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.

抽象的： 缺血性中风仍然是全球死亡率和长期残疾的主要原因。这是 随着人口越来越大的年龄，变得更加明显。包括我们在内的许多研究都揭示了 年轻人和年龄大脑之间的实质差异，包括与年龄相关的大脑变化 脉管形态和血氧。治疗中风后大脑的第一个任务是恢复血液 对副群的灌注依赖于脑血管网络的完整性。已经显示 小血管（直径小于100 µm）经历缺血性中风后最多的损失，导致 在障碍中，血液再灌注和大脑重塑的延迟。而且，缺血性中风后，两个 主要的血管修复过程，急性相的动脉生成以及延迟相的血管生成是 主要在小容器水平上激活。 Vascualr损害和解决方案均为异质 受缺血影响的不同大脑区域。因此，促进本地微血管的发展具有 被公认为是一种特别有前途的治疗策略。但是，靶向血管建模尚未 成功的临床中风操作成功，这主要是由于我们对微血管功能的了解有限 中风后大脑，尤其是在老年大脑中。当前的大脑成像技术，尤其是光学显微镜， 各种各样的分辨率，低速和/或浅渗透深度，因此无法填补所需的 知识差距。在这里，依靠技术创新（例如快速多边形扫描和超宽带） 超声检测，我们建议开发一个真正的相互作用的光声和UTLASOUND成像系统 （ipausi）将比其他成像方式具有明显的优势。 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， 曲折性），血流和血液氧合，并具有高空间和临时细节。由这些启用 功能，我们将对小血管损伤和重塑进行全面分析 中风后鼠标大脑。最终，我们期望获得小型附带重塑的详细信息 老年人脑中的急性相中的血管和延迟相的血管生成。我们将完成 通过追求以下特定目的，我们的整体目标：（1）AIM1：开发和优化综合的 具有高空间和临时分辨率的光声和超声成像系统。 （2）目标2：开发一个 一组新型的成像方法，以准确量化小血管的氧合和血流 脑。 （3）AIM 3：研究年轻的小鼠小鼠中小血管重塑的年龄特异性影响 和年龄。如果成功，我们的结果预计将在中风后对老年大脑产生新的见解， 将为针对较早中风患者的小血管重塑的新策略的制定提供信息。