Advanced MRI in Blast-Related TBI: Early Predictors of PTSD Christine Mac Donald, PhD Department of Neurology Washington University School of Medicine
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
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
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
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
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
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
Advanced MR Imaging Project Department of Defense Grant Congressionally Directed Medical Research Program (CDMRP)
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
Study Participants Enrollment Participant Characteristics All Subjects met DoD Definition for mild, uncomplicated TBI Mac Donald et al, NEJM 2011
Brain Regions of Interest Mac Donald et al, NEJM 2011
Comparison of DTI to Conventional MRI Mac Donald et al, NEJM 2011
Regions Commonly Reported in Civilian TBI Dashed lines indicated 2 SD below mean control Mac Donald et al, NEJM 2011
Simulations predict high shear stresses in specific regions, independent of blast orientation Taylor et al, J Biomedical Engineering 2009
Regions Predicted to be Vulnerable to Blast Dashed lines indicated 2 SD below mean control Mac Donald et al, NEJM 2011
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.
The implementation of these imaging methods is logistically feasible in this population.
This approach is useful at the individual subject level.
The results are broadly consistent with animal models and simulations of blast.
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