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: 10471807
• 负责人: Junjie Yao
• 金额: $ 51万
• 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/10471807
• 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; Persons; 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; ultrasound

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世界死亡和长期残疾的主要原因。这是 随着人口老龄化的加剧，这种现象变得更加明显。许多研究，包括我们的研究，都表明 年轻和老年大脑之间存在显着差异，包括与年龄相关的大脑变化 脉管系统形态和血液氧合。治疗脑卒中后的首要任务是恢复血液 脑实质的灌注依赖于脑血管网络的完整性。已经显示了 小血管（直径小于 100 µm）在缺血性中风后损失最多，导致 血液再灌注障碍和大脑重塑延迟。此外，缺血性中风后，两个 主要的血管修复过程，急性期的动脉生成和延迟期的血管生成是 主要在小血管水平激活。血管损伤和恢复都是异质的 受缺血影响的不同大脑区域。因此，促进局部微血管的发育具有重要意义。 被认为是一种特别有前途的治疗策略。然而，针对血管建模尚未得到广泛应用。 在临床中风管理中取得成功，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。当前的脑成像技术，特别是光学显微镜， 不同程度地遭受低分辨率、低速度和/或浅穿透深度的影响，因此无法填充所需的 知识差距。在这里，依靠快速多边形扫描、超宽带等技术创新 超声检测，我们建议开发真正集成的光声和超声成像系统 (iPAUSI) 与其他成像方式相比具有明显的优势。 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、 曲折度）、血流和血氧，具有高空间和时间细节。通过这些启用 能力，我们将对小血管损伤和重塑进行全面分析 中风后小鼠大脑。最终，我们期望获得小型企业抵押重塑的详细信息。 在老年中风大脑中，急性期的血管和延迟期的血管生成。我们将完成 我们的总体目标是通过追求以下具体目标： (1) 目标 1：开发和优化集成的 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：开发 一套新颖的成像方法，可准确量化深部小血管的氧合和血流量 脑。 (3) 目标3：研究年龄特异性对年轻小鼠缺血性脑卒中小血管重塑的影响 和年龄。如果成功，我们的结果预计将为中风后衰老的大脑提供新的见解，这 将为针对老年中风患者小血管重塑的新策略的制定提供信息。