Redefining traumatic brain injury prevention protection and repair
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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…

  • 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)


Redefining traumatic brain injury prevention protection and repair

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


Head injuries in very popular culture

Head injuries in very popular culture


So why do we study football players

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]


So why do we study football players1

So Why Do We Study Football Players?


The original question

The Original Question…

“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

  • 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


Concussion biomechanics

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.


Concussion biomechanics1

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.


Concern head injuries

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


Enormous forces during collisions

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!


Enormous forces during collisions1

Enormous Forces During Collisions

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


Redefining traumatic brain injury prevention protection and repair

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


What we did the players

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


What we did the procedures

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


Mr imaging and spectroscopy

MR Imaging and Spectroscopy

  • Purdue MRI Facility

    • 3T General Electric SignaHDx

    • 16ch Nova Medical Brain Array


Football helmet telemetry

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


Sensors inside the helmet record collision events

Sensors inside the helmet record collision events


What we found pronounced neurological deficits occur without clinically observable symptoms

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


Impact

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


Impact1

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.


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


Redefining traumatic brain injury prevention protection and repair

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


Scatter plot for coi foi group1

Scatter plot for COI-/FOI- group


Scatter plot for coi foi group2

Scatter plot for COI-/FOI+ group


Broader finding hits hurt

Broader Finding: Hits Hurt!

Data combined from 2009 & 2010 seasons


Hits do correlate with fmri changes

Hits DO Correlate with fMRI Changes

Breedlove et al. J Biomechanics (in press)


Redefining traumatic brain injury prevention protection and repair

CONCUSSED PLAYERS


Redefining traumatic brain injury prevention protection and repair

NON-CONCUSSED PLAYERS


Extent of injury in season

Extent of Injury – In Season


Extent of injury post season

Extent of Injury – Post Season


Proton 1 h mr spectroscopy

Proton (1H) MR Spectroscopy


Mrs regions examined

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.


Mrs results across sports

MRS: Results Across Sports

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?

  • 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

  • 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

  • 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


Redefining traumatic brain injury prevention protection and repair

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


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  • 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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