The central vein sign is a marker for multiple sclerosis (MS) and is the imaging manifestation of the perivenular nature of demyelinating plaques. It is not pathognomonic but can be useful in helping differentiate multiple sclerosis from mimics, such as cerebral small vessel disease, neuromyelitis optica spectrum disorder, migraine, and inflammatory vasculopathies (e.g. lupus).
The sign was proposed as a highly sensitive and specific biomarker for multiple sclerosis (as early as 2011), mainly on the basis of results from ultra high field MRI e.g. 7 T. Multiple studies carried out since then with 1.5 T and 3 T MRIs have been able to detect this sign, mainly on T2* sequences.
Multiple different threshold criteria have been suggested to distinguish multiple sclerosis (MS) from non-MS diseases such as the '40% rule', first introduced by Evangelou and colleagues 1, which assesses the percentage of lesions with a central vein and uses a cut-off value of 40% to radiologically distinguish MS from non-MS disease states. A much more recent study, demonstrated a sensitivity of 68.1% and specificity of 82.9%, for a cut-off value of 35% 11.
However, this rule has some limitations, as counting the number of lesions would be time-consuming in patients with high lesion load and, as highlighted above, >40% of brain lesions can be positive for central vein sign in some patients without MS (i.e. may not be 100% specific at this threshold) 2-4. Other studies have used different percentages or even just an absolute number of lesions that are central vein sign positive 5. For patients with high lesion loads, rather than every single lesion being assessed, some studies have suggested simpler rules with the classification process taking no more than two minutes per case 6. A recent 2019 systematic review and meta-analysis found that while individual cut-off values ranged from 30% to 67%, the optimal cut-off value was 45%, resulting in a sensitivity of 97% and specificity of 99% 5. Automated detection of the central vein sign has also shown promise 7.
Research suggests that although the sign can be seen in T2* sequence alone (e.g. susceptibility-weighted imaging) 1, it may be best visualized by combining sequences 8,9.
The central vein sign has been defined as a hypointensity appearing at the center of a surrounding hyperintense lesion in at least 2 of 3 orthogonal planes 10. The North American Imaging in Multiple Sclerosis Cooperative has further proposed the following definition:
Central vein exhibits the following properties on T2*-weighted images:
- appears as a thin hypointense line or small hypointense dot
- can be visualized in at least two perpendicular MRI planes, and appears as a thin line in at least one plane
- has a small apparent diameter (<2 mm)
- runs partially or entirely through the lesion
- is positioned centrally in the lesion (that is, located approximately equidistant from the lesion's edges and passing through the edge at no more than two places), regardless of the lesion's shape
Exclusion criteria for lesions:
- <3 mm in diameter in any plane
- merges with another lesion (confluent lesions)
- has multiple distinct veins
- poorly visible (owing to motion or other MRI artifacts)
As outlined above, a threshold cut-off of 40% or 45% can be used to help distinguish MS from non-MS lesions with a high sensitivity and specificity.
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