Volumetric and Diffusion Tensor Imaging Abnormalities Are Associated With Behavioral Changes Post-Concussion in a Youth Pig Model of Mild Traumatic Brain Injury.

Journal: NMR in biomedicine
Published Date:

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.

Authors

  • Islam Sanjida
    Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
  • Netzley Alesa
    Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Li Chenyang
    Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, New York, USA.
  • Zhang Jiangyang
    Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, New York, USA.
  • Dávila-Montero Bianca
    Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
  • Vazquez Ana
    Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA.
  • Subbaiah Shaun
    Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
  • Meoded Avner
    Department of Radiology, Children's Mercy Hospital, Kansas City, Missouri, USA.
  • Munoz Kirk
    Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, Columbus, Ohio, USA.
  • Colbath Aimee
    Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
  • Huang Jie
    Department of Radiology, Michigan State University, East Lansing, Michigan, USA.
  • Mejia-Alvarez Ricardo
    Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.
  • Manfredi Jane
    Department of Large Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, East Lansing, Michigan, USA.
  • Pelled Galit
    Mechanical Engineering, Michigan State University, East Lansing, Michigan, USA.