Bioengineering tools for aortic pathologies: the role of in vivo mechanics

主动脉病理的生物工程工具：体内力学的作用

• 批准号: RGPIN-2014-04043
• 负责人: DiMartino, Elena
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=649223
• 关键词: Bioengineering; tools; aortic; pathologies; role

The overall goal of this research program is the development of bio-mechanical assessment tools for living tissues in vivo. The proposed research will focus on the specific challenge of establishing prognostic classification of aortic aneurysms. The tools generated, however, will have wide applicability to dynamic modelling of soft tissues.**Aortic aneurysms are characterized by a permanent and localized dilatation of the aorta and are generally asymptomatic. However, when they do become symptomatic, they often present in catastrophic fashion, with rupture or dissection, causing severe pain, massive internal hemorrhaging and/or death. Therefore, there is urgency to determine which aneurysms are benign and which are prone to life-threatening complications. This urgency is further heightened because treatment can have its own complications and is reserved for aneurysms at the highest risk of rupture. **The Aortic Aneurysm Challenge: The research plan focuses on the identification of biomechanical-based indices that can help clarify the interplay between the local mechanical stresses and the degree of weakening of the wall of the pathologic aorta. After the initial insult (which may be a combination of genetic, behavioural and mechanical influences), the aortic wall tissue responds to sustained mechanical stresses modifying the balance of synthesis and degradation of its constituents. In the early stages, the balance is shifted towards higher collagen production. However, as the pathology progresses, the inflammatory process takes precedence; and, the growth/remodeling balance shifts towards progressive degeneration of the structural components, with the ultimate result of a locally weak wall prone to fast dilatation and rupture. We will investigate stress-mediated weakening using a custom-designed micro-biaxial device under a confocal microscope. *Previous studies have shown significant changes in the material properties as well as in the collagen content and orientation in the wall of an aneurysm. In particular, the wall deformability appears to be related to its strength and a local increase in deformation could help identifying areas at elevated risk of rupture. However, such information cannot be derived non-invasively with current clinical imaging modalities. Building on our preliminary results with optical flow detection of wall deformation we will develop a software suite to obtain in vivo maps of deformation and local material properties. Once the local material properties are estimated, we will employ a multi-scale approach to fully characterize the in vivo mechanical state of the tissue. This is essential information to assess rupture potential.*The novel approach proposed allows the estimation of indices that are individualized to patient-specific data (inter-patient variability), while also considering the well-known regional heterogeneity within the thoracic segments (intra-patient variability). The technique will be applied to identify engineering-based indices of accelerated growth and dissection for aortic aneurysms and to provide early reliable indications for intervention. **The end result will be an engineering software tool that provides an estimate of stress-mediated degeneration of soft tissues through in-vivo mechanics assessment. The technology can be applied to other soft tissues, including the wall of left atrium to identify recurrence of atrial fibrillation, as well as to cartilage and tendons.

本研究计划的总体目标是开发活体组织的生物力学评估工具。提出的研究将集中于建立主动脉瘤预后分类的具体挑战。然而，所产生的工具将广泛适用于软组织的动态建模。**主动脉瘤的特征是主动脉永久性和局部扩张，通常无症状。然而，当它们出现症状时，它们往往以灾难性的方式出现，破裂或剥离，导致剧烈疼痛，大量内出血和/或死亡。因此，迫切需要确定哪些动脉瘤是良性的，哪些容易产生危及生命的并发症。由于治疗可能有其自身的并发症，并且仅用于破裂风险最高的动脉瘤，因此这种紧迫性进一步提高。**主动脉瘤挑战：该研究计划的重点是确定基于生物力学的指标，这些指标可以帮助阐明局部机械应力与病理性主动脉壁弱化程度之间的相互作用。在最初的损伤（可能是遗传、行为和机械影响的组合）之后，主动脉壁组织对持续的机械应力做出反应，改变其成分合成和降解的平衡。在早期阶段，这种平衡倾向于胶原蛋白的生成。然而，随着病理进展，炎症过程优先；并且，生长/重塑平衡转向结构部件的进行性退变，最终导致局部薄弱的壁容易快速扩张和破裂。我们将在共聚焦显微镜下使用定制设计的微型双轴装置来研究应力介导的减弱。*先前的研究表明，动脉瘤壁的材料特性以及胶原蛋白含量和方向发生了显著变化。特别是，墙的变形能力似乎与其强度有关，局部变形的增加可以帮助识别破裂风险较高的区域。然而，目前的临床成像方式不能无创地获得这些信息。基于我们对墙体变形的光流检测的初步结果，我们将开发一个软件套件来获得变形和局部材料属性的体内图。一旦估计了局部材料特性，我们将采用多尺度方法来充分表征组织的体内力学状态。这是评估破裂可能性的重要信息。*提出的新方法允许根据患者特定数据（患者间变异性）对指标进行个性化估计，同时也考虑了众所周知的胸椎段区域异质性（患者内变异性）。该技术将应用于识别基于工程的加速生长和动脉瘤解剖指标，并为干预提供早期可靠的指征。**最终结果将是一个工程软件工具，通过体内力学评估提供应力介导的软组织变性的估计。该技术可以应用于其他软组织，包括左心房壁，以识别心房颤动的复发，以及软骨和肌腱。