Contributions
Abstract: P491
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Axonal degeneration is a key pathological driver of disability in MS. Diffusion-weighted MRI can non-invasively detect microstructural changes in white matter that are associated with axonal loss. A novel diffusion-weighted MRI measure, “apparent fiber density” (AFD) can be obtained from the fiber orientation distributions (FODs) computed by spherical deconvolution techniques. Using this approach it is possible to estimate differences in both Fiber Density (FD) and Fiber Cross-section (FC), for each fiber element (termed "fixel") in each voxel (Raffelt et al. 2012).
Objective: We sought to determine whether FD and/or FC differences exist specifically in the visual pathways in patients with a history of acute optic neuritis compared to healthy controls.
Methods: Diffusion-weighted scans were acquired for 17 patients with historical optic neuritis (disease duration: 4.48 ± 0.61 years) and 14 healthy controls with the following parameters: TR/TE=7800/112ms; voxel size=2.5x2.5x2.5mm3, b=3000s/mm2, 7 non-diffusion and 60 diffusion encoded scans. For fixel-specific measures, a population-average FOD template was generated from subject specific FOD images obtained by a novel method that accounts for non-white matter tissues (Dhollander et al. 2016). Each subject"s FOD image was then registered to the template, allowing for whole-brain fixel-based comparison between patients and controls. The statistical analysis was performed using connectivity fixel enhancement (5000 permutations) to identify regions of reduced FD and FC (Raffelt et al. 2015). All results were family wise error (FWER) corrected for multiple comparisons.
Results: Optic neuritis patients showed significantly lower FD bilaterally in the inferior fronto-occipital fasciculus compared with heathy controls (FWER corrected p< 0.05). A significant FC difference was not detected.
Conclusion: AFD is sensitive to trans-synaptic axonal degeneration in the visual pathways of patients with historical optic neuritis. Fixel-specific markers of axonal degeneration could be used as markers in early therapeutic trials or to monitor disease progression.
References:
Raffelt, D., et al, NeuroImage, (2012). 59(4): p. 3976-3994
Raffelt, D., et al, Neuroimage, (2015). 117: p. 40-55
Dhollander, T., Connelly, A., Proc. ISMRM (2016). 24: p. 3010
Disclosure: Sanuji Gajamange: nothing to disclose
David Raffelt: nothing to disclose
Thijs Dhollander: nothing to disclose
Annie Shelton: nothing to disclose
Owen White: receives research support from Novartis and Biogen Idec
Trevor Kilpatrick: nothing to disclose
Alan Connelly: nothing to disclose
Joanne Fielding: receives research support from Novartis and Biogen Idec
Scott Kolbe: receives honoraria from Novartis
Abstract: P491
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Axonal degeneration is a key pathological driver of disability in MS. Diffusion-weighted MRI can non-invasively detect microstructural changes in white matter that are associated with axonal loss. A novel diffusion-weighted MRI measure, “apparent fiber density” (AFD) can be obtained from the fiber orientation distributions (FODs) computed by spherical deconvolution techniques. Using this approach it is possible to estimate differences in both Fiber Density (FD) and Fiber Cross-section (FC), for each fiber element (termed "fixel") in each voxel (Raffelt et al. 2012).
Objective: We sought to determine whether FD and/or FC differences exist specifically in the visual pathways in patients with a history of acute optic neuritis compared to healthy controls.
Methods: Diffusion-weighted scans were acquired for 17 patients with historical optic neuritis (disease duration: 4.48 ± 0.61 years) and 14 healthy controls with the following parameters: TR/TE=7800/112ms; voxel size=2.5x2.5x2.5mm3, b=3000s/mm2, 7 non-diffusion and 60 diffusion encoded scans. For fixel-specific measures, a population-average FOD template was generated from subject specific FOD images obtained by a novel method that accounts for non-white matter tissues (Dhollander et al. 2016). Each subject"s FOD image was then registered to the template, allowing for whole-brain fixel-based comparison between patients and controls. The statistical analysis was performed using connectivity fixel enhancement (5000 permutations) to identify regions of reduced FD and FC (Raffelt et al. 2015). All results were family wise error (FWER) corrected for multiple comparisons.
Results: Optic neuritis patients showed significantly lower FD bilaterally in the inferior fronto-occipital fasciculus compared with heathy controls (FWER corrected p< 0.05). A significant FC difference was not detected.
Conclusion: AFD is sensitive to trans-synaptic axonal degeneration in the visual pathways of patients with historical optic neuritis. Fixel-specific markers of axonal degeneration could be used as markers in early therapeutic trials or to monitor disease progression.
References:
Raffelt, D., et al, NeuroImage, (2012). 59(4): p. 3976-3994
Raffelt, D., et al, Neuroimage, (2015). 117: p. 40-55
Dhollander, T., Connelly, A., Proc. ISMRM (2016). 24: p. 3010
Disclosure: Sanuji Gajamange: nothing to disclose
David Raffelt: nothing to disclose
Thijs Dhollander: nothing to disclose
Annie Shelton: nothing to disclose
Owen White: receives research support from Novartis and Biogen Idec
Trevor Kilpatrick: nothing to disclose
Alan Connelly: nothing to disclose
Joanne Fielding: receives research support from Novartis and Biogen Idec
Scott Kolbe: receives honoraria from Novartis