Personalized lesion modification optimizes atherosclerosis intervention

个性化病变修饰优化动脉粥样硬化干预

• 批准号: 10544180
• 负责人: Elazer R Edelman
• 金额: $ 69.33万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544180
• 关键词: Adipose tissue; Affect; Amaze; Angioplasty; Area; Arteries; Atherectomy; Atherosclerosis; Balloon Angioplasty; Benefits and Risks; Binding; Biology; Biomechanics; Blood Vessels; Calcium; Cardiovascular Diseases; Characteristics; Clinical; Clinical Data; Clinical Trials; Communities; Complex; Computer Models; Computing Methodologies; Consensus; Coronary; Coronary Arteriosclerosis; Coronary heart disease; Data Analyses; Dedications; Devices; Diameter; Dimensions; Disease; Drops; Drug Delivery Systems; Engineering; Equilibrium; Esthesia; Event; Feedback; Future; Human; Image; Image Analysis; Industrialization; Intervention; Investigation; Learning; Left; Lesion; Link; Lipids; Lithotripsy; Measures; Mechanics; Methods; Microanatomy; Modeling; Modification; Morality; Morphology; Outcome; Penetration; Performance; Perioperative; Pharmaceutical Preparations; Procedures; Property; Science; Scientist; Shapes; Standardization; Stents; Stress; Techniques; Technology; Therapeutic Intervention; Touch sensation; Treatment outcome; United States National Institutes of Health; Vascular Diseases; Visualization; Work; calcification; deep learning; drug distribution; experience; experimental study; follow-up; grasp; image processing; imaging modality; implantation; innovation; insight; interdisciplinary approach; intervention delivery; local drug delivery; pharmacokinetic model; pre-clinical; predictive tools; response; restenosis; sound; success; treatment optimization; trend; uptake; virtual

The past half-century has seen an amazing trend. Linked advances in vascular biology, endovascular intervention and drug delivery have dropped morality from cardiovascular disease 4.5 fold. NIH support has blessed us with involvement in these endeavors and we are humbled by the accomplishments of the community. Yet, atherosclerotic disease is not eradicated, we do not fully grasp the vascular biology of obstructive vascular diseases, and interventional therapy is not at a standardized consensus. There is much to be learned in all areas especially for complex lesions where lesion modification is deemed indispensable. Increasingly sophisticated methods (e.g. orbital atherectomy, lithotripsy etc.) modify complex plaque before angioplasty or implantation of devices like stents, and yet modifications are still guided by operator personal experience. There are no criteria as to which technology to use and when, what constitutes sufficient modification and how to balance benefits and risks. Intravascular imaging can help visualize lesions peri-modification, but provides no functional feedback, forcing even experienced interventionalists to guide intricate procedures by sensation (touch, feel, even sound). What is needed and what our team of academic and industrial scientists, engineers and clinicians aims to develop are mechanistic insight into the biology of modification and tools for predicting function from imaging and validated criteria for treatment outcomes. We will relate alterations in lesion micro-morphology (calcium, lipid, fibrous, fibro-fatty content) to changes in spatial micro-mechanical (compliance, stress) and local drug delivery (uptake, retention) response, and correlate image-based quantification of lesion micro-morphology to interventional outcome, providing a framework to predict and optimize, therapy. Our aims are to (1) Quantify changes in clinical lesion micro-morphology of complex arterial disease as a function of lesion modification using deep-learning-based image analysis, and investigate how initial lesion state can predict micro-morphological alterations for different modifications. (2) Use image processing and lesion- specific inverse modelling to examine effects of lesion modification on micro-mechanics and local drug distribution in excised human lesions, and (3) compare predictions with clinical performance after angioplasty and stenting. Combining aims 1 and 2 with computational virtual stent implantation we will predict vascular responses after modification of vascular morphology, and compare these predictions to outcomes from clinical trials that have imaging and longitudinal follow-up. In whole we will distinguish clinical outcomes that arise from optimization of lumen dimensions, from optimization of micro-morphology, -mechanics and drug distribution. The significance of our work lies in providing a mechanistic framework to explore increasing use of lesion modification pre-intervention and a means to leverage such insight to guide and optimize effect. The novelty is in using imaging and computational methods developed with the past NIH support to achieve this understanding. We are honored that our science may have clinical impact in treating complex vascular disease.

在过去的半个世纪里，出现了一个令人惊叹的趋势。血管生物学、血管内技术的相关进展 干预和药物输送使心血管疾病的死亡率下降了4.5倍。美国国立卫生研究院的支持 我们有幸参与了这些努力，我们对社区的成就感到谦卑。 然而，动脉粥样硬化性疾病并没有根除，我们还没有完全掌握阻塞性血管的血管生物学 疾病，而介入治疗还没有形成标准化的共识。在各个领域都有很多需要学习的地方 尤其是对于复杂的病变，病变修改被认为是必不可少的。日益复杂 方法(如眼眶动脉粥样硬化切除术、碎石术等)在血管成形术或植入术前修改复杂斑块 像支架这样的设备，但修改仍然是由操作员的个人经验指导的。没有标准 关于使用哪种技术以及何时使用，什么构成充分的修改以及如何平衡利益 和风险。血管内成像可以帮助显示修复期的病变，但不提供功能反馈， 迫使即使是经验丰富的干预主义者也要通过感觉(触摸、感觉，甚至声音)来指导复杂的程序。 我们的学术和工业科学家、工程师和临床医生团队需要什么以及目标是什么 开发的是对修饰生物学的机械性洞察和从成像预测功能的工具 和经过验证的治疗结果标准。我们将介绍病变微观形态的变化(钙、脂、 纤维、纤维脂肪含量)与空间微机械(顺应性、应激)和局部给药的变化有关 (摄取、保留)反应，并将基于图像的病变微形态量化与 介入结果，为预测和优化治疗提供了一个框架。 我们的目标是(1)将复杂动脉疾病的临床病变微形态的变化量化为 使用基于深度学习的图像分析来修改病变的功能，并调查初始病变状态 可以预测不同修饰的微观形态变化。(2)使用图像处理和病变- 特异逆模型检验病变修饰对微观力学和局部药物的影响 在切除的人体病变中的分布，以及(3)血管成形术后的预测与临床表现的比较 和支架植入。将目标1和目标2与计算虚拟支架植入相结合，我们将预测血管 血管形态改变后的反应，并将这些预测与临床结果进行比较 进行成像和纵向随访的试验。总体而言，我们将区分产生于 管腔尺寸的优化，从微观形态、力学和药物分布的优化。 我们工作的意义在于提供了一个机制框架来探索越来越多的病变的使用 修改前干预，以及利用这种洞察力来指导和优化效果的手段。新奇之处在于 在使用过去NIH支持下开发的成像和计算方法来实现这一理解。 我们感到荣幸的是，我们的科学可能会对治疗复杂的血管疾病产生临床影响。