Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study
Background: There is significant heterogeneity in the recovery course from mild-to-moderate traumatic brain injury (mmTBI), with many individuals reporting cognitive symptoms during the chronic phase. Although blood-based biomarkers have been identified as a marker of injury severity in the acute ph...
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Elsevier
2025-01-01
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| Series: | NeuroImage: Clinical |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158225001081 |
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| author | Abigail B. Waters Samantha H. Penhale Shoumi Sarkar Somnath Datta Damon G. Lamb Claudia Robertson Richard Rubenstein Amy K. Wagner Firas Kobeissy Kevin Wang John B. Williamson |
| author_facet | Abigail B. Waters Samantha H. Penhale Shoumi Sarkar Somnath Datta Damon G. Lamb Claudia Robertson Richard Rubenstein Amy K. Wagner Firas Kobeissy Kevin Wang John B. Williamson |
| author_sort | Abigail B. Waters |
| collection | DOAJ |
| description | Background: There is significant heterogeneity in the recovery course from mild-to-moderate traumatic brain injury (mmTBI), with many individuals reporting cognitive symptoms during the chronic phase. Although blood-based biomarkers have been identified as a marker of injury severity in the acute phase, the relevance of candidate biomarkers in chronic mmTBI is less clear. Establishing links between blood-based biomarkers, neuroimaging, and cognitive performance is necessary to differentiate subphenotypes in chronic TBI and improve prognostic models. Methods: Sixty Veterans and non-Veterans with mmTBI completed cognitive testing (WAIS-IV), MRI, and blood collection for blood-based CNS biomarker assessment for cross-sectional comparison. A data fusion technique (Linked Independent Component Analysis [LICA]) was used to simultaneously model structural variability across T1-weighted and diffusion-weighted MRI modalities. Blood serum samples were assayed using an ultrasensitive immunoassay using digital array technology to measure GFAP, NFL, total tau, and UCH-L1 protein levels. A correlation matrix was used to identify which LICA-derived MRI components were associated with (1) a blood-based biomarker, (2) a WAIS-IV index score and (3) clinical characteristics of TBI, using an effect-size cut-off. Results: LICA-derived Component 4 was associated with a biomarker (UCH-L1), reduced processing speed, and the total number of TBIs. This component was characterized by increased mean diffusivity along the ventral surface of the frontal lobe and decreased fractional anisotropy in bilateral corticospinal tracts and cerebral peduncles. Conclusions: Our findings contribute to the larger body of literature examining the utility of biomarkers for chronic TBI and underscore the importance of examining heterogeneity within this population. |
| format | Article |
| id | doaj-art-90e44e959c6947778814f6d9f1852e77 |
| institution | Matheson Library |
| issn | 2213-1582 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj-art-90e44e959c6947778814f6d9f1852e772025-07-04T04:46:29ZengElsevierNeuroImage: Clinical2213-15822025-01-0147103838Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging studyAbigail B. Waters0Samantha H. Penhale1Shoumi Sarkar2Somnath Datta3Damon G. Lamb4Claudia Robertson5Richard Rubenstein6Amy K. Wagner7Firas Kobeissy8Kevin Wang9John B. Williamson10Brain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA; Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; Corresponding authors at: Brain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA.Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USADepartment of Biostatistics, University of Florida, Gainesville, FL, USABrain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA; Department of Biostatistics, University of Florida, Gainesville, FL, USABrain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA; Department of Psychiatry, Center for OCD and Anxiety Related Disorders, University of Florida, Gainesville, FL, USADepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, USADepartment of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, USADepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USADepartment of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, USADepartment of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, USABrain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA; Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; Department of Psychiatry, Center for OCD and Anxiety Related Disorders, University of Florida, Gainesville, FL, USA; Corresponding authors at: Brain Rehabilitation Research Center, North Florida/South Georgia VAMC, Gainesville, FL, USA.Background: There is significant heterogeneity in the recovery course from mild-to-moderate traumatic brain injury (mmTBI), with many individuals reporting cognitive symptoms during the chronic phase. Although blood-based biomarkers have been identified as a marker of injury severity in the acute phase, the relevance of candidate biomarkers in chronic mmTBI is less clear. Establishing links between blood-based biomarkers, neuroimaging, and cognitive performance is necessary to differentiate subphenotypes in chronic TBI and improve prognostic models. Methods: Sixty Veterans and non-Veterans with mmTBI completed cognitive testing (WAIS-IV), MRI, and blood collection for blood-based CNS biomarker assessment for cross-sectional comparison. A data fusion technique (Linked Independent Component Analysis [LICA]) was used to simultaneously model structural variability across T1-weighted and diffusion-weighted MRI modalities. Blood serum samples were assayed using an ultrasensitive immunoassay using digital array technology to measure GFAP, NFL, total tau, and UCH-L1 protein levels. A correlation matrix was used to identify which LICA-derived MRI components were associated with (1) a blood-based biomarker, (2) a WAIS-IV index score and (3) clinical characteristics of TBI, using an effect-size cut-off. Results: LICA-derived Component 4 was associated with a biomarker (UCH-L1), reduced processing speed, and the total number of TBIs. This component was characterized by increased mean diffusivity along the ventral surface of the frontal lobe and decreased fractional anisotropy in bilateral corticospinal tracts and cerebral peduncles. Conclusions: Our findings contribute to the larger body of literature examining the utility of biomarkers for chronic TBI and underscore the importance of examining heterogeneity within this population.http://www.sciencedirect.com/science/article/pii/S2213158225001081Traumatic brain injuryCNS biomarkersMultimodality neuroimaging |
| spellingShingle | Abigail B. Waters Samantha H. Penhale Shoumi Sarkar Somnath Datta Damon G. Lamb Claudia Robertson Richard Rubenstein Amy K. Wagner Firas Kobeissy Kevin Wang John B. Williamson Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study NeuroImage: Clinical Traumatic brain injury CNS biomarkers Multimodality neuroimaging |
| title | Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study |
| title_full | Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study |
| title_fullStr | Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study |
| title_full_unstemmed | Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study |
| title_short | Linked alterations in structure and autoimmunity biomarkers in remote mild-to-moderate TBI: A multi-modal brain imaging study |
| title_sort | linked alterations in structure and autoimmunity biomarkers in remote mild to moderate tbi a multi modal brain imaging study |
| topic | Traumatic brain injury CNS biomarkers Multimodality neuroimaging |
| url | http://www.sciencedirect.com/science/article/pii/S2213158225001081 |
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