Energy failure following traumatic brain injury: Potential mechanisms and impact of normobaric hyperoxia

Cerebral ischaemia is a frequent finding in post mortem studies following traumatic brain injury (TBI), but clinical studies using 15oxygen positron emission tomography (15O PET) suggest that classical ischaemia is uncommon beyond the first 24 hours after injury. Evidence of metabolic failure in the absence of classical ischaemia may represent ongoing neuronal dysfunction and progressive neuronal loss. Any therapeutic intervention that mitigates such metabolic derangements before they result in irreversible neuronal injury may improve tissue fate and improve the functional outcome for patients. Energy failure was spatially defined, characterised, and mapped using 15O and 18Fluoromisinidazole ([18F] FMISO) positron emission tomography. This enabled differentiation of classical ischaemia, diffusion hypoxia, and established infarction, and provided data on the dominant local mechanism at any given time after TBI. My thesis also aimed to examine the utility of diffusion tensor imaging and whole-brain proton MR spectroscopy (WB 1H MRS) as imaging biomarkers to investigate normobaric hyperoxia as a therapeutic option following traumatic brain injury (TBI). Using ([18F] FMISO PET evidence of tissue hypoxia consistent with microvascular ischaemia was found across the injured brain. The impact of normobaric hyperoxia (NBH) was examined in a clinical TBI cohort using diffusion tensor imaging and WB 1H MRS. Some evidence of benefit was found within the perilesional brain, but further studies should examine the value of a longer period of exposure to NBH and whether this has implications for functional outcome.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Veenith , Tonny V

Advisors dc:contributor.advisor

• Coles , Jonathan
• Menon , David

• Traumatic Brain Injury
• Neurotrauma
• Proton Spectroscopy
• DTI

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/fee5ddf4-6dbc-4b87-9d14-78d4d6609a0a/download
• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language

en

Author Identifier

0000-0002-4125-8804

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/300900