3D Reconstruction of Optic Nerve Heads

描述(申请人提供)：长期以来，高眼压(IOP)一直被认为是青光眼对视神经头(ONH)损害的原因之一。然而，眼压如何触发导致视网膜神经节细胞死亡的一连串事件仍不清楚。有研究认为，高眼压可1)对视神经头结缔组织和轴突施加直接机械张力，2)损害ONH的血液供应，导致ONH组织缺氧和随后的细胞死亡。利用ONH的三维重建和生物力学工程原理，我们研究了青光眼高眼压的力学效应。然而，高眼压的机械效应和血管效应之间的关系仍然不清楚。血管系统和缺血在疾病的发生和发展中起什么作用？ONH血流是否与IOP引起的ONH结缔组织变形有关？ONH结缔组织和血管系统的健壮性是了解个体青光眼易感性的关键吗？为了回答这些问题，需要确定眼压引起的ONH结缔组织变形与ONH血流量之间的关系的方法。我们建议开发一种系统，该系统构成了量化眼血流灌注的重要第一步，眼血流灌注是青光眼损害的重要危险因素。虽然还需要考虑许多其他变量，但在ONH的三维(3D)重建中分离、量化和建模共同定位的血管和结缔组织结构的能力将是ONH易感性研究的强大进步。在初步测试中，ONH结缔组织和视网膜血管分别由自发和获得性荧光显示。建议的系统将提供ONH的血管和结缔组织结构的同步、共定位、高分辨率的3D重建。我们还建议量化和关联分别在急性眼压为10和45 mm Hg的急性眼压下对侧眼的结缔组织变形、毛细血管通畅度和血管体积的局部变化。在建议的3D重建中，我们可以对耦合的结缔组织和血管系统进行几何量化和生物力学建模，以预测眼压引起的ONH血流变化。长期以来，眼压升高一直被认为是青光眼性视神经头损伤的原因，但眼压相关的结缔组织变形和视神经头血流之间的相互作用尚不清楚。我们建议开发一种系统，该系统将生成ONH的血管和结缔组织结构的同步、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高眼压的机械和血管效应。

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.