3D Reconstruction of Optic Nerve Heads

描述（由申请人提供）：眼压升高（IOP）一直被认为是造成视神经头（ONH）青光眼损害的原因。然而，目前尚不清楚IOP是如何引发导致视网膜神经节细胞死亡的一系列事件的。有研究认为，IOP升高可对视神经头的结缔组织和轴突产生直接的机械应变，损害ONH的血液供应，导致ONH组织缺氧，导致细胞死亡。我们利用ONH的三维重建和生物力学工程原理，研究了青光眼IOP升高的力学效应。然而，IOP升高的机械效应和血管效应之间的关系尚不清楚。脉管系统和缺血在疾病发生发展中的作用是什么？ONH血流量与io诱导的ONH结缔组织变形有关吗？ONH结缔组织和脉管系统的健壮性是了解个体对青光眼易感性的关键吗？为了回答这些问题，我们需要一种方法来确定io诱导的ONH结缔组织变形与ONH血流之间的关系。我们建议开发一个系统，构成量化眼灌注的重要第一步，这是青光眼损伤的重要危险因素。虽然需要考虑许多其他变量，但在ONH的三维（3D）重建中分离，量化和模拟共定位血管和结缔组织结构的能力将是ONH易感性研究的有力进展。在初步测试中，ONH结缔组织和视网膜血管分别通过自发荧光和获得荧光显示。该系统将提供ONH血管和结缔组织结构的同步、共定位、高分辨率3D重建。我们还建议量化并关联对侧眼在急性IOPs分别为10和45 mm Hg时结缔组织变形、毛细血管通畅和血管体积的区域变化。在提出的3D重建中，我们可以对耦合结缔组织和血管系统进行几何量化和生物力学建模，以预测iopo诱导的ONH血流变化。长期以来，人们一直认为眼压升高在青光眼视神经头损伤（ONH）中起着致病作用，但眼压相关结缔组织变形与ONH血流之间的相互作用尚不清楚。我们建议开发一个系统，该系统将生成ONH的血管和结缔组织结构的同时，共定位，高分辨率，三维（3D）重建。利用这些ONH的三维重建和生物力学工程原理，我们可以模拟青光眼IOP升高的力学和血管效应。

DESCRIPTION (provided by applicant): Elevated intraocular pressure (IOP) has long been assumed to play a causative role in glaucomatous damage to the optic nerve head (ONH). It is still unclear, however, how IOP triggers the cascade of events that lead to retinal ganglion cell death. It has been proposed that the elevated IOP can 1) exert a direct mechanical strain on the connective tissues and axons in the optic nerve head, and 2) impair the blood supply to the ONH, resulting in hypoxia of the ONH tissues and subsequent cell death. Using three-dimensional (3D) reconstructions of the ONH, and principles of biomechanical engineering, we have studied the mechanical effects of elevated IOP in glaucoma. However, the relationship between the mechanical and vascular effects of elevated IOP is still unclear. What is the role of the vasculature and ischemia in the development and progression of the disease? Is ONH blood flow related to IOP-induced deformation of the ONH connective tissues? Are the robustness of the ONH connective tissues and the vasculature the key to understanding individual susceptibility to glaucoma? To answer these questions, methods for determining the relationship between IOP-induced deformation of ONH connective tissues and ONH blood flow are needed. We propose to develop a system that constitutes the essential first step in quantifying ocular perfusion, an important risk factor for glaucomatous damage. While many additional variables will need to be considered, the ability to isolate, quantify, and model co-localized vascular and connective tissue structures within three- dimensional (3D) reconstructions of the ONH will be a powerful advance in studies of ONH susceptibility. In a preliminary test, both the ONH connective tissue and retinal vasculature were revealed by spontaneous and acquired fluorescence, respectively. The proposed system will provide simultaneous, co-localized, high- resolution, 3D reconstructions of the vascular and connective tissue structures of the ONH. We also propose to quantify and correlate the regional changes in connective tissue deformation, capillary patency, and vascular volume in contralateral eyes perfusion-fixed at acute IOPs of 10 and 45 mm Hg, respectively. Within the proposed 3D reconstructions, we can perform geometric quantification and biomechanical modeling of the coupled connective tissue and vascular systems to predict IOP-induced changes in ONH blood flow. Elevated intraocular pressure (IOP) has long been assumed to play a causative role in glaucomatous damage to the optic nerve head (ONH), but the interplay between IOP-related connective tissue deformation and ONH blood flow is unclear. We propose to develop a system that will generate simultaneous, co-localized, high- resolution, three-dimensional (3D) reconstructions of the vascular and connective tissue structures of the ONH. Using these 3D reconstructions of the ONH and principles of biomechanical engineering, we can model the mechanical and vascular effects of elevated IOP in glaucoma.