Objective Concussion Assessment Using MRI and Metabolomics
NCT ID: NCT05993351
Last Updated: 2025-05-15
Study Results
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Basic Information
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RECRUITING
100 participants
OBSERVATIONAL
2023-08-11
2026-12-15
Brief Summary
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Detailed Description
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Brain injuries are classified as mild, moderate or severe based on patient reported symptoms, cognitive impairment and structural damage visualized using medical imaging (Bodin et al. 2012; DeCuypere and Kilmo 2012; DeMatteo et al. 2010; Roozenbeek et al. 2013). A major challenge facing mTBI diagnosis has been standardizing assessment, predicting prognosis, and clearing people to return to work or sport. In order to more accurately diagnose and treat patients, healthcare providers require a better understanding of how to brain is affected acutely, and the timeline for when it returns to a pre-concussion state. Recent technological innovations show promise to supplement the current behavioural and psychological assessments. Current concussion and mTBI diagnosis are often based on tests that assess a patient's sensory feedback, mental cognition, motor control, and post-concussion symptoms (Bodin et al. 2012; DeCuypere and Klimo 2012).
To supplement symptom tracking, magnetic resonance imaging (MRI) has been shown in research to be an invaluable concussion tool. The health of brain white matter can be predicted based on the relativistic shape of the myelin surrounding axons and the diffusivity of water along the length of the axons by using a MRI technique called diffusion tensor imaging (DTI)(Asken et al. 2018; Jonkman et al. 2015). In addition, the function of brain grey matter can be assessed using functional magnetic resonance imaging (fMRI) by measuring the paramagnetic differences between oxygenated and deoxygenated blood, based on the Blood-Oxygen Level Dependent (BOLD) signal (Horn et al. 2014; Liu et al. 2018; Ogawa et al. 1990). Activated brain regions have a greater BOLD signal due to magnetic field inhomogeneities caused by changes in blood volume, blood flow, and local metabolism (Ogawa et al. 1990). An fMRI can be used to analyze brain resting state activation patterns, a primary connective system is the Default Mode Network (DMN)(Mak et al. 2017). The DMN has been shown to have decreased activity following a mTBI (Bonnelle et al. 2011; Zhou et al. 2012).
A serious issue surrounding head injuries is the need for a method to diagnose athletes immediately following the injury. The growing interest in using metabolomics for the discovery of clinically relevant biomarkers associated with mild traumatic brain injury (mTBI) could be a solution. However, most studies to date have relied exclusively on blood specimens and/or targeted metabolite panels involving small cohorts of patients without adequate replication, and validation of aberrant metabolic changes in circulation to independent MRI-based brain imaging (Fiandaca et al. 2018; Orešič et al. 2016). We propose to include an analysis of fasting saliva and urine specimens from mTBI patients for comprehensive metabolite profiling using high throughput multi-segment injection-capillary electrophoresis-mass spectrometry technology (DiBattista et al. 2019; Yamamoto et al. 2019), which allows for rapid non-targeted analysis of polar/hydrophilic metabolites, as well as non-polar/ionic lipids with stringent quality control (Azab et al. 2019).
This study aims to track concussion recovery over 6-months using clinical standards of concussion symptoms and objective MRI and metabolomics metrics. Concussion participants will complete three study visits: acutely within 2-weeks of a concussion, 3-month follow-up and 6-month follow-up. Participants will be recruited from St. Joseph's Healthcare Hamilton and local athletic organizations. The study protocol will be identical for all three study visits. Participants will complete the Post-Concussion Symptom Scale (PCSS) and Depression Anxiety Stress Scale (DASS-42) to measure the presence and self-reported severity of common post-concussion symptoms. The MRI data will be used to measure brain function (resting state fMRI) and microstructural properties (diffusion tenor imaging), while the metabolomics will measure if metabolites have abnormal presence or concentration post-concussion based on urine and saliva samples. These quantitative methods will be compared to the subjective concussion symptom scores to identify if brain and physiological abnormalities persist past symptom resolution, and if certain brain regions are more frequently affected by concussion. It is hypothesized that across all three time points that brain function will have decreased BOLD signal fractal complexity and network connectivity (representative of concussion-related injuries), and white matter damage will be present based on the primary DTI metric of fractional anisotropy. It is also hypothesized that post-concussion symptoms will be self-reported as resolved or almost resolved by the 3-month follow-up study visit.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Concussion
Individuals who have recently sustained a concussion within the past 2-weeks.
Magnetic resonance imaging (MRI)
All participants will have 3 MRI scanning sessions to track brain health over time following the same protocol each time. The MRI sessions will occur acutely (\<2 weeks post-concussion), 3-months and 6-months post-concussion. A series of MRI scans will be acquired including T1, T2, T2-FLAIR, SWI, ASL, rsfMRI, and DTI scans to characterize structural, microstructural, functional and tissue perfusion changes within the brain over time.
Urine and saliva samples
At each study visit all participants will be asked to provide small urine and saliva samples for a metabolomic analysis using a high throughput multi-segment injection-capillary electrophoresis-mass spectrometry technology. This will allow for rapid non-targeted analysis of polar/hydrophilic metabolites, as well as non-polar/ionic lipids with stringent quality control.
Questionnaires
The Post-Concussion Symptom Scale (PCSS) and the Depression Anxiety Stress Scale (DASS-42) will be used to assess the self-reported presence and severity of known concussion-related symptoms.
Healthy Control
Individuals who have limited to no concussion history, and have not recently sustained a concussion.
Magnetic resonance imaging (MRI)
All participants will have 3 MRI scanning sessions to track brain health over time following the same protocol each time. The MRI sessions will occur acutely (\<2 weeks post-concussion), 3-months and 6-months post-concussion. A series of MRI scans will be acquired including T1, T2, T2-FLAIR, SWI, ASL, rsfMRI, and DTI scans to characterize structural, microstructural, functional and tissue perfusion changes within the brain over time.
Urine and saliva samples
At each study visit all participants will be asked to provide small urine and saliva samples for a metabolomic analysis using a high throughput multi-segment injection-capillary electrophoresis-mass spectrometry technology. This will allow for rapid non-targeted analysis of polar/hydrophilic metabolites, as well as non-polar/ionic lipids with stringent quality control.
Questionnaires
The Post-Concussion Symptom Scale (PCSS) and the Depression Anxiety Stress Scale (DASS-42) will be used to assess the self-reported presence and severity of known concussion-related symptoms.
Interventions
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Magnetic resonance imaging (MRI)
All participants will have 3 MRI scanning sessions to track brain health over time following the same protocol each time. The MRI sessions will occur acutely (\<2 weeks post-concussion), 3-months and 6-months post-concussion. A series of MRI scans will be acquired including T1, T2, T2-FLAIR, SWI, ASL, rsfMRI, and DTI scans to characterize structural, microstructural, functional and tissue perfusion changes within the brain over time.
Urine and saliva samples
At each study visit all participants will be asked to provide small urine and saliva samples for a metabolomic analysis using a high throughput multi-segment injection-capillary electrophoresis-mass spectrometry technology. This will allow for rapid non-targeted analysis of polar/hydrophilic metabolites, as well as non-polar/ionic lipids with stringent quality control.
Questionnaires
The Post-Concussion Symptom Scale (PCSS) and the Depression Anxiety Stress Scale (DASS-42) will be used to assess the self-reported presence and severity of known concussion-related symptoms.
Eligibility Criteria
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Inclusion Criteria
* Recently sustained a concussion (within the last 2 weeks)
Exclusion Criteria
* Unable to provide consent (e.g., poor English language skills, etc.)
* History of liver or kidney disease
* MRI contraindications:
* Pacemaker
* Stent
* Joint prothesis
* Implanted devices
* Claustrophobia
* Pregnant
* Permanent piercings
* Chronic/abusive use of alcohol and/or illicit drugs
* Previous stroke or moderate/severe traumatic brain injury, subarachnoid hemorrhage, or intracranial hemorrhage
* Healthy control participants must not have a concussion history or recently sustained a concussion
9 Years
50 Years
ALL
Yes
Sponsors
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McMaster University
OTHER
St. Joseph's Healthcare Hamilton
OTHER
Responsible Party
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Michael Noseworthy PhD
Director of MRI Research, Imaging Research Centre
Principal Investigators
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Michael D Noseworthy, PhD, PEng
Role: PRINCIPAL_INVESTIGATOR
McMaster University
Dinesh A Kumbhare, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University Health Network, Toronto
Locations
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Imaging Research Center at St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada
Countries
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Central Contacts
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Facility Contacts
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References
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Azab S, Ly R, Britz-McKibbin P. Robust Method for High-Throughput Screening of Fatty Acids by Multisegment Injection-Nonaqueous Capillary Electrophoresis-Mass Spectrometry with Stringent Quality Control. Anal Chem. 2019 Feb 5;91(3):2329-2336. doi: 10.1021/acs.analchem.8b05054. Epub 2019 Jan 7.
Bodin, D., Yeates, K. O., & Klamar, K. (2012). Definition and Classification of Concussion. In J. N. Apps & K. D. Walter (Eds.), Pediatric and Adolescent Concussion (pp. 9-19). New York, NY: Springer New York. https://doi.org/10.1007/978-0-387-89545-1_2
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Other Identifiers
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Concussion MRI & recovery
Identifier Type: -
Identifier Source: org_study_id
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