Yong
Wang , Peng Sun , Qing Wang , Kathryn Trinkaus , Robert E. Schmidt ,
Robert T. Naismith , Anne H. Cross , Sheng-Kwei SongDifferentiation and
quantification of inflammation, demyelination and axon injury or loss in
multiple sclerosis. Brain 2015
Axon injury/loss,
demyelination and inflammation are the primary pathologies in multiple
sclerosis lesions. Despite the prevailing notion that axon/neuron loss
is the substrate of clinical progression of multiple sclerosis, the
roles that these individual pathological processes play in multiple
sclerosis progression remain to be defined. An imaging modality capable
to effectively detect, differentiate and individually quantify axon
injury/loss, demyelination and inflammation, would not only facilitate
the understanding of the pathophysiology underlying multiple sclerosis
progression, but also the assessment of treatments at the clinical trial
and individual patient levels. In this report, the newly developed
diffusion basis spectrum imaging was used to discriminate and quantify
the underlying pathological components in multiple sclerosis white
matter. Through the multiple-tensor modelling of diffusion weighted
magnetic resonance imaging signals, diffusion basis spectrum imaging
resolves inflammation-associated cellularity and vasogenic oedema in
addition to accounting for partial volume effects resulting from
cerebrospinal fluid contamination, and crossing fibres. Quantitative
histological analysis of autopsied multiple sclerosis spinal cord
specimens supported that diffusion basis spectrum imaging-determined
cellularity, axon and myelin injury metrics closely correlated with
those pathologies identified and quantified by conventional histological
staining. We demonstrated in healthy control subjects that diffusion
basis spectrum imaging rectified inaccurate assessments of diffusion
properties of white matter tracts by diffusion tensor imaging in the
presence of cerebrospinal fluid contamination and/or crossing fibres. In
multiple sclerosis patients, we report that diffusion basis spectrum
imaging quantitatively characterized the distinct pathologies underlying
gadolinium-enhanced lesions, persistent black holes, non-enhanced
lesions and non-black hole lesions, a task yet to be demonstrated by
other neuroimaging approaches. Diffusion basis spectrum imaging-derived
radial diffusivity (myelin integrity marker) and non-restricted
isotropic diffusion fraction (oedema marker) correlated with
magnetization transfer ratio, supporting previous reports that
magnetization transfer ratio is sensitive not only to myelin integrity,
but also to inflammation-associated oedema. Our results suggested that
diffusion basis spectrum imaging-derived quantitative biomarkers are
highly consistent with histology findings and hold promise to accurately
characterize the heterogeneous white matter pathology in multiple
sclerosis patients. Thus, diffusion basis spectrum imaging can
potentially serve as a non-invasive outcome measure to assess treatment
effects on the specific components of underlying pathology targeted by
new multiple sclerosis therapies.
Much
effort is being invested into making MRI measures more specific for the
pathological changes taking place in the course of MS. The more
detailed one can observe what is happening in the brain with/-out
treatment, the better the effects of interventions can be assessed.
Standard MRI is helpful in making a diagnosis of MS, however to detect
specific changes in the tissue, for example, remyelination, one has to
"tweak" the way the MRI signal is being acquired and/or processed. There
are plenty of ways of doing this, and in this paper the directionality
of water diffusion in the brain is used as the basis to predict changes
in specific tissue components (myelin, axons, inflammatory cells, etc).
Labels: MRI