Decoding Diffusivity in Multiple Sclerosis: Analysis of Optic Radiation Lesional and Non-Lesional White Matter

Diffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterati...

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Vydáno v:	PloS one Ročník 10; číslo 3; s. e0122114
Hlavní autoři:	Klistorner, Alexander, Vootakuru, Nikitha, Wang, Chenyu, Yiannikas, Con, Graham, Stuart L., Parratt, John, Garrick, Raymond, Levin, Netta, Masters, Lynette, Lagopoulos, Jim, Barnett, Michael H.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 25.03.2015 Public Library of Science (PLoS)
Témata:	Adult Apoptosis Axons Brain Brain research Case-Control Studies Decoding Degeneration Demyelination Diffusion Tensor Imaging Diffusivity Elevation Female Fibers Health aspects Hospitals Humans Image Interpretation, Computer-Assisted Lesions Magnetic Resonance Imaging Male Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - complications Multiple Sclerosis, Relapsing-Remitting - pathology Myelin Nerve Fibers, Myelinated - pathology Neurodegeneration Neuroimaging NMR Nuclear magnetic resonance Optic Neuritis - etiology Optic Neuritis - pathology Pathogenesis Pathology Radiation Radiation (Physics) Radiation damage Radiography Studies Substantia alba Substrates Tissues White Matter - diagnostic imaging White Matter - pathology Australia
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Diffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage. Several compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR. Asymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI. This study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: This work was partially funded by Novartis. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: AK. Performed the experiments: AK NV CW NL LM. Analyzed the data: AK NV CW CY NL. Contributed reagents/materials/analysis tools: LM JL SLG RG JP MHB. Wrote the paper: AK CY SLG JL MNB.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0122114