Ahmed El-Rafei

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 mm2 s−1; P < 0.05) and OR (0.79 ± 0.23 versus 0.62 ± 0.14·10−3 mm2 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 framework for voxel-based morphometric analysis of the optic radiation using diffusion tensor imaging in glaucoma.

Glaucoma is an optic neuropathy affecting the entire visual system. The understanding of the glaucoma mechanism and causes remains unresolved. Diffusion tensor imaging (DTI) has been used to analyze the optic nerve and optic radiation showing global fiber abnormalities associated with glaucoma. Nevertheless, the complex structure of the optic radiation and the limitations of DTI make the localization of the glaucoma effect a difficult task. The aim of this work is to establish a framework for the determination of the local changes of the optic radiation due to glaucoma using DTI. The proposed system utilizes a semiautomated algorithm to produce an efficient identification of the optic radiation. Segmented optic radiations are transformed to a unified space using shape-based nonrigid registration. Using the deformation fields that resulted from the registration, the maps of the diffusion tensor-derived parameters are transformed to the unified space. This allows for statistical voxel-wise analysis to produce significant abnormality maps. The proposed system is applied to a group of 13 glaucoma patients and a normal control group of 10 subjects. The groups are age matched to eliminate the age effect on the analysis. Diffusion-related parameters (axial, radial and mean diffusivities) and an anisotropy index (fractional anisotropy) are studied. The anisotropy analysis indicates that the majority of the significant voxels show decreased fractional anisotropy in the glaucoma patients compared with the control group. In addition, the significant regions are mainly distributed in the middle (in reference to anterior-posterior orientation) of the optic radiation. Glaucoma subjects have increased radial diffusivity and mean diffusivity significant voxels with a main concentration in the proximal part of the right optic radiation. The proposed analysis provides a framework to capture the significant local changes of the optic radiation due to glaucoma. The preliminary analysis suggests that the glaucomatous optic radiation may suffer from localized white matter degeneration. The framework facilitates further studies and understanding of the pathophysiology of glaucoma.

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.

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 patients 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.

Integrität/Demyelinisierung der Radiatio optica, Morphologie der Papille und Kontrastsensitivität bei Glaukompatienten.

BACKGROUND In primary open angle glaucoma (POAG) and its non-barotraumatic subgroup, normal tension glaucoma (NTG), the pathophysiological differences are not clear. A participation of the 4th neuron of the visual pathway (optic radiation) appears possible on the basis of related experimental studies. The goal of the present study was the evaluation of the optic radiation by diffusion tensor imaging (DTI), which is based on the magnetic resonance imaging. The diffusion and anisotropy parameters of the optic radiation as a marker of axonal integrity and demyelination/damage of glial cells, respectively, were used to investigate the relation between the morphology of the papilla (BLDF, linear discriminant function of Burk) and the contrast sensitivity (FDT, frequency doubling test). PATIENTS AND METHODS In this prospective observational study 13 POAG patients, 13 NTG patients, and 7 control patients of the same mean age were included. For segmentation of the optic radiation a semi-automated algorithm was applied and the diffusion and anisotropy parameters were calculated. The importance of the covariates age, BLDF, and FDT for the DTI parameters was determined using partial correlation analysis. RESULTS Analysis of the covariates partially showed a clear autocorrelation. The correlations between the DTI parameters and BLDF were significant in all groups after correction of the measurement values for the covariates. FDT correlated with DTI parameters in controls and POAG. The NTG group did not show this correlation due to a strong spreading of the FDT values. CONCLUSION After statistical elimination of the autocorrelation of the covariates age, BLDF, and FDT the morphology of the papilla correlated with the axonal integrity and demyelination/glia cell impairment of the optic radiation in controls and glaucoma. In NTG the impaired contrast sensitivity is highly variable and is not associated with the condition of the 3rd or 4th neuron, respectively, as compared to POAG. The autocorrelation between individual covariates represents an important element for the judgement of the visual pathway.

Automatic Segmentation of the Optic Radiation Using DTI in Healthy Subjects and Patients with Glaucoma

The complexity of the diffusion tensor imaging (DTI) data and the interpersonal variability of the brain fiber structure make the identification of the fibers a difficult and time consuming task. In this work, an automated segmentation system of the optic radiation using DTI is proposed. The system is applicable to normal subjects and glaucoma patients. It is intended to aid future glaucoma studies. The automation of the system is based on utilizing physiological and anatomical information to produce robust initial estimates of the optic radiation. The estimated optic radiation initializes a statistical level set framework. The optic radiation is segmented by the surface evolution of the level set function. The system is tested using eighteen DTI-datasets of glaucoma patients and normal subjects. The segmentation results were compared to the manual segmentation performed by a physician experienced in neuroimaging and found to be in agreement with the known anatomy with 83% accuracy. The automation eliminates the necessity of medical experts’ intervention and facilitates studies with large number of subjects.

Glaucoma classification based on histogram analysis of diffusion tensor imaging measures in the optic radiation

Glaucoma is associated with axonal degeneration of the optic nerve leading to visual impairment. This impairment can progress to a complete vision loss. The transsynaptic disease spread in glaucoma extends the degeneration process to different parts of the visual pathway. Most of glaucoma diagnosis focuses on the eye analysis, especially in the retina. In this work, we propose a system to classify glaucoma based on visual pathway analysis. The system utilizes diffusion tensor imaging to identify the optic radiation. Diffusion tensor-derived indices describing the underlying fiber structure as well as the main diffusion direction are used to characterize the optic radiation. Features are extracted from the histograms of these parameters in regions of interest defined on the optic radiation. A support vector machine classifier is used to rank the extracted features according to their discrimination ability between glaucoma patients and healthy subjects. The seven highest ranked features are used as inputs to a logistic regression classifier. The system is applied to two age-matched groups of 39 glaucoma subjects and 27 normal controls. The evaluation is performed using a 10-fold cross validation scheme. A classification accuracy of 81.8% is achieved with an area under the ROC curve of 0.85. The performance of the system is competitive to retina based classification systems. However, this work presents a new direction in detecting glaucoma using visual pathway analysis. This analysis is complementary to eye examinations and can result in improvements in glaucoma diagnosis, detection, and treatment.