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Supplemental material, sj-docx-1-msj-10.1177_13524585221097560 for Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study by Omar Al-Louzi, Sargis Manukyan, Maxime Donadieu, Martina Absinta, Vijay Letchuman, Brent Calabresi, Parth Desai, Erin S Beck, Snehashis Roy, Joan Ohayon, Dzung L Pham, Anish Thomas, Steven Jacobson, Irene Cortese, Pavan K Auluck, Govind Nair, Pascal Sati and Daniel S Reich in Multiple Sclerosis Journal

Supplemental material, sj-pdf-2-msj-10.1177_13524585211002097 for Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS by Jiwon Oh, Suradech Suthiphosuwan, Pascal Sati, Martina Absinta, Blake Dewey, Melanie Guenette, Daniel Selchen, Aditya Bharatha, Emily Donaldson, Daniel S Reich and Anthony Feinstein in Multiple Sclerosis Journal

Supplemental material, sj-pdf-1-msj-10.1177_13524585211002097 for Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS by Jiwon Oh, Suradech Suthiphosuwan, Pascal Sati, Martina Absinta, Blake Dewey, Melanie Guenette, Daniel Selchen, Aditya Bharatha, Emily Donaldson, Daniel S Reich and Anthony Feinstein in Multiple Sclerosis Journal

Supplemental material, sj-pdf-2-msj-10.1177_13524585211002097 for Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS by Jiwon Oh, Suradech Suthiphosuwan, Pascal Sati, Martina Absinta, Blake Dewey, Melanie Guenette, Daniel Selchen, Aditya Bharatha, Emily Donaldson, Daniel S Reich and Anthony Feinstein in Multiple Sclerosis Journal

Supplemental material, sj-pdf-1-msj-10.1177_13524585211002097 for Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS by Jiwon Oh, Suradech Suthiphosuwan, Pascal Sati, Martina Absinta, Blake Dewey, Melanie Guenette, Daniel Selchen, Aditya Bharatha, Emily Donaldson, Daniel S Reich and Anthony Feinstein in Multiple Sclerosis Journal

The automatic assessment of paramagnetic rim lesions in multiple sclerosis is important, and a deep learning-based algorithm called RimNet has recently been proposed. This work evaluates the generalizability of RimNet and its longitudinal performance on MRI data acquired at different clini-cal centers. We found that RimNet’s performance was nearly as good on totally unseen data as in the original paper (receiver-operating-characteristic area-under-the-curve (AUC) 0.88 vs. 0.94, pre-cision-recall AUC 0.69 vs. 0.70), and it made consistent predictions on longitudinal data (binary con-sistency 82%, probability consistency 93%).

ObjectiveTo summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.MethodsClinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.ResultsA wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.ConclusionsImaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p < 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4; p = 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (β add , 16.3; 95% confidence interval [CI], 4.6-28.0; p < 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; β add , 30.4; 95% CI, 15.6-45.2; p < 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (β add , 1.1; 95% CI, 0.3-1.9; p < 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p = 0.004 and p = 0.0002, respectively). Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Paramagnetic rim lesions (PRL) in multiple sclerosis are chronic inflammatory lesions depicted in susceptibility-based MRI where high PRL lesion burden has been associated with a more aggressive disease course. As their visual detection is subjective and time-consuming, a convolutional neural network (RimNet) has recently been developed and applied to 3T susceptibility contrast MR images. In this work, we evaluate a unimodal RimNet architecture based on either the MP2RAGE uniform contrast or the concurrently obtained T1 map at both 3T and 7T. Results show that prediction improves considerably at 7T, suggesting that 7T MP2RAGE might be helpful for automatically identifying PRL.

In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on magnetic resonance imaging by their paramagnetic rims, and increasing evidence supports their association with severity of clinical disease. We studied their potential role in differential diagnosis, screening an international multicenter clinical research-based sample of 438 individuals affected by different neurological conditions (MS, other inflammatory, infectious, and non-inflammatory conditions). Paramagnetic rim lesions, rare in other neurological conditions (52% of MS vs 7% of non-MS cases), yielded high specificity (93%) in differentiating MS from non-MS. Future prospective multicenter studies should validate their role as a diagnostic biomarker. ANN NEUROL 2020;88:1034-1042.

Background: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective. Objectives: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases. Methods: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory “red flags” (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed. Results: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%; p < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value. Conclusion: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the “central vein sign”) improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). Methods: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing–remitting MS, 3-dimensional T2*-weighted and T2–fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. Results: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. Interpretation: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283–294., SCOPUS: ar.j, info:eu-repo/semantics/published