Contributions
Abstract: P586
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Multiple sclerosis (MS) T2 lesions contribute to brain volume loss (BVL) through focal tissue loss and associated Wallerian and retrograde degeneration. However, the correlation between baseline T2 lesion volume (T2LV) and BVL is weak, potentially due to underestimation of tissue loss within chronic lesions, in which astrogliosis reduces the susceptibility to structural collapse associated with axonal loss. Diffusion magnetic resonance imaging (dMRI) is sensitive to changes in tissue microstructure, and provides an opportunity to refine BVL measurements with an indicative measure of tissue loss.
Objective: To develop a composite biomarker for assessing brain tissue loss (BTL) in MS by combining macro- and micro-structural imaging techniques.
Methods: dMRI, 3D T1, and 3D FLAIR were acquired at baseline and 12 months on a 3T GE MRI scanner from 64 RRMS patients. T2LV and percentage brain volume change (PBVC) over 12 months were assessed by SIENA/FSL. dMRI was motion, eddy-current and EPI susceptibility distortion corrected, prior to tensor-reconstruction and co-registration with structural images. Whole brain mean diffusivity (MD) was weighted and averaged with the co-registered brain parenchyma partial volume estimation map (SIENAX/FSL) using lesion-inpainted 3D T1 images. A voxel-wise 2-compartment (tissue-free water) model was developed and used to 'correct' PBVC results based on MD change within the brain.
Results: Sixty-four patients with RRMS; 83.1% female; mean age 36.7(8.83) years; mean disease duration 7.55(6.92) years and mean baseline EDSS 1.9(1.4) were evaluated. The association (Pearson´s r) between baseline T2LV and PBVC was -0.523 (p< 0.001) and -0.610 (p< 0.001) prior to and after application of the BTL model respectively.
Conclusion: The improved correlation between baseline T2 lesion burden and short term PBVC following adjustment for change in whole brain MD supports the hypothesis that MS lesions contribute directly, and indirectly, to BVL in MS. Conventional volumetric analysis underestimates tissue loss and a composite biomarker based on a 2-compartment (tissue-free water) model has the potential to more faithfully delineate BTL in MS.
Disclosure: Chenyu Wang declared no conflict of interest.
Alexander Klistorner declared no conflict of interest.
Heidi N Beadnall has received compensation for education travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck and Sanofi-Genzyme.
Joshua Barton declared no conflict of interest.
Linda Ly declared no conflict of interest.
Stephen Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.
Abstract: P586
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Multiple sclerosis (MS) T2 lesions contribute to brain volume loss (BVL) through focal tissue loss and associated Wallerian and retrograde degeneration. However, the correlation between baseline T2 lesion volume (T2LV) and BVL is weak, potentially due to underestimation of tissue loss within chronic lesions, in which astrogliosis reduces the susceptibility to structural collapse associated with axonal loss. Diffusion magnetic resonance imaging (dMRI) is sensitive to changes in tissue microstructure, and provides an opportunity to refine BVL measurements with an indicative measure of tissue loss.
Objective: To develop a composite biomarker for assessing brain tissue loss (BTL) in MS by combining macro- and micro-structural imaging techniques.
Methods: dMRI, 3D T1, and 3D FLAIR were acquired at baseline and 12 months on a 3T GE MRI scanner from 64 RRMS patients. T2LV and percentage brain volume change (PBVC) over 12 months were assessed by SIENA/FSL. dMRI was motion, eddy-current and EPI susceptibility distortion corrected, prior to tensor-reconstruction and co-registration with structural images. Whole brain mean diffusivity (MD) was weighted and averaged with the co-registered brain parenchyma partial volume estimation map (SIENAX/FSL) using lesion-inpainted 3D T1 images. A voxel-wise 2-compartment (tissue-free water) model was developed and used to 'correct' PBVC results based on MD change within the brain.
Results: Sixty-four patients with RRMS; 83.1% female; mean age 36.7(8.83) years; mean disease duration 7.55(6.92) years and mean baseline EDSS 1.9(1.4) were evaluated. The association (Pearson´s r) between baseline T2LV and PBVC was -0.523 (p< 0.001) and -0.610 (p< 0.001) prior to and after application of the BTL model respectively.
Conclusion: The improved correlation between baseline T2 lesion burden and short term PBVC following adjustment for change in whole brain MD supports the hypothesis that MS lesions contribute directly, and indirectly, to BVL in MS. Conventional volumetric analysis underestimates tissue loss and a composite biomarker based on a 2-compartment (tissue-free water) model has the potential to more faithfully delineate BTL in MS.
Disclosure: Chenyu Wang declared no conflict of interest.
Alexander Klistorner declared no conflict of interest.
Heidi N Beadnall has received compensation for education travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck and Sanofi-Genzyme.
Joshua Barton declared no conflict of interest.
Linda Ly declared no conflict of interest.
Stephen Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.