MRI in Severe Traumatic Brain Injury: Micro- and Macrostructural Changes

Abstract

The principal aim of the present PhD project was to study quantitatively the long-term microand macrostructural brain changes in survivors from severe traumatic brain injury (TBI). A total of 31 patients admitted for early rehabilitation following severe TBI were included and underwent magnetic resonance imaging (MRI), including Diffusion Tensor Imaging (DTI), at mean 8 weeks post-injury. Follow-up MRI at mean 12 months post-injury was acquired in 25 of the patients. For comparison, healthy matched controls were scanned twice with a similar time interval. Clinical rating during rehabilitation and at 1-year follow-up was performed by experienced staff. Two papers make up the basis of this thesis. Paper I considers the DTI results. This MRI modality was chosen in order to evaluate diffusional changes in brain tissue, potentially useful for characterising the extent of microscopic white matter injury, as well as for tracking microstructural changes during recovery. Using a region-of-interest approach, four white matter regions were studied with additional regions in grey matter and CSF. At the initial scan, patients had abnormal fractional anisotropy (FA) in all white matter regions, which in the cerebral peduncle correlated with 1-year outcome, suggesting that DTI may have prognostic value. At follow-up, FA had partly normalised in some white matter regions, but deviated even more from normal values in other regions. Although these longitudinal findings warrant cautious interpretation, they might indicate microstructural reorganization. Paper II describes a study on the macrostructural brain changes during recovery. Global and regional brain volume changes between the two scan time points were investigated using voxelwise analyses. Despite remarkable clinical improvement in most patients, they all exhibited continued brain volume loss during the scan interval. Global volume change correlated with clinical injury severity, functional status at both scans, and with 1-year outcome. The areas which underwent the most change were structures particularly susceptible to traumatic axonal injury and consequent Wallerian degeneration, indicating that the long-term atrophy is attributable to consequences of axonal injury. Together, these MRI analyses complemented each other in the quantitative assessment of structural brain changes following severe TBI. Applied in the late subacute/early chronic phase of TBI, DTI may capture biological severity at the microstructural level and provide prognostic information. Serial application of the MRI techniques applied in this study enables the monitoring of the extent and distribution of micro- and macrostructural changes during TBI rehabilitation.