NMDA PET in TBI
Research type
Research Study
Full title
Imaging NMDA receptor activation following head injury using positron emission tomography
IRAS ID
179934
Contact name
Jonathan P Coles
Contact email
Duration of Study in the UK
2 years, 2 months, 31 days
Research summary
Traumatic brain injury (TBI) is a major cause of death and disability, leading to great personal suffering to victims and relatives, and huge costs to society. While TBI results in brain bruises (contusions), bleeding (haemorrhage) and disruption of connections (diffuse axonal injury) at the time of injury, injury extent can increase over days to months due to various pathological processes. These include the release of a range of chemicals, one of which is glutamate an excitatory mediator within the brain. Glutamate increases excitatory transmission through activation of the NMDA (N-methyl-D-aspartate) receptor and experimental studies have shown that excess NMDA activation is harmful resulting in epilepsy and poor recovery. In patients brain glutamate levels can be measured within specialist neurosciences intensive care units (ICU) by means of a standard monitoring technique called microdialysis.
The aim of this pilot study is to delineate the pattern of glutamate – NMDA receptor activation within the brain following TBI and its impact on the evolution of structural injury, epilepsy and functional recovery. This will be done using a whole brain imaging technique called positron emission tomography (PET) and a novel tracer (18F-GE-179) that binds to activated NMDA receptors. PET imaging within 48 hours, day 5 – 14 and at 6 – 18 months post injury in 18 TBI patients will be compared with continuous focal microdialysis glutamate levels and standard monitoring on the ICU. Patients will undergo serial magnetic resonance (MR) imaging to map the burden of injury and its development from ictus to recovery. Ten healthy controls will undergo similar imaging and patient outcome assessments will identify the incidence of post-traumatic epilepsy, functional recovery and quality of life. The data will refine our PET imaging technique, and inform the design and conduct of future clinical trials that aim to improve outcome following TBI.
REC name
East of England - Essex Research Ethics Committee
REC reference
15/EE/0247
Date of REC Opinion
17 Jul 2015
REC opinion
Further Information Favourable Opinion