Biomechanical mapping of the optic nerve head and peripapillary sclera using high frequency ultrasonic elastography

阿尔茨海默氏病（AD）在美国折磨着650万人，在全世界折磨着1500万人， 给社会带来经济负担。然而，目前还没有治愈AD的方法，迫切需要识别AD 在出现认知症状/不可逆的病理变化之前，从而允许早期干预， 延缓疾病的发生和发展。脑血管功能障碍是最早的病理性 与AD发病机制有关的变化和早期AD诊断的潜在标志物，但评估 人脑血管网络功能的改变受到高成本、低可用性和低灵敏度的限制。 研究表明，许多AD病理也发生在视网膜和眼后部，包括Aβ 沉积和微血管功能障碍。视网膜和脑微血管系统具有相似的结构和功能。 生理特性，并且可以直接通过OCTA成像。事实上，AD视网膜中的血管功能障碍 在AD患者中检测到，包括毛细血管密度降低，血流量减少和周细胞丢失，类似于 AD的脑血管改变。然而，在很大程度上仍不清楚ONH和椎板后 与脑部变化相连的微血管与其他AD病理变化相关，因为OCTA不能 穿透视网膜背面本提案的目标是使用高频超声血流图像来填充这些 通过检查AD小鼠ONH和层后微血管的纵向变化来了解知识差距。 有两个目的：Aim 1将检查血管功能的时间变化，包括血流、毛细血管 密度和周细胞损失的不同病理阶段的AD小鼠（5XFAD）;目的 2将确定微血管改变和沉积之间的关系，在大脑和背部， 眼、血脑屏障破坏和行为改变。

Alzheimer's disease (AD) afflicts 6.5 million individuals in US and 15 million worldwide and elicits a huge economic burden to the society. However, there is no cure for AD and there is an urgent need to identify AD before occurrence of cognitive symptoms/irreversible pathological changes, thus allowing early interventions to delay the onset and progression of the disease. Cerebral vascular dysfunction is among the earliest pathological changes implicated in AD pathogenesis and a potential marker for early AD diagnosis, but the evaluation of the alterations in human cerebral vascular network function is limited by high cost, and low availability and sensitivity. Studies have demonstrated that many AD pathologies also occur in retina and back of eye, including Aβ deposition and microvascular dysfunction. Retinal and cerebral microvasculature share similar structural and physiological properties and can be directly imaged by OCTA. Indeed, vascular dysfunctions in AD retina has been detected in AD patients, including lower capillary density, reduced blood flow and pericyte loss, similar to cerebral vascular changes in AD. However, it remains largely unknown how the ONH and retrolaminar microvascular connecting to brain changes are related to other AD pathological changes because OCTA cannot penetrate back of retina. The goal of this proposal is to use high frequency ultrasound flow image to fill up these knowledge gaps by examining the longitudinal change of ONH and retrolaminar microvasculature in AD mice. There are two aims: Aim1 will examine the temporal changes of vascular function, including blood flow, capillary density, and pericyte loss in different pathological stages of AD mice (5XFAD) by high resolution ultrasound; Aim 2 will determine the relationship between the microvascular alterations and deposition in both brain and back of eye, BBB breakdown and behavior change in AD mice.