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

使用高频超声弹性成像对视神经乳头和视乳头周围巩膜进行生物力学测绘

• 批准号: 10712180
• 负责人: Qifa Zhou
• 金额: $ 41.3万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10712180
• 关键词: 3-Dimensional; Acoustics; Address; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; American; Area; Award; Back; Biomechanics; Blindness; Blood Vessels; Blood capillaries; Blood flow; Brain; California; Cerebrovascular Disorders; Characteristics; Computer software; Cornea; Deposition; Development; Disease; Disease Progression; Early Diagnosis; Early Intervention; Economic Burden; Elasticity; Elements; Engineering; Evaluation; Eye; Frequencies; Glaucoma; Goals; Human; Image; Imaging Techniques; Individual; Knowledge; Maps; Measures; Mechanics; Microvascular Dysfunction; Monitor; Mus; Neurobehavioral Manifestations; Optic Disk; Oryctolagus cuniculus; Papillary; Parents; Pathogenesis; Pathologic; Patients; Penetration; Pericytes; Persons; Phase; Physiologic Intraocular Pressure; Physiological; Principal Investigator; Property; Race; Radiation; Research; Research Personnel; Resolution; Resources; Retina; Retinal Diseases; Risk Factors; Scientist; Sclera; Shapes; Site; Societies; Statistical Data Interpretation; Stress; System; Techniques; Technology; Testing; Tissues; Transducers; Ultrasonic Transducer; Ultrasonics; Ultrasonography; United States National Institutes of Health; Universities; Variant; Vascular Diseases; abeta deposition; aging population; behavior change; cerebral microvasculature; cerebrovascular; cost; density; disorder risk; elastography; ex vivo imaging; experience; imaging modality; imaging platform; imaging system; in vivo imaging system; in vivo optical imaging; mechanical properties; new technology; novel; optic nerve disorder; optical imaging; success; tool; ultrasound

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.

阿尔茨海默病 (AD) 困扰着美国 650 万人和全球 1500 万人，并引发了巨大的经济损失 给社会带来经济负担。然而，AD 无法治愈，迫切需要识别 AD 在认知症状/不可逆的病理变化发生之前，从而可以进行早期干预 延缓疾病的发生和进展。脑血管功能障碍是最早的病理学之一 AD 发病机制中涉及的变化以及早期 AD 诊断的潜在标志物，但对 AD 发病机制的评估 人类脑血管网络功能的改变受到成本高、可用性和敏感性低的限制。 研究表明，许多 AD 病变也发生在视网膜和眼后部，包括 Aβ 沉积和微血管功能障碍。视网膜和大脑微血管具有相似的结构和特征 生理特性，可以通过 OCTA 直接成像。事实上，AD 视网膜的血管功能障碍 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，与 AD脑血管变化。然而，ONH 和层流后如何 连接大脑的微血管变化与其他 AD 病理变化有关，因为 OCTA 无法 穿透视网膜后部。该提案的目标是使用高频超声流图像来填充这些 通过检查 AD 小鼠 ONH 和层后微血管的纵向变化来弥补知识差距。 有两个目标：Aim1将检查血管功能的时间变化，包括血流、毛细血管 高分辨率超声检测AD小鼠（5XFAD）不同病理阶段的密度和周细胞损失；目的 2 将确定大脑和背部的微血管改变和沉积之间的关系 AD 小鼠的眼睛、血脑屏障崩溃和行为变化。