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How Wearables are Helping to Monitor and Manage Head Impact Risks in SportsJohn Ralston, Jason Thibado, Jonathan Woodard, X2 Biosystems, Redwood City, CA Scott Grafton, Matthew Cieslak, Alex Asturias, Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA

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Acknowledgements

Customers

Development Partners

School ofKinesiology

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Wide range of impairments that can arise from repetitive head impacts now recognized as an enormous public health challenge.

Motivation

3Since 2010, X2 Biosystems has been developing wearable sensors to monitor, assess, and react in real-time to reduce the incidence, risks, and costs of injuries resulting from repetitive head impacts.Much attention directed specifically at the issue of concussion injuriesGrowing volume of evidence is revealing that significant brain injuries may result even in the absence of clinically diagnosed concussion symptoms

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X2 Pioneered Wearable Head Impact MonitorsDeployed today in wide range of athletic & military environments

Football (youth, high school, collegiate, pro)HockeySoccerLacrosseRugby (amateur and professional)Australian Rules FootballBaseballField HockeyWrestlingBoxingTaekwondoMixed Martial ArtsSkiingBMX CyclingUS Army Soldiers, Military Police, and ParatroopersUS DoD Special Forces

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The Importance of Coupling Sensors to the Head

Accurate head impact dynamics?5

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Actionable Data: Behavioral Modification, Risk Reduction6X-Patch: Track head impacts for each playeras a function of position / activityduring individual practices / gamesover extended periods of timeExceeds thresholds? Single impactAccumulated loadN

Remove from playPlayer coachingActivity modificationEquipment modificationRules changes

YX-Patch helps identify, reduce, eliminate high-risk head impacts

PlayersScreened

>70G 40-70G 10-40G

FrontRight SideTopBackLeft SideBottom

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X-Patch Helps Reduce High-Risk Head Impacts 30% - 70%71. Early Results of a Helmetless-Tackling Intervention to Decrease Head Impacts in Football Players, Swartz et al, J. Athletic Training, Jan 2016

A Biosensing Approach for Detecting and Managing Head Injuries in American Football, Morrison et al., J. Biosensors & Bioelectronics, Nov 2015

Practice Type Effects on Head Impact in Collegiate Football, Reynolds et al., J. Neurosurgery, Aug 2015

4. DATALYS Center / USA Football Study: Effectiveness of HEADS UP FOOTBALL Program, Dompier et al, February 2015http://usafootball.com/sites/default/files/datalys_center_study_methods.pdf

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What We Have Learned

Impact dynamics are complex, no 2 impacts are the same, tissue damage can be widely distributedImportant to track indirect impacts and accumulated smaller impacts, as well as single big impactsLarge data sets are key - data analytics and machine learning can enhance impact classificationWith sensors coupled to head, measured impact dynamics can provide strong predictors of concussion

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Large Impact Data Sets Enhance Impact Classification

Real Head Impact

Spurious Sensor Impact

Loosely Attached Sensor

Sensor with Offset Error

RunningLeveraging X2s database of over 5.5 million head impact records to develop advanced data analytics and machine learning algorithms for automated real-time head impact and injury risk classification.9

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Key Components of Proposed Neuro-Trauma Dosimeter10

Finite element simulations to model compressive, tensile, and rotational shear stress utilizing measured impact data, predict time-evolving tissue injury and changes in structural brain connectivity

Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma MechanicsReuben H. Kraft1, Phillip Justin Mckee2, Amy M. Dagro1, Scott T. Grafton31 Soldier Protection Sciences Branch, Protection Division, U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland2 Dynamic Science, Inc., Aberdeen Proving Ground, Maryland3 Department of Psychology, University of California, Santa Barbara, Santa Barbara, California

Head-mounted sensors to measure & record impact biomechanics (linear and rotational motion)High-resolution brain imaging (MRI/DSI) to correlate predicted damage, evolution of observed symptoms (cognitive, motor, sensory, emotional, behavioral)

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Impact Sensor Data Used as Input to Finite Element Brain Models11

Beta-amyloid deposition in CTET.D. Stein et al, Acta Neuropathol (2015)

possible explanation for spatially localized damage

Biomechanics of Traumatic Brain Injury: Influences of the Morphologic Heterogeneities of the Cerebral CortexR.J.H. Cloots et al, Annals of Biomed Eng (2008)

Homogeneous ModelHeterogeneous Geometry

Spatially localized stress enhancement (predicted)Six degree of freedom (6DOF) measurements of human mTBI F. Hernandez et al, Annals of Biomedical Eng (2015)

Impact Biomechanics

Finite Element Models to Simulate Stresses in Brain, Potential Tissue Damage Location and SeverityStrong predictors of concussion injury risk have physical basis in torque, power, and deformation:Total impact power transferred to the brainPeak rotational acceleration magnitude during impactPeak principal strain in corpus callosum

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Correlation with Hi-Resolution Brain Imaging (MDA DSI)12Multi-dimensional anisotropy DSI reveals spatially localized diffusion changes after single soccer season. Distribution in frontal / occipital cortex consistent with damage from frontal headers.

BottomFirst in-vivo observations of localized damage at cortical sulci, consistent with localized stress enhancement at these structures.

High resolution MRI/DSI baseline image

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Damage Severity Scales with Cumulative Impact Load13BottomTopAbnormal Voxels in ScanCumulative Head Impact Power (kW)

Soccer Header (~ 20G, 1 kW)Football Drill (~ 40G, 2-3kW)Abnormal Voxels vs. Cumulative HIP (Linear + Rotational)050100150200

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Damage Threshold vs. Concussion Threshold14BottomTopAbnormal Voxels in ScanCumulative Head Impact Power (kW)

Abnormal Voxels vs. Cumulative HIP (Linear + Rotational)

Probability of Concussion vs. HIP (Linear + Rotational)050100150200Probability of ConcussionHead Impact Power (kW)A Proposed New Biomechanical Head Injury Assessment Function Head Impact PowerStapp Car Crash Journal, Vol. 44 (P-362), Proceedings of 44th Stapp Car Crash Conference, Atlanta, GA, Nov 6-8, 2000.Concussion

Brain Injury

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Impact Biomechanics and Concussion Diagnostics15

Zetterberg, H. et al., Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood, Nat. Rev. Neurol. 2013

Giza, Christopher C.; Hovda, David A. The New Neurometabolic Cascade of ConcussionNeurosurgery. 75():S24-S33, October 2014.

X-Patch measurements of real-time impact biomechanics can help assess effectiveness of new head injury diagnostics such as biomarkers detected in saliva, perspiration, blood, urine.Concussion Injury PathophysiologyBiomarkers of mTBI

Impact Biomechanics

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Cumulative head trauma measured with X-Patch shown to correlate with brain damage predicted by finite element simulations and observed via brain imaging

Conclusions

16Significant progress being made developing and combining the components of a proposed neuro-trauma dosimeterX-Patch head-mounted impact sensorsfinite element simulationshigh-resolution MRI/DSI Promising approach to monitoring cumulative damage due to repetitive sub-concussive head impacts, and developing comprehensive personalized remove-from-play thresholds.

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New X-Patch Pro Sensor + Impact Data Management SystemMeasure motion of head with accuracy, sensitivity, and reproducibility to enable analyses of complex impact dynamics and injury risksSimple Band-Aid-like X-Patch application via medical-grade adhesive Record / analyze single impacts and multiple accumulated impacts Compatible with any athletic, military, or industrial environmentHigh-volume low-cost manufacturing

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2016 Launch

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Thank You!

John Ralston, PhDChairman & CEOjohn.ralston@x2bio.com650.215.8418www.x2bio.comSilicon Valley Office:X2 Biosystems, Inc.2686 Middlefield Rd., Suite DRedwood City, CA 94063Seattle Office:X2 Biosystems, Inc.1927 Post Alley, Suite 200 Seattle, WA 98101

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