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Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study.

Klistorner A, Wang C, Yiannikas C, Graham SL, Parratt J, Barnett MH - PLoS ONE (2016)

Bottom Line: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM.This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period.In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Save Sight Institute, University of Sydney, Sydney, Australia.

ABSTRACT

Objective: To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months.

Methods: The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions).

Results: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes.

Conclusions: The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

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Related in: MedlinePlus

Optic radiation tractography and definition of OR lesions and non-lesional NAWM.Optic radiation was defined using probabilistic tractography. Optic radiation fibres were separated into lesional, i.e. traversing the lesion fibers (yellow), and non-lesional, i.e. non-traversing the lesion fibers (blue). Intersection between lesional fibers and brain lesion mask formed OR lesion ROI (red). Non-lesional fibers were transformed to non-lesional NAWM ROI.
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pone.0149245.g001: Optic radiation tractography and definition of OR lesions and non-lesional NAWM.Optic radiation was defined using probabilistic tractography. Optic radiation fibres were separated into lesional, i.e. traversing the lesion fibers (yellow), and non-lesional, i.e. non-traversing the lesion fibers (blue). Intersection between lesional fibers and brain lesion mask formed OR lesion ROI (red). Non-lesional fibers were transformed to non-lesional NAWM ROI.

Mentions: MS lesions of the entire brain were identified on the co-registered T2 FLAIR and contrast-enhanced T1 images at baseline and follow up visits. Lesions were segmented automatically using ITK-SNAP 2 (ITK-SNAP, version 2, University of Pensilvania). Seed points were set by a single user (AK). Lesions were then intersected with OR fibers to identify and measure the volume of T2 FLAIR lesions within the OR. An OR lesion mask was then applied to baseline and follow-up DTI images and diffusivity was measured inside the mask using a voxel-based method (Fig 1).


Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study.

Klistorner A, Wang C, Yiannikas C, Graham SL, Parratt J, Barnett MH - PLoS ONE (2016)

Optic radiation tractography and definition of OR lesions and non-lesional NAWM.Optic radiation was defined using probabilistic tractography. Optic radiation fibres were separated into lesional, i.e. traversing the lesion fibers (yellow), and non-lesional, i.e. non-traversing the lesion fibers (blue). Intersection between lesional fibers and brain lesion mask formed OR lesion ROI (red). Non-lesional fibers were transformed to non-lesional NAWM ROI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4764675&req=5

pone.0149245.g001: Optic radiation tractography and definition of OR lesions and non-lesional NAWM.Optic radiation was defined using probabilistic tractography. Optic radiation fibres were separated into lesional, i.e. traversing the lesion fibers (yellow), and non-lesional, i.e. non-traversing the lesion fibers (blue). Intersection between lesional fibers and brain lesion mask formed OR lesion ROI (red). Non-lesional fibers were transformed to non-lesional NAWM ROI.
Mentions: MS lesions of the entire brain were identified on the co-registered T2 FLAIR and contrast-enhanced T1 images at baseline and follow up visits. Lesions were segmented automatically using ITK-SNAP 2 (ITK-SNAP, version 2, University of Pensilvania). Seed points were set by a single user (AK). Lesions were then intersected with OR fibers to identify and measure the volume of T2 FLAIR lesions within the OR. An OR lesion mask was then applied to baseline and follow-up DTI images and diffusivity was measured inside the mask using a voxel-based method (Fig 1).

Bottom Line: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM.This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period.In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Save Sight Institute, University of Sydney, Sydney, Australia.

ABSTRACT

Objective: To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months.

Methods: The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions).

Results: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes.

Conclusions: The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

Show MeSH
Related in: MedlinePlus