Monday, 25 January 2016

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.

8 comments:

  1. What about if you lesions pattern is only infratentorial as mine are?

    Isn't it true lesions characteristic of MS are not just restricted to the ventricles or subcorticle region?

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    1. Four areas are considered characteristic for MS lesion location including as you say periventricular, sub-cortical, infratentorial (brainstem, cerebellum) and spinal cord. In order to meet the current 'dissemination in space' criteria you have to have lesions in at least two of these areas. Please remember, you can have MS without fulfilling these cirteria, and you can NOT have MS despite fulfilling these criteria. Their sensitivity and specificity are not perfect. Which is a key reason for this research.

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  2. Do you think that NEDA using MRI is currently very limited, as most hospital MRI machines (in the UK) are only 3T strength. Where as reviewing the same MRI under a 7T machine can reveal inflammation that is small and hidden from 3T MRI. Which would make sense as currently the highly effective drugs are not proven to stop progression to progressive disease from RRMS. (Though that is often implied)

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    1. Due to the inherent shortcomings of available techniques, including MRI, relapse and disability assessment NEDA remains an estimate, as well as an ambition (after all many pwMS are not NEDA, even with current assessment tools, despite being on highly active treatment). A clinical 7T scanner will show more lesions, however whether NEDA including MRI acquired @ 7T is superior versus 3T has, as far as I'm aware, not been investigated. It be great if the available kit would be used more systematically, given the evidence is indeed strong that early treatment may effectively suppress disease activity. In terms of treatment decisions the clinical distinction between RRMS and SPMS is increasingly outdated (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117366/pdf/NEUROLOGY2013555623.pdf).

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  3. Do you think the results will be continent-specific? If the study is well-designed and adequately powered, US data should be equallyk applicable to Europe.

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    1. Can you trust 'em...:-) But seriously, in my view it would make sense for this technique, which can be implemented on a standard clinical MRI system, to spread knowledge creation and experience across the Globe, including centres in Asia, where concerns about applicability of "Western" diagnostic algorithms are due to different clinical presentations, disease phenotypes, and a lower MS prevalence which can be similar to NMO.

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    2. Oooh here in Brazil we are very even late!! Most MRI machines are 1 or 1.5 T.

      DRK so in Asia NMO is more prevalent than a MS?

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    3. The prevalence of MS and NMO is quite similar, and low, in countries like Taiwan or Japan.

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