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Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?
Author(s) -
Grussu Francesco,
Schneider Torben,
Tur Carmen,
Yates Richard L.,
Tachrount Mohamed,
Ianuş Andrada,
Yiannakas Marios C.,
Newcombe Jia,
Zhang Hui,
Alexander Daniel C.,
DeLuca Gabriele C.,
Gandini WheelerKingshott Claudia A. M.
Publication year - 2017
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.445
Subject(s) - neurite , spinal cord , medicine , multiple sclerosis , pathology , magnetic resonance imaging , myelin , white matter , neuroscience , central nervous system , biology , radiology , biochemistry , psychiatry , in vitro , endocrinology
Objective Conventional magnetic resonance imaging ( MRI ) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement ( neurite orientation dispersion and density imaging, NODDI ), to demonstrate the strong potential of the new marker. Methods We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging ( DTI ) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. Results We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI ‐derived dispersion matches its histological counterpart ( P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. Interpretation Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

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