sphincter dysfunction. Those with relapsing MOG-antibody disease showed a reduction in cord cross-sectional area compared to those with monophasic disease, even when relapses occurred elsewhere (P = 0.012). This suggests that relapsing MOG-antibody disease is a more severe phenotype. We then applied a principle component analysis, followed by an orthogonal partial least squares analysis. MOG-antibody disease was discriminated from both AQP4-antibody disease and multiple sclerosis with moderate predictive values. Finally, we assessed the clinical relevance of these metrics using a multiple regression model. Cervical cord cross-sectional area associated with disability scores (B = −0.07, P = 0.0440, R2 = 0.20) and cervical cord spinothalamic tract fractional anisotropy associated with pain scores (B = −19.57, P = 0.016, R2 = 0.55). No spinal cord metric captured fatigue. This work contributes to our understanding of myelitis in these conditions and highlights the clinical relevance of quantitative spinal cord MRI.

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Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI

Neurology ◽

10.1212/wnl.0000000000005002 ◽

2018 ◽

Vol 90 (8) ◽

pp. e707-e716 ◽

Cited By ~ 13

Author(s):

Federica Agosta ◽

Edoardo Gioele Spinelli ◽

Ivan V. Marjanovic ◽

Zorica Stevic ◽

Elisabetta Pagani ◽

...

Keyword(s):

Spinal Cord ◽

Cortical Thickness ◽

Brain Mri ◽

Cross Sectional Area ◽

Cervical Cord ◽

Magnetization Transfer Ratio ◽

Healthy Controls ◽

Sectional Area ◽

Cross Sectional ◽

Sporadic Als

ObjectiveTo explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase (SOD1) gene compared with sporadic ALS.MethodsTwenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR).ResultsPatients with SOD1 ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls (p = 0.001−0.02) and SOD1-related ALS (p = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS (p < 0.001). No cord MTR differences were found between patient groups.ConclusionsPatients with SOD1 ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive SOD1 ALS therapies.

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Quantification of Cervical Cord Cross-Sectional Area: Which Acquisition, Vertebra Level, and Analysis Software? A Multicenter Repeatability Study on a Traveling Healthy Volunteer

Frontiers in Neurology ◽

10.3389/fneur.2021.693333 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carsten Lukas ◽

Barbara Bellenberg ◽

Ferran Prados ◽

Paola Valsasina ◽

Katrin Parmar ◽

...

Keyword(s):

Spinal Cord ◽

Healthy Volunteer ◽

Brain Mri ◽

Cross Sectional Area ◽

Image Resolution ◽

Cervical Cord ◽

Surface Model ◽

Sectional Area ◽

Cross Sectional ◽

Brain Images

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images.Aim: To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI.Method: One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1–C2; C2/3) on SC and brain images and the entire cervical cord (C1–C7) on SC images only.Results: CSA estimates were significantly smaller using SCT compared to NQL and ASM (p < 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1–C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all p ≤ 0.006 at the C1–C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings.Conclusion: For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches.

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Five-year longitudinal changes in quantitative spinal cord MRI in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520923970 ◽

2020 ◽

pp. 135245852092397 ◽

Cited By ~ 1

Author(s):

Jiwon Oh ◽

Min Chen ◽

Kateryna Cybulsky ◽

Suradech Suthiphosuwan ◽

Estelle Seyman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Diffusion Tensor ◽

Magnetization Transfer ◽

Longitudinal Change ◽

Magnetization Transfer Ratio ◽

Cross Sectional ◽

Longitudinal Changes ◽

Subject Specific

Background: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). Objectives: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. Methods: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3–C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. Results: SC-CSA and MTR decreased ( p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson’s r with FA = −0.23 ( p < 0.001); MD = 0.31 ( p < 0.001); λ⊥ = 0.34 ( p < 0.001); λ|| = −0.12 ( p = 0.05), MTR = −0.37 ( p < 0.001); SC-CSA = −0.47 ( p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated ( r = 0.93–0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). Conclusion: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.

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Association of iron rim lesions with brain and cervical cord volume in relapsing multiple sclerosis

European Radiology ◽

10.1007/s00330-021-08233-w ◽

2021 ◽

Author(s):

Claudia E. Weber ◽

Julia Krämer ◽

Matthias Wittayer ◽

Johannes Gregori ◽

Sigurd Randoll ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Grey Matter ◽

Cervical Cord ◽

Cross Sectional ◽

Upper Cervical ◽

Cortical Grey Matter ◽

Multiple Sclerosis Patients ◽

Brain And Spinal Cord

Abstract Objectives In multiple sclerosis (MS), iron rim lesions (IRLs) are indicators of chronic low-grade inflammation and ongoing tissue destruction. The aim of this study was to assess the relationship of IRLs with clinical measures and magnetic resonance imaging (MRI) markers, in particular brain and cervical cord volume. Methods Clinical and MRI parameters from 102 relapsing MS patients (no relapses for at least 6 months, no contrast-enhancing lesions) were included; follow-up data obtained after 12 months was available in 49 patients. IRLs were identified on susceptibility-weighted images (SWIs). In addition to standard brain and spinal cord MRI parameters, normalised cross-sectional area (nCSA) of the upper cervical cord was calculated. Results Thirty-eight patients had at least one IRL on SWI MRI. At baseline, patients with IRLs had higher EDSS scores, higher lesion loads (brain and spinal cord), and lower cortical grey matter volumes and a lower nCSA. At follow-up, brain atrophy rates were higher in patients with IRLs. IRLs correlated spatially with T1-hypointense lesions. Conclusions Relapsing MS patients with IRLs showed more aggressive MRI disease characteristics in both the cross-sectional and longitudinal analyses. Key Points • Multiple sclerosis patients with iron rim lesions had higher EDSS scores, higher brain and spinal cord lesion loads, lower cortical grey matter volumes, and a lower normalised cross-sectional area of the upper cervical spinal cord. • Iron rim lesions are a new lesion descriptor obtained from susceptibility-weighted MRI. Our data suggests that further exploration of this lesion characteristic in regard to a poorer prognosis in multiple sclerosis patients is warranted.

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Quantitative Magnetic Resonance Imaging Analysis of Early Markers of Upper Cervical Cord Atrophy in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Multiple Sclerosis International ◽

10.1155/2021/9917582 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Iman Adibi ◽

Afshin Najafi ◽

Fouad Merajifar ◽

Neda Ramezani ◽

Hosein Nouri ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Spinal Cord ◽

Magnetic Resonance ◽

Neuromyelitis Optica ◽

Cross Sectional Area ◽

Neuromyelitis Optica Spectrum Disorder ◽

Sectional Area ◽

Resonance Imaging ◽

Cross Sectional

Purpose. To quantitatively analyze the C2/C3 segments of the spinal cord on magnetic resonance imaging (MRI) scans of neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) patients in their first five years of the disease and to investigate the intergroup differences regarding markers of spinal cord atrophy and their correlations with expanded disability status scale (EDSS). Materials and Methods. Twenty NMOSD patients and twenty RRMS patients, within their first five years of the disease, were enrolled in this cross-sectional study. All patients underwent spinal cord MR imaging using 1.5 Tesla systems, and C2/C3 portions of the spinal cord were segmented in the obtained scans. C2/C3 anteroposterior diameter (C2/C3 SC-APD), transversal diameter (C2/C3 SC-TD), and cross-sectional area (C2/C3 SC-CSA) were quantitatively measured using Spinal Cord Toolbox v.4.3. Results. Three NMOSD patients were seropositive for anti-AQP4 IgG. The mean C2/C3 SC-CSA in NMOSD patients was significantly lower than in RRMS patients. NMOSD patients had significantly lower C2/C3 SC-TDs than RRMS patients. With the three anti-AQP4+ patients excluded from the analysis, C2/C3 SC-TD was negatively correlated with EDSS. Conclusion. In the early stages of the disease, quantitative evaluation of C2/C3 spinal cord parameters, including cross-sectional area and transversal diameter in NMOSD patients, appears to be of potential diagnostic and prognostic value.

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Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

Multiple Sclerosis Journal ◽

10.1177/1352458506070714 ◽

2006 ◽

Vol 12 (5) ◽

pp. 662-665 ◽

Cited By ~ 18

Author(s):

A Charil ◽

D Caputo ◽

R Cavarretta ◽

M P Sormani ◽

P Ferrante ◽

...

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Magnetization Transfer ◽

Small Sample ◽

Cervical Cord ◽

Magnetization Transfer Ratio ◽

Short Term ◽

Disease Evolution ◽

Transfer Ratio ◽

Relapsing Remitting

Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

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