The Role of Thalamic Damage in Mild Traumatic Brain Injury.

There is growing alarm in the United States about an epidemiologically large occurrence of mild traumatic brain injury with serious long lasting consequences. Although conventional imaging has been unable to identify damage capable of explaining its organic origin or discerning patients at risk of developing long-term or permanently disabling neurological impairment, most disease models assume that diffuse axonal injury in white matter must be present but is difficult to resolve. The few histopathological investigations conducted, however, show only limited evidence of such damage, which cannot account for the stereotypical globalized nature of symptoms generally reported in patients. This review examines recent proposals that in addition to white matter, the thalamus may be another important further site of injury. Although its possible role still remains largely under-investigated, evidence from experimental human and animal models, as well as simulational and analytical representations of mild head injury and other related conditions, suggest that this strategically vital region of the brain, which has reciprocal projections to the entire cerebral cortex, could feasibly play an important role in understanding pathology and predicting outcome.

N-acetyl-aspartate levels correlate with intra-axonal compartment parameters from diffusion MRI.

Diffusion MRI combined with biophysical modeling allows for the description of a white matter (WM) fiber bundle in terms of compartment specific white matter tract integrity (WMTI) metrics, which include intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De||), extra-axonal radial diffusivity (De┴), axonal water fraction (AWF), and tortuosity (α) of extra-axonal space. Here we derive these parameters from diffusion kurtosis imaging to examine their relationship to concentrations of global WM N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myo-Inositol (mI), as measured with proton MR spectroscopy ((1)H-MRS), in a cohort of 25 patients with mild traumatic brain injury (MTBI). We found statistically significant (p<0.05) positive correlations between NAA and Daxon, AWF, α, and fractional anisotropy; negative correlations between NAA and De,┴ and the overall radial diffusivity (D┴). These correlations were supported by similar findings in regional analysis of the genu and splenium of the corpus callosum. Furthermore, a positive correlation in global WM was noted between Daxon and Cr, as well as a positive correlation between De|| and Cho, and a positive trend between De|| and mI. The specific correlations between NAA, an endogenous probe of the neuronal intracellular space, and WMTI metrics related to the intra-axonal space, combined with the specific correlations of De|| with mI and Cho, both predominantly present extra-axonally, corroborate the overarching assumption of many advanced modeling approaches that diffusion imaging can disentangle between the intra- and extra-axonal compartments in WM fiber bundles. Our findings are also generally consistent with what is known about the pathophysiology of MTBI, which appears to involve both intra-axonal injury (as reflected by a positive trend between NAA and Daxon) as well as axonal shrinkage, demyelination, degeneration, and/or loss (as reflected by correlations between NAA and De┴, AWF, and α).

Thalamus and cognitive impairment in mild traumatic brain injury: a diffusional kurtosis imaging study.

Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (mTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in mTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of mTBI patients, and can help ascertain if thalamic injury is associated with cognitive impairment. Twenty-two mTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within 1 year after injury exhibited variously altered DTI- and DKI-derived measures in the thalamus and the internal capsule, while in addition to these regions, patients examined more than 1 year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated with MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome.

Mild traumatic brain injury: is diffusion imaging ready for primetime in forensic medicine?

Mild traumatic brain injury (MTBI) is difficult to accurately assess with conventional imaging because such approaches usually fail to detect any evidence of brain damage. Recent studies of MTBI patients using diffusion-weighted imaging and diffusion tensor imaging suggest that these techniques have the potential to help grade tissue damage severity, track its development, and provide prognostic markers for clinical outcome. Although these results are promising and indicate that the forensic diagnosis of MTBI might eventually benefit from the use of diffusion-weighted imaging and diffusion tensor imaging, healthy skepticism and caution should be exercised with regard to interpreting their meaning because there is no consensus about which methods of data analysis to use and very few investigations have been conducted, of which most have been small in sample size and examined patients at only one time point after injury.

Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T.

OBJECTIVE: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes. MATERIALS AND METHODS: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia. RESULTS: The mean regional CBF was significantly lower in patients with MTBI (45.9 +/- 9.8 ml/100 g min(-1)) as compared to normal controls (57.1 +/- 8.1 ml/100 g min(-1); p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients. CONCLUSIONS: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease.

Measurement of deep gray matter perfusion using a segmented true-fast imaging with steady-state precession (True-FISP) arterial spin-labeling (ASL) method at 3T.

PURPOSE: To study the feasibility of using the MRI technique of segmented true-fast imaging with steady-state precession arterial spin-labeling (True-FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T. MATERIALS AND METHODS: A flow-sensitive alternating inversion-recovery (FAIR) ASL perfusion preparation was used in which the echo-planar imaging (EPI) readout was replaced with a segmented True-FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years +/- 9.9). RESULTS: Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET). CONCLUSION: Segmented True-FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI-based methods of ASL.