Contributions
Abstract: P527
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Axon injury and loss, demyelination, and inflammation are the primary pathologies in multiple sclerosis (MS). Despite the prevailing thought that axon loss is the substrate of clinical progression, the roles that these individual pathological processes play in MS progression are ill-defined.
Goal: To investigate whole brain white matter (WM) changes with particular focus on axons, we compared secondary progressive (SPMS) patients to healthy controls (HC) using diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI, quantitatively distinguishes isotropic from anisotropic diffusion) and a tract-based spatial statistics (TBSS) method for analysis.
Methods: Human studies committee approval was obtained. All subjects gave informed consent. Sixteen patients with established SPMS and eleven HC underwent diffusion weighted MRI using a multi-b value diffusion weighting scheme (99 directions, maximum b-value 1500 s/mm2) and a 32-channel head coil at 3T. Whole brain voxel-wise (2×2×2 mm3) DTI and DBSI analyses were performed. Group analyses were done with TBSS (part of FSL). DTI and DBSI indices were projected onto the TBSS skeleton for statistical analyses. Nonparametric permutation tests (5000) were used for voxel-wise statistical comparisons between HC and SPMS, with significance threshold for group differences of P < 0.05.
Results: Not unexpectedly, abnormal diffusion changes were widespread in SPMS WM tracts: decreased DTI-FA, and increased DTI-axial (AD) and radial (RD) diffusivity. DBSI-AD did not change in the regions with increased DTI-AD. Increased non-restricted isotropic diffusion tensor components (interpreted as edema or loss of tissue structural integrity) was seen in SPMS WM tracts. Results revealed that the confounding effect of edema or tissue loss contributed to the observed increase in DTI-AD. The anisotropic diffusion tensor fraction, as determined by DBSI, was reduced in regions of corpus callosum in SPMS, suggesting axonal loss.
Conclusions: Tract based DBSI analyses showed loss of anisotropic components, consistent with axon loss in SPMS WM tracts. This imaging method may be useful for monitoring progression in MS.
Disclosure:
Anne H. Cross has performed consulting for: AbbVie, Biogen, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Mallinckrodt, Novartis, Teva.
Peng Sun has no disclosures. Ajit George has no disclosures. Sheng-Kwei Song has no disclosures.
Robert T. Naismith has performed consulting for: Alkermes, Acorda, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Pfizer, Teva.
Funding: Supported by the U.S. National Institutes of Health P01 NS059560.
Abstract: P527
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Axon injury and loss, demyelination, and inflammation are the primary pathologies in multiple sclerosis (MS). Despite the prevailing thought that axon loss is the substrate of clinical progression, the roles that these individual pathological processes play in MS progression are ill-defined.
Goal: To investigate whole brain white matter (WM) changes with particular focus on axons, we compared secondary progressive (SPMS) patients to healthy controls (HC) using diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI, quantitatively distinguishes isotropic from anisotropic diffusion) and a tract-based spatial statistics (TBSS) method for analysis.
Methods: Human studies committee approval was obtained. All subjects gave informed consent. Sixteen patients with established SPMS and eleven HC underwent diffusion weighted MRI using a multi-b value diffusion weighting scheme (99 directions, maximum b-value 1500 s/mm2) and a 32-channel head coil at 3T. Whole brain voxel-wise (2×2×2 mm3) DTI and DBSI analyses were performed. Group analyses were done with TBSS (part of FSL). DTI and DBSI indices were projected onto the TBSS skeleton for statistical analyses. Nonparametric permutation tests (5000) were used for voxel-wise statistical comparisons between HC and SPMS, with significance threshold for group differences of P < 0.05.
Results: Not unexpectedly, abnormal diffusion changes were widespread in SPMS WM tracts: decreased DTI-FA, and increased DTI-axial (AD) and radial (RD) diffusivity. DBSI-AD did not change in the regions with increased DTI-AD. Increased non-restricted isotropic diffusion tensor components (interpreted as edema or loss of tissue structural integrity) was seen in SPMS WM tracts. Results revealed that the confounding effect of edema or tissue loss contributed to the observed increase in DTI-AD. The anisotropic diffusion tensor fraction, as determined by DBSI, was reduced in regions of corpus callosum in SPMS, suggesting axonal loss.
Conclusions: Tract based DBSI analyses showed loss of anisotropic components, consistent with axon loss in SPMS WM tracts. This imaging method may be useful for monitoring progression in MS.
Disclosure:
Anne H. Cross has performed consulting for: AbbVie, Biogen, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Mallinckrodt, Novartis, Teva.
Peng Sun has no disclosures. Ajit George has no disclosures. Sheng-Kwei Song has no disclosures.
Robert T. Naismith has performed consulting for: Alkermes, Acorda, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Pfizer, Teva.
Funding: Supported by the U.S. National Institutes of Health P01 NS059560.