Quantitative and novel MR imaging to improve disease characterisation and diagnosis in people with Multiple-Sclerosis


All our work focusing on Multiple Sclerosis (MS) is carried out in close collaboration with Dr Klaus Schmierer, a neurologist at the Blizzard Institute (QMUL).

MS is an inflammatory and degenerative disease of the Central Nervous System (CNS) white and grey matter that currently has no cure. Disease onset is usually between the ages of 20 and 40 and it is the commonest disabling neurological disease in young adults, though it is unusual for it to occur before adolescence. MS is two to three times more common in females than in males and affects about 120,000 people in the UK. The current diagnostic criteria for MS are based on clinical and paraclinical evidence, including MRI of dissemination in time and space of lesions suggestive of inflammatory demyelination. A limitation of current MRI techniques is apparent in people with MS who also have risk factors for cerebral small vessel disease. Comorbidity may compromise correct allocation of new lesions to their cause. Such uncertainty may directly impact on treatment decisions.

In an effort to improve the specificity of changes detected using MRI, a characteristic histological feature of MS has recently been revisited: the vein about which MS lesions almost invariably evolve. A way to improve detection of this feature is to combine two sets of images: one where the lesions are well delineated (FLAIR) with on sensitive to blood vessels (T2*-weighted). The resulting image is referred to as FLAIR* and we are currently applying it to different patient groups (e.g. MS, small vessel disease, migraine) to assess its value in MS diagnosis.


MS Lesion with a vein
Figure 1. FLAIR (A), T2* (B) and FLAIR* (C) image showing a typical MS lesion with a vein (C, arrow)

In recent years, groups have been applying numerous quantitative MRI methods (T1, T2, DESPOT etc) to MS. The hope is that MRI could be used not only to diagnose the disease but quantify disease progression and in particular demyelination. Most of the research as so far been carried out in the brain, however, it is undeniable the the spinal cord plays a key role in disability progression and we have starting applying similar methods in post-mortem MS brains and spines. In order to validate those measurements, the sample are also undertaking detailed histology and the slides matched to the MRI slices.


MS Lesion in the cervical cord
Figure 2. Left: Images of an MS post-mortem spinal cord, cervical (A) thoracic (B) and lumbar (C), and corresponding T1 map (bottom row). Right: a typical MS lesion in the cervical cord.

Funding:

Schmierer K, Miquel M, Martin J, Giovannoni G, 2011, Quantifying the fundamental pathology of multiple sclerosis to understand mechanisms underlying disease progression, Barts and the London Charity, £397,216 Smith RJP, Schmierer K, Evanson J, Miquel ME, 2013, FLAIR* to distinguish lesions caused by multiple sclerosis from cerebral small vessel disease, Royal College of Radiologist Pump Priming Grant, £9,380


For further details, please see:

McDowell A (2016) Imaging T1, T2 and Myelin Water Fraction in the Postmortem Multiple-Sclerosis Central Nervous System. PhD thesis (submitted), Queen Mary University of London.

McDowell A, Petrova N, Vavasour I, Thomas D, Carassiti D, Miquel M , Kolind S, Schmierer K (2016) Myelin water imaging in multiple sclerosis post-mortem spinal cord. Proceedings of the International Society for Magnetic Resonance in Medicine 24: 2837.

McDowell AR, Wood TC, Petrova N, Carrassiti D, Miquel M, Thomas D, Barker GJ, Schmierer K (2015) Myelin and more: mcDESPOT applied to post mortem multiple sclerosis spinal cord. Proceedings of the International Society for Magnetic Resonance in Medicine 23:3277.

Campion T, Smith P, Altmann DR, Turner BP, Evanson J, George IC, Sati P, Reich DS, Miquel ME, Schmierer K (2014) FLAIR* for the non-invasive histological diagnosis of MS. Multiple Sclerosis Journal 20:289-90.

Collaborators:

Klaus Schmierer, Blizard Institute, Queen Mary University D. Reich & P. Sati, Radiology & Imaging Sciences, NIH G Barker & T Wood, Centre for Neuroimaging Science, King’s College London.