Cerebral microinfarcts in primary open-angle glaucoma correlated with DTI-derived integrity of optic radiation.

PURPOSE: To evaluate the correlation between the extent of cerebral white matter lesions (WMLs) and the integrity of the visual pathway represented by fractional anisotropy (FA) in patients with primary open-angle glaucoma (POAG). METHODS: This case-control study included a total of 61 German patients (39 POAG patients, 22 controls) matched for age and sex. Fractional anisotropy of the optic radiation was determined by 3-Tesla diffusion tensor imaging. White matter lesions and brain volumes were manually measured by using a T2-weighted, 3-D fluid-attenuated inversion recovery sequence. RESULTS: In POAG patients WML volumes were significantly (P = 0.04) increased in the subcortical area. This applied for both absolute and relative units to the specific patient's brain volume, compared to controls. The WML volumes were significantly (P = 0.003) greater in middle-aged (40-59 years) POAG patients than control patients. In controls there was a significant age correlation of WML volumes in the total brain, subcortical, and optic radiation regions of interest. There was a significant correlation between FA and WML in POAG regarding the total brain, the periventricular region, and the optic radiation in both hemispheres. In POAG, FA left and right optic radiation correlated significantly with age (P = 0.002). CONCLUSIONS: We were able to demonstrate that (1) POAG patients aged 40 to 60 years had higher volumes of cerebral microinfarcts and (2) POAG patients showed a significant correlation between cerebral microinfarcts and degeneration of the optic radiation. This indicates that cerebral microinfarcts might be an intracerebral risk factor for glaucomatous optic nerve atrophy.

Changes of radial diffusivity and fractional anisotropy in the optic nerve and optic radiation of glaucoma patients.

Purpose of this study was to evaluate with diffusion-tensor imaging (DTI) changes of radial diffusivity (RD) and fractional anisotropy (FA) in the optic nerve (ON) and optic radiation (OR) in glaucoma and to determine whether changes in RD and FA correlate with disease severity. Therefore, glaucoma patients and controls were examined using 3T. Regions of interest were positioned on RD and FA maps, and mean values were calculated for ON and OR and correlated with optic nerve atrophy and reduced spatial-temporal contrast sensitivity (STCS) of the retina. We found, that RD in glaucoma patients was significantly higher in the ON (0.74 ± 0.21 versus 0.58 ± 0.17·10(-3) mm(2) s(-1); P < 0.05) and OR (0.79 ± 0.23 versus 0.62 ± 0.14·10(-3) mm(2) s(-1); P < 0.05) compared to controls. Aside, FA was significantly decreased (0.48 ± 0.15 versus 0.66 ± 0.12 and 0.50 ± 0.20 versus 0.66 ± 0.11; P < 0.05). Hereby, correlation between changes in RD/FA and optic nerve atrophy/STCS was observed (r > 0.77). In conclusion, DTI at 3 Tesla allows robust RD and FA measurements in the ON and OR. Hereby, the extent of RD increase and FA decrease in glaucoma correlate with established ophthalmological examinations.

A new approach to assess intracranial white matter abnormalities in glaucoma patients: changes of fractional anisotropy detected by 3T diffusion tensor imaging.

RATIONALE AND OBJECTIVES: The aims of this study was to evaluate, using 3-T diffusion tensor imaging, changes of fractional anisotropy (FA) in the orbital and intracranial part of the optic nerve (ON), the optic chiasm, the lateral geniculate nucleus, and different parts of the optic radiation (OR) in patients with glaucoma compared to controls and to determine whether FA correlates with disease severity. MATERIALS AND METHODS: Twenty patients with glaucoma and 22 age-matched controls were examined using 3-T diffusion tensor imaging. Regions of interest were positioned on the FA maps, and mean values were calculated for each ON, optic chiasm, lateral geniculate nucleus, and OR. Results were compared to those from controls and correlated with ON atrophy and reduced spatial-temporal contrast sensitivity of the retina. RESULTS: Compared to controls, FA in patients with glaucoma was significantly lower in the intracranial part of the ON (0.48 ± 0.15 vs 0.66 ± 0.12, P < .05) and in the OR (0.40 ± 0.16 to 0.48 ± 0.17 vs 0.53 ± 0.20 to 0.64 ± 0.11, P < .05). A high correlation between reduced FA in the intracranial ON and OR and ON atrophy and spatial-temporal contrast sensitivity of the retina was observed (r > 0.81). Otherwise, there was no significant difference in FA between patients with glaucoma and controls measured in the orbital part of the ON, optic chiasm, and lateral geniculate nucleus. CONCLUSIONS: Diffusion tensor imaging at 3 T allows robust FA measurements in the intracranial part of the ON and the OR. FA is significantly reduced in patients with glaucoma compared to controls, with a good correlation with established ophthalmologic examinations.

Diffusion tensor imaging detects rarefaction of optic radiation in glaucoma patients.

RATIONALE AND OBJECTIVES: Diffusion tensor imaging (DTI) can depict rarefaction of the optical fibres. Hence, we applied DTI to assess pathological changes of the optic radiation in glaucoma patients. MATERIALS AND METHODS: Fifty glaucoma patients and 50 healthy age-matched controls were examined by a 3T high-field magnetic resonance scanner. Fiber tracts were volume rendered using a semiquantitative approach to assess rarefaction and results were correlated with the extent of optic nerve atrophy and reduced spatial-temporal contrast sensitivity of the retina using established ophthalmological examinations. RESULTS: Twenty-two glaucoma patients (44%) showed significant rarefaction of the optic radiation: the volume was reduced to 67 ± 16% compared with controls. Hereby, the glaucomatous optic nerve atrophy stage correlated with the presence of DTI-derived rarefied optic radiation (Kendall tau-b 0.272, P = .016). Aside, cerebral microangiopathy affecting the optic radiation was significantly higher among glaucoma patients compared to controls (10 patients compared with 2 patients, P < .05). CONCLUSION: In patients with glaucomatous optic nerve atrophy, there is anterograde and-most likely because of microangiopathic lesions within the optic radiation-retrograde transneuronal rarefaction of the optic radiation that can be assessed in vivo using DTI with good correlation to established ophthalmological examinations.

Diffusion tensor imaging for in vivo detection of degenerated optic radiation.

Glaucomatous optic nerve atrophy may continue to the linked optic radiation by transneuronal degeneration, as described in animal models of glaucoma. In vivo visualization of the visual pathway represents a new challenge in the field of ophthalmology. We present a new approach for illustration of the optic radiation by diffusion tensor imaging (DTI) based on magnetic resonance imaging (MRI). The DTI was established by use of a 3T high-field scanner. The case of a patient with primary open-angle glaucoma is opposed to this one of a healthy subject to demonstrate the visible rarefication of the optic radiation. The goal was to introduce the technique of the DTI also in ophthalmology and to demonstrate that it may be useful to judge glaucoma-related differences.

Excessive transcription of the human serum and glucocorticoid dependent kinase hSGK1 in lung fibrosis.

The excessive matrix deposition in lung fibrosis is thought to be due to enhanced formation and activity of TGFbeta1, which stimulates synthesis and inhibits degradation of matrix proteins. The cellular mechanisms triggered by TGFbeta1 are still incompletely understood. Recently, a novel transcriptional target of TGFbeta1 has been identified, i.e. the human serum and glucocorticoid dependent kinase hSGK1. The present study has been performed to explore whether TGFbeta1 stimulates hSGK1 transcription in lung fibroblasts and whether lung fibrosis is associated with enhanced hSGK1 expression. As evident from Northern Blotting, TGFbeta1 strongly upregulates hSGK1 in human lung fibroblasts, an effect partially reversed by p38-kinase inhibitor SB203580. In situ hybridization experiments reveal that in intact lung tissue hSGK1 is expressed in single type II alveolar pneumocytes and macrophages. In contrast, in fibrotic lung tissue a dramatic upregulation of hSGK1 mRNA as well as a strong expression of hSGK1 protein is observed in epithelial cells and interstitial cells comprising macrophages and fibroblasts. In conclusion, in lung fibrosis, the serine/threonine kinase hSGK1 is upregulated, an effect at least partially accounted for by TGFbeta1. The full effect of TGFbeta1 requires the activation of p38 kinase.