Solving the Concussion Puzzle

The Mātai Medical Research Institute’s first major mild traumatic brain injury (mTBI/concussion) study started last year with support from the Gisborne Boys High School First XV and Second XV rugby teams, to help us monitor and understand any changes in the brain from injury.

The research involves brain scans at Mātai, using some of the world’s most advanced brain imaging technology in partnership with GE (General Electric) Healthcare; HITIQ high-tech mouthguards to monitor head impacts; eye-movement monitoring; small-RNA analysis by the Institute of Environmental Science and Research Ltd (ESR); and advanced biomechanical modelling by Dr Vickie Shim and the team at the Auckland Bioengineering Institute (ABI); as well as work by Professor Draper at the University of Canterbury; and the Auckland University of Technology (AUT). The research is funded in part by the MBIE Catalyst Strategic Fund, Kānoa Regional Economic Development & Investment Unit, Trust Tairāwhiti, and the JN and HB Williams Foundation.

Thirty-three players across two teams were involved, and data was acquired from 11 games and 30 training sessions.

Dr Patrick McHugh, local medical practitioner says. Brain injury in sport is a problem that is garnering more attention world-wide and what with a number of prominent ex-Gisborne rugby players having their professional careers cut short by brain injury the involvement of Gisborne Boys High with this research has been deeply appreciated. 

Head impacts are not uncommon in collision sports. Fast and improved head injury detection can better help with appropriate actions, such as removing a player from the game for a certain time period to help reduce the risk of negative long-term outcomes. The data will also aid objective surveillance, assessment and rehabilitation of injuries occurring on the sports field.

Using brain imaging, and by pushing the limits of technology, the team aim to gain new knowledge necessary to implement practical solutions to concussion and help identify interventions and preventative measures.

Dr Samantha Holdsworth, Mātai Medical Research Institute’s Director of Research, Associate Professor at the University of Auckland, and Principal Investigator at the Centre for Brain Research (CBR), is a leading researcher in brain imaging and emerging MRI (magnetic resonance imaging) technologies. She says the level of collaboration between multi-disciplinary experts makes the project unique. MRI is a promising technology for detecting changes in the brain resulting from impacts to the head. Advances in imaging technology are opening opportunities to see previously invisible damage in the brain caused by mTBI. As our ability to see and understanding of the damage improves, we can help outline pathways from brain injury diagnosis to prevention, education, and treatment. Combining advanced MRI with other technologies may increase our chances of finding and validating reliable gold-standard tests for concussion, increase our understanding of the injuries, and should help support rehabilitation programmes”.

Mātai Research Fellow Dr Eryn Kwon said, “This is one of the most comprehensive, multi-modal datasets being used in concussion research. A player may feel that they have recovered from a brain injury, and function satisfactorily on standard concussion tests. But in some cases our MRI scans still show signs of damage in the white matter fibres, or functional changes in the brain, which show the person has not quite recovered. This might put the player in increased risk if they suffer another concussion by returning to play. Through our collaborations we aim to further understand these risks and to find a simple test that can objectively tell when a person has recovered completely to return to play safely.”

The aim of his research is to fill gaps in what we know about how to manage concussion and empower clinicians to make a real difference in outcomes for those struggling with ‘invisible’ but debilitating symptoms. If we can see the damage inside the brain, we can understand the efficacy of different rehabilitation approaches to inform precision medicine in the future. For example, if we could eventually visualise the damage in much the same way we can see a broken bone on an x-ray, we may be better equipped to predict different recovery outcomes and prescribe early interventions accordingly. There are many benefits to participating in sport, and some of the narrative about the long-term effects of playing sports like rugby extend beyond the available scientific evidence. This project will provide evidence to address this issue and we hope to identify new ways of understanding how to mitigate the issues mTBI cause in sport.

Rich Easton, CEO of the Neurological Foundation of New Zealand, who are funders of part of the research says, “We are very proud to be supporting research that investigates how we can make a game we all know and love safer for the human brain. Neurological research such as this is so important for future generations.”

Mātai is collaborating with other groups nationwide, including Professor Nick Draper and his team at the University of Canterbury, whose goal is to examine collisions and their effects on neurocognition rugby in junior rugby players and ultimately to contribute to making the game safer for junior players. Their recently commenced study involves assessing the effects of impacts for junior rugby players through a combination of methods including brain imaging. Prof Draper says “we are doing our best to sync brain imaging protocols with the goal of improving the predictive capability of the imaging”.

Gisborne Boys High student Nathaniel Hauiti wears a customed made advanced HITIQ mouthguard to monitor head knocks.

Team training – As part of the concussion study, the rugby players at Gisborne Boys High undergo some of the world’s most advanced brain imaging, in the search to better understand and manage mTBI. The team at Mātai would like to thank the boys, their whānau, the coaches and all those involved for who helped make this study possible and for the important role they have in this collaboration.

One of the Gisborne Boys High players undergoes a MRI scan on a 3T GE Premier system at Mātai, using a number of advanced MRI sequences, including several types of structural imaging scans, diffusion imaging, resting-state and task-based functional MRI (fMRI), blood flow imaging, and amplified MRI (aMRI).

Trying to create a protocol to find unknown subtle markers utilising MRI can be difficult. As these signs are yet unknown it is hard to discredit any single sequence for fear of missing these unknown signs. At Mātai we have tried to balance the needs of clinical and research data while maintaining achievable scan times for volunteers, especially those suffering from mTBI.

Paul Condron | Mātai MRI Charge Technologist

ADVANCED IMAGING & BIOMARKER RESEARCH

Concussion is not a single injury type, it could be the result of damage to any one or a combination of damage types, or other unknowns. In addition, the damage is unique to each individual.

Operating a state-of-the-art 3T GE Premier MRI, Mātai has a partnership with GE Healthcare to assist with the advanced imaging protocols. GE Healthcare has placed research scientist Dr Hari Kumar on site part time in Gisborne who provides off-site technical support from various locations world-wide. Together with MR technologist Paul Condron, Hari implemented the functional MRI protocols so the team could probe altered cognition that may occur in concussion. To implement the diffusion MRI sequence used to assess impacts to the brain wiring, GE Clinical Science Specialist Dr Jerome Maller, based in Melbourne Australia, custom wrote method to generate high resolution data in a very short time. Dr Maller generated a method that is under 4 minutes – much shorter than standard methods, yet still providing excellent data.

One of Mātai’s goals is to use brain imaging to track recovery, through examining the regrowth of the brain wiring and view the effectiveness of different rehabilitation approaches. Maryam Tayebi, a PhD student from Auckland Bioengineering Institute working on the image analysis pipeline at the Auckland Bioengineering Institute says “While we can easily see the damage caused by a severe injury as shown in the image, there is still much work to be done using advanced imaging and data processing to pinpoint the currently ‘invisible’ damage done by more mild injuries”.

If we can increase our understanding of mTBI biomarkers (indicators of disorders or injury) by visually seeing the damage via our combination of MRI, saliva tests, eye-tracking, computer simulations, and other methods, it will enable precision medicine and we can better tailor treatment for individuals based on the type and depth of injuries in the brain and better predict the length of time required for recovery, and track recovery over time.

Brain Wiring: The image above shows an age-matched set of normal healthy brain wiring (left), compared with absent wiring to the front of the head as the result of a car accident. Such damage can result in pain, agitation, fatigue, muscle spasms, headaches, blurred vision and other complications. One goal is to use brain imaging to track recovery, through examining the regrowth of the brain wiring. While we can easily see the damage caused by a severe injury as shown in the image, there is still work to be done to pinpoint the currently ‘invisible’ damage that could occur with more mild injuries.

Data acquired on a 3T GE Premier system at Mātai, using a diffusion method implemented by GE Clinical Specialist Dr Jerome Maller, and post-processed by Maryam Tayebi from the Auckland Bioengineering Institute.

The team is looking closely for the effects of brain impacts in the corpus callosum – and which is thought to be vulnerable to concussion. This is the brain structure that connects the brain’s two hemispheres.

BIOMECHANICAL MODEL SIMULATIONS

Rapid prediction of Brain Injury Pattern in mTBI by Combining Finite Element analysis with a Machine-Learning based approach: Using NFL data from the USA, Dr Vickie Shim, from the Auckland Bioengineering Institute, in collaboration with Mātai, and a number of institutions, has developed a simulation model that can process brain injury data in a matter of minutes, rather than hours taken by previous models, making this more applicable in clinical settings.

The model analysed a number of different head impact scenarios in which a football player would sustain a minor brain injury and computed internal brain strain patterns. Previous models required a prohibitively large amount of computational power as well as pre and post processing expertise that made them unrealistic for use in clinical settings. This new model, which combines finite element analysis with a machine learning, may play an important role in developing a diagnostic tool for concussion/mild Traumatic Brain Injury that can predict the severity of head impacts.

Dr Shim

HitIQ HIGH-TECH MOUTHGUARDS

Using some of the world’s most advanced mouthguard technology from HITIQ in Australia we can collect objective data of potentially unseen injuries. The mouthguards contain an array of sensors that measure the head impact forces sustained during sub concussive and concussive contact events. The data captured during these events are correlated to other biomarkers, including eye tracking, clinical assessment, and neuroimaging at Mātai, in collaboration with GE Healthcare.

Players commonly do not report brain injuries, and some may not even realise they have suffered a medically significant head injury during a match. Immediate and improved brain injury detection can better help with appropriate actions, such as recommendation of appropriate treatment options, or removing a player from the game for a certain time period to help prevent long term damage.

EYE TRACKING

A significant amount of brain power is dedicated to eye movements, and testing is underway to determine the extent to which we can potentially detect brain injury through abnormal eye-movements using cost-effective 3D printed eye-tracking glasses. The eye-tracking is led by Dr Matthew McDonald and Professor Helen Danesh-Meyer and is funded by an HRC clinical research fellowship.

SMALL-RNA

The detection and analysis of small-RNA from saliva is added to the study.  Small RNA (ribonucleic acid) are molecules found in all our cells. The most studied to date are called microRNA. They can be secreted from cells and act as messengers – for instance as a result of stress to the brain caused by concussion. These microRNA are detectable in saliva and we are interested in finding out if they can be used to detect concussion. If so, then a test could be developed to objectively diagnose concussion.  It may also be possible to develop a hand-held device that could detect these microRNA and which could be used, for instance, on the side-line at a rugby game. In the future it might also be possible to monitor these microRNA molecules after a concussion to follow recovery from the injury – our understanding of this will be helped by the MRI and eye-tracking analyses.

This research will be done by Dr Rachel Fleming and Dr Donia Macartney-Coxson, through a collaboration with the Institute of Environmental Science and Research Ltd (ESR) who are experts in the analysis (sequencing and computational) of these small RNA molecules.

Through this multidisciplinary collaborative approach, in addition to validation of the tests using MRI, we may be able to come up with practical, quick, reliable, cost-effective tools. Such tools would have many applications, including determining the extent of an injury on sports side-lines, the scene of motor vehicle accidents and more. An important component that makes this study unique, in addition to the collaborations, is the use of some of the world’s most advanced imaging technologies to have validate new tools, techniques and rehabilitation methods.

AUT

Matai is also working closely with Dr Mangor Pederseon, Senior Lecturer  at AUT and core member of the AUT Traumatic Brain Injury Network, whose HRC-funded research fellowship also aims to reveal the mechanisms of concussion in Rugby union players using a novel combination of advanced MRI methods to statistically quantify brain abnormalities.

Any one, or a combination, of the tests above could be developed into diagnostic tools with multiple applications, including sports injuries and motor vehicle accidents. The aim of the research is to learn more about the complex processes of concussion in order to be able to develop and deliver affordable, portable, and objective tests for concussion detection that can be used on sport sidelines and at the scene of accidents. The data will also aid objective surveillance, assessment, and rehabilitation of injuries.