The ability to directly monitor head impact biomechanics using wearable sensors has fundamentally changed our understanding of the corresponding risks in a wide range of sports. One key finding is that significant tissue damage and changes in neural connectivity may result even in the absence of clinically diagnosed concussion symptoms. We will discuss our recent advances in evolving wearable sensors into advanced neuro-trauma dosimeters, suitable for monitoring cumulative damage due to repetitive head impacts and developing remove-from-play thresholds. These efforts combine measured head impact biomechanics, finite element modeling of the corresponding forces generated in the brain, and high resolution MRI imaging of the resulting changes in neural connectivity. We will also discuss related applications of wearable head impact sensors in the development of new concussion diagnostics such as blood biomarkers and eye tracking. Augmented World Expo (AWE) is back for its seventh year in our largest conference and expo featuring technologies giving us superpowers: augmented reality (AR), virtual reality (VR) and wearable tech. Join over 4,000 attendees from all over the world including a mix of CEOs, CTOs, designers, developers, creative agencies, futurists, analysts, investors, and top press in a fantastic opportunity to learn, inspire, partner, and experience first hand the most exciting industry of our times. See more at http://AugmentedWorldExpo.com

1. 1
How Wearables are Helping to Monitor and Manage Head Impact Risks in Sports
John 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

2. Acknowledgements
Customers Development Partners
School
of
Kinesiology
2

3.  Wide range of impairments that can arise from repetitive head impacts now recognized as
an enormous public health challenge.
Motivation
3
 Since 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 injuries
• Growing volume of evidence is revealing that significant brain injuries may result even in
the absence of clinically diagnosed concussion symptoms

4. X2 Pioneered Wearable Head Impact Monitors
Deployed today in wide range of athletic & military environments
• Football (youth, high
school, collegiate, pro)
• Hockey
• Soccer
• Lacrosse
• Rugby (amateur and
professional)
• Australian Rules
Football
• Baseball
• Field Hockey
• Wrestling
• Boxing
• Taekwondo
• Mixed Martial Arts
• Skiing
• BMX Cycling
• US Army Soldiers,
Military Police, and
Paratroopers
• US DoD Special
Forces
4

5. The Importance of Coupling Sensors to the Head
Accurate head
impact dynamics?
5

6. Actionable Data: Behavioral Modification, Risk Reduction
6
X-Patch: Track head impacts
• for each player
• as a function of position / activity
• during individual practices / games
• over extended periods of time
Exceeds thresholds?
• Single impact
• Accumulated loadN
• Remove from play
• Player coaching
• Activity modification
• Equipment modification
• Rules changes
Y
X-Patch helps identify, reduce,
eliminate high-risk head impacts
Players
Screened
>70G 40-70G 10-40G
Front Right Side Top
Back Left Side Bottom

7. X-Patch Helps Reduce High-Risk Head Impacts 30% - 70%
7
1. “Early Results of a Helmetless-Tackling Intervention to Decrease Head Impacts in
Football Players”, Swartz et al, J. Athletic Training, Jan 2016
2. “A Biosensing Approach for Detecting
and Managing Head Injuries in American
Football”, Morrison et al., J. Biosensors
& Bioelectronics, Nov 2015
3. “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 2015
http://usafootball.com/sites/default/files/datalys_center_study_methods.pdf

8. What We Have Learned
• Impact dynamics are complex, no 2 impacts are the same, tissue damage can be widely distributed
• Important to track indirect impacts and accumulated “smaller” impacts, as well as single “big” impacts
• Large data sets are key - data analytics and machine learning can enhance impact classification
• With sensors coupled to head, measured impact dynamics can provide strong predictors of concussion
8

9. Large Impact Data Sets Enhance Impact Classification
Real Head Impact
Spurious Sensor Impact
Loosely Attached SensorSensor with Offset Error
Running
Leveraging X2’s 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

10. Key Components of Proposed Neuro-Trauma Dosimeter
10
• 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 Mechanics
Reuben H. Kraft1, Phillip Justin Mckee2, Amy M. Dagro1, Scott T. Grafton3
1 Soldier Protection Sciences Branch, Protection Division, U.S. Army Research Laboratory,
Aberdeen Proving Ground, Maryland
2 Dynamic Science, Inc., Aberdeen Proving Ground, Maryland
3 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)

11. Impact Sensor Data Used as Input to Finite Element Brain Models
11
“Beta-amyloid deposition in CTE”
T.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 Cortex”
R.J.H. Cloots et al, Annals of Biomed Eng (2008)
Homogeneous Model
Heterogeneous 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
Severity
Strong predictors of concussion injury risk have
physical basis in torque, power, and deformation:
• Total impact power transferred to the brain
• Peak rotational acceleration magnitude during impact
• Peak principal strain in corpus callosum

12. Correlation with Hi-Resolution Brain Imaging (MDA DSI)
12
Multi-dimensional anisotropy DSI reveals spatially
localized diffusion changes after single soccer
season. Distribution in frontal / occipital cortex
consistent with damage from frontal headers.
Bottom First in-vivo observations of
localized damage at cortical sulci,
consistent with localized stress
enhancement at these structures.High resolution MRI/DSI
baseline image

13. Damage Severity Scales with Cumulative Impact Load
13
Bottom
Top
AbnormalVoxelsinScan
Cumulative Head Impact Power (kW)
Soccer Header
(~ 20G, 1 kW)
Football Drill
(~ 40G, 2-3kW)
Abnormal Voxels vs. Cumulative HIP (Linear + Rotational)
0 50 100 150 200

14. Damage Threshold vs. Concussion Threshold
14
Bottom
Top
AbnormalVoxelsinScan
Cumulative Head Impact Power (kW)
Abnormal Voxels vs. Cumulative HIP
(Linear + Rotational)
Probability of Concussion vs. HIP
(Linear + Rotational)
0 50 100 150 200
ProbabilityofConcussion
Head Impact Power (kW)
A Proposed New Biomechanical Head Injury Assessment
Function – Head Impact Power
Stapp Car Crash Journal, Vol. 44 (P-362), Proceedings of 44th
Stapp Car Crash Conference, Atlanta, GA, Nov 6-8, 2000.
Concussion
Brain Injury

15. Impact Biomechanics and Concussion Diagnostics
15
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 Concussion
Neurosurgery. 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 Pathophysiology Biomarkers of mTBI
Impact Biomechanics

16.  Cumulative head trauma measured with X-Patch shown to correlate with brain damage
predicted by finite element simulations and observed via brain imaging
Conclusions
16
 Significant progress being made developing and combining the components of a proposed
neuro-trauma “dosimeter”
• “X-Patch” head-mounted impact sensors
• finite element simulations
• high-resolution MRI/DSI
 Promising approach to monitoring cumulative damage due to repetitive sub-concussive head
impacts, and developing comprehensive personalized remove-from-play thresholds.

17. New X-Patch Pro Sensor + Impact Data Management System
• Measure motion of head with accuracy, sensitivity, and reproducibility to
enable analyses of complex impact dynamics and injury risks
• Simple 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 environment
• High-volume low-cost manufacturing
17
2016
Launch

18. 18
Thank You!
John Ralston, PhD
Chairman & CEO
john.ralston@x2bio.com
650.215.8418
www.x2bio.com
Silicon Valley Office:
X2 Biosystems, Inc.
2686 Middlefield Rd., Suite D
Redwood City, CA 94063
Seattle Office:
X2 Biosystems, Inc.
1927 Post Alley, Suite 200
Seattle, WA 98101