The Concussion Health Summit Sponsor Showcase: Concussions and Sub-Concussive Head Injuries – Is it Time for a Dosimeter?
While there is a growing concern of the short term and long term effects of sports-related concussion, little attention has been given to sub-concussive impacts. Sub-concussive impacts are identified as blows below the threshold to cause or elicit any signs or symptoms of a concussions (Shultz et al, 2012). More recently, a handful of studies have shown that sub-concussive blows result in physiological changes of the brain although the athlete does not exhibit any symptoms or change in performance (Dashnaw et al, 2012). The greatest concern is the long term accumulative effect of repeat concussive blows, especially in relation to accelerated age-related cognitive decline that may occur later in life.
As part of our Summit Sponsor Showcase and as one of the case study winners to present at the upcoming Concussion Health Summit, John Ralston, PhD and CEO of IMPAXX shares the following blog, Concussions and Sub-Concussive Head Injuries – Is it Time for a Dosimeter?, on combining sensor and imaging informatics to monitor and assess cumulative sub-concussive head impact injury risks.
Concussions and Sub-Concussive Head Injuries – Is it Time for a Dosimeter?
The direct medical costs for sports and recreational concussions in the US exceed $100 billion each year, including emergency room visits, hospitalizations, and health insurance billings. Yet concussions are now known to represent just the tip of the iceberg. A significant body of research published since 2010 has revealed that physiological changes in the brain resulting from the accumulation of many small direct or indirect head impacts, none of which on their own trigger any concussion symptoms, can also lead to neurological injuries and long-term degenerative neural disorders [1-10].
Because of this evidence, concussions are beginning to be viewed not as a single distinct class of injury, but as one segment of a wide and continuous spectrum of cumulative head impact injuries that all trigger some level of axonal damage, often referred to as diffuse axonal injury (DAI) . This spectrum of injuries is characterized by highly heterogeneous and multifactorial disorders, complex and diverse pathological changes that may continue for months or years, and some epidemiological support showing associations with other classical chronic neurodegenerative disorders . The incidence and costs of sub-concussive impact injuries may ultimately dwarf the above costs of reported concussions. Although all 50 states have now introduced youth head injury safety laws, and stricter head injury safety guidelines have been introduced by the NCAA, the current standard of care is still to wait until an athlete demonstrates observable concussion symptoms before they are removed from play, even though such symptoms may take several days to fully present, and even though the far greater number of sub-concussive head impacts may be causing even greater risks to athletes’ physical and academic performance.
Wearable sensors are routinely used in many recreational, medical, industrial, and military applications as injury prevention dosimeters. These devices monitor and limit exposures below tissue/organ damage thresholds from environmental hazards such as ultraviolet light, loud noises, high temperatures, toxic chemicals, biological agents, ionizing radiation, and X-rays. A variety of personal monitoring devices are also used to protect athletes from the damaging consequences of conditions such as dehydration, physical exhaustion, high blood pressure, low blood oxygen, and elevated/irregular heart rate. Could a dosimeter be designed to help monitor and protect against head impact injuries?
Silicon-Valley-based IMPAXX Solutions, Inc., has recently demonstrated a promising new class of wearable head impact dosimeter  that leverages advanced sensor and imaging informatics to deliver the injury screening capabilities of an MRI machine in a sensor that is worn behind the ear as a small adhesive patch (Fig. 1). The IMPAXX dosimeter combines an innovative wearable sensor design and recently demonstrated neuro-mechanical biomarker to monitor the onset and accumulation of both transient and persistent physiological changes in the brain resulting from repetitive sub-concussive head impacts. The device is designed to generate an alert when the accumulated impact dose exceeds preset neural damage thresholds. Alerts are delivered via a companion mobile app and cloud-based data platform, equipping coaches, trainers, and other authorized personnel with a more comprehensive injury prevention and management solution that enables:
Figure 1. A suitably designed wearable sensor can monitor the onset and accumulation of physiological changes in the brain resulting from sub-concussive head impacts.
The underlying discovery emerged from a recent collaboration between IMPAXX and the UC Santa Barbara (UCSB) Brain Imaging Center, in which members of the UCSB NCAA Division I women's soccer team (along with a group of age-matched controls) were monitored for the effects of cumulative head impacts throughout a 3-month soccer season and a 3-month post-season washout period. Data from prototype skin-affixed wearable sensors were used to quantify the number and severity of head impacts. In parallel, high-resolution diffusion spectrum MRI (DSI) brain image acquisition and per-voxel analysis techniques developed at the UCSB Brain Imaging Center were used to quantify corresponding physiological changes in the brain. The results revealed that the cumulative impact power transferred from the external environment to the brain is a promising neuro-mechanical biomarker that can be derived directly from a suitably designed wearable sensor, and utilized to monitor the onset and accumulation of both transient and persistent physiological changes in the brain resulting from sub-concussive head impacts [9,10].
Impact Measurements: An average of 215 head impacts per player were registered over the season (low = 95, high = 327), or 20 impacts per player per week. Fig. 2 shows histograms for the calculated (a) total power (linear + rotational) transferred to the brain from all individual head impacts, and (b) the daily total cumulative impact powers for all athletes over the entire 3-month season. The total impact power distribution in Fig. 2(a) peaks between 0.5kW and 1.5kW per impact, with few impacts beyond 5kW.
Figure 2. Histograms of (a) total impact powers (linear + rotational) transferred to the brain for all individual head impacts, and (b) the daily total cumulative impact powers for all athletes throughout the 3-month soccer season.
The individual impact values reported here are all significantly lower than those reported to have a high probability of causing a concussion , and none of the athletes were diagnosed with or reported any concussion symptoms. The cumulative daily impact power distribution in Fig. 2(b) reveals routine daily impact loads extending out to 60 kW, with 6 players receiving daily impact loads between 68kW and 110kW.
Imaging Results: The imaging results revealed the accumulation of widely distributed clusters of “outlier voxels” for the athletes, showing significant changes in WM diffusion anisotropy throughout the season, when normalized with respect to baseline values . For the controls, none of the in-season scans were statistically different from the corresponding baseline scans. As shown in Fig. 3, these clusters of outlier voxels were observed for the players in both deep WM and at the white matter-cortical border, including at the cortical sulci. This observation is consistent with finite element modeling of head impacts, which predict that relative displacements and deformations are widely distributed throughout the brain due to coupling of linear and rotational degrees of freedom [17,18]. Because of the off-center location of the brain and its anchor on the brain stem, “pure linear motion” of the head will still lead to rotational motion of the brain, and “pure rotational motion” of the head will still lead to linear motion of the brain.
Figure 3. Clusters of outlier voxels are observed for players but not age matched controls, showing significant changes in white-matter diffusion anisotropy when normalized with respect to baseline vales (p < 0.005).
More advanced finite element brain models that include tissue-specific mechanical properties and detailed structural morphologies have predicted several additional important impact responses, including spatial localization of stress fields and tissue damage at morphologic features such as the cortical sulci [19,20,21], which we have also observed. One implication of these findings is that even modest impacts, at levels traditionally thought to be safe, may generate localized regions of high stress and potentially irreversible changes in the brain. This localization and change of cellular function has been proposed as one possible explanation for recent observations that beta amyloid deposition is concentrated at the cortical sulci in the brains of professional football players who were diagnosed post mortem to have suffered from CTE [22,23]. The prevalence of CTE in subjects with no history of concussion suggests that sub-concussive hits are sufficient to lead to the development of CTE , and it has recently been argued that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease . The results reported here demonstrate the potential ability to monitor, and even prevent the onset of such localized damage using a wearable head impact dosimeter.
Correlating Sensor and Imaging Data: When the number of outlier voxels in the above WM clusters was plotted as a function of the maximum cumulative daily impact dose, along with the total cumulative impact power measured over the 2, 3, and 4 week periods immediately preceding each player’s mid-season scan (Fig. 4), the data exhibited a non-linear relationship, with a pronounced threshold behavior for the onset of outlier voxels. The cumulative power threshold above which outlier voxels are observed is on the order of 35-50 kW, which falls within the range of typical cumulative daily impact loads for all athletes in this study. The differences between the results for 2, 3, and 4 weeks indicate that a significant fraction of the observed outlier voxel groupings emerge and persist during the two-week period following impact exposure, and that some fraction then begins to dissipate. Further analyses  revealed that accumulated daily exposure doses <50 kW initially triggered transient physiological changes in the brain WM, whereas accumulated daily exposure doses above 100 kW triggered persistent WM changes, or WM changes that required longer recovery times.
As can be seen in Fig. 2(b), these threshold values fall within the range of routine daily head impact loads for the athletes, highlighting the importance of taking preemptive action to avoid more serious injuries accumulating over time.
Figure 4. Calculated number of outlier voxels vs. maximum cumulative daily impact dose, and total cumulative impact power measured over 2, 3, and 4 week periods immediately preceding each player’s mid-season DSI scan.
Understanding the Observed Head Impact Threshold: The threshold behavior observed above has several potential explanations. A significant body of research has demonstrated that, independent of the nature of the head impact, common hallmarks of the resulting damage include mechanical breaking of microtubules in axons, compromised axonal transport, focal axonal swelling (FAS), and mitochondrial dysfunction [24,25,26,27]. Recent studies, using cultured neurons and atomic force microscopy to directly measure the threshold mechanical forces required to cause such damage, have also observed an initial threshold for transient local deformation of the axons, and a more abrupt higher threshold above which irrecoverable axonal damage occurs [25,27]. These threshold forces fall well within the range predicted by finite element models to be generated by routine sub-concussive head impacts observed in many athletic activities .
Further Dosimeter Investigations: IMPAXX has shown that a dosimeter can indeed be designed to help monitor and protect against cumulative sub-concussive head impact injuries, and transform the current reactive treatment of concussion injuries after they have already occurred, to proactive, personal-dosimeter-based injury risk monitoring and prevention. IMPAXX is now preparing to deliver larger numbers of the devices for more comprehensive field testing with leading sub-concussive head injury research groups around the world. Investigations of dosimeter threshold variations across larger study populations are also being coordinated with leading sports medicine clinic chains and healthcare/concussion injury insurance providers, to expand their own head injury prevention initiatives.
Thank you to IMPAXX for kicking off our Summit Sponsor Showcase! We look forward to future blogs from our sponsors leading up to The Concussion Health Summit. Register today to attend the Summit and join the conversation discussing the latest knowledge and technology regarding concussion management.
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