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，我们看到了一个惊人的趋势。血管生物学、血管内 干预和药物输送使心血管疾病死亡率下降了4.5倍。NIH的支持 祝福我们参与这些努力，我们对社区的成就感到谦卑。 然而，动脉粥样硬化疾病并没有根除，我们没有完全掌握阻塞性血管的血管生物学， 疾病，介入治疗尚未达成标准化共识。在所有领域都有许多东西需要学习 特别是对于其中病变修改被认为是必不可少的复杂病变。日益复杂 方法（例如眼眶斑块切除术、碎石术等）在血管成形术或植入前修改复杂斑块 例如支架的装置，但是修改仍然由操作者个人经验指导。没有标准 关于使用哪种技术以及何时使用，什么是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可视化病变周围修饰，但不提供功能反馈， 甚至迫使有经验的介入医生通过感觉（触摸、感觉、甚至声音）来指导复杂的手术。 我们的学术和工业科学家，工程师和临床医生团队的目标是什么 开发了对修饰生物学的机械见解和从成像中预测功能的工具 和有效的治疗结果标准。我们将涉及病变微形态（钙，脂质， 纤维、纤维脂肪含量）对空间微机械（顺应性、应力）和局部药物递送的变化的影响 （摄取，保留）反应，并将病变微形态的基于图像的定量与 介入结果，提供了一个框架，以预测和优化，治疗。 我们的目的是（1）量化复杂动脉疾病的临床病变微形态学变化， 使用基于深度学习的图像分析的病变修改功能，并研究初始病变状态 可以预测不同修饰的微形态变化。(2)使用图像处理和病变- 特定的逆向建模，以检查病变修改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）比较预测与血管成形术后的临床表现 和支架植入术。结合目标1和2与计算虚拟支架植入，我们将预测血管 改变血管形态后的反应，并将这些预测与临床结果进行比较。 有影像学和纵向随访的试验。总之，我们将区分临床结果， 从微观形态学、力学和药物分布的优化来优化管腔尺寸。 我们的工作的意义在于提供一个机制框架，以探讨增加使用病变 修改预干预和一种手段，以利用这种洞察力，以指导和优化效果。新颖之处在于 在使用成像和计算方法开发与过去的国家卫生研究院的支持，以实现这一理解。 我们很荣幸我们的科学可能在治疗复杂血管疾病方面产生临床影响。