Imaging
Imaging
TBI-REPORTER makes use of high field strength 3T MRI to conduct structural and functional neuroimaging studies. Routinely-collected clinical CT will also be available. Critically, many of the centres in the Experimental Medicine Network have advanced MR compatible physiological monitoring and experience of taking critically ill TBI patients for MRI – thus facilitating use of MRI as an intermediate end point.
Imaging Core Sequences
TBI-REPORTER makes use of high field strength 3T MRI to conduct structural and functional neuroimaging studies. Routinely-collected clinical CT will also be available. Critically, many of the centres in the Experimental Medicine Network have advanced MR compatible physiological monitoring and experience of taking critically ill TBI patients for MRI – thus facilitating use of MRI as an intermediate end point.
| Time (mins) | Voxel Size | Matrix | Key Parameters | Usage | |
|---|---|---|---|---|---|
| T1 (MPRAGE) | 4:54 | 1.0 x 1.0 x 1.0 | 256 x 256 x 208 | TI/TR = 800/2000ms, R=2 | Volume estimation, lesion mapping |
| T2 FLAIR (SPACE) | 4.32 | 1.0 x 1.0 x 1.05 | 256 x 256 x 192 | TI/TR/TE = 1800/500/395ms, R=3 | Clinical read, lesion mapping |
| T2 Axial | 1:26 | 0.5 x 0.5 x 4 | 512 x 512 x 29 | TR/TE = 4000/99, R=2 | Clinical read, lesion mapping |
| SWI (QSM) | 2.08 | 0.9 x 0.9 x 3.0 | 256 x 232 x 48 | TE1/TE2/TR = 9.4/20/27ms, R=2 | Vascular injury |
| dMRI (multi shell) | 7:08 | 2.0 x 2.0 x 2.0 | 104 x 104 x 72 | TR = 3600ms, 50 dirs/ shell, b=0,1000,2000 s/ mm2, MB=3 | White matter structural connectivity |
| rsfMRI | 7:37 | 3 x 3 x 3 | 70 x 70 x 64 | TE/TR = 30/1470ms, MB=2, R=2, 300 volumes | Brain network function |
| 2D FLAIR | 4:28 | 0.7 x 0.7 x 4 | 320 x 260 x 30 | TR/TE/TI = 7840/96/2500ms | Clinical read, lesion mapping |
Imaging Analysis
Researchers within TBI-REPORTER have worldleading experience in MRI structural and functional analysis. Data pre-processing and analysis pipelines are standardised across TBI-REPORTER and include the latest novel approaches. Seminal work that has come out of the labs within TBI-REPORTER include:
- Automated quantification of CT findings to provide biomarkers of disease severity and progression, as well as therapy response.9
- Clear demonstration of the added benefit of structural MRI over CT, and DTI over structural MRI, in detecting lesions in TBI, particularly mild TBI; and demonstrating prognosis-defining lesions which are not visible on CT.10,11
- Demonstration that white matter and volume loss continues after TBI in association with ongoing raised plasma levels of TBI blood biomarkers.12,13
- Cognitive dysfunction and post-TBI symptoms are related to disrupted functional connectivity between key brain networks.14,15,16
- Multi-modality approaches demonstrate how MRI measures of white matter injury are associated with response to a cognitive intervention17
Fig: Progressive white matter loss over 12 months following severe TBI (based on data from: Newcombe et al. Neurorehabil Neural Repair 2016 (DOI: 10.1177/1545968315584004. Also see Refs 10 and 11)
Trans-cranial direct current stimulation corrects abnormalities in response inhibition, measured on the stop signal reaction time (SSRT) in TBI, and the extent of traumatic axonal injury within the salience network strongly influences behavioural responses to stimulation. Increasing damage to the tract connecting the stimulated right inferior frontal gyrus/anterior insula to the rest of the salience network was associated with reduced beneficial effects of stimulation – demonstrating the need for a personalized approach to non-invasive brain stimulation therapy (from Ref 15).
Advanced Imaging
As well as 3T MRI as standard, the TBI-REPORTER network has capacity to acquire and analyse a range of advanced neuroimaging technique.
The Connectome Scanner at Cardiff: This platform provides access to imaging with a maximum gradient strength of 300 mT/m and slew rate of 200 T/m/s,18 thus facilitating high resolution microstructural imaging. The scanner will be particularly used to explore disease mechanisms and imaging biomarkers in mild TBI and sportsrelated concussion.
7T MRI: Capitalising on the recent advanced in MRI, ultra high-field MRI (7T) provides a number of distinct advantages over the more readily accessible 3T MRI scan. These include highly sensitive lesion detection and greater anatomical coverage (particularly brainstem regions). The TBI-REPORTER network includes MRI physicists that ensure that novel sequences can be prepared for studies, thereby bringing the most innovative MRI research capabilities to TBI-REPORTER. Several of the sites in our Experimental Medicine Network are part of the DP UK 7T network and will draw on its experience.
3T (left) and 7T (right) images from the same individual showing the superior sensitivity to brainstem anatomy in the 7T sequence
Visit Assessment:
Choice Reaction Time
Caudate 123I-ioflupane specific
binding ratio classification
SPECT/ PET Imaging: With the use of established and novel ligands, SPECT/ PET imaging brings the capacity to investigate brain metabolism and neurochemistry. Ligands that have been used before by labs with the TBI-REPORTER network include: [18F]FDG;19 a range of TSPO ligands to image microglial activation;20,21 [11C]PiB for imaging amyloid;22 [18F]flortaucipir to image Tau;23 [11C] flumazenil for imaging neuronal loss;24 [11C]PHNO to map D2 receptors;25 [11C]UCB-J to image SV2A receptors and synaptic density;26 and 123-I-ioflupane for presynaptic dopamine receptor mapping.27 These cover energy metabolism, neuronal loss, amyloid and tau deposition, neurotransmitter pathways and neuroinflammation. TBI-REPORTER network studies using these ligands have reported early amyloid and tau deposition in chronic TBI and used imaging for patient stratification for drug intervention.27