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Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
Mac Donald, Christine
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Mac Donald, Christine

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  • CONFIDENTIAL
  • CONFIDENTIAL
  • CONFIDENTIAL
  • Transcript

    • 1. Advanced MRI in Blast-Related TBI:  Early Predictors of PTSD
      Christine Mac Donald, PhD
      Department of Neurology
      Washington University School of Medicine
    • 2. Research Rationale
      Traumatic brain injury (TBI) is a major cause of morbidity and mortality in both civilian and military populations
      Improvised explosive devices (IEDs) have emerged as a popular weaponry tactic in Operation Iraqi Freedom (OIF), now Operation New Dawn (OND) and Operation Enduring Freedom (OEF)
      Blast-related TBI has been called the “signature injury” of the war yet much is still unknown about this particular mechanism of TBI and its impact on the brain.
      Axonal damage is a major pathophysiological process following TBI
      Possibly a primary cause of adverse neurological outcome
      Current clinical imaging modalities have been optimized for the visualization of hemorrhage and ischemia but are inadequate for direct assessment of axonal injury
      Diffusion Tensor Imaging may be more sensitive to changes following axonal injury
    • 3. Statistical Perspective
      The percentage of combat casualties accounted for by explosive mechanisms in Iraq and Afghanistan
      78
      320,000
      79
      88
      0
      Belanger et al., J Int Neuropsych Soc 2009
    • 4. Statistical Perspective
      78
      320,000
      79
      88
      0
      The number of service members of the deployed force who potentially suffer from TBI (19.2%)
      Long et al., J Neurotrauma2009; Moore et al., NeuroImage2009; RAND Report 2008
    • 5. Statistical Perspective
      78
      320,000
      79
      88
      0
      The percentage of soldiers reporting LoC who were injured via blast explosion
      Belanger et al., J Int Neuropsych Soc 2009
    • 6. Statistical Perspective
      78
      320,000
      79
      88
      0
      The percentage of injuries seen at a second echelon treatment site that were due to blast
      Warden, J Head Trauma Rehab 2006
    • 7. Statistical Perspective
      78
      320,000
      15
      79
      88
      0
      The current success rate of TBI therapies translating from animal models to human
      Benzinger et al., J Neurotrauma 2009
    • 8. Advanced MR Imaging Project
      Department of Defense Grant
      Congressionally Directed Medical Research Program (CDMRP)
    • 9. Study Objectives
      Determine whether DTI will noninvasively reveal abnormalities that are not present on CT or conventional MRI acutely following blast-related TBI
      Use DTI to understand whether there are principal similarities and differences between blast-related TBI and TBI due to other mechanisms (e.g. motor vehicle accidents, falls, and direct blows to the head)
      Test the hypothesis that specific pattern of injuries detected with these methods will predict specific longer-term psychological deficits
    • 10. Study Participants
      Enrollment
      Participant Characteristics
      All Subjects met DoD Definition for mild, uncomplicated TBI
      Mac Donald et al, NEJM 2011
    • 11. Brain Regions of Interest
      Mac Donald et al, NEJM 2011
    • 12. Comparison of DTI to Conventional MRI
      Mac Donald et al, NEJM 2011
    • 13. Regions Commonly Reported in Civilian TBI
      Dashed lines indicated 2 SD below mean control
      Mac Donald et al, NEJM 2011
    • 14. Simulations predict high shear stresses in specific regions, independent of blast orientation
      Taylor et al, J Biomedical Engineering 2009
    • 15. Regions Predicted to be Vulnerable to Blast
      Dashed lines indicated 2 SD below mean control
      Mac Donald et al, NEJM 2011
    • 16. Is this Clinically Relevant?
    • 17. Clinical Predictors: PTSD
      DTI addition was significant (βDTI= -0.28, p=0.016)
    • 18. PTSD Severity by Criteria
    • 19. Clinical Predictors: Hyperarousal
    • 20. Study Objectives
      Determine whether DTI will noninvasively reveal abnormalities that are not present on CT or conventional MRI acutely following blast-related TBI
      DTI demonstrated abnormal signal consistent with traumatic axonal injury following blast-related TBI not apparent on conventional MR acquired at the time.
      Use DTI to understand whether there are principal similarities and differences between blast-related TBI and TBI due to other mechanisms (e.g. motor vehicle accidents, falls, and direct blows to the head)
      Abnormalities were observed in regions commonly reported following civilian TBI however a greater prevalence of patients had abnormalities in regions hypothesized to be vulnerable to blast.
      Test the hypothesis that specific pattern of injuries detected with these methods will predict specific longer-term psychological deficits
      Predictive correlations were observed between DTI regions of interest combined with initial clinical data and the severity of Post-Traumatic Stress Disorder determined 6 – 12 months later.
    • 21. Implications and Future Directions
      • The implementation of these imaging methods is logistically feasible in this population.
      • 22. This approach is useful at the individual subject level.
      • 23. The results are broadly consistent with animal models and simulations of blast.
      • 24. Further studies are ongoing to attempt to expand upon these findings in a larger cohort and better understand how they relate to functional outcome
    • Acknowledgements
      Landstuhl Regional Medical Center
      Washington University
      Trauma Surgery & Critical Care
      Dept of Radiology
      LRMC PI: LTC Raymond Fang, MD (2009 – Present)
      LRMC PI: COL Stephen Flaherty, MD (2007-2009)
      Marcus Raichle, MD
      Josh Shimony, MD PhD
      Avi Snyder, MD PhD
      MAJ Shawna Scully, MD Caroline Tuman
      Dept of Psychiatry
      Elliot Nelson, MD
      Dept of Radiology – MRI Clinic
      Dept of Neuropsychology
      COL Stephen Sauter, MD
      LTC John Witherow, MD
      Tim Roberts
      TSgt Kris Robertson
      SSgt Kelly McKay
      Tim McKay
      Carl Russell
      Don Albrant
      SGT Antoinette Sherman
      HM2 Ludwig Williams
      MSGT Kenny Caywood
      Nicole Werner, PhD
      Clinical Coordination
      Annie Johnson
      Psychometricians
      Leslie French, PhD
      Justin Hampton
      Erik Schumaker
      Elaine Tamez
      TBI Screen Team
      Kathie Martin Karen Williams
      SGT Shawn Nelson Pam Nyman
      Linda Wierzechowski Janna Welsh

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