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Neuroimaging in Sports-Related
Traumatic Brain Injury
Inga Katharina Koerte, MDRoss Zafonte, Alexander Lin, Julie Stamm, David Kaufmann, Marc Muehlmann,
Michael Mayinger, Karl Helmer, Michael Coleman, Ofer Pasternak, Robert A. Stern, Martha E. Shenton
Professor of Neurobiological Research in Child and Adolescent PsychiatriyDepartment of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
Visiting ProfessorPsychiatry Neuroimaging Laboratory, Brigham and Women‘s Hospital, Harvard Medical School
AAPM&R, October 1st 2015, Boston Inga Katharina Koerte 2
I have no relevant financial relationships with the products or services described, reviewed, evaluated,
or compared in this presentation.
Disclosure
AAPM&R, October 1st 2015, Boston Inga Katharina Koerte 3
1. Neuroimaging of sports-related concussion
Impaired function and structure of the brain can be detected and characterized using advanced MRI.
2. Neuroimaging of sports-related subconcussion
Advanced MRI makes the invisible visible by detecting brain alterations in the absence of acute symptoms.
3. Future Directions
Individual injury profiles, identification of risk factors.
Agenda and Key Messages
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• During a mTBI, the brain undergoes shear deformation producing a stretch of axons
• alterations in axonal membrane permeability
• impaired oxidative metabolism• energy failure and breakdown of
microtubules
Bleeding due to stretch of blood vessels Edema (swelling of the brain) Diffuse axonal injury (DAI)
Mechanisms of Injury
Giza et al. (2001) J Athl Train; Binder et al. (2005) Biochim Biophys Acta; Serbest et al. (2007) Neurochem Res
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Multistage Disease Model
Koerte and Lin et al. Brain Pathology 2015
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Advanced Neuroimaging of Sports-Related Concussion
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Bleeding due to stretch of blood vessels Edema (swelling of the brain) Diffuse axonal injury (DAI)
Neuroimaging of Traumatic Brain Injury
Giza et al. (2001) J Athl Train; Binder et al. (2005) Biochim Biophys Acta; Serbest et al. (2007) Neurochem Res; Niogi et al. (2010) J Head Trauma Rehabil, Shenton et al. (2012) Brain Imaging and Behavior
Conventional imaging NOT sensitive for DAI, the most common type of injury in concussion!
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• In DAI Susceptibility Weighted Imaging (SWI) is 10 times more sensitive to microbleeds than conventional MRI.
• The number of detected microbleeds in SWI significantly correlates with acute symptoms and long-term outcome in TBI patients.
Ashwal et al. (2006) AJNR, Beauchamp et al. (2013) Cortex, Colbert et al. (2010) Radiology, Tong et al. (2003) Radiology, Park et al. (2009) J Korean Neurosurg Soc
SWI is Sensitive to Microhemorrhages
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• Ice hockey players show an increase in hyperintensities following concussion
• Women had more hyperintensities than men
Helmer et al. 2014 Journal of Neurosurgery
Hyperintensities During a Play Season
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Symptoms and Imaging Findings Resolve
Koerte and Lin et al. Brain Pathology 2015
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• Automated volumetric analysis of cortical and subcortical structures using FreeSurfer
Brain Regional Volumetry - T1w MRI
Caveat:
•Most atlases are based on the brains of adults and have to be carefully assessed for quality and potentially be edited
Skull-stripped brain Brain segmentation Regional volumes
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• Former professional, now symptomatic American Football Players (n=71) show Reduced amygdala volume Reduced cingulate gyrus volume
• Hippocampal volume correlated with impaired memory function
• Volume of cingulate gyrus correlated with severity of depressive symptoms
Muehlmann et al. in preparation
Brain Volumetry in NFL players
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Symptoms and Imaging Findings Resolve
Koerte and Lin et al. Brain Pathology 2015
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Automated analysis of cortical thickness using FreeSurfer
Cortical Thickness
Caveat:
•Interindividual variability can’t be fully appreciated with automated techniques of group analyses
Skull-stripped brain Cortical segmentation Differences in cortical thickness
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Former professional American football players show Decrease in cortical thickness with age This decrease with age is more pronounced than in controls
Koerte et al. 2014, IBIA
Cortical Thickness in NFL Players
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DTI shows
•Increased FA and decreased MD following acute trauma
•Decreased FA and increased MD, radial and axonal diffusivity in neurodegenerative processes
Microarchitecture of the White Matter - DTI
H2O
H2O
Axonal Loss / DemyelinationAxonal Swelling
▲ FA
▼ MD
▼FA ▲ MD
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College ice hockey players show Increase in trace over the course of a play season This increase is most pronounced in those with concussion Most other players also show increase in trace
Koerte and Kaufmann et al. J of Neurosurgery 2012
Increased Diffusivity in Ice Hockey Players
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Advanced Neuroimaging of Subconcussive Sports-Related Brain Trauma
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Soccer is the most popular sport in the world
• More than 250 Mio active players worldwide
• 4 Mio registered players in the US (80% below 18 yrs)
Figure source: Spiotta et al. 2012
Tysvaer 1981; Ekblom 1986; Matser 1998; Boden 1998; Fuller 2005; Rieder 2011; Tysvaer1992; Tysvaer 1989; Field 2003; Wozniak 2007; Matser 1998; Straume-Naesheim 2005; Witol and Webbe 2003; Stephens 2005; Jordan 1996; McKee 2009; Stern 2011; Guskiewicz 2004; Guskiewicz 2005; Guskiewicz 2007; Guskiewicz 2003; McCrea 2003; Mihalik 2010; Aubry 2002; McCrory 2009; McCrory 2007; Broglio 2012, Zhang 2013
Subconcussive Brain Trauma in Soccer
Heading the ball makes soccer unique
• Unprotected head is a primary point of contact
• Heading causes forces of up to 60 g
• 6-12 headings per soccer game
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Soccer is the most popular sport in the world
• More than 250 Mio active players worldwide
• 4 Mio registered players in the US (80% below 18 yrs)
Figure source: Spiotta et al. 2012
Tysvaer 1981; Ekblom 1986; Matser 1998; Boden 1998; Fuller 2005; Rieder 2011; Tysvaer1992; Tysvaer 1989; Field 2003; Wozniak 2007; Matser 1998; Straume-Naesheim 2005; Witol and Webbe 2003; Stephens 2005; Jordan 1996; McKee 2009; Stern 2011; Guskiewicz 2004; Guskiewicz 2005; Guskiewicz 2007; Guskiewicz 2003; McCrea 2003; Mihalik 2010; Aubry 2002; McCrory 2009; McCrory 2007; Broglio 2012, Zhang 2013
Subconcussive Brain Trauma in Soccer
Heading the ball makes soccer unique
• Unprotected head is a primary point of contact
• Heading causes forces of up to 60 g
• 6-12 headings per soccer game
Neuropsychological function in soccer players
• Impaired memory, reduced attention span
• Controversial results studies
Alterations of the brain’s microstructure without symptomatic concussion?
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Professional soccer players compared to swimmers: Increased radial diffusivity of white matter First prove of microstructural alterations following repetitive
subconcussive brain traumaKoerte et al. JAMA 2012
Microarchitecture of White Matter - DTI
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Ergebnisse Traktographie
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SocCtr SocCtr
**
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SocCtr SocCtr
* *
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College football players showed Increase in trace over the
course of a play season in the temporal pole and brain stem
Followed by a decrease during 6 months of non-contact rest
Mayinger and Merchant-Brona et al. in preparation
Longitudinal WM Changes - DTI
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Those with strong hits don’t recover completely
Mayinger and Merchant-Brona et al. in preparation
Longitudinal WM Changes - DTI
Peak HITsp vs. Trace T1 / T3
50 100 150 200 250
-0.0002
-0.0001
0.0000
0.0001
0.0002Athletes
Peak HITspCha
nge
Trac
e
AAPM&R, October 1st 2015, Boston Inga Katharina Koerte 30 Koerte et al. Brain Imaging and Behavior 2015
Pronounced Cortical Thinning in Soccer Players
• Former professional soccer players show cortical thinning with age
• Cortical thickness correlated with exposure to repetitive head impacts
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NAA
Glx
Cr
ChomI
Membrane marker
Glial marker
Energy marker
Neurotransmitter
Neuronal marker
Lin et al. (2012) Brain Imaging and Behavior
MR Spectroscopy – The Virtual Biopsy
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Alterations in Neurochemistry - MRS
Possible neuroinflammation in former professional soccer players
• Former professional soccer players show increased cholin (membrane marker) and increased myoinositol (glial activation).
• Metabolites correlate with intensity of exposure to repetitve subconcussive head impacts while heading the ball in soccer.
(Koerte and Lin et al., J Neurotrauma 2015)
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Future Directions
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NFLControl
MR Spectroscopy – The Virtual Biopsy
• Decreased N-acetylaspartate
• Increased Choline
• Increased Threonine
• 2D COSY highly specific
Courtesy of Alexander LinLin et al. (2012) Brain Imaging and Behavior
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Age at first exposure to tackle football has an effect on the brain’s microstructure lower FA in CC if training started before age 12 years the earlier training started the lower FA in CC
Stamm, Koerte et al. J Neurotrauma 2015
White Matter Microstructure - DTI
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• 3D normative atlas based on 50 controls
• Comparison of individual with normative atlas Individual injury profile
Alterations of WM - DTI
(Bouix et al., PLOS one 2013)
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• Concussion and even repetitive subconcussion may lead to alterations of the brain’s structure, metabolism, and function – in some likely reversible, in some maybe not.
• Underlying mechanisms are not fully understood. Neuroimaging findings indicate neuroinflammation, demyelination, and neurodegeneration.
• Risk factors need to be identified. Neuroimaging findings suggest age at first exposure, intensity of head impact and/or exposure to repetitive subconcussive brain trauma.
• Future studies need to include: longitudinal studies to identify risk factors and individual profiles of injury.
Summary
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Collaborators
Ludwig-Maximilians-University
Prof. Dr. Maximilian Reiser
FACR, FRCR
Prof. Birgit Ertl-Wagner
David Kaufmann
Marc Mühlmann
Michael Mayinger
Denise Steffinger
Barbara Fisch
Harvard University
Prof. Martha Shenton
Prof. Marek Kubicki
Prof. Sylvain Bouix
Prof. Yogesh Rathi
Prof. Alexander Lin
Dr. Ofer Pasternak
Dr. Maulik Purohit
Ryan Eckbo
Boston University
Prof. Robert Stern
Spaulding Rehabilitation Center
Prof. Ross Zafonte
University of British Columbia, Canada
Dr. Paul Echlin
Funding: Else Kröner-Fresenius Stiftung
Deutscher Akademischer Austauschdienst
Thank you for your attention!
Please visit our website:
http://pnl.bwh.harvard.edu
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BACKUP
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DTI chatracterizes microstructure
Common parameters are calculated using the eigen vectors
• Fractional Anisotropy (FA): directionality of diffusion
• Mean Diffusivity (MD): mean diffusion in all directions
• Radial Diffusivity (RD): diffusion parallel to main axis
• Axial Diffusivity (AD): diffusion perpendicular to main axisAD = λ1
RD = (λ2 + λ3) / 2
MD = (λ1 + λ2 + λ3) / 3
FA =
Diffusion Parameters
Basser et al. (1994) Biophys J, Pierpaoli et al. (1996) Radiology