Magnetic resonance imaging and serum biomarkers of traumatic brain injury – methodological and clinical considerations

Traumatic brain injury (TBI) constitutes a major public health problem. The advent of collaborative neuro-imaging studies, advances in magnetic resonance imaging (MRI) and development of serum protein biomarkers have created an opportunity to gain new insights into the recovery after TBI. This thesis aimed to understand the role of MRI and serum biomarkers for outcome prediction after TBI. Before this clinical question could be answered, two methodological challenges had to be resolved. First, outcome data is often missing when patients are lost to follow up. We conducted a systematic review and created a novel framework for the statistical handling of missing outcome data in TBI. Second, MRI data collected at different sites may require harmonization. We examined the effect of different harmonization methods on a variety of imaging parameters, to inform our choice of method for subsequent chapters. The next two chapters concentrated on patients with mild TBI, as they represent the largest proportion of TBI patients and are in great need for better prognostic models. We demonstrated that structural white matter changes are detectable with advanced MRI, including diffusion tensor imaging (DTI), acutely after mild TBI even when conventional MRI is normal, and that these changes correlate with symptoms and recovery. We therefore assessed whether the association between DTI and outcome withstands the scrutiny of a formal prognostic study design and found that DTI substantially improves exiting prognostic models. We next focused on patients with moderate-severe TBI in whom the low level of consciousness is incompletely explained by CT appearances but might be explained by injury detectable with MRI or serum biomarkers. Unlike in mild TBI patients an MRI transfer in such critically ill patients constitutes a clinical risk. We show that protein biomarkers can help triage patients with moderate-severe TBI for MRI. We proceeded to investigate whether serum biomarkers could be used for prognosis directly, without the need for MRI. We found that serum biomarkers did significantly improve established prognostic models in this patient group with discordant CT appearances and conscious level. To conclude, this thesis presents methodological advances in the study of TBI, shows how DTI can transform outcome prediction after mild TBI and how serum biomarkers can improve MRI triage and prognosis in certain patients with moderate-severe TBI.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Richter, Sophie

Advisors dc:contributor.advisor

• Menon, David
• Newcombe, Virginia

• biomarkers
• diffusion tensor imaging
• GFAP
• head injury
• MRI
• neuroimaging
• traumatic brain injury

Licence

• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.95731

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/348308