Volumetric and Diffusion Tensor Imaging Abnormalities Are Associated With Behavioral Changes Post-Concussion in a Youth Pig Model of Mild Traumatic Brain Injury.
Authors
Affiliations (11)
Affiliations (11)
- Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
- Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
- Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, New York, USA.
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA.
- Institute of Quantitative Health, Science and Engineering, Michigan State University, East Lansing, Michigan, USA.
- Department of Radiology, Children's Mercy Hospital, Kansas City, Missouri, USA.
- Department of Radiology, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, Columbus, Ohio, USA.
- Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
- Department of Radiology, Michigan State University, East Lansing, Michigan, USA.
- Department of Large Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, East Lansing, Michigan, USA.
Abstract
Mild traumatic brain injury (mTBI) caused by sports-related incidents in children and youth often leads to prolonged cognitive impairments but remains difficult to diagnose. In order to identify clinically relevant imaging and behavioral biomarkers associated concussion, a closed-head mTBI was induced in adolescent pigs. Twelve (n = 4 male and n = 8 female), 16-week old Yucatan pigs were tested; n = 6 received mTBI and n = 6 received a sham procedure. T1-weighted imaging was used to assess volumetric alterations in different regions of the brain and diffusion tensor imaging (DTI) to examine microstructural damage in white matter. The pigs were imaged at 1- and 3-month post-injury. Neuropsychological screening for executive function and anxiety were performed before and in the months after the injury. The volumetric analysis showed significant longitudinal changes in pigs with mTBI compared with sham, which may be attributed to swelling and neuroinflammation. Fractional anisotropy (FA) values derived from DTI images demonstrated a 21% increase in corpus callosum from 1 to 3 months in mTBI pigs, which is significantly higher than in sham pigs (4.8%). Additionally, comparisons of the left and right internal capsules revealed a decrease in FA in the right internal capsule for mTBI pigs, which may indicate demyelination. The neuroimaging results suggest that the injury had disrupted the maturation of white and gray matter in the developing brain. Behavioral testing showed that compare to sham pigs, mTBI pigs exhibited 23% increased activity in open field tests, 35% incraesed escape attempts, along with a 65% decrease in interaction with the novel object, suggesting possible memory impairments and cognitive deficits. The correlation analysis showed an associations between volumetric features and behavioral metrics. Furthermore, a machine learning model, which integrated FA, volumetric features and behavioral test metrics, achieved 67% accuracy, indicating its potential to differentiate the two groups. Thus, the imaging biomarkers were indicative of long-term behavioral impairments and could be crucial to the clinical management of concussion in youth.