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Redefining Traumatic Brain Injury – Prevention, Protection, and Repair. Eric A. Nauman*, Ph.D., Larry Leverenz, Ph.D., Tom Talavage, Ph.D. *Director, HIRRT Laboratory

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Redefining traumatic brain injury prevention protection and repair

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


The team
…The Team… Protection, and Repair

  • 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)


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


Head injuries in popular culture
Head injuries in popular culture falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves


Head injuries in very popular culture
Head injuries in very popular culture falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves


So why do we study football players
So Why Do We Study Football Players? falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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]


So why do we study football players1
So Why Do We Study Football Players? falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves


The original question
The Original Question… falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

“Why do some players, who have similar magnitude and number of blows to the head, sustain concussions and others do not?”


Traumatic brain injury
Traumatic Brain Injury falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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”


Traditional concussion mechanics
Traditional Concussion Mechanics falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves


Concussion biomechanics
Concussion Biomechanics falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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.


Concussion biomechanics1
Concussion Biomechanics falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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.


Concern head injuries
Concern: Head Injuries falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • More than simply concussion

  • Repeated blows can affect brain physiology

  • How do sub-concussive blows contribute to impairment?

Concussion

Sub-Concussive

Injury


Enormous forces during collisions
Enormous Forces During Collisions falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

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!


Enormous forces during collisions1
Enormous Forces During Collisions falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

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


Pre-season assessment by ImPACT, MRI, fMRI, falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves HITS to record collisionsImPACT, MRI, fMRI, repeated in-season


What we did the players
What We Did: The Players falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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


What we did the procedures
What We Did: The Procedures falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • 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


Mr imaging and spectroscopy
MR Imaging and Spectroscopy falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

  • Purdue MRI Facility

    • 3T General Electric SignaHDx

    • 16ch Nova Medical Brain Array


Football helmet telemetry
Football Helmet Telemetry falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves

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


Sensors inside the helmet record collision events
Sensors inside the helmet record collision events falls, etc. while soldiers experience, impacts, ballistic insults, and blast waves


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


Impact
ImPACT™ without clinically observable symptoms

  • 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


Impact1
ImPACT™ without clinically observable symptoms

  • 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.


Peak acceleration and number of hits are similar between coi foi and coi foi players
Peak Acceleration and Number of Hits are Similar between COI+/FOI+ and COI-/FOI- Players

Breedlove et al. 2012


Head accelerations were similar across all groups
Head accelerations were similar across all groups COI+/FOI+ and COI-/FOI- Players


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


Scatter plot for coi foi group
Scatter plot for COI+/FOI+ group but damage is focused in working verbal memory and integrative functions


Scatter plot for coi foi group1
Scatter plot for COI-/FOI- group but damage is focused in working verbal memory and integrative functions


Scatter plot for coi foi group2
Scatter plot for COI-/FOI+ group but damage is focused in working verbal memory and integrative functions


Broader finding hits hurt
Broader Finding: but damage is focused in working verbal memory and integrative functionsHits Hurt!

Data combined from 2009 & 2010 seasons


Hits do correlate with fmri changes
Hits but damage is focused in working verbal memory and integrative functionsDO Correlate with fMRI Changes

Breedlove et al. J Biomechanics (in press)


CONCUSSED PLAYERS but damage is focused in working verbal memory and integrative functions


NON-CONCUSSED PLAYERS but damage is focused in working verbal memory and integrative functions


Extent of injury in season
Extent of Injury – In Season but damage is focused in working verbal memory and integrative functions


Extent of injury post season
Extent of Injury – Post Season but damage is focused in working verbal memory and integrative functions


Proton 1 h mr spectroscopy
Proton ( but damage is focused in working verbal memory and integrative functions1H) MR Spectroscopy


Mrs regions examined
MRS: Regions Examined but damage is focused in working verbal memory and integrative functions

  • 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.


Mrs results across sports
MRS: Results Across Sports but damage is focused in working verbal memory and integrative functions

Football

(N=17)

Soccer

(N=6)

Red= Likely evidence of impairment Blue = Likely compensatory mechanisms


Can we detect injury w o baseline
Can We Detect Injury W/O Baseline? but damage is focused in working verbal memory and integrative functions

  • 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


Summary of findings
Summary of Findings but damage is focused in working verbal memory and integrative functions

  • 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


Future work
Future Work but damage is focused in working verbal memory and integrative functions

  • 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


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


Partners in aaaaa http spin ecn purdue edu png
Partners in relate mechanical loads across multiple length scalesaaaaa(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)


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