Deformation-based morphometry identifies deep brain structures protected by ocrelizumab
Background: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. Methods: We developed and applied a method of longitudinal deformation-...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158222000249 |
| _version_ | 1828366036580171776 |
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| author | Zhuang Song Anithapriya Krishnan Laura Gaetano Nicholas J. Tustison David Clayton Alex de Crespigny Thomas Bengtsson Xiaoming Jia Richard A.D. Carano |
| author_facet | Zhuang Song Anithapriya Krishnan Laura Gaetano Nicholas J. Tustison David Clayton Alex de Crespigny Thomas Bengtsson Xiaoming Jia Richard A.D. Carano |
| author_sort | Zhuang Song |
| collection | DOAJ |
| description | Background: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. Methods: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy. Results: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.05), a humanized anti-CD20 + monoclonal antibody approved for the treatment of multiple sclerosis. Additionally, identified brainstem shrinkage, as well as brain ventricle expansion, was associated with a greater risk for confirmed disability progression (p < 0.05). Conclusions: The identification of deep brain structures has a strong implication for developing new biomarkers of brain atrophy reduction to advance drug development for multiple sclerosis, which has an increasing focus on targeting the progressive biology. |
| first_indexed | 2024-04-14T05:39:50Z |
| format | Article |
| id | doaj.art-f33d9eb048974392882708206b4b1e98 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-04-14T05:39:50Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-f33d9eb048974392882708206b4b1e982022-12-22T02:09:31ZengElsevierNeuroImage: Clinical2213-15822022-01-0134102959Deformation-based morphometry identifies deep brain structures protected by ocrelizumabZhuang Song0Anithapriya Krishnan1Laura Gaetano2Nicholas J. Tustison3David Clayton4Alex de Crespigny5Thomas Bengtsson6Xiaoming Jia7Richard A.D. Carano8Personalized Healthcare Imaging, Genentech, Inc., South San Francisco, CA 94080, USA; Corresponding author at: Product Development - Personalized Healthcare Imaging, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.Personalized Healthcare Imaging, Genentech, Inc., South San Francisco, CA 94080, USAProduct Development Medical Affair, F. Hoffmann-La Roche Ltd, CH-4070 Basel, SwitzerlandDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22904, USAClinical Imaging Group, Genentech, Inc., South San Francisco, CA 94080, USAClinical Imaging Group, Genentech, Inc., South San Francisco, CA 94080, USAPersonalized Healthcare Imaging, Genentech, Inc., South San Francisco, CA 94080, USABiomarker Development, Genentech, Inc., South San Francisco, CA 94080, USAPersonalized Healthcare Imaging, Genentech, Inc., South San Francisco, CA 94080, USABackground: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. Methods: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy. Results: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.05), a humanized anti-CD20 + monoclonal antibody approved for the treatment of multiple sclerosis. Additionally, identified brainstem shrinkage, as well as brain ventricle expansion, was associated with a greater risk for confirmed disability progression (p < 0.05). Conclusions: The identification of deep brain structures has a strong implication for developing new biomarkers of brain atrophy reduction to advance drug development for multiple sclerosis, which has an increasing focus on targeting the progressive biology.http://www.sciencedirect.com/science/article/pii/S2213158222000249Deformation-based morphometryBrain atrophyMultiple sclerosisBiomarkersOcrelizumab |
| spellingShingle | Zhuang Song Anithapriya Krishnan Laura Gaetano Nicholas J. Tustison David Clayton Alex de Crespigny Thomas Bengtsson Xiaoming Jia Richard A.D. Carano Deformation-based morphometry identifies deep brain structures protected by ocrelizumab NeuroImage: Clinical Deformation-based morphometry Brain atrophy Multiple sclerosis Biomarkers Ocrelizumab |
| title | Deformation-based morphometry identifies deep brain structures protected by ocrelizumab |
| title_full | Deformation-based morphometry identifies deep brain structures protected by ocrelizumab |
| title_fullStr | Deformation-based morphometry identifies deep brain structures protected by ocrelizumab |
| title_full_unstemmed | Deformation-based morphometry identifies deep brain structures protected by ocrelizumab |
| title_short | Deformation-based morphometry identifies deep brain structures protected by ocrelizumab |
| title_sort | deformation based morphometry identifies deep brain structures protected by ocrelizumab |
| topic | Deformation-based morphometry Brain atrophy Multiple sclerosis Biomarkers Ocrelizumab |
| url | http://www.sciencedirect.com/science/article/pii/S2213158222000249 |
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