High-resolution High-speed Photoacoustic and Ultrasound Imaging of SmallVessel Functions in Ischemic Stroke

缺血性中风小血管功能的高分辨率高速光声和超声成像

• 批准号: 10232087
• 负责人: Junjie Yao
• 金额: $ 57.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10232087
• 关键词: 3-Dimensional; Acoustics; Acute; Affect; Age; Aging; Animals; Blood; Blood Vessels; Blood flow; Brain; Brain imaging; Brain region; Caliber; Cerebrovascular Disorders; Cerebrovascular system; Cerebrum; Clinical; Detection; Development; Elderly; Focused Ultrasound; Goals; Healthcare Systems; Heterogeneity; Histologic; Image; Imaging technology; Impairment; Ischemia; Ischemic Stroke; Knowledge; Magnetic Resonance; Measurement; Measures; Methods; Microbubbles; Microscopy; Middle Cerebral Artery Occlusion; Modeling; Monitor; Morphology; Mus; Optics; Outcome; Patients; Penetration; Perfusion; Phase; Physiologic pulse; Population; Process; Recovery; Recovery of Function; Reperfusion Therapy; Resolution; Risk; Scanning; Slice; Speed; Stroke; Structure; System; Technology; Therapeutic; Time; Tissues; Transducers; Ultrasonic Transducer; Ultrasonography; United States; Vascular remodeling; Width; Yang; age effect; aged; aging brain; aging population; angiogenesis; base; blood perfusion; brain remodeling; cerebrovascular; clinical practice; cranium; density; disability; effective therapy; experience; human old age (65+); imaging modality; imaging platform; imaging system; improved; innovation; insight; mange; mortality; novel; older patient; optical imaging; photoacoustic imaging; post stroke; repaired; response; restoration; serial imaging; stroke model; stroke outcome; stroke patient; temporal measurement; therapeutic angiogenesis; treatment response

Abstract: Ischemic stroke continues to be a leading cause of both mortality and long-term disability worldwide. This is becoming more pronounced with an increasingly aging population. Many studies, including ours, have revealed substantial differences between the young and aged brains, including age-associated changes in cerebral vasculature morphology and blood oxygneation. The first task in treating poststroke brain is to restore the blood perfusion to the parenchyma, which relies on the integrity of the cerebral vascular network. It has been shown that small blood vessels (diameters less than 100 µm) experience the most loss after ischemic stroke, resulting in the impediment of blood reperfusion and a delay in brain remodeling. Moreover, after ischemic stroke, two major vascular repair processes, arteriogenesis in the acute phase and angiogenesis in the delayed phase, are activated mostly at the small vessel levels. Both the vascualr impairment and resotration are heterogeneous at different brain regions affected by ischemia. Therefore, promoting the development of local microvessels has been recognized as a particularly promising therapeutic strategy. Yet, targeting vascular modeling has not been successful in clinical stroke mangement, primarily due to our limited understanding of microvascular functions in poststroke brains, especially in aged brains. Current brain imaging technologies, especially optical microscopy, variously suffer from low resolution, low speed, and/or shallow penetration depth, and thus cannot fill the needed knowledge gap. Here, relying on the tehnical innovations such as the fast polygon scanning and ultra-wideband ultrasound detection, we propose to develop a truly interagred photoacoustic and utlrasound imaging system (iPAUSI) that will provide clear advantages over other imaging modalities. iPAUSI will offering longitudinal structural and functional measurements of small vessels, including vascular morphology (density, volume, tortuosity), blood flow, and blood oxygenation, with high spatial and temporal details. Enabled by these capabilities, we will perform a comprehensive analysis of small vascular impairment and remodeling in the poststroke mouse brain. Ultimiately, we expect to obtain detailed information of collateral remodeling of small vessels in the acute phase and angiogenesis in the delayed phase, in the aged stroke brains. We will accomplish our overall objective by pursuing the following specific aims: (1) Aim1: Develop and optimize an integrated photoacoustic and ultrasound imaging system with high spatial and temporal resolutions. (2) Aim 2: Develop a set of novel imaging methods to accurately quantify the oxygenation and blood flow of small vessels in deep brain. (3) Aim 3: Study the age specific effects on small vessel remodeling in ischemic stroke in mice at young and age. If successful, our results are expected to generate new insights on the aged brains after stroke, which will inform development of new strategies targeting small vascular remodeling for elderly stroke patients.

摘要： 缺血性卒中仍然是全球死亡率和长期残疾的主要原因。这是 随着人口老龄化的加剧，包括我们在内的许多研究都表明 年轻人和老年人大脑之间的实质性差异，包括与年龄相关的大脑变化， 血管形态学和血液氧合。脑卒中后治疗的首要任务是恢复血液 灌注到实质，这依赖于脑血管网络的完整性。已经表明 小血管（直径小于100 µm）在缺血性卒中后损失最多， 血液再灌注障碍和大脑重塑延迟。此外，缺血性中风后，两人 主要的血管修复过程，即急性期的动脉生成和延迟期的血管生成， 主要在小血管水平激活。血管损伤和再吸收均为异质性， 不同的大脑区域受到缺血的影响。因此，促进局部微血管的发展， 被认为是一种特别有前途的治疗策略。然而，针对血管建模还没有被 临床中风管理的成功，主要是由于我们对微血管功能的了解有限， 中风后的大脑，尤其是老年大脑。目前的脑成像技术，特别是光学显微镜， 不同地遭受低分辨率、低速度和/或浅穿透深度，并且因此不能满足所需的 知识差距。在这里，依靠快速多边形扫描和超宽带等技术创新， 超声检测，我们建议开发一个真正的光声和超声成像系统 （iPAUSI），其将提供优于其他成像模式的明显优势。iPAUSI将提供纵向 小血管的结构和功能测量，包括血管形态（密度，体积， 弯曲度）、血流和血氧，具有高的空间和时间细节。通过这些 能力，我们将进行一个全面的分析小血管损伤和重塑， 中风后小鼠大脑最终，我们希望获得详细的信息，侧支重塑的小， 血管在急性期和血管生成在延迟期，在老年中风脑。要全面完成 我们的总体目标是追求以下具体目标：（1）目标1：发展和优化一个综合的 具有高空间和时间分辨率的光声和超声成像系统。(2)目标2：制定 一套新的成像方法，以准确地量化氧合和深血管的血流 个脑袋(3)目的3：研究缺血性脑卒中小血管重构的年龄效应 和年龄。如果成功的话，我们的研究结果有望对中风后的老年大脑产生新的见解， 将为针对老年卒中患者小血管重塑的新策略的开发提供信息。