Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.
22 April 2009 in Journal of Magnetic Resonance Imaging
Purpose: To evaluate the late effects of radiation‐induced damages in the rat brain by means of in vivo multiparametric MRI.Materials and Methods: The right hemibrains of seven Sprague‐Dawley rats were irradiated with a highly collimated 6 MV photon beam at a single dose of approximately 28 Gy. Diffusion tensor imaging (DTI), proton MR spectroscopy (1H‐MRS), T2‐weighted imaging, and T1‐weighted imaging were performed to the same animals 12 months after radiation treatment.Results: Compared with the contralateral side, a significantly higher percentage decrease in fractional anisotropy was observed in the ipsilateral fimbria of hippocampus (29%) than the external capsule (8%) in DTI, indicating the selective vulnerability of fimbria to radiation treatment. Furthermore, in1H‐MRS, significantly higher choline, glutamate, lactate, and taurine peaks by 24%, 25%, 87%, and 58%, respectively, were observed relative to creatine in the ipsilateral brain. Postmortem histology confirmed these white matter degradations as well as glial fibrillary acidic protein and glutamine synthetase immunoreactivity increase in the ipsilateral brain.Conclusion: The microstructural and metabolic changes in late radiation‐induced brain injuries were documented in vivo. These multiparametric MRI measurements may help understand the white matter changes and neurotoxicity upon radiation treatment in a single setting. J. Magn. Reson. Imaging 2009;29:1013–1020.