Three‐Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis

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dc.contributor.authorSivakolundu, Dinesh K.
dc.contributor.authorHansen, Madison R.
dc.contributor.authorWest, Kathryn L.
dc.contributor.authorWang, Yeqi
dc.contributor.authorStanley, Thomas
dc.contributor.authorWilson, Andrew
dc.contributor.authorMcCreary, Morgan
dc.contributor.authorTurner, Monroe P.
dc.contributor.authorPinho, Marco C.
dc.contributor.authorNewton, Braeden D.
dc.contributor.authorGuo, Xiaohu
dc.contributor.authorRypma, Bart
dc.contributor.authorOkuda, Darin T.
dc.contributor.utdAuthorSivakolundu, Dinesh K.
dc.contributor.utdAuthorWest, Kathryn L.
dc.contributor.utdAuthorWang, Yeqi
dc.contributor.utdAuthorStanley, Thomas
dc.contributor.utdAuthorWilson, Andrew
dc.contributor.utdAuthorTurner, Monroe P.
dc.contributor.utdAuthorGuo, Xiaohu
dc.contributor.utdAuthorRypma, Bart
dc.date.accessioned2019-07-15T19:59:36Z
dc.date.available2019-07-15T19:59:36Z
dc.date.created2019-05-30
dc.descriptionFull text access from Treasures at UT Dallas is restricted to current UTD affiliates (use the provided Link to Article). Non UTD affiliates will find the web address for this item by clicking the "Show full item record" link, copying the "dc.relation.uri" metadata and pasting it into a browser.
dc.description.abstractBACKGROUND AND PURPOSE Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2‐dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion‐phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3‐dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes. METHODS Lesions were identified in 3T T₂‐FLAIR images and segmented using geodesic active contouring. A calibrated fMRI sequence permitted measurement of cerebral blood flow (CBF), blood‐oxygen‐level‐dependent signal (BOLD), and cerebral metabolic rate of oxygen (CMRO₂). These metrics were measured within lesions and surrounding tissue in concentric layers exact to the 3D‐lesion shape. BOLD slope was calculated as BOLD changes from a lesion to its surrounding perimeters. White matter integrity was measured using diffusion kurtosis imaging. Associations between these metrics and 3D‐lesion phenotypes were studied. RESULTS One hundred nine lesions from 23 MS patients were analyzed. We identified a noninvasive biomarker, BOLD slope, to metabolically characterize lesions. Positive BOLD slope lesions were metabolically active with higher CMRO₂ and CBF compared to negative BOLD slope or inactive lesions. Metabolically active lesions with more intact white matter integrity had more symmetrical shapes and more complex surface textures compared to inactive lesions with less intact white matter integrity. CONCLUSION The association of lesion phenotypes with their metabolic signatures suggests the prospect for translation of such data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self‐repair. Our findings also provide a platform for disease surveillance and outcome quantification involving myelin repair therapeutics.
dc.description.departmentErik Jonsson School of Engineering and Computer Science
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.departmentCenter for BrainHealth
dc.description.sponsorshipNational Multiple Sclerosis Society Research Grant (RG-1507-04951)
dc.identifier.bibliographicCitationSivakolundu, D. K., K. L. West, M. R. Hansen, et al. 2019. "Three‐dimensional lesion phenotyping and physiologic characterization inform remyelination ability in multiple sclerosis." Journal of Neuroimaging, doi:10.1111/jon.12633
dc.identifier.issn1051-2284
dc.identifier.urihttps://hdl.handle.net/10735.1/6705
dc.language.isoen
dc.publisherAmerican Society of Neuroimaging
dc.relation.urihttps://doi.org/10.1111/jon.12633
dc.rights©2019 American Society of Neuroimaging
dc.source.journalJournal of Neuroimaging
dc.subjectPhenotype
dc.subjectMagnetic resonance imaging
dc.subjectMultiple sclerosis--Magnetic resonance imaging
dc.subjectRemyelination
dc.subjectMetabolism
dc.titleThree‐Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis
dc.type.genrearticle

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