Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines

Filippi, Massimo; Preziosa, Paolo; Banwell, Brenda; Barkhof, Frederik; Ciccarelli, Olga; Stefano, Nicola De; Geurts, Jeroen J. G.; Paul, Friedemann; Reich, Daniel S.; Toosy, Ahmed; Traboulsee, Anthony; Wattjes, Mike P.; Yousry, Tarek; Gass, Achim; Lubetzki, Catherine; Weinshenker, Brian G.; Rocca, Maria A.

doi:10.1093/brain/awz144

Cited by 334 publications

(331 citation statements)

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“…Between September 2016 and December 2018, patients with a clinical presentation suggestive of MS but who had clinical, imaging, or laboratory features atypical for MS 15,17,18 were prospectively enrolled in four academic research hospitals: the Lausanne University Hospital (Lausanne, Switzerland), the Erasme and Brugmann University Hospitals (Brussels, Belgium), and the San Raffaele University Hospital (Milan, Italy). Patients were excluded from the study if (1) they did not experience at least one clinical episode compatible with a focal or multifocal demyelinating event in the CNS, (2) they did not reach a clinical diagnosis at the end of the study period, (3) they had a contraindication for MRI or intravenous injection of gadolinium-based contrast material, and (4) MRI image quality was suboptimal because of motion artifact.…”

Section: Patientsmentioning

confidence: 99%

“…All 39 patients who received a clinical diagnosis by the end of the study (30 females and 9 males), median age 46 years (range 19-74 years), experienced at least one clinical episode compatible with a focal or multifocal demyelinating event in the CNS 2 and had at least one clinical, laboratory, or imaging feature atypical for MS, hereafter termed "red flags" (Table 2). 2,15,17,18 Of note, minor clinical red flags (denoted as "Minor" in Table 2) were features not specific of a disease involving the CNS but potentially associated with another systemic inflammatory/autoimmune disorder (SAD) involving the CNS. Patients carrying minor red flags needed at least another red flag to be included in this study.…”

Section: Patientsmentioning

confidence: 99%

“…A number of important reviews have identified differentiating clinical, laboratory, or imaging features ("red flags") to guide clinicians during the diagnostic work-up of patients with suspected MS but with atypical features for the diagnosis. 2,4,[13][14][15][16][17][18] Data regarding the prospective diagnostic value of the CVS in these challenging conditions are lacking. In this multicenter study, we prospectively tested the diagnostic value of the CVS at clinical 3T MRI in patients with possible MS but with atypical clinical, laboratory, or imaging features.…”

Section: Introductionmentioning

confidence: 99%

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The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: A prospective multicenter 3T study

et al. 2019

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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.

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Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: A prospective multicenter 3T study

et al. 2019

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“…Current magnetic resonance imaging (MRI) diagnostic criteria for multiple sclerosis (MS) are based on the dissemination in time and space of characteristic imaging features of the disease. Although highly useful, the specificity of these criteria is limited, and the risk of misdiagnoses based on MRI is still substantial . Consequently, identification of more specific imaging biomarkers for MS is a high‐priority area of research …”

Section: Introductionmentioning

confidence: 99%

CVSnet: A machine learning approach for automated central vein sign assessment in multiple sclerosis

et al. 2020

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The central vein sign (CVS) is an efficient imaging biomarker for multiple sclerosis (MS) diagnosis, but its application in clinical routine is limited by inter-rater variability and the expenditure of time associated with manual assessment. We describe a deep learning-based prototype for automated assessment of the CVS in white matter MS lesions using data from three different imaging centers. We retrospectively analyzed data from 3 T magnetic resonance images acquired on four scanners from two different vendors, including adults with MS (n = 42), MS mimics (n = 33, encompassing 12 distinct neurological diseases mimicking MS) and uncertain diagnosis (n = 5). Brain white matter lesions were manually segmented on FLAIR* images. Perivenular assessment was performed according to consensus guidelines and used as ground truth, yielding 539 CVS-positive (CVS + ) and 448 CVS-negative (CVS − ) lesions. A 3D convolutional neural network ("CVSnet") was designed and trained on 47 datasets, keeping 33 for testing. FLAIR* lesion patches of CVS + /CVS − lesions were used for training and validation (n = 375/298) and for testing (n = 164/150). Performance was evaluated lesion-wise and subject-wise and compared with a state-of-the-art vesselness filtering approach through McNemar's test. The proposed CVSnet approached human performance, with lesion-wise median balanced accuracy of 81%, and subject-wise balanced accuracy of 89% on the validation set, and 91% on the test set. The process of CVS assessment, in previously manually segmented lesions, was~600-fold faster using the proposed CVSnet compared with human visual assessment (test set: 4 seconds vs. 40 minutes). On the validation and test sets, the lesion-wise performance outperformed the vesselness filter method (P < 0.001). The proposed deep learning prototype shows promising performance in differentiating MS from its mimics. Our approach was evaluated using data from different hospitals, enabling larger multicenter trials to evaluate the benefit of introducing the CVS marker into MS diagnostic criteria.Abbreviations used: AUC, area under the curve; CVS, central vein sign; FLAIR, 3D T2-weighted fluid-attenuated inversion recovery; GPU, graphics processing unit; MRI, magnetic resonance imaging; MS, multiple sclerosis; NIR, no information rate; ReLU, rectified linear unit; ROC, receiver operating characteristic; T2*-EPI, T2*-weighted segmented echo-planar imaging; 3D, threedimensional; WM, white matter.Pietro Maggi and Mário João Fartaria contributed equally to this work.

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“…Susceptibility-weighted images (SWIs) have short acquisition times and are readily available, but they appear to be less sensitive than other imaging sequences in detecting the CVS. 2,4,5 Proper comparisons among sequences and general protocols used in MS are thus necessary. If such technical issues are not solved, the translation of the CVS to the clinical practice may prove limited.…”

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confidence: 99%

Detection of central vein should be part of MS diagnostic criteria – No

Arrambide

2020

Mult Scler

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The central vein sign (CVS) has been proposed as a specific biomarker for multiple sclerosis (MS). 1 Although best visualized at ultra-high field magnetic resonance imaging (MRI), recent evidence demonstrates that the CVS can be detected with MRI at 3.0 and 1.5 T, 2-4 making it potentially useful in the clinical practice. The high specificity of the CVS in MS derives from comparisons with other neurological diseases with focal white matter hyperintensities. 5 This is precisely one of the reasons the CVS cannot, at this point, be part of the MS diagnostic criteria. The McDonald criteria were not developed to differentiate MS from other diseases, but to confirm the diagnosis of MS in patients with typical symptoms once other diagnoses have been reasonably ruled out. 6 Nevertheless, incorporating more disease-specific biomarkers in the diagnostic criteria would of course be desirable. In this sense, we could then consider the results of previous studies as proof-of-concept of the high specificity of the CVS in MS lesions, which reflects the perivenous inflammatory demyelination occurring in this disease. To do so, the CVS should be assessed in the context of the 2017 McDonald criteria to determine whether its inclusion does increase the diagnostic specificity while maintaining a high sensitivity.There are, however, several issues to consider first. One is that the CVS can also be seen in diseases other than MS, 5 thus requiring the use of a proportion threshold of lesions with CVS which is usually but not always ⩾40%. 3,4 Using a proportion-based approach is not practical in the daily clinical practice, particularly in patients with a high lesion load. Furthermore, the proportion threshold appears to depend on the type of non-MS diseases the comparison is made against. 3,4,7 Instead, identifying a minimum number of lesions with CVS could simplify its use. However, past efforts in small, retrospective studies have suggested differing cut-offs. Whereas in one of these studies MS was diagnosed if at least 6 out of 10 randomly assessed lesions were perivenular, 8 in the other MS was diagnosed when 3 out of 3 randomly assessed lesions were perivenular. 9 Moreover, a third, small, retrospective study showed that the proportion-based approach, using a 50% and a 40% rule, yielded a higher diagnostic accuracy compared to the six-and three-lesion rule. 3 Another point to consider in these studies is that the mean/median disease duration in patients with MS was 7.7-10.0 years, besides one of the studies including both relapsing and progressive forms of the disease. 3,8,9 With such disease duration, the lesion load would be expected to be high and, at that point in the evolution of the disease, few reasonable doubts about the diagnosis would exist. Diagnosing MS in earlier stages in which the lesion count is usually lower is certainly more challenging. Efforts should thus be directed toward the assessment of the CVS in this setting, especially when considering that the CVS is more difficult to visualize in infratentorial and sp...

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Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines

Cited by 334 publications

References 120 publications

The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: A prospective multicenter 3T study

The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: A prospective multicenter 3T study

CVSnet: A machine learning approach for automated central vein sign assessment in multiple sclerosis

Detection of central vein should be part of MS diagnostic criteria – No

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