Redefining Traumatic Brain Injury – Prevention, Protection, and Repair

1. Redefining Traumatic Brain Injury – Prevention, Protection, and Repair Eric A. Nauman*, Ph.D., Larry Leverenz, Ph.D., Tom Talavage, Ph.D. *Director, HIRRT Laboratory Evan Breedlove, Byron Deorosan, Anne Zakrajsek, Meghan Robinson, Victoria Poole, Umit Yoruk, Katie Morigaki, Kent Butz, Paul, Rosenberger, Matt Rasmussen, David Schiffmiller School of Mechanical Engineering, Weldon School of Biomedical Engineering, Department of Health and Kinesiology, Department of Basic Medical Sciences, School of Electrical and Computer Engineering Purdue University

2. …The Team… • Consortium of Purdue research entities established to investigate the neurological consequences of repetitive blows to the head • Human Injury Research & Regenerative Technologies (Nauman) • Purdue MRI Facility (Talavage) • Department of Health & Kinesiology (Leverenz) • Funding (2009 – 2013: $365,000 to date) • Indiana Spinal Cord and Brain Injury Research Fund (Indiana State Department of Health) • Indiana Clinical and Translational Sciences Institute (CTSI) • General Electric Healthcare • Simbex (alpha-phase testing)

3. Civilian cases of TBI arise from MVC, sports injuries, falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves • Est. 22% of casualties have TBI • Vietnam: 12-14% of combat casualties had TBI • Kevlar body armor and helmets have significantly improved survival rate New England Journal of Medicine. Vol.352:2043-2047

4. Head injuries in popular culture

5. Head injuries in very popular culture

6. So Why Do We Study Football Players? • Consider American Football... • More than 1.1 million youth (almost exclusively male) play high school football each year • 67,000 are diagnosed with concussion (mild TBI) each year [Broglio et al., 2009; Gregory et al., 2010] • Probable that a like number go unreported [McCrea et al., 2004] • Players who continue to play with TBI are at greater risk for future injury [Guskiewicz et al., 2003] • Biomechanics suggest that injury can accumulate over time [Ommaya et al., 1994] • Supported by post-mortem evaluation of professional athletes [Omalu et al., 2005, 2006] • Players who experience sub-concussive impacts may also accumulate neural injury! [McKee et al., 2009]

7. So Why Do We Study Football Players?

8. The Original Question… “Why do some players, who have similar magnitude and number of blows to the head, sustain concussions and others do not?”

9. Traumatic Brain Injury • TBI Case Definition (CDC, 1995): • Injury to the head with one or more of • Skull fracture, • Observed or self-reported decrease/loss of consciousness • Amnesia • Neurological or neuropsychological abnormality • Diagnosed intracranial lesion (hemorrhage, contusion, penetrating wound) • Death resulting from head trauma “Concussion”

10. Traditional Concussion Mechanics

11. Concussion Biomechanics • Not a contact phenomenon • Brain does not hit cranial vault in mild TBI • Rotational shear and pressure gradients • Whiplash induces concussions (Ommaya 1968) • Concussions without head motion (Gurdjian 1976) • Frontal lobe (anterior fossa) a critical injury ROI in biomechanics and in CTE (Ommaya 1974; McKee 2009) Time Adapted from P.V. Bayly, et al. J Neurotrauma. 2005 Aug; 22(8):845-56.

12. Concussion Biomechanics • Focal Injury • Coup/contrecoup phenomenon • Primary axotomy & hematoma • Diffuse injury • Result of whole-brain shearing • Linked to Wallerian degeneration • Rotational acceleration • Tied to focal & diffuse injury • Rotational strains may penetrate to brainstem to induce motor/consciousness deficits • Not reflected in any head injury criteria P.V. Bayly, et al. J Neurotrauma. 2005 Aug; 22(8):845-56.

13. Concern: Head Injuries • More than simply concussion • Repeated blows can affect brain physiology • How do sub-concussive blows contribute to impairment? Concussion Sub-Concussive Injury

14. Enormous Forces During Collisions Typical blows of 50-100G result in delivery of 100-200 lbs. of force to the helmet/head/neck. This goes up if player is “ready” for the hit!

15. Enormous Forces During Collisions Helmet-first contact for LeGrand, Stingley and Everett resulted in more than 5,000 lbs. of force on the neck!

16. Pre-season assessment by ImPACT, MRI, fMRI, HITS to record collisionsImPACT, MRI, fMRI, repeated in-season

17. What We Did: The Players • Two year study of a single high school (Lafayette Jefferson) • Year 1 participants • 21 participated for full season • Year 2 participants • 28 participated for full season • 16 returning participants • For Year 3 we have added • Second high school football team • West Lafayette High School • High school girls’ soccer team • Lafayette Jefferson

18. What We Did: The Procedures • Before (Pre-) season • Cognitive test (ImPACT) • MRI (DTI, SWI) • Functional MRI (fMRI) • New for 2011: MR Spectroscopy (MRS) • During (In-) season • Head collision monitoring (HITS, X2Impact) • ImPACT, MRI, fMRI, MRS • After (Post-) season • ImPACT, MRI, fMRI, MRS

19. MR Imaging and Spectroscopy • Purdue MRI Facility • 3T General Electric SignaHDx • 16ch Nova Medical Brain Array

20. Football Helmet Telemetry Image from Chicago Tribune, 6 October 2010 • Football: Helmet Impact Telemetry (HIT™) System (Simbex; Lebanon, NH) • Measures six linear accelerations • Approximates linear acceleration at head center of mass • Approximates impact location • Soccer: Prototype sensor (X2Impact, LLC; Seattle, WA) • Concept similar to HIT System

21. Sensors inside the helmet record collision events

22. What we found - Pronounced neurological deficits occur without clinically observable symptoms

23. ImPACT™ • Computerized neurocognitive test • Six Modules measure • Verbal recognition memory • Spatial recognition memory • Visual working memory • Cognitive speed • Visual-motor speed • Verbal working memory and cognitive speed • Gives immediate test results and flags scores that deviate from the individual’s baseline score or population normative data. www.impacttest.com

24. ImPACT™ • There was some moderate correlation between the verbal composite score or worst score and signal changes in the frontal, temporal, and parietal lobes • What is the Worst Score? • A unique way to interpret ImPACT™ scores. • The score with the greatest change from baseline, positive or negative, in either verbal or visual composite.

25. Peak Acceleration and Number of Hits are Similar between COI+/FOI+ and COI-/FOI- Players Breedlove et al. 2012

26. Head accelerations were similar across all groups

27. Concussed players exhibit deficits in multiple locations, but damage is focused in working verbal memory and integrative functions

28. Scatter plot for COI+/FOI+ group

29. Scatter plot for COI-/FOI- group

30. Scatter plot for COI-/FOI+ group

31. Broader Finding: Hits Hurt! Data combined from 2009 & 2010 seasons

32. Hits DO Correlate with fMRI Changes Breedlove et al. J Biomechanics (in press)

33. CONCUSSED PLAYERS

34. NON-CONCUSSED PLAYERS

35. Extent of Injury – In Season

36. Extent of Injury – Post Season

37. Proton (1H) MR Spectroscopy

38. MRS: Regions Examined • Primary Motor Cortex (M1) • Controls execution of movement • Classical TBI finding is reduced tCr, NAA, Glx • Dorsolateral Prefrontal Cortex (DLPFC) • Motor planning, organization, and regulation, working memory • Damage affects judgment, memory, abstract thinking and intentionality • Cerebellum • Motor control, cognitive functions (e.g. attention and language) • Damage affects fine movement, equilibrium, motor learning.

39. MRS: Results Across Sports Football (N=17) Soccer (N=6) Red= Likely evidence of impairment Blue = Likely compensatory mechanisms

40. Can We Detect Injury W/O Baseline? • Unequivocal maybe! • fMRI data without baseline is suggestive • Controls: 6.1/121 ROIs outside 95% c.i. • Football players: 11.8/121 ROIs outside 95% c.i. • Unpaired t-test yields p < 0.0001 • Targeted examination of deviant ROIs may prove sufficient, particularly with MRS • Now collecting MRS on Non-Contact Controls

41. Summary of Findings • Temporal and spatial distributions of hits are linked to distinct functional outcomes • Sport’s (typical) level of head contact affects neurophysiology (fMRI, MRS) • Metabolic changes are presumably sport and gender dependent • Metabolic changes in asymptomatic football players are consistent with TBI

42. Future Work • DETECTION • Target early identification of brain injury without baseline scans • MITIGATION • Construct new materials for impact mitigation • COMPUTATIONAL MODELS • Relate human and animal experiments using mixture theory

43. Development of novel computational methods required to relate mechanical loads across multiple length scales

44. Partners in aaaaa(http://spin.ecn.purdue.edu/png) • Colleagues Prof. Eric Nauman (PU-ME) Prof. Tom Talavage (PU-ECE/BME)Prof. Wayne Chen (PU-AAE) Prof. Larry Leverenz (PU-HK) Dr. Julian Bailes (U Chicago) Prof. Stephen Roth (UMD) Prof. Charles Bouman (PU-ECE) Jonathan Murray (GEHC) Dr. Henry Feuer (IUSM) Prof. Doug Adams (PU-ME) Dr. Randall Benson (Wayne State) Prof. Jeff Gilger (UC-Merced) Greg Tamer, PhD (PU-BME) Mr. Denny Miller (PU-IAD) • Our dedicated graduate students KausarAbbas (ECE) Evan Breedlove (ME) Kent Butz (ME) Il-Yong Chun (ECE) Katherine Morigaki (HK) Victoria Poole (BME) Meghan Robinson (BME) Anne (Dye) Zakrajsek (ME) • Assisting undergraduate students Allan Diaz (ECE) Jeff King (ECE) Lisa Li (ECE) Kyle O’Keefe (ME) Matthew Rasmussen (ME) Paul Rosenberger (ECE)