Imaging in MS

The proceedings of two recent European MS meetings provided updates on MS immunology and neurobiology.  In the first two parts of this Viewpoint Series the discussion was on the emerging insights into the complex interactions between elements of the immune system and the central nervous system (CNS), and how these interactions are thought to contribute to the different phases of the MS process.  The current Viewpoint serves to highlight recent advances in the medical imaging of MS, including the use of MRI, and progress in new imaging techniques.

Earlier diagnosis of MS

Magnetic resonance imaging (MRI) continues to have a major impact on the MS field.  Over the last two decades clinicians have increasingly come to rely on MRI to support the diagnosis of MS.  Readers will recall that in order to establish the diagnosis of MS, there has to be evidence for lesions in multiple sites in the CNS, as well as evidence for new activity developing over time.  This means that a firm diagnosis of MS requires proof of 'multiplicity in space' as well as 'multiplicity in time'.  (The reason for the latter requirement is that, occasionally, individuals may have a single clinical episode involving multiple sites in the CNS, but may never develop further lesions.  Such individuals should not be diagnosed with MS and should not be on MS therapies.)

MRI is very good at identifying lesions in various sites in the CNS and as such help to confirm 'multiplicity in space'.  Until recently, the 'multiplicity in time' clause could only be met if the person had a second clinical attack.  The trouble is, we now appreciate that in MS there can be considerable disease activity occurring beneath the radar of clinical detection.  Some experts estimate that clinically visible attacks represent as little as 10% of MS activity.  Since the activity that takes place under the surface is also thought to contribute to CNS damage, care providers strive to establish a definitive diagnosis of MS as soon as possible.  This enables earlier treatment, which should result in a better outcome.

 In 2001, an updated set of diagnostic criteria for MS was published which uses MRI to meet the 'evolution over time' requirement (1).  McDonald and co-workers suggested that follow-up MRI of the brain three or more months after an initial episode may be helpful since any findings on the subsequent MRI could be taken as evidence for 'multiplicity in time', enabling the diagnosis of MS.  While the McDonald criteria are not perfect, many leading MS centers and community clinicians have adopted the concept of using MRI to follow patients proactively after a single clinical episode, rather than waiting to see whether a new clinical episode emerges.

A common question in MS is whether additional follow-up MRIs are important once the diagnosis of MS is established.  While the role of MRI in the diagnosis of MS is obvious, it is less clear how one evaluates repeat MRIs in the same patient over time.  For one thing, the MS process fluctuates a great deal, and any single MRI is merely a snapshot that may not accurately capture ongoing disease activity.  Furthermore, unlike serial research scans, repeat clinical scans are rarely done with the exact same head positioning, and because the MRI only captures 'slices' of the brain, it is often difficult to know whether small lesions that appear new on a repeat scan were actually there before.  Another limitation with standard clinical scans relates to the fact that the commonly used MRI technique identifies abnormalities in the brain as "bright spots," which appear as white spots on the images.  Anything that increases water content in a region of the brain will result in the appearance of a bright spot on MRI, regardless of the underlying cause of the increased water content.  For example, local swelling without any tissue damage may have the exact same appearance as a brain region in which severe tissue injury has occurred.  This means that while MRI is highly sensitive, it cannot always discriminate well between lesions that represent mild versus severe injury.  Thus, tracking MRIs over time in the clinical setting may be misleading.

Newer MRI techniques provide more specific windows into the disease

Several new MRI approaches, including magnetic resonance spectroscopy (MRS), magnetic transfer ratio (MTR) imaging, diffusion tensor imaging (DTI) and even functional MRI (fMRI) have been developed in research laboratories and are distinct from traditional MRI.  These newer methods are gradually being applied in clinical trials of MS as helpful ways of monitoring changes in the brain of individual patients over time.  MRS and MTR are more specific than traditional MRI, in that lesions they detect provide a better reflection of the underlying tissue damage.

MRS studies, the biochemical content of a brain region and can be used to focus on the integrity of the axons.  As I reviewed in the previous Viewpoints in this series, axonal injury is likely to be the major factor contributing to disability in patients with MS.  The ability to study how axons are compromised and how treatments may impact on axons is extremely valuable.

MTR imaging provides a way of studying myelin integrity and emerging studies are considering whether sophisticated MTR assessment may be able to discriminate between areas of the CNS that are demyelinating-getting worse-versus those that are re-myelinating-getting better.

Similarly, diffusion weighted imaging (DWI), and DTI, may provide additional windows into the pathological process underlying different MS lesions.  Functional imaging (fMRI) and positron emission tomography (PET) scans are capable of viewing physiological changes such as blood flow and tissue metabolism, as well as the dynamics of particular molecules.  They have already been used to show that the plasticity in MS patients-the ability of the brain to re-model itself after injury-can be considerable.  A fast developing field is that of molecular imaging, which in principle strives to identify ways in which individual molecules or cells can be visualized and tracked in patients.  Including these various imaging modalities in clinical studies is providing very valuable insights into the changes patients experience over time as well as the impact of therapies under study.  It is hoped that selected research tools will eventually leave the research setting, and transition into more routine clinical practice.

References:

(1) McDonald et al, Recommended diagnostic criteria for MS.  Annals of Neurology 2001, 50:121-127

(2) Wolinsky J Ed., Neurology Clinics, 2005. The Veritas Medicine