Validating atlas-based lesion disconnectomics in multiple sclerosis: a retrospective multi-centric study

The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are known to be sensitive to the presence of white matter lesions and therefore leading to interpretation pitfalls and poor inter-subject comparability in clinical applications such as multiple sclerosis. Second, tractography quality is highly dependent on the acquisition parameters of diffusion sequences, leading to a trade-off between acquisition time and tractography precision. Here, we propose an atlas-based approach to study the interplay between structural disconnectivity and lesions without requiring individual diffusion imaging. In a multi-centric setting involving three distinct multiple sclerosis datasets (containing both 1.5T and 3T data), we compare our atlas-based structural disconnectome computation pipeline to disconnectomes extracted from individual tractography and explore its clinical utility for reducing the gap between radiological findings and clinical symptoms in multiple sclerosis. Results using topological graph properties showed that overall, our atlas-based disconnectomes were suitable approximations of individual disconnectomes from diffusion imaging. Small-worldness was found to decrease for larger total lesion volumes thereby suggesting a loss of efficiency in brain connectivity of MS patients. A graph embedding technique followed by dimensionality reduction found a topological organization that mirrored disability. Finally, the global efficiency of the created brain graph, combined with total lesion volume, allowed to stratify patients into subgroups with different clinical scores in all three cohorts.

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Contrasting the brain imaging features of MOG-antibody disease, with AQP4-antibody NMOSD and multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/13524585211018987 ◽

2021 ◽

pp. 135245852110189

Author(s):

Silvia Messina ◽

Romina Mariano ◽

Adriana Roca-Fernandez ◽

Ana Cavey ◽

Maciej Jurynczyk ◽

...

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Diffusion Imaging ◽

White Matter Lesions ◽

Lesion Volume ◽

Imaging Features ◽

Strongly Correlated ◽

Deep Grey Matter ◽

Magnetic Resonance Imaging Mri ◽

Aqp4 Antibody

Background: Identifying magnetic resonance imaging (MRI) markers in myelin-oligodendrocytes-glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder-aquaporin-4 positive (NMOSD-AQP4) and multiple sclerosis (MS) is essential for establishing objective outcome measures. Objectives: To quantify imaging patterns of central nervous system (CNS) damage in MOGAD during the remission stage, and to compare it with NMOSD-AQP4 and MS. Methods: 20 MOGAD, 19 NMOSD-AQP4, 18 MS in remission with brain or spinal cord involvement and 18 healthy controls (HC) were recruited. Volumetrics, lesions and cortical lesions, diffusion-imaging measures, were analysed. Results: Deep grey matter volumes were lower in MOGAD ( p = 0.02) and MS ( p = 0.0001), compared to HC and were strongly correlated with current lesion volume (MOGAD R = −0.93, p < 0.001, MS R = −0.65, p = 0.0034). Cortical/juxtacortical lesions were seen in a minority of MOGAD, in a majority of MS and in none of NMOSD-AQP4. Non-lesional tissue fractional anisotropy (FA) was only reduced in MS ( p = 0.01), although focal reductions were noted in NMOSD-AQP4, reflecting mainly optic nerve and corticospinal tract pathways. Conclusion: MOGAD patients are left with grey matter damage, and this may be related to persistent white matter lesions. NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes, but reduced non-lesional tissue FA. Observations from our study can be used to identify new markers of damage for future multicentre studies.

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A multi-shell multi-tissue diffusion study of brain connectivity in early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519845105 ◽

2019 ◽

Vol 26 (7) ◽

pp. 774-785 ◽

Cited By ~ 2

Author(s):

Carmen Tur ◽

Francesco Grussu ◽

Ferran Prados ◽

Thalis Charalambous ◽

Sara Collorone ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Connectivity ◽

Diffusion Imaging ◽

Orientation Distribution ◽

Distribution Functions ◽

Network Modularity ◽

Clinical Measures ◽

Network Metrics ◽

Better Than ◽

Single Shell

Background: The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated. Objective: To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols. Methods: Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients. Results: Patients had lower mean nodal strength ( p = 0.003) and greater network modularity than controls ( p = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load ( p = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones. Conclusion: Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.

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Age related susceptibility to grey matter demyelination and neurodegeneration is associated with meningeal neutrophil accumulation in an animal model of Multiple Sclerosis

10.1101/2021.12.23.474008 ◽

2021 ◽

Author(s):

Michelle Zuo ◽

Naomi Fettig ◽

Louis-Philippe Bernier ◽

Elisabeth Possnecker ◽

Shoshana Spring ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Th17 Cells ◽

Grey Matter ◽

Clinical Symptoms ◽

White Matter Lesions ◽

Neutrophil Accumulation ◽

Cns Inflammation ◽

Age Related ◽

Meningeal Inflammation

People living with multiple sclerosis (MS) experience episodic central nervous system (CNS) white matter lesions instigated by autoreactive T cells. With age, MS patients show evidence of grey matter demyelination and experience devastating non-remitting symptomology. What drives progression is unclear and has been hampered by the lack of suitable animal models. Here we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induces a non-remitting clinical phenotype that is associated with persistent meningeal inflammation and cortical pathology in old, but not young SJL/J mice. While the quantity and quality of T cells did not differ in the brains of old vs young EAE mice, an increase in neutrophils and a decrease in B cells was observed in the brains of old mice. Neutrophils were also found in the meninges of a subset of progressive MS patient brains that showed evidence of meningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and grey matter pathology are dictated by age and associated with other immune cells such as neutrophils.

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The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo

Multiple Sclerosis Journal ◽

10.1177/135245859800400602 ◽

1998 ◽

Vol 4 (6) ◽

pp. 471-474 ◽

Cited By ~ 3

Author(s):

Massimo Filippi ◽

Tarek A Yousry ◽

Maria A Rocca ◽

Clodoaldo Pereira ◽

Hatem Alkadhi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cross Talk ◽

Spin Echo ◽

Brain Magnetic Resonance Imaging ◽

Acquisition Time ◽

Lesion Volume ◽

Turbo Spin Echo ◽

Turbo Spin ◽

Acquisition Scheme ◽

Significant Difference

We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patient and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3. 1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesion volumes were significantly higher when scheme B was used (P= 0.024). This was due to higher lesion volumes on TSE images (P= 0.006), especially on even-numbered slices (P= 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

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2D in-vivo L-COSY spectroscopy identifies neurometabolite alterations in treated multiple sclerosis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419877081 ◽

2019 ◽

Vol 12 ◽

pp. 175628641987708 ◽

Cited By ~ 2

Author(s):

Scott Quadrelli ◽

Karen Ribbons ◽

Jameen Arm ◽

Oun Al-iedani ◽

Jeannette Lechner-Scott ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Symptoms ◽

Brain Lesion ◽

Nonparametric Tests ◽

Correlation Spectroscopy ◽

Resonance Spectroscopy ◽

Attention And Memory ◽

Lesion Volume ◽

Whole Brain

Background: We have applied in vivo two-dimensional (2D) localized correlation spectroscopy (2D L-COSY), in treated relapsing relapsing-remitting multiple sclerosis (RRMS) to identify novel biomarkers in normal-appearing brain parenchyma. Methods: 2D L-COSY magnetic resonance spectroscopy (MRS) spectra were prospectively acquired from the posterior cingulate cortex (PCC) in 45 stable RRMS patients undergoing treatment with Fingolimod, and 40 age and sex-matched healthy control (HC) participants. Average metabolite ratios and clinical symptoms including, disability, cognition, fatigue, and mental health parameters were measured, and compared using parametric and nonparametric tests. Whole brain volume and MRS voxel morphometry were evaluated using SIENAX and the SPM LST toolbox. Results: Despite the mean whole brain lesion volume being low in this RRMS group (6.8 ml) a significant reduction in PCC metabolite to tCr ratios were identified for multiple N-acetylaspartate (NAA) signatures, gamma-aminobutyric acid (GABA), glutamine and glutamate (Glx), threonine, and isoleucine/lipid. Of the clinical symptoms measured, visuospatial function, attention, and memory were correlated with NAA signatures, Glx, and isoleucine/lipid in the brain. Conclusions: 2D L-COSY has the potential to detect metabolic alterations in the normal-appearing MS brain. Despite examining only a localised region, we could detect metabolic variability associated with symptoms.

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