Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study
Multi-site neuroimaging studies have become increasingly common in order to generate larger samples of reproducible data to answer questions associated with smaller effect sizes. The data harmonization model NeuroCombat has been shown to remove site effects introduced by differences in site-related...
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Frontiers Media S.A.
2025-08-01
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| author | G. Kislik R. Fox A. V. Korotcov A. V. Korotcov J. Zhou M. Febo Babak Moghadas Adnan Bibic Adnan Bibic Yunfan Zou Jieru Wan R. C. Koehler T. Adebayo T. Adebayo M. P. Burns J. T. McCabe K. K. Wang J. R. Huie A. R. Ferguson A. Paydar I. B. Wanner N. G. Harris N. G. Harris the TOP-NT Investigators |
| author_facet | G. Kislik R. Fox A. V. Korotcov A. V. Korotcov J. Zhou M. Febo Babak Moghadas Adnan Bibic Adnan Bibic Yunfan Zou Jieru Wan R. C. Koehler T. Adebayo T. Adebayo M. P. Burns J. T. McCabe K. K. Wang J. R. Huie A. R. Ferguson A. Paydar I. B. Wanner N. G. Harris N. G. Harris the TOP-NT Investigators |
| author_sort | G. Kislik |
| collection | DOAJ |
| description | Multi-site neuroimaging studies have become increasingly common in order to generate larger samples of reproducible data to answer questions associated with smaller effect sizes. The data harmonization model NeuroCombat has been shown to remove site effects introduced by differences in site-related technical variance while maintaining group differences, yet its effect on improving statistical power in pre-clinical models of CNS disease is unclear. The present study examined fractional anisotropy data computed from diffusion weighted imaging data at 3 and 30 days post-controlled cortical impact injury from 184 adult rats across four sites as part of the Translational-Outcome-Project-in-Neurotrauma (TOP-NT) Consortium. Findings supported prior clinical reports that NeuroCombat fails to remove site effects in data containing a high proportion-of-outliers (>5%) and skewness, which introduced significant variation in non-outlier sites. After removal of one outlier site and harmonization using a pooled sham population, the data displayed an increase in effect size and group level effects (p < 0.01) in both univariate and voxel-level volumes of pathology. This was characterized by movement toward similar distributions in voxel measurements (Kolmogorov–Smirnov p < <0.001 to >0.01) and statistical power increases within the ipsilateral cortex. Harmonization improved statistical power and frequency of significant differences in areas with existing group differences, thus improving the ability to detect regions affected by injury rather than by other confounds. These findings indicate the utility of NeuroCombat in reproducible data collection, where biological differences can be accurately revealed to allow for greater reliability in multi-site neuroimaging studies. |
| format | Article |
| id | doaj-art-16e98ea406a64925b71f985b0f3295f7 |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-16e98ea406a64925b71f985b0f3295f72025-08-20T13:52:12ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.16125981612598Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium studyG. Kislik0R. Fox1A. V. Korotcov2A. V. Korotcov3J. Zhou4M. Febo5Babak Moghadas6Adnan Bibic7Adnan Bibic8Yunfan Zou9Jieru Wan10R. C. Koehler11T. Adebayo12T. Adebayo13M. P. Burns14J. T. McCabe15K. K. Wang16J. R. Huie17A. R. Ferguson18A. Paydar19I. B. Wanner20N. G. Harris21N. G. Harris22the TOP-NT InvestigatorsUCLA Brain Injury Research Center, Department of Neurosurgery, Geffen Medical School, University of California at Los Angeles, Los Angeles, CA, United StatesUCLA Brain Injury Research Center, Department of Neurosurgery, Geffen Medical School, University of California at Los Angeles, Los Angeles, CA, United StatesDepartment of Radiology & Bioengineering, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United StatesDepartment of Radiology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Psychiatry, University of Florida, Gainesville, FL, United StatesDepartment of Radiology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Radiology, Johns Hopkins University, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesDepartment of Radiology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Radiology & Bioengineering, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United StatesDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States0Morehouse School of Medicine, Atlanta, GA, United States1University of California San Francisco, San Francisco, CA, United States1University of California San Francisco, San Francisco, CA, United StatesUCLA Brain Injury Research Center, Department of Neurosurgery, Geffen Medical School, University of California at Los Angeles, Los Angeles, CA, United States2Semel Institute for Neuroscience and Human Behavior, Intellectual Development and Disabilities Research Center, University of California at Los Angeles, Los Angeles, CA, United StatesUCLA Brain Injury Research Center, Department of Neurosurgery, Geffen Medical School, University of California at Los Angeles, Los Angeles, CA, United States2Semel Institute for Neuroscience and Human Behavior, Intellectual Development and Disabilities Research Center, University of California at Los Angeles, Los Angeles, CA, United StatesMulti-site neuroimaging studies have become increasingly common in order to generate larger samples of reproducible data to answer questions associated with smaller effect sizes. The data harmonization model NeuroCombat has been shown to remove site effects introduced by differences in site-related technical variance while maintaining group differences, yet its effect on improving statistical power in pre-clinical models of CNS disease is unclear. The present study examined fractional anisotropy data computed from diffusion weighted imaging data at 3 and 30 days post-controlled cortical impact injury from 184 adult rats across four sites as part of the Translational-Outcome-Project-in-Neurotrauma (TOP-NT) Consortium. Findings supported prior clinical reports that NeuroCombat fails to remove site effects in data containing a high proportion-of-outliers (>5%) and skewness, which introduced significant variation in non-outlier sites. After removal of one outlier site and harmonization using a pooled sham population, the data displayed an increase in effect size and group level effects (p < 0.01) in both univariate and voxel-level volumes of pathology. This was characterized by movement toward similar distributions in voxel measurements (Kolmogorov–Smirnov p < <0.001 to >0.01) and statistical power increases within the ipsilateral cortex. Harmonization improved statistical power and frequency of significant differences in areas with existing group differences, thus improving the ability to detect regions affected by injury rather than by other confounds. These findings indicate the utility of NeuroCombat in reproducible data collection, where biological differences can be accurately revealed to allow for greater reliability in multi-site neuroimaging studies.https://www.frontiersin.org/articles/10.3389/fneur.2025.1612598/fulldiffusion-weighted imagingtraumatic brain injuryharmonizationmulti-sitecontrolled cortical impact injuryaxonal injury |
| spellingShingle | G. Kislik R. Fox A. V. Korotcov A. V. Korotcov J. Zhou M. Febo Babak Moghadas Adnan Bibic Adnan Bibic Yunfan Zou Jieru Wan R. C. Koehler T. Adebayo T. Adebayo M. P. Burns J. T. McCabe K. K. Wang J. R. Huie A. R. Ferguson A. Paydar I. B. Wanner N. G. Harris N. G. Harris the TOP-NT Investigators Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study Frontiers in Neurology diffusion-weighted imaging traumatic brain injury harmonization multi-site controlled cortical impact injury axonal injury |
| title | Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study |
| title_full | Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study |
| title_fullStr | Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study |
| title_full_unstemmed | Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study |
| title_short | Improved injury detection through harmonizing multi-site neuroimaging data after experimental TBI: a Translational Outcomes Project in Neurotrauma consortium study |
| title_sort | improved injury detection through harmonizing multi site neuroimaging data after experimental tbi a translational outcomes project in neurotrauma consortium study |
| topic | diffusion-weighted imaging traumatic brain injury harmonization multi-site controlled cortical impact injury axonal injury |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1612598/full |
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