Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques
ABSTRACT Traumatic brain injury (TBI) is a classic model of monophasic neuronal and axonal injury, in which tissue damage mainly occurs at the moment of trauma. There is some evidence of delayed progression of the neuronal and axonal loss. Our purpose was to test the hypothesis that quantitative MR imaging techniques can estimate the biologic changes secondary to delayed neuronal and axonal loss after TBI.
Nine patients (age, 11-28 years; 5 male) who sustained a moderate or severe TBI were evaluated at a mean of 3.1 years after trauma. We applied the following techniques: bicaudate (BCR) and bifrontal (BFR) ventricle-to-brain ratios; T2 relaxometry; magnetization transfer ratio (MTR); apparent diffusion coefficient (ADC); and proton spectroscopy, by using an N-acetylaspartate/creatine (NAA/Cr) ratio measured in normal-appearing white matter (NAWM) and the corpus callosum (CC). The results were compared with those of a control group.
BCR and BFR mean values were significantly increased (P < or = .05) in patients due to secondary subcortical atrophy; increased T2 relaxation time was observed in the NAWM and CC, reflecting an increase in water concentration secondary to axonal loss. Increased ADC mean values and reduced MTR mean values were found in the NAWM and CC, showing damage in the myelinated axonal fibers; and decreased NAA/Cr ratio mean values were found in the CC, indicating axonal loss.
These quantitative MR imaging techniques could noninvasively demonstrate the neuronal and axonal damage in the NAWM and CC of human brains, secondary to moderate or severe TBI.
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ABSTRACT: To determine whether quantitative measure of magnetic resonance imaging data from patients with the inherited leukodystrophy, Pelizaeus-Merzbacher disease (PMD) correlates with clinical severity or progression. In our current work we have analyzed the clinical phenotypes and MRI scans of 51 male patients with PMD and 10 female carriers for whom the PLP1 genotype had been determined. In addition, we developed a 32-point functional disability scoring (FDS) system for PMD, and validated it for inter-rater reliability. Using conventional T1- and T2-weighted MRI images of the whole brain, we measured white matter and total brain volume (WMV and TBV), inter-caudate ratio (ICR), and corpus callosum area. There was a significant positive correlation of FDS with white matter fraction (WMV/TBV) and corpus callosum area. Also, when applying a median split based on FDS, patients with lower FDS showed reduced white matter fraction and corpus callosum area, and increased ICR compared to patients with relatively higher FDS, regardless of age. Although this patient population is heterogeneous, with multiple genetic and molecular mechanisms causing PMD, these data imply that white matter atrophy is a major pathological determinant of the clinical disability in most patients. Development of reliable non-invasive quantitative biomarkers of disease activity would be useful not only for following the natural history of the disease, but also raising the potential for evaluating future therapies.Journal of the neurological sciences 08/2013; 335(1-2). DOI:10.1016/j.jns.2013.08.030 · 2.26 Impact Factor
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ABSTRACT: Understanding tissue alterations at an early stage following traumatic brain injury (TBI) is critical for injury management and limiting severe consequences from secondary injury. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) at 2 and 4 h following a controlled cortical impact injury in the rat brain using a 7.0 Tesla animal MRI system and compared profiles to baseline. Significant decrease in mean diffusivity (MD) and increased fractional anisotropy (FA) was found near the impact site (hippocampus and bilateral thalamus; p<0.05) immediately following TBI, suggesting cytotoxic edema. Although the DTI parameters largely normalized on the contralateral side by 4 h, a large inter-individual variation was observed with a trend towards recovery of MD and FA in the ipsilateral hippocampus and a sustained elevation of FA in the ipsilateral thalamus (p<0.05). Significant reduction in metabolite to total creatine ratios of N-acetylaspartate (NAA, p=0.0002), glutamate (p=0.0006), myo-inositol (Ins, p=0.04), phosphocholine and glycerophosphocholine (PCh+GPC, p=0.03), and taurine (Tau, p=0.009) were observed ipsilateral to the injury as early as 2 h, while glutamine concentration increased marginally (p=0.07). These metabolic alterations remained sustained over 4 h after TBI. Significant reductions of Ins (p=0.024) and Tau (p=0.013) and marginal reduction of NAA (p=0.06) were also observed on the contralateral side at 4 h after TBI. Overall our findings suggest significant microstructural and metabolic alterations as early as 2 h following injury. The tendency towards normalization at 4 h from the DTI data and no further metabolic changes at 4 h from MRS suggest an optimal temporal window of about 3 h for interventions that might limit secondary damage to the brain. Results indicate that early assessment of TBI patients using DTI and MRS may provide valuable information on the available treatment window to limit secondary brain damage.Journal of neurotrauma 07/2011; 28(10):2091-102. DOI:10.1089/neu.2010.1739 · 3.97 Impact Factor
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ABSTRACT: The neuropathological hallmark of Parkinson's disease is the loss of dopaminergic neurons in the pars compacta of the substantia nigra (SNc). The degenerative process starts unilaterally and spreads to the dopaminergic system of both hemispheres. However, the complete characterization of the nigra lesion and the subsequent changes in basal ganglia nuclei activity has not yet been achieved in vivo. The aim of this study was to characterize the time course of the nigral lesion in vivo, using longitudinal T2 relaxometry and diffusion tensor imaging, and the changes in basal ganglia nuclei activity, using manganese-enhanced magnetic resonance imaging, in 6-hydroxydopamine (6-OHDA)-lesioned rats. Our results showed that a unilateral SNc lesion induces bilateral alterations, as indicated by the enhancement of magnetic resonance imaging T2 relaxation times in both the ipsilateral and contralateral SNc. Moreover, axial and radial diffusivities demonstrated bilateral changes at 3 and 14 days after 6-OHDA injection in the pars reticulata of the substantia nigra and cortex, respectively, in comparison to the sham group, suggesting bilateral microstructural alterations in these regions. Unexpectedly, manganese-enhanced magnetic resonance imaging showed decreased axonal transport from the ipsilateral subthalamic nucleus to the ventral pallidum in 6-OHDA-lesioned animals compared with the sham group. These findings demonstrate, for the first time in vivo, the temporal pattern of bilateral alteration induced by the 6-OHDA model of Parkinson's disease, and indicate decreased axonal transport in the ipsilateral hemisphere.European Journal of Neuroscience 03/2011; 33(8):1551-60. DOI:10.1111/j.1460-9568.2011.07639.x · 3.67 Impact Factor