Abstract

The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0–40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

Highlights

  • The sclera and cornea are dense and fibrous connective tissues that form the outer coat of the eye, which act to support and protect the eye from the surrounding environments

  • Our group demonstrated the use of the magic-angle enhancement effect to improve Magnetic resonance imaging (MRI) sensitivity for detecting the structural details of the collagen-rich sclera and cornea tissues, and their changes in T2 and T2* transverse relaxation times in tissues fixed at various levels of IOP25

  • Effects of dynamic intraocular pressures (IOP) changes on corneoscleral tissues by ex vivo T2 magnetic resonance relaxometry

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Summary

Introduction

The sclera and cornea are dense and fibrous connective tissues that form the outer coat of the eye, which act to support and protect the eye from the surrounding environments. The corneoscleral shell structure has been studied extensively using atomic force[14], transmission[15] and scanning electron microscopies[16], polarized light[5], bright field[10] and nonlinear microscopies[17], as well as small-angle light scattering[18] and small and wide-angle x-ray scattering[19,20,21,22] These ex vivo imaging techniques have provided fundamental information on the microarchitecture and biochemistry of the tissue microstructures and collagen across ocular tissues with excellent resolution and sensitivity[7], most of these techniques require chemical tissue processing or tissue sectioning, which is highly invasive and can be destructive or affect the true morphology of the collagen (e.g. substantial tissue shrinkage during preparation for histological labeling). We tested the feasibility and sensitivity of T2-weighted MRI, DTI and MTI profiling to assess the treatment effects of cross-linking and glycosaminoglycan depletion on the sclera and cornea with different concentrations of glyceraldehyde and chondroitinase-ABC solutions, respectively

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