Neuroimaging in Sports-Related Traumatic Brain Injury Inga Katharina Koerte, MD Ross Zafonte,...

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


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


• 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


Multistage Disease Model

Koerte and Lin et al. Brain Pathology 2015


Advanced Neuroimaging of Sports-Related Concussion


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!


• 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


• 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


Symptoms and Imaging Findings Resolve



• 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


• 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


Symptoms and Imaging Findings Resolve



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


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


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


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


Advanced Neuroimaging of Subconcussive Sports-Related Brain Trauma


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





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?


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


Ergebnisse Traktographie


SocCtr SocCtr

**


SocCtr SocCtr

* *


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


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


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


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)


Future Directions


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


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


• 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)


• 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


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


BACKUP



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

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Neuroimaging in Sports-Related Traumatic Brain Injury Inga Katharina Koerte, MD Ross Zafonte,...

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