Rupture prone plaque diagnosis by IVUS-guided time-resolved spectroscopy

通过 IVUS 引导的时间分辨光谱诊断易破裂斑块

• 批准号: 8486300
• 负责人: Laura Marcu
• 金额: $ 46.48万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486300
• 关键词: Advanced Development; Affect; Arterial Fatty Streak; Atherosclerosis; Back; Beds; Biochemical; Blood; Blood flow; Boston; Breast Microcalcification; Cardiology; Catheterization; Catheters; Cause of Death; Classification; Clinical; Coronary; Coronary artery; Data; Data Collection; Detection; Development; Devices; Diagnosis; Diagnostic; Effectiveness; Elements; Evaluation; Experimental Designs; Family suidae; Feedback; Fluorescence Spectroscopy; Flushing; Frequencies; Future; Histology; Histopathology; Human; Image; Imaging Techniques; In Vitro; Individual; Intervention; Lipids; Measurement; Methods; Microanatomy; Modeling; Monitor; Motion; Motor; Optical Methods; Optical Rotation; Optics; Pathology; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Predictive Value; Procedures; Radial; Research Personnel; Risk; Rotation; Rupture; Safety; Sensitivity and Specificity; Spectrum Analysis; Structure; Symptoms; System; Techniques; Technology; Testing; Time; Tissues; Transducers; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Validation; Visual; Work; clinically relevant; data acquisition; design; design and construction; evaluation/testing; experience; improved; in vivo; in vivo Model; innovation; prototype; reconstruction; research clinical testing; tissue phantom; virtual

DESCRIPTION (provided by applicant): This competitive renewal application will advance the development of an intravascular bi-modal technology for diagnosis of arterial wall pathologies including rupture-prone (vulnerable) atherosclerotic plaques. We propose to optimize, construct and test a unique clinically-compatible system that combines fast, time-resolved fluorescence spectroscopy (TRFS) to dynamically evaluate atherosclerotic plaque composition under pull-back motion, with intravascular ultrasound (IVUS) that allows for both visual reconstruction of plaque microanatomy and guidance of TRFS measurements. The resulting system will enable detection and monitoring of biochemical, functional and structural features of atherosclerotic lesions with clinical relevance (e.g. predictive of plaque rupture). In this renewal application, we propose to advance the integration and in-vivo validation of this bi-modal technology and prepare for clinical intravascular evaluation through the following specific aims: Aim 1. To design, construct and optimize prototype bi-modal (TRFS-IVUS) intravascular catheters to demonstrate (1) the technical feasibility of integrating the TRFS with single element transducer IVUS catheters and (2) the ability of the bi-modal system to provide real-time diagnostic feedback information concerning arterial wall composition and structure. To achieve this we will build two catheter systems and validate their technical performance in-vitro (tissue phantoms, arterial segments). Aim 2. To demonstrate in-vivo the validity of continuous/radial TRFS data acquisition under pull-back motion and under IVUS guidance. To achieve this we will conduct transluminal procedures in an atherosclerotic pig model using Catheter Assembly I. We will determine optimal experimental parameters for dynamic TRFS acquisition in pulsatile blood flow conditions, evaluate the limiting design factors for the bi-modal catheter, and determine design and experimental parameters to optimize co-registration of TRFS and IVUS data. Aim 3. To determine the ability of optimized Catheter Assembly II to operate intravascularly in various arterial beds, including coronary arteries, and to determine its diagnostic capability. This will be achieved by testing the bi-modal technique in an atherosclerotic pig model (in-vivo) and in human coronary segments (ex-vivo). This will demonstrate the feasibility of the catheter prototype to operate effectively intravascularly under conditions of blood flow and motion, to collect co-registered TRFS/IVUS, and to generate diagnostic information. Aim 4. Establish the feasibility of TRFS-IVUS to dynamically and in near-real time (few seconds) characterize, discriminate and visualize relevant intravascular pathologies. To achieve this we will develop computational/classification models employing features derived from TRFS-data, IVUS RF-data ("virtual histology") and IVUS greyscale ("echogenicity") images; apply these models to data derived from bi-modal measurements (Aims 2 & 3) to determine the sensitivity, specificity, and overall predictive value of the proposed method; and validate this data against tissue histopathology. Aim 5. Prepare and submit an application for an FDA Sponsor-Investigator Investigational Device Exemption (IDE) for future clinical evaluation of the bi-modal system. This will make use of experimental data and results obtained in Aim 3 and Aim 4 and additional tests for evaluation of safety, effectiveness, and diagnostic capabilities as required by the FDA.

描述（由申请人提供）：该竞争性更新申请将推进血管内双峰技术的开发，用于诊断动脉壁病变，包括易破裂（易损）动脉粥样硬化斑块。我们建议优化，构建和测试一个独特的临床兼容的系统，结合快速，时间分辨荧光光谱（TRFS），动态评估动脉粥样硬化斑块成分下拉回运动，血管内超声（IVUS），允许斑块微观解剖结构的视觉重建和TRFS测量的指导。由此产生的系统将能够检测和监测具有临床相关性的动脉粥样硬化病变的生化、功能和结构特征（例如，预测斑块破裂）。在本次更新申请中，我们建议推进该双模式技术的集成和体内验证，并通过以下具体目标为临床血管内评价做好准备：目标1。设计、构建和优化原型双模（TRFS-IVUS）血管内导管，以证明（1）TRFS与单元件换能器IVUS导管集成的技术可行性和（2）双模系统提供有关动脉壁组成和结构的实时诊断反馈信息的能力。为了实现这一目标，我们将构建两个导管系统，并在体外验证其技术性能（组织体模、动脉段）。目标2.旨在证明在回撤运动和IVUS引导下的体内连续/径向TRFS数据采集的有效性。为了实现这一点，我们将使用导管组件I在动脉粥样硬化猪模型中进行经腔手术。我们将确定脉动血流条件下动态TRFS采集的最佳实验参数，评估双模导管的限制设计因素，并确定设计和实验参数，以优化TRFS和IVUS数据的配准。目标3.旨在确定优化的导管组装件II在各种动脉床（包括冠状动脉）中进行血管内操作的能力，并确定其诊断能力。这将通过在动脉粥样硬化猪模型（体内）和人冠状动脉节段（体外）中测试双模式技术来实现。这将证明导管原型在血流和运动条件下在血管内有效操作、收集共配准TRFS/IVUS并生成诊断信息的可行性。目标4。确定TRFS-IVUS动态和近实时（几秒钟）表征、区分和可视化相关血管内病变的可行性。为了实现这一点，我们将开发计算/分类模型，采用来自TRFS数据，IVUS RF数据（“虚拟组织学”）和IVUS灰度（“回声”）图像的特征;将这些模型应用于来自双模态测量的数据（目标2和3），以确定所提出的方法的灵敏度，特异性和总体预测值;并根据组织组织病理学验证该数据。目标5。准备并提交FDA申办者-研究者试验用器械豁免（IDE）申请，以便将来对双模系统进行临床评价。这将利用目标3和目标4中获得的实验数据和结果，以及FDA要求的安全性、有效性和诊断能力评价的其他测试。