Diffusion tensor analysis of white matter tracts is prognostic of persisting post-concussion symptoms in collegiate athletes, 2024, Bertò et al.

SNT Gatchaman

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Diffusion tensor analysis of white matter tracts is prognostic of persisting post-concussion symptoms in collegiate athletes
Bertò; Rooks; Broglio; McAllister; McCrea; Pasquina; Giza; Brooks; Mihalik; Guskiewicz; Goldman; Duma; Rowson; Port; Pestilli

BACKGROUND AND OBJECTIVES
After a concussion diagnosis, the most important issue for patients and loved ones is how long it will take them to recover. The main objective of this study is to develop a prognostic model of concussion recovery. This model would benefit many patients worldwide, allowing for early treatment intervention.

METHODS
The Concussion Assessment, Research and Education (CARE) consortium study enrolled collegiate athletes from 30 sites (NCAA athletic departments and US Department of Defense service academies), 4 of which participated in the Advanced Research Core, which included diffusion-weighted MRI (dMRI) data collection. We analyzed the dMRI data of 51 injuries of concussed athletes scanned within 48 hours of injury. All athletes were cleared to return-to-play by the local medical staff following a standardized, graduated protocol. The primary outcome measure is days to clearance of unrestricted return-to-play. Injuries were divided into early (returnto-play < 28 days) and late (return-to-play >= 28 days) recovery based on the return-to-play clinical records. The late recovery group meets the standard definition of Persisting PostConcussion Symptoms (PPCS). Data were processed using automated, state-of-the-art, rigorous methods for reproducible data processing using brainlife.io. All processed data derivatives are made available at https://brainlife.io/project/63b2ecb0daffe2c2407ee3c5/dataset. The microstructural properties of 47 major white matter tracts, 5 callosal, 15 subcortical, and 148 cortical structures were mapped. Fractional Anisotropy (FA) and Mean Diffusivity (MD) were estimated for each tract and structure. Correlation analysis and Receiver Operator Characteristic (ROC) analysis were then performed to assess the association between the microstructural properties and return-to-play. Finally, a Logistic Regression binary classifier (LR-BC) was used to classify the injuries between the two recovery groups.

RESULTS
The mean FA across all white matter volume was negatively correlated with return-toplay (r=-0.38, p=0.00001). No significant association between mean MD and return-to-play was found, neither for FA nor MD for any other structure. The mean FA of 47 white matter tracts was negatively correlated with return-to-play (r =-0.27; r =0.08; rmin =-0.1; rmax =-0.43). Across all tracts, a large mean ROC Area Under the Curve (AUCFA ) of 0.71 ± 0.09 SD was found. The top classification performance of the LR-BC was AUC=0.90 obtained using the 16 statistically significant white matter tracts.

DISCUSSION
Utilizing a free, open-source, and automated cloud-based neuroimaging pipeline, a prognostic model has been developed, which predicts athletes at risk for slow recovery (PPCS) with an AUC=0.90, balanced accuracy = 0.89, sensitivity = 1.0, and specificity = 0.79. The small number of participants in this study (51 injuries) is a significant limitation and supports the need for future large concussion dMRI studies and focused on recovery.

Link | PDF (NeuroImage: Clinical)
 
These athletes unfortunately meet the 28-day definition of slow recovery, commonly referred to as either Persistent Post Concussion Symptoms (PPCS) or Post Concussion Syndrome. In non-sports-medicine environments, the prevalence of PPCS is even higher, with PPCS of 23-59% among civilians visiting the emergency department, and a staggering 75% at 6 months post-injury in active duty warfighters with blast-related mild Traumatic Brain Injury (mTBI). Recovering slowly from a concussion is detrimental for all these populations, and a clinical tool that could accurately predict PPCS would be revolutionary in both concussion management and concussion science.

Our results, with an AUC of 0.90, indicate white matter integrity may be a clinically useful tool. The choice of the 16 tracts used in the prognostic model are data driven, future research with much larger data will hopefully yield explanations to why these tracts are prognostic.
 
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