Super Resolution Ultrasound Imaging of Vasa Vasorum to Characterize the Progression of Atherosclerotic Plaques and Predict Rupture Vulnerability

血管超分辨率超声成像可表征动脉粥样硬化斑块的进展并预测破裂脆弱性

• 批准号: 10557917
• 负责人: KANG KIM
• 金额: $ 75.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557917
• 关键词: 3-Dimensional; Acoustics; Address; Affect; Algorithms; Animal Disease Models; Animals; Area; Arterial Fatty Streak; Autopsy; Blood Vessels; Bolus Infusion; Carotid Atherosclerotic Disease; Characteristics; Cholesterol; Clinic; Clinical; Confocal Microscopy; Contrast Media; Data; Devices; Disease; Europe; Feasibility Studies; Foundations; Frequencies; Future; Goals; Growth; Histology; Human; Image; Imaging Device; Imaging technology; In Vitro; Infiltration; Influentials; Injections; Intervention; Intravenous; Investigation; Kidney Diseases; Life; Logistic Regressions; Logistics; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Microbubbles; Microfluidics; Modeling; Morbidity - disease rate; Myocardial Infarction; Names; Noise; Non-Invasive Detection; Optics; Oryctolagus cuniculus; Outcome; Pathology; Performance; Physiologic pulse; Physiological; Pilot Projects; Play; Population; Preventive treatment; Procedures; ROC Curve; Radiation; Resolution; Risk; Role; Rupture; Scanning; Senile Plaques; Signal Transduction; Specificity; Stroke; Stroke prevention; Surrogate Markers; System; Techniques; Testing; Ultrasonography; United States; Validation; Work; acute coronary syndrome; angiogenesis; animal imaging; atherosclerotic plaque rupture; clinical application; clinical translation; clinically relevant; contrast enhanced; density; high resolution imaging; high risk; human subject; image reconstruction; imaging approach; imaging capabilities; imaging probe; in vivo; innovation; innovative technologies; meter; microCT; microscopic imaging; mortality; neovascularization; novel; patient stratification; spatiotemporal; stroke risk; technology development; tomography; tool; translational goal; ultra high resolution; ultrasound; uptake; vasa vasorum

PROJECT SUMMARY Acute coronary syndromes and strokes together constitute a leading cause of morbidity and mortality in the United States and Europe, approximately 80% of which are caused by atherosclerotic plaque (AP) rupture. Over the past decade, extensive efforts have been made to identify a rupture-prone AP. Among others, infiltration of dense neovascularization arising from vasa vasorum (VV) into the AP core plays a critical role in AP rupture. Postmortem studies revealed key involvement of VV in AP. However, a persistent lack of a noninvasive, high-resolution imaging tool to longitudinally assess abnormal microvascular expansion remains a critical barrier to adequate in-vivo investigation on how VV affects AP progression and contributes to eventual rupture. To address this dire unmet need, we propose an innovative transcutaneous super resolution ultrasound (SRU) imaging. The technology development in this project seeks to shift the current US imaging approach in identifying microvessels of AP from “intravascular” to a “fully noninvasive transcutaneous” imaging approach. This is only possible by achieving unprecedented high spatial resolution at large depth, breaking acoustic diffraction limit of the ultrasound frequency that governs spatial resolution. Our group has performed in-depth feasibility studies where SRU imaging successfully identified neomicrovessels in cholesterol-fed rabbit AP, evaluated against µCT and histology. Additionally, areas requiring further technical optimization were identified. Such technology developments and preliminary data thus far rigorously support our overarching hypothesis that enhanced and optimized SRU will accurately stage plaque progression and identify rupture- prone plaques by directly measuring VV changes with exquisite detail. To test the hypothesis, we will use a well-established, clinically relevant cholesterol-fed rabbit AP rupture model, which has shown the most similarity to human plaque pathology including VV neovascularization, to validate the novel SRU system to 1) Successfully quantify changes in vessel density and 2) Identify rupture-prone AP. To achieve these goals, we propose the following specific aims: 1) To develop enhanced SRU at high frequency using a commercial small animal imaging probe 2) To determine if VV changes estimated by SRU correlate with AP progression and are predictive of AP rupture. The immediate outcomes of the proposed work are an affordable noninvasive small animal SRU imaging tool and it’s validation on a clinically relevant rabbit AP model, which also can be used for other important small animal disease models, which are associated with microvessel abnormality such as cancer angiogenesis and kidney diseases to name a few. With proper adaptations into a clinical mid frequency probe and validation in clinical settings in future, this work will lead to our long-term translational goal to integrate SRU in a facile manner into the current clinical standard of carotid duplex sonography that has shown poor specificity to plaque vulnerability. This will help to effectively stratify patients at high risk of strokes and guide adequate intervention/treatment options for stroke prevention, exerting highly influential clinical impact.

项目摘要 急性冠状动脉综合征和中风构成了发病率和死亡率的主要原因 美国和欧洲，大约80％是由动脉粥样硬化斑块（AP）破裂引起的。 在过去的十年中，已经做出了广泛的努力来确定容易发生的AP。等等 由Vasa vasorum（VV）引起的AP核心引起的致密新血管形成在AP核心中起着至关重要的作用 AP破裂。验尸研究表明，VV在AP中的关键参与。但是，持续缺乏 纵向评估异常微血管膨胀的无创，高分辨率成像工具仍然是 关于VV如何影响AP进展的充分体内调查的关键障碍，并有助于最终 破裂。为了满足这种可怕的未满足需求，我们提出了一种创新的经性超级分辨率 超声（SRU）成像。该项目中的技术开发试图改变当前的美国成像 识别从“血管内”到“完全无创的经皮”成像的AP微血管的方法 方法。只有通过在大深度上实现前所未有的高空间分辨率才能实现这一可能 控制空间分辨率的超声频率的声学衍射极限。我们的小组表演了 深入的可行性研究，SRU成像成功地鉴定 AP，针对µCT和组织学评估。此外，需要进一步优化的领域是 确定。这样的技术发展和初步数据到目前为止，严格支持我们的总体 增强和优化的SRU的假设将准确地分阶段斑块进展，并确定破裂 - 通过直接测量VV变化的独家细节来俯卧斑。为了检验假设，我们将使用 建立良好的，临床上相关的胆固醇喂养的兔子AP破裂模型，该模型显示出最多的 与人类斑块病理（包括VV新血管化）相似，以验证新型SRU系统至1） 成功地量化了血管密度的变化，2）识别容易破裂的AP。为了实现这些目标，我们 提案以下特定目的：1）使用商业小 动物成像探针2）确定SRU估计的VV变化是否与AP进展相关，并且 预测AP破裂。拟议作品的直接结果是负担得起的无创小小的 动物SRU成像工具及其对临床相关的兔子AP模型的验证，也可以用于 其他重要的小动物疾病模型，这些模型与微血管异常有关 癌症血管生成和肾脏疾病仅举几例。适当适应临床中频频率 将来的临床环境中的探测和验证，这项工作将导致我们的长期翻译目标 以一种简便的方式集成的SRU纳入了颈动脉双工超声的当前临床标准 斑块脆弱性的特异性不佳。这将有助于有效地对患者的中风风险高，并 指导预防中风的适当干预/治疗选择，产生高影响力的临床影响。