Evaluation of Delayed Neuronal and Axonal Damage Secondary to Moderate and Severe Traumatic Brain Injury Using Quantitative MR Imaging Techniques
Department of Radiology, Cancer Hospital of Barretos-Fundacao Pio XII, Barretos, Sao Paulo, Brazil. American Journal of Neuroradiology
(Impact Factor: 3.59).
02/2009; 30(5):947-52. DOI: 10.3174/ajnr.A1477
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.
Available from: Jeffrey A. Stanley
- "To establish a simple MRI measure to follow the disease progression, we measured the inter-caudate ratio for 52 individuals with PLP1 mutations , 16 of whom were less than 6 years of age. We chose to measure the inter-caudate ratio (ICR), since it has been validated as a surrogate marker of brain atrophy in multiple sclerosis, traumatic brain injury and evaluating cognitive decline in Alzheimers disease     . A major advantage of measuring the ICR is that it can be performed quickly without the requirement of special training to operate computer-based software programs, and for MRI scans from heterogeneous protocols. "
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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 · 2.47 Impact Factor
Available from: David J Poulsen
- "Extensive axonal degeneration is the common result of traumatic brain injury , . Injury, however, inversely induces axonal sprouting , , and new synaptic connections and myelination are present in both injured and neighboring regions . "
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ABSTRACT: We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day prior to TBI, and at 1 and 3 days post TBI, and then weekly for 6 weeks. The lesion volumes of TBI damaged cerebral tissue were demarcated by elevated values in T2 maps and were histologically identified by hematoxylin and eosin (H&E) staining. The fractional anisotropy (FA) values within regions-of-interest (ROI) were measured in FA maps deduced from DTI, and were directly compared with Bielschowsky's silver and Luxol fast blue (BLFB) immunohistological staining. No therapeutic effect on lesion volumes was detected during 6 weeks after TBI. However, treatment significantly increased FA values in the recovery ROI compared with the control group at 5 and 6 weeks after TBI. Myelinated axons histologically measured using BLFB were significantly increased (p<0.001) in the treated group (25.84±1.41%) compared with the control group (17.05±2.95%). Significant correlations were detected between FA and BLFB measures in the recovery ROI (R = 0.54, p<0.02). Methamphetamine treatment significantly reduced modified neurological severity scores from 2 to 6 weeks (p<0.05) and foot-fault errors from 3 days to 6 weeks (p<0.05) after TBI. Thus, the FA data suggest that methamphetamine treatment improves white matter reorganization from 5 to 6 weeks after TBI in rats compared with saline treatment, which may contribute to the observed functional recovery.
PLoS ONE 04/2013; 8(4):e61241. DOI:10.1371/journal.pone.0061241 · 3.23 Impact Factor
Available from: Jiachen Zhuo
- "Axial diffusivity is believed to be sensitive to axonal integrity and radial diffusivity reflects myelin integrity (Song et al., 2002, 2003). Previous TBI studies on both humans and animals have shown altered MD (Alsop et al., 1996; Huisman et al., 2003; Liu et al., 1999; Mamere et al., 2009), and FA in white matter regions (Arfanakis et al., 2002; Bazarian et al., 2007; Huisman et al., 2004; Mac Donald et al., 2007a,b; Mayer et al., 2010; Wilde et al., 2006; Wozniak et al., 2007) anywhere from 24 h to several days after injury. "
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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 · 3.71 Impact Factor
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