Allen, Christopher Martin
(2024)
Translational diagnostic neuroimaging in mild traumatic brain injury and multiple sclerosis.
PhD thesis, University of Nottingham.
Abstract
Translation of promising neuroimaging technologies into diagnostic tests requires diagnostic test accuracy studies. This thesis describes two such studies, MEGAbIT and DECISIve. As well as assessing analytical performance, this thesis will attempt to determine the effects of these new technologies on patients and the wider healthcare system.
Magnetoencephalography is an imaging technology that is used to study the function of the brain, and as a result provide insight into the acute consequences of mild traumatic brain injury. A systematic literature review and MEGAbIT assessed the diagnostic role of magnetoencephalography in acute mild traumatic brain injury. Head injuries are responsible for 1.4 million visits to UK hospitals annually. Most patients are discharged the same day and make a full recovery, but some will have persistent symptoms. The sensitivity and specificity of magnetoencephalography changes were assessed by including a cohort of non-head acute trauma controls and using a database of healthy controls.
The systematic literature review led to excess delta power being selected as the primary outcome for MEGAbIT. MEGAbIT revealed measurement of magnetoencephalography delta power did not differentiate those with mild traumatic brain injury from those with non-head trauma. A pre-specified measure of connectivity did demonstrate a statistically significant group level difference, between those with mild traumatic brain injury and healthy controls, and therefore, warrants further study to explore its diagnostic value.
An optimised structural MRI sequence, T2*, has been developed which can demonstrate the perivenular nature of multiple sclerosis inflammatory lesions, the central vein sign, and now needs thorough assessment prior to possible implementation within the NHS. DECISIve assessed the diagnostic role of the T2* MRI sequence, in persons suspected of having multiple sclerosis. Approximately 130 patients are diagnosed with multiple sclerosis each week in the UK. Having an MRI scan is not painful and carries few or no risks, unlike the current alternative of having a lumbar puncture. The aim was to provide the NHS with a test which is more sensitive, safer, cheaper, quicker, and importantly, more acceptable to patients.
The DECISIve interim analysis has shown that the sensitivity of the central vein sign is higher than testing for oligoclonal bands by lumbar puncture for the diagnosis of multiple sclerosis. The full DECISIve dataset will have sufficient power to identify a clinically meaningful difference if one exists. The introduction of the central vein sign to the diagnostic pathway of multiple sclerosis is likely to generate cost savings for the NHS, and may positively impact health utility indirectly, by leading to quicker diagnosis and prompter treatment. DECISIve participants have expressed a unanimous preference for MRI scans over undergoing a lumbar puncture. However, for those who do still require lumbar puncture, recommendations have been made to improve the patient experience.
This thesis has focussed on translational diagnostic neuroimaging studies. It included a robust diagnostic accuracy study of functional neuroimaging, to help resolve major unanswered scientific questions in mild traumatic brain injury and initiating the first head-to-head comparison of the central vein sign and oligoclonal band testing in the diagnostic pathway of multiple sclerosis.
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