Contributions
Abstract: EP1516
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: A recently developed MRI technique, diffusion basis spectrum imaging (DBSI) provides markers related to oedema, inflammation, demyelination and axonal loss. Ocrelizumab has been shown to be an effective treatment in relapsing multiple sclerosis (RMS) in preventing new relapses, disability progression and new MRI lesions. We hypothesise that this potent anti-inflammatory therapy will be associated with improvement in DBSI imaging biomarkers in normal-appearing white matter (NAWM) and chronic lesions.
Objective: To investigate the effect of ocrelizumab treatment on tissue microstructure as found by DBSI for RMS patients beginning treatment with ocrelizumab over 1 year.
Methods: 16 RMS patients (9M/7F, ages 21-44 (mean 31)) participating in a substudy of VELOCE (NCT02545868) had advanced 3T MRI including DBSI prior to and 1 year after first ocrelizumab treatment. 10 healthy controls (HC) were scanned once. DBSI was analysed to calculate maps of hindered and restricted fractions (related to oedema and microglia content), fibre fraction (fibre density), fractional anisotropy (FA, affected by axon/myelin loss) and axial and radial diffusivities (axon and myelin integrity, respectively). Mean values in NAWM and chronic lesions (without Gd enhancement) were calculated.
Results: Mean ± standard deviation values in RMS NAWM improved over 1 year (p≤0.0001):
- Hindered fraction decreased from 0.27±0.02 to 0.24±0.03 (HC 0.19±0.02)
- Restricted fraction decreased from 0.08±0.01 to 0.06±0.01 (HC 0.07±0.01)
- Fibre fraction increased from 0.54±0.02 to 0.6±0.03 (HC 0.63±0.03))
- FA increased from 0.66±0.02 to 0.72±0.02 (HC 0.76±0.01)
- Axial diffusivity increased from 1.41±0.03 to 1.58±0.06 (HC 1.57±0.07)
- Radial diffusivity decreased from 0.4±0.02 to 0.37±0.02 (HC 0.32±0.01)
Conclusions: The decreases in hindered and restricted fractions may reflect receding oedema and decreased microglia content across MS brain. Changes in FA and radial diffusivity could correspond to myelin recovery. DBSI is sensitive to detecting microstructural changes in a relatively small group within 1 year of follow-up. Longitudinal results showed improvement towards HC values in patients treated with ocrelizumab over 1 year. DBSI could improve the understanding of the mechanism of action of MS therapies beyond the effect of preventing new lesion formation.
Disclosure: This study was funded by F. Hoffmann-La Roche. Anika Wurl: nothing to disclose. Irene Vavasour: nothing to disclose. Adam Dvorak: nothing to disclose. Cornelia Laule receives research funding from the MS Society of Canada and NSERC. Roger Tam: nothing to disclose. David Li is the Emeritus Director of the UBC MS/MRI Research group which has been contracted with Novartis, Perceptives, Roche and Sanofi-Aventis, and received grant support from Genzyme, Merck-Serono, Novartis and Roche. Dr. Li received grant funding from the MS society of Canada, the Canadian Institute of Health Research, the Academy of Health Care Learning, Biogen, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva, and consultancy honoraria from Vertex, Opexa, Adelphi, Celgene, Novartis and Roche. Robert Carruthers is Site Investigator for studies funded by Novartis, MedImmune, and Roche and receives research support from Teva Innovation Canada, Roche Canada and Vancouver Coastal Health Research Institute. He has received consultancy honoraria from Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. Alex MacKay: nothing to disclose. Sheng-Kwei Song is a cofounder of DxGPS LLC. Washington University may receive royalty income based on a technology licensed by Washington University to DxGPS LLC. That technology is evaluated in this research. Peng Sun: nothing to disclose. Hideki Garren is an employee of Genentech. Anthony Traboulsee receives research funding from Chugai, Roche, Novartis, Genzyme, Biogen, and consultancy honoraria from Genzyme, Roche, Teva, Biogen and Serono. Shannon Kolind receives research funding from the MS Society of Canada, NSERC, Roche and Sanofi-Genzyme.
Abstract: EP1516
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: A recently developed MRI technique, diffusion basis spectrum imaging (DBSI) provides markers related to oedema, inflammation, demyelination and axonal loss. Ocrelizumab has been shown to be an effective treatment in relapsing multiple sclerosis (RMS) in preventing new relapses, disability progression and new MRI lesions. We hypothesise that this potent anti-inflammatory therapy will be associated with improvement in DBSI imaging biomarkers in normal-appearing white matter (NAWM) and chronic lesions.
Objective: To investigate the effect of ocrelizumab treatment on tissue microstructure as found by DBSI for RMS patients beginning treatment with ocrelizumab over 1 year.
Methods: 16 RMS patients (9M/7F, ages 21-44 (mean 31)) participating in a substudy of VELOCE (NCT02545868) had advanced 3T MRI including DBSI prior to and 1 year after first ocrelizumab treatment. 10 healthy controls (HC) were scanned once. DBSI was analysed to calculate maps of hindered and restricted fractions (related to oedema and microglia content), fibre fraction (fibre density), fractional anisotropy (FA, affected by axon/myelin loss) and axial and radial diffusivities (axon and myelin integrity, respectively). Mean values in NAWM and chronic lesions (without Gd enhancement) were calculated.
Results: Mean ± standard deviation values in RMS NAWM improved over 1 year (p≤0.0001):
- Hindered fraction decreased from 0.27±0.02 to 0.24±0.03 (HC 0.19±0.02)
- Restricted fraction decreased from 0.08±0.01 to 0.06±0.01 (HC 0.07±0.01)
- Fibre fraction increased from 0.54±0.02 to 0.6±0.03 (HC 0.63±0.03))
- FA increased from 0.66±0.02 to 0.72±0.02 (HC 0.76±0.01)
- Axial diffusivity increased from 1.41±0.03 to 1.58±0.06 (HC 1.57±0.07)
- Radial diffusivity decreased from 0.4±0.02 to 0.37±0.02 (HC 0.32±0.01)
Conclusions: The decreases in hindered and restricted fractions may reflect receding oedema and decreased microglia content across MS brain. Changes in FA and radial diffusivity could correspond to myelin recovery. DBSI is sensitive to detecting microstructural changes in a relatively small group within 1 year of follow-up. Longitudinal results showed improvement towards HC values in patients treated with ocrelizumab over 1 year. DBSI could improve the understanding of the mechanism of action of MS therapies beyond the effect of preventing new lesion formation.
Disclosure: This study was funded by F. Hoffmann-La Roche. Anika Wurl: nothing to disclose. Irene Vavasour: nothing to disclose. Adam Dvorak: nothing to disclose. Cornelia Laule receives research funding from the MS Society of Canada and NSERC. Roger Tam: nothing to disclose. David Li is the Emeritus Director of the UBC MS/MRI Research group which has been contracted with Novartis, Perceptives, Roche and Sanofi-Aventis, and received grant support from Genzyme, Merck-Serono, Novartis and Roche. Dr. Li received grant funding from the MS society of Canada, the Canadian Institute of Health Research, the Academy of Health Care Learning, Biogen, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva, and consultancy honoraria from Vertex, Opexa, Adelphi, Celgene, Novartis and Roche. Robert Carruthers is Site Investigator for studies funded by Novartis, MedImmune, and Roche and receives research support from Teva Innovation Canada, Roche Canada and Vancouver Coastal Health Research Institute. He has received consultancy honoraria from Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. Alex MacKay: nothing to disclose. Sheng-Kwei Song is a cofounder of DxGPS LLC. Washington University may receive royalty income based on a technology licensed by Washington University to DxGPS LLC. That technology is evaluated in this research. Peng Sun: nothing to disclose. Hideki Garren is an employee of Genentech. Anthony Traboulsee receives research funding from Chugai, Roche, Novartis, Genzyme, Biogen, and consultancy honoraria from Genzyme, Roche, Teva, Biogen and Serono. Shannon Kolind receives research funding from the MS Society of Canada, NSERC, Roche and Sanofi-Genzyme.