Multiple Sclerosis Journal - October 2017 - 1455

R Kapoor
advanced techniques show promise for differentiating disease mechanisms. Diffusion basis spectrum
imaging7 has the potential to resolve myelin, axons
and inflammation; high-field MRI can detect
sub-surface abnormalities potentially driven by
meningeal pathology;8 and techniques which
examine metabolic events in the injury pathway
include sodium imaging,9 cerebral perfusion and
N-acetylaspartate as a mitochondrial signal. Functional MRI sits alongside these techniques because
it offers the possibility of determining whether cerebral networks which are disordered by pathology
can be renormalized by therapies which have restorative or repair potential.10 Such functional changes
would complement improvements in other outcomes
for testing repair strategies.
Apart from being available widely, MRI also has the
advantage of versatility: multiple structural, functional and metabolic measurements can be made in
single subjects. Experience in other conditions including Alzheimer's disease suggests that multimodal
imaging may provide a more robust biomarker with
which to measure disease activity, and combined
imaging of the spinal cord in MS using conventional
and more advanced MRI techniques appears to support this view.11
For all of these techniques, validation against disability outcomes and responsiveness to therapy need
much further study. Longitudinal natural history studies are helpful, but validation is likely to be achieved
more efficiently if selected measures are included as
outcomes in placebo and treated groups in future clinical trials. Given restricted resources and a limited
appetite for risk, should preference be given to developing techniques based on MRI over others? The distinction may ultimately be unhelpful: rather than
choosing between MRI and PET, for example, it may
be more relevant to evaluate the potential of specific
techniques to measure the effects of treatments based
on their ability to address a given mechanism of
action, irrespective of modality.
In conclusion, this brief overview presents a case for
developing rational pipelines for drug discovery to
meet major unmet needs in progressive MS by validating a number of advanced biomarkers which show
promise for quantifying specific cellular and pathological aspects of neurodegeneration and repair. It
seems unlikely that any single modality will be sufficient to assess all of the mechanisms which underlie
these processes, but MRI-based techniques are likely
to predominate simply because the versatility and
availability of MRI compared with other modalities
makes it easier to implement.
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Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or
publication of this article.
Funding
The author(s) declared receipt of the following
financial support for the research, authorship and/or
publication of this article: This research was supported by the UK National Institute of Health
Research UCLH/UCL Biomedical Research Centre.

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