New MRI technique for an early diagnosis of MS

Clinical 3-tesla FLAIR* MRI improves diagnostic accuracy in multiple sclerosis.

George IC, Sati P, Absinta M, Cortese IC, Sweeney EM, Shea CD, Reich DS. Mult Scler. 2016 Jan 14. pii: 1352458515624975. [Epub ahead of print]


OBJECTIVE: To evaluate clinical fluid-attenuated inversion recovery (FLAIR)* 3T magnetic resonance imaging (MRI), which is sensitive to perivenular inflammatory demyelinating lesions, in diagnosing multiple sclerosis (MS). BACKGROUND: Central veins may be a distinguishing feature of MS lesions. FLAIR*, a combined contrast derived from clinical MRI scans, has not been studied as a clinical tool for diagnosing MS. METHODS: Two experienced MS neurologists evaluated 87 scan pairs (T2-FLAIR/FLAIR*), separately and side-by-side, from 68 MS cases, 8 healthy volunteers, and 11 individuals with other neurological diseases. Raters judged cases based on experience, published criteria, and a visual assessment of the "40% rule," whereby MS is favored if >40% of lesions demonstrate a central vein. Diagnostic accuracy was determined with area under the receiver operating characteristic curve (AUC), and inter-rater reliability was assessed with Cohen's kappa (κ).  RESULTS: Diagnostic accuracy was high: rater 1, AUC 0.94 (95% confidence interval: 0.89, 0.97) for T2-FLAIR, 0.95 (0.92, 0.98) for FLAIR*; rater 2, 0.94 (0.90, 0.98) and 0.90 (0.85, 0.95). AUC improved when images were considered together: rater 1, 0.99 (0.98, 1.00); rater 2, 0.98 (0.96, 0.99). Inter-rater agreement was substantial for T2-FLAIR (κ = 0.68) and FLAIR* (κ = 0.74), despite low agreement on the 40% rule (κ = 0.47) ([Formula: see text] in all cases). CONCLUSIONS: Joint clinical evaluation of T2-FLAIR and FLAIR* images modestly improves diagnostic accuracy for MS and does not require counting lesions with central veins.

It is self-evident why we need both an early AND accurate diagnosis - to be able to live up to the treatment paradigm of NEDA as early as possible. 

MRI is the most important tool to speed up the diagnosis of MS, however the currently used "McDonald" criteria remain imperfect.  A relatively recent approach to make MRI more specific to support (or rule out) a diagnosis of MS is based on detection of a histological hallmark of MS lesions: the central vein around which lesions develop.  


The "central vein sign" (CVS) can be visualised using an MRI technique (or several thereof) that is particularly sensitive to iron, which is present in every haemoglobin molecule. We've looked at this before: http://multiple-sclerosis-research.blogspot.com/2015/03/testing-your-metal-imaging veins-in-ms.html.

I agree with Ilena George and co-workers what would be useful now is a study involving multiple centres to evaluate whether the CVS stands up to its promises, however I'm told this proposal (by a US team) will not necessarily include European centres, so we may have to come up with our own multi-centre study.

CoI: We are collaborating with some of the authors of this research.