Multimodal MRI investigation of eye and visual brain

Abstract

Although the eyes are physically isolated from the visual brain, the physiology and integrity of the eye are central to several eye diseases and neurodegeneration in the visual brain. MRI provides non-invasive, longitudinal and multi-parametric assessments of the visual system without depth limitation. The objective of this doctoral work is to develop and apply multimodal MRI for the assessment of aqueous humor dynamics, ocular fibrous tissue and visual pathway integrity in the visual system. The functional response in neural systems were further explored with BOLD and diffusion fMRI. Firstly, dynamic Gd-MRI was applied to visualize and assess aqueous humor dynamics upon sustained intraocular pressure elevation and pharmacological interventions. The results reflect the reduced gadolinium clearance upon microbead occlusion and respective drug actions after ocular hypotensive drug treatment. Abnormal gadolinium leakage into the vitreous was found in compromised aqueous-vitreous or blood-ocular barrier integrity. Gd-MRI allows spatiotemporal and quantitative evaluation of altered aqueous humor dynamics and ocular tissue permeability. Secondly, MAMRI was employed to reveal the structural details of the corneoscleral shell and their changes upon intraocular pressure elevation. At magic angle, high-resolution MRI revealed distinct scleral and corneal lamellar fibers, and collagen fiber crimps. Loaded sclera and cornea possessed significantly higher T2 and T2* than unloaded tissues at magic angle, suggestive of the changes in collagen fiber crimp and alignment. MAMRI can detect ocular fibrous microstructures without contrast agents, and can reveal their MR tissue property changes with IOP loading. Thirdly, multimodal MRI was utilized to investigate the effects of biomechanical or biochemical modulation on the sclera and cornea tissues. T2 in corneoscleral shell increased non-linearly with IOP loading and remained longer than unloaded tissues after being unpressurized. Biomechanical loading increased fractional anisotropy in the corneoscleral shell, while increasing glyceraldehyde and chondroitinase-ABC concentrations decreased diffusivities and increased magnetization transfer in cornea. Glyceraldehyde also increased magnetization transfer in sclera. The changes in MRI contrast mechanisms upon various modulation of the eye provide insight to the pathophysiological mechanisms in the corneoscleral shell and the efficacy of corneoscleral treatments. Fourthly, the effects of excitotoxic retinal injury on the retinal thickness, microstructual integrity and anterograde transport was evaluated in vivo by DTI, MEMRI and OCT. Directional diffusivities in the visual pathway and their correlations with retinal thickness suggested anterograde axonal degeneration and delayed demyelination along the visual pathway. The splenium of corpus callosum was reorganized at 4 weeks post injury. Furthermore, the NMDA-injured visual pathway showed reduced anterograde manganese transport. These results characterized the spatiotemporal changes in white matter integrity, the eye-brain relationships and structural-physiological relationships in the visual system. Lastly, BOLD and diffusion fMRI were used to explore the functional responses of neural systems. The efficacy of using unisensory stimuli to elicit cross-modal activation was examined by BOLD fMRI improving the understanding to cortical cross-modal activity and its influences on the sub-cortex. Kurtosis model, which describes the non-Gaussian diffusion in restricted media, was applied to diffusion fMRI for the first time to characterize non-Gaussian diffusion changes during neural activation.