Concha, L., Gross, D. W., Wheatley, B. M. & Beaulieu, C. Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients. Neuroimage 32, 1090-1099

Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
NeuroImage (Impact Factor: 6.36). 10/2006; 32(3):1090-9. DOI: 10.1016/j.neuroimage.2006.04.187
Source: PubMed


Axonal degeneration of white matter fibers is a key consequence of neuronal or axonal injury. It is characterized by a series of time-related events with initial axonal membrane collapse followed by myelin degradation being its major hallmarks. Standard imaging cannot differentiate these phenomena, which would be useful for clinical investigations of degeneration, regeneration and plasticity. Animal models suggest that diffusion tensor magnetic resonance imaging (DTI) is capable of making such distinction. The applicability of this technique in humans would permit inferences on white matter microanatomy using a non-invasive technique. The surgical bisection of the anterior 2/3 of the corpus callosum for the palliative treatment of certain types of epilepsy serves as a unique opportunity to assess this method in humans. DTI was performed on three epilepsy patients before corpus callosotomy and at two time points (1 week and 2-4 months) after surgery. Tractography was used to define voxels of interest for analysis of mean diffusivity, fractional anisotropy and eigenvalues. Diffusion anisotropy was reduced in a spatially dependent manner in the genu and body of the corpus callosum at 1 week and remained low 2-4 months after the surgery. Decreased anisotropy at 1 week was due to a reduction in parallel diffusivity (consistent with axonal fragmentation), whereas at 2-4 months, it was due to an increase in perpendicular diffusivity (consistent with myelin degradation). DTI is capable of non-invasively detecting, staging and following the microstructural degradation of white matter following axonal injury.

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Available from: Luis Concha
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    • "Age-related modifications for AD were less consistent (Bennett et al., 2010; Burzynska et al., 2010). The pattern of FA decrease/RD increase, also observed in pathological conditions such as multiple sclerosis (Roosendaal et al., 2009; Liu et al., 2012), certainly reflects demyelination process, whereas the pattern of FA decrease/AD decrease reflects axonal degeneration as observed in callosotomy condition (Concha et al., 2006). The aging brain is also characterized by the presence of White Matter Hyperintensities (WMH) observed on T2-weighted sequences. "
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    ABSTRACT: Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n=19, mean age=33 SD=7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n=20, mean age=78, SD= 3.2) and one presenting high-level-WMH (n=20, mean age=79, SD= 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e. Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA or RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter-dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes.
    Full-text · Article · Feb 2016 · Frontiers in Aging Neuroscience
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    • "Under this assumption, RD increases reflect demyelination [68], while changes in AD are more complex and time-dependent. Decreases in AD are thought to occur in response to acute axonal damage and inflammation [69]; conversely AD increases reflect expanded extra-cellular spaces resulting from Wallerian degeneration and other more gross atrophic processes [70] [71]. However, we would caution against the over-interpretation of instances where, for example , AD was significant and RD was not. "
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    ABSTRACT: Background: Huntington’s disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease’s characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum. Objective: To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period. Methods: In 48 early-stage HD patients and 36 controls from the multi-site PADDINGTON project, diffusion tensor imaging (DTI) was employed to measure changes in fractional anisotropy (FA) and axial (AD) and radial diffusivity (RD) in 24 white matter regions-of-interest (ROIs). Results: Cross-sectional analysis indicated widespread baseline between-group differences, with significantly decreased FA and increased AD and RD found in HD patients across multiple ROIs. Longitudinal rates of change differed significantly between HD patients and controls in the genu and body of corpus callosum, corona radiata and anterior limb of internal capsule. Change in RD in the body of the corpus callosum was significantly associated with baseline disease burden, but other clinical associations were not significant. Conclusions: We detected subtle longitudinal white matter changes in early HD patients. Progressive white matter abnormalities in HD may not be uniform throughout the brain, with some areas remaining static in the early symptomatic phase. Longer assessment periods across disease stages will help map this progressive trajectory.
    Full-text · Article · Dec 2015 · Journal of Huntington's disease
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    • "brain . Moreover , myelin abnormalities seem to be partially persistent in long - term abstinent alcohol - dependent patients . For example , Estilaei et al . ( 2001 ) showed a persistent phospholipid abnormality in the WM of alcoholics abstinent for 31 months . A decrease in AD is thought to reflect potential axonal injury ( Song et al . , 2003 ; Concha et al . , 2006 ) . Interestingly , we found that AD was also significantly higher in long - term abstinent alcohol - dependent patients than in healthy controls in the frontal , temporal and parietal WM . Changes in AD values are difficult to interpret because they depend in a complex way on the underlying tissue structure . One plausible explanation "
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    ABSTRACT: A number of diffusion tensor imaging (DTI) studies have reported substantial white matter (WM) abnormalities in alcohol-dependent patients. These studies were usually performed in recovering alcohol-dependent patients who had been abstinent for days to several weeks. The current study was designed to examine WM microstructure and decision-making in a sample of long-term abstinent alcohol-dependent patients. The study included 12 subjects with alcohol dependence who had been abstinent for at least 6 months before testing and scanning and 13 healthy control subjects. The Iowa Gambling Task (IGT) was used to measure decision-making. We found that the long-term abstinent alcohol-dependent group had significantly higher radial and axial diffusivity (RD and AD, respectively) values in frontal, temporal and parietal WM than was found in the healthy control group despite showing no difference in fractional anisotropy (FA) values in comparison to controls. In conclusion, we found widespread WM changes in long-term abstinent alcohol-dependent patients compared with healthy controls. Our findings suggested that AD and RD should be included in analyses of DTI data in addition to the more commonly studied FA. In the current study, FA values of the detoxified alcoholics had recovered and were comparable to those of the controls, whereas significant changes in AD and RD were still observed in some clusters in the frontal, parietal and temporal lobes of detoxified alcoholics even after 27.8 months.
    Full-text · Article · Oct 2014 · Psychiatry Research: Neuroimaging
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