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Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

Scott G, Hellyer PJ, Ramlackhansingh AF, Brooks DJ, Matthews PM, Sharp DJ - J Neuroinflammation (2015)

Bottom Line: Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.These findings support a link between axonal damage and persistent inflammation after brain injury.

View Article: PubMed Central - PubMed

Affiliation: Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK.

ABSTRACT

Background: Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.

Findings: Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.

Conclusions: These findings support a link between axonal damage and persistent inflammation after brain injury.

No MeSH data available.


Related in: MedlinePlus

Increased thalamic microglial activation and white matter damage in TBI. a Statistical parametric maps (reproduced from [3]) rendered onto a standard T1 MRI image showing areas of significantly increased [11C]-PK11195 (PK) binding potentials (BP) in the TBI patients relative to controls. Bilateral increases in PK binding are seen in thalami. t values are shown. Voxels are shown significantly surpassing the voxel-wise threshold (p < 0.001) and the spatial extent threshold (10 voxels). Voxel-wise contrasts were performed on spatially normalised PK BP images, smoothed with a 12-mm full-width at half maximum (FWHM) Gaussian kernel, using SPM5 (see [3] for details). b PK BP in the thalamus and cortical grey matter, defined using anatomical regions of interest, in TBI patients (red) and controls. Group mean ± standard error of the mean (SEM) is shown; ***p < 0.001. c Tract mask (blue) connecting the left thalamus (red) to the left anterior cingulate cortex (ACC) (green), produced using probabilistic tractography in healthy controls (see [12]). Fractional anisotropy (FA) was sampled using bilateral thalamo-cortical tract masks. d FA in thalamo-cortical (Thal-Ctx) body of the corpus callosum (CC) and across the white matter skeleton (Skel) in TBI patients (red) and controls; **p < 0.01
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Fig1: Increased thalamic microglial activation and white matter damage in TBI. a Statistical parametric maps (reproduced from [3]) rendered onto a standard T1 MRI image showing areas of significantly increased [11C]-PK11195 (PK) binding potentials (BP) in the TBI patients relative to controls. Bilateral increases in PK binding are seen in thalami. t values are shown. Voxels are shown significantly surpassing the voxel-wise threshold (p < 0.001) and the spatial extent threshold (10 voxels). Voxel-wise contrasts were performed on spatially normalised PK BP images, smoothed with a 12-mm full-width at half maximum (FWHM) Gaussian kernel, using SPM5 (see [3] for details). b PK BP in the thalamus and cortical grey matter, defined using anatomical regions of interest, in TBI patients (red) and controls. Group mean ± standard error of the mean (SEM) is shown; ***p < 0.001. c Tract mask (blue) connecting the left thalamus (red) to the left anterior cingulate cortex (ACC) (green), produced using probabilistic tractography in healthy controls (see [12]). Fractional anisotropy (FA) was sampled using bilateral thalamo-cortical tract masks. d FA in thalamo-cortical (Thal-Ctx) body of the corpus callosum (CC) and across the white matter skeleton (Skel) in TBI patients (red) and controls; **p < 0.01

Mentions: Standard MRI T1 and DTI protocols were used (see [3]). For DTI analysis, we used a method for assessing thalamo-cortical white matter connections that is robust to the presence of TAI [12]. We combined ten thalamo-cortical tracts, previously defined in healthy controls using probabilistic tractography, into a single region of interest (ROI) (see Fig. 1c for example of one tract, and [12]). A mask of cortico-cortical tracts through the body of the corpus callosum was used as a control (from [13]), since these tracts were not connected to the thalamus. Voxel-wise maps of fractional anisotropy (FA), a measure of directionality of water flow along white matter tracts and hence their integrity, were calculated, and FA maps were skeletonised [14], leaving the central section of tracts, to minimise partial volume effects (see [12]). We calculated the mean FA of voxels within the ROIs and of all voxels in the skeleton. The B0 data for one patient contained an image artefact, so their DTI data were excluded.Fig. 1


Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

Scott G, Hellyer PJ, Ramlackhansingh AF, Brooks DJ, Matthews PM, Sharp DJ - J Neuroinflammation (2015)

Increased thalamic microglial activation and white matter damage in TBI. a Statistical parametric maps (reproduced from [3]) rendered onto a standard T1 MRI image showing areas of significantly increased [11C]-PK11195 (PK) binding potentials (BP) in the TBI patients relative to controls. Bilateral increases in PK binding are seen in thalami. t values are shown. Voxels are shown significantly surpassing the voxel-wise threshold (p < 0.001) and the spatial extent threshold (10 voxels). Voxel-wise contrasts were performed on spatially normalised PK BP images, smoothed with a 12-mm full-width at half maximum (FWHM) Gaussian kernel, using SPM5 (see [3] for details). b PK BP in the thalamus and cortical grey matter, defined using anatomical regions of interest, in TBI patients (red) and controls. Group mean ± standard error of the mean (SEM) is shown; ***p < 0.001. c Tract mask (blue) connecting the left thalamus (red) to the left anterior cingulate cortex (ACC) (green), produced using probabilistic tractography in healthy controls (see [12]). Fractional anisotropy (FA) was sampled using bilateral thalamo-cortical tract masks. d FA in thalamo-cortical (Thal-Ctx) body of the corpus callosum (CC) and across the white matter skeleton (Skel) in TBI patients (red) and controls; **p < 0.01
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Fig1: Increased thalamic microglial activation and white matter damage in TBI. a Statistical parametric maps (reproduced from [3]) rendered onto a standard T1 MRI image showing areas of significantly increased [11C]-PK11195 (PK) binding potentials (BP) in the TBI patients relative to controls. Bilateral increases in PK binding are seen in thalami. t values are shown. Voxels are shown significantly surpassing the voxel-wise threshold (p < 0.001) and the spatial extent threshold (10 voxels). Voxel-wise contrasts were performed on spatially normalised PK BP images, smoothed with a 12-mm full-width at half maximum (FWHM) Gaussian kernel, using SPM5 (see [3] for details). b PK BP in the thalamus and cortical grey matter, defined using anatomical regions of interest, in TBI patients (red) and controls. Group mean ± standard error of the mean (SEM) is shown; ***p < 0.001. c Tract mask (blue) connecting the left thalamus (red) to the left anterior cingulate cortex (ACC) (green), produced using probabilistic tractography in healthy controls (see [12]). Fractional anisotropy (FA) was sampled using bilateral thalamo-cortical tract masks. d FA in thalamo-cortical (Thal-Ctx) body of the corpus callosum (CC) and across the white matter skeleton (Skel) in TBI patients (red) and controls; **p < 0.01
Mentions: Standard MRI T1 and DTI protocols were used (see [3]). For DTI analysis, we used a method for assessing thalamo-cortical white matter connections that is robust to the presence of TAI [12]. We combined ten thalamo-cortical tracts, previously defined in healthy controls using probabilistic tractography, into a single region of interest (ROI) (see Fig. 1c for example of one tract, and [12]). A mask of cortico-cortical tracts through the body of the corpus callosum was used as a control (from [13]), since these tracts were not connected to the thalamus. Voxel-wise maps of fractional anisotropy (FA), a measure of directionality of water flow along white matter tracts and hence their integrity, were calculated, and FA maps were skeletonised [14], leaving the central section of tracts, to minimise partial volume effects (see [12]). We calculated the mean FA of voxels within the ROIs and of all voxels in the skeleton. The B0 data for one patient contained an image artefact, so their DTI data were excluded.Fig. 1

Bottom Line: Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.These findings support a link between axonal damage and persistent inflammation after brain injury.

View Article: PubMed Central - PubMed

Affiliation: Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK.

ABSTRACT

Background: Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.

Findings: Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.

Conclusions: These findings support a link between axonal damage and persistent inflammation after brain injury.

No MeSH data available.


Related in: MedlinePlus