Multiple Sclerosis Journal - October 2017 - 1458

Multiple Sclerosis Journal 23(11)
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Multiple Sclerosis Journal
2017, Vol. 23(11) 1458-1460
DOI: 10.1177/
https://doi.org/10.1177/1352458517713344
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Advanced MRI measures like DTI or fMRI
should be outcome measures in future clinical
trials - Commentary
Nicola De Stefano and Antonio Giorgio

Correspondence to:
Nicola De Stefano
Department of Medicine,
Surgery and Neuroscience,
University of Siena, Viale
Bracci 2, 53100 Siena, Italy.
destefano@unisi.it
Nicola De Stefano
Antonio Giorgio
Department of Medicine,
Surgery and Neuroscience,
University of Siena, Siena,
Italy

A number of paraclinical outcome measures have
been used in multiple sclerosis (MS) clinical studies
in addition to clinical endpoints to monitor disease
progression and treatment efficacy. In this context,
magnetic resonance imaging (MRI)-based measures
are of paramount relevance due to their sensitivity in
detecting and quantifying the focal and diffuse pathology occurring in MS.1 Indeed, MRI measures of white
matter lesional activity (i.e. new/enlarging T2 lesions
or Gd-enhancing T1 lesions) and those of brain atrophy (i.e. percentage of brain volume change) have
shown to be valid surrogate endpoints for clinical outcomes and have been accepted as endpoints in the
most recent pharmacologic clinical trials.2
In addition to these MRI measures, newer and more
tissue-specific MRI measures able to assess the
microscopic tissue damage (e.g. magnetization transfer imaging (MTI), diffusion tensor imaging (DTI))
and the functional cortical reorganization (i.e. functional magnetic resonance imaging (fMRI)) occurring
in the brain of MS patients have been proposed. In
these controversies in MS, Kapoor advocates that
these advanced MRI metrics should be outcome
measures in future clinical trials, while Matthews

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counters that, at present, they have limited practical
utility and are far from being 'clinical trial ready'.
As correctly indicated by Kapoor, while we have efficient MRI biomarkers able to surrogate MS relapse
and the related inflammation (i.e. active lesions), the
situation looks much more confused when the aim
becomes the assessment of disease progression and
the related neurodegeneration. In this context, we
agree that measurement of brain atrophy is not and
cannot be the solution, as this represents a sort of
global measure of various mechanisms of tissue injury
that is influenced by a complex interplay across multiple cellular compartments. Biomarkers that are specific for tissue injury and repair are therefore necessary
to provide more pathologically specific endpoints.
The main question is: can MRI provide these biomarkers in the near future?
There is no doubt that most of the advanced MRI methods, including DTI and fMRI, are powerful research
tools that have shed a new light into MS and its pathogenetic mechanisms (i.e. altered brain connectivity and
changes in functional reorganization). We may also
agree, as stressed by Kapoor, that these MRI techniques

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