The Role of MEG in Assessment and Diagnosis In mTBI

Study Overview
=================
Brief Summary
-----------------
Head injuries are responsible for 1.4 million visits to hospital each year in the United Kingdom (UK). Most patients are allowed home the same day and make a full recovery, but some will have persistent symptoms. The investigators aim to use the latest generation of imaging technology to investigate those with mild traumatic brain injury (mTBI) to better assess them. The investigators will invite patients presenting following trauma to the Emergency Department at Queen's Medical Centre, Nottingham, UK to participate. The investigators will compare those who have a suffered an mTBI to those who have non-head traumatic injuries. The investigators will use two magnetoencephalogram (MEG) systems and ultra-high field magnetic resonance imaging (MRI) to record the functioning and structure of the brain within days of participants' injury. The investigators will test memory and thinking skills, then follow participants for six months, record the severity of participants' symptoms, and find out who does not make a full recovery. Multimodal imaging will consist of a standard MEG device using Superconducting Quantum Interference Device (SQUID) sensors, a novel MEG device using Optically Pumped Magnetometer (OPM) sensors and seven Tesla MRI. The investigators will test whether these innovative imaging techniques are more sensitive to the acute damage that mTBI causes than routine imaging. The investigators will also test whether early imaging can reveal who is most seriously affected, identifying those who will not recover without additional support. It is currently not clear what the predominant mechanism of damage that causes these long-term problems is and the investigators hope this study will address this. The Medical Research Council is funding this work

Official Title
-----------------
MEGAbIT The Role of OPM MEG in Assessment and Diagnosis In mTBI. An Observational Study

Conditions
-----------------
Brain Injuries, Traumatic

Intervention / Treatment
-----------------
* Other: Multimodal imaging


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Participant is willing and able to give informed consent for participation in the study Male or female, aged 18-35 In the Investigator's opinion, is able and willing to comply with all study requirements. Willing to allow his or her General Practitioner to be notified of participation in the study Two groups will be recruited: Diagnosed by the clinical ED team with mTBI (without abnormality on standard brain structural imaging, LOC ≤30mins, amnesia for ≤24hours, GCS ≥13 at all times and recovery to GCS 15 within 24hours) Diagnosed by the clinical ED team with non-head trauma, matched for age and sex with the mTBI group. Exclusion criteria Patient requiring hospitalisation for ≥24 hours at presentation Any contraindication to undergo 7T MRI scan Pregnancy Other neurological, developmental or psychiatric disorders e.g. brain tumour, stroke, epilepsy, Alzheimer disease, schizophrenia, post-traumatic stress disorder, major depressive disorder, bipolar disorder or history of learning disability Previous hospital attendance with TBI Substance or alcohol abuse within six months of enrolment Taking certain medications thought to alter MEG signals: opioids and synthetic opioids (excluding codeine and dihydrocodeine), anti-epileptic drugs, sedatives, neuroleptics, and hypnotics Extensive metal dental hardware e.g. braces and large metal dentures (excluding fillings), implanted medical devices or other metal objects in the head, neck, or face areas that although they hold no risk to participants during a MEG recording may cause non-removable artefacts in the MEG data. Participants who have participated in another research study involving an investigational product in the past 12 weeks. Any other significant disease or disorder, which, in the opinion of the Investigator, may put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mTBI cases<br>Those diagnosed with mild traumatic brain injury (mTBI) without abnormality on standard brain structural imaging, LOC ≤30mins, amnesia for ≤24hours, GCS ≥13 at all times and recovery to GCS 15 within 24hours) | Other: Multimodal imaging<br>* All participants will attend the Sir Peter Mansfield Imaging Centre for a scanning session using three imaging systems (SQUID MEG, OPM MEG and 7T MRI), cognitive testing and symptom questionnaires. Remote symptom monitoring and cognitive testing at three and six months.<br>|
| Acute trauma controls<br>Non-head trauma controls matched for age and sex with the mTBI group | Other: Multimodal imaging<br>* All participants will attend the Sir Peter Mansfield Imaging Centre for a scanning session using three imaging systems (SQUID MEG, OPM MEG and 7T MRI), cognitive testing and symptom questionnaires. Remote symptom monitoring and cognitive testing at three and six months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Can mTBI participants be differentiated from non-head injured controls by measuring brain wave activity? | To measure and localize abnormal resting-state slow wave activity in an mTBI population in the acute stage (< 2 weeks post injury). Voxel-wise source reconstruction of MEG resting state data using a beamforming approach will be used to generate a normative database of brain activity in the cohort of age and sex matched non-head injured trauma participants. The investigators will compare the oscillatory power in the theta and alpha frequency band between the mTBI cohort and the normative database to generate statistical maps of abnormal brain activity on a per participant basis. These will be assessed for statistically significant loci of abnormal slow wave power. | Within two weeks of injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Is the SQUID or OPM MEG system preferred by participants for tolerability and ease of use? | Participant preference for the SQUID or OPM MEG system will be recorded after both scanning sessions have been completed. | Within two weeks of injury | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Magnetoencephalography, Magnetic Resonance Imaging, Mild traumatic brain injury