Longitudinal Associations Between Blood Biomarkers and White Matter MRI in Sport-Related Concussion
Bibliographic record
Abstract
Objective To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1)) and white-matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24-hours post-injury to 1 week after return-to-play. Methods We analyze clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours post-injury, point of becoming asymptomatic, and 7 days following return-to-play. DTI probabilistic tractography was performed for each subject at each time point to render 27 subject-specific major white-matter tracts. The microstructural organization of these tracts was characterized by four DTI metrics. Mixed-effects models with random intercepts were applied to test whether white-matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test if the association varies across time points. A lagged model was used to test if early blood-based biomarkers predict later microstructural changes. Results Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, tau was positively associated with radial diffusivity (RD) in the right corticospinal tract (β=0.25, SE=0.07, pFDR-adjusted=0.016) and superior thalamic radiation (β=0.21, SE=0.07, pFDR-adjusted=0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|β|s>0.12, SEs<0.09, psFDR-adjusted<0.05) and GFAP showed a significant association only at 7-days following return-to-play (βs>0.14, SEs<0.06, psFDR-adjusted<0.05). The p-values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in seven white-matter tracts. Conclusions This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white-matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white-matter microstructural changes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".