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

该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。拟议的研究将集中在建立主动脉瘤预后分类的具体挑战。然而，所产生的工具将具有广泛的适用性，软组织的动态建模。主动脉瘤的特征在于主动脉的永久性和局部扩张，并且通常无症状。然而，当它们确实出现症状时，它们通常以灾难性的方式出现，破裂或夹层，引起剧烈疼痛，大规模内部创伤和/或死亡。因此，迫切需要确定哪些动脉瘤是良性的，哪些动脉瘤容易发生危及生命的并发症。这种紧迫性进一步提高，因为治疗可能有自己的并发症，并保留在破裂风险最高的动脉瘤。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，这些指标可以帮助澄清局部机械应力与病理主动脉壁弱化程度之间的相互作用。在初始损伤（其可能是遗传、行为和机械影响的组合）之后，主动脉壁组织响应于持续的机械应力，从而改变其成分的合成和降解的平衡。在早期阶段，平衡转向更高的胶原蛋白生产。然而，随着病理学进展，炎症过程优先;并且，生长/重塑平衡向结构组件的进行性退化转移，最终结果是局部薄弱的壁易于快速扩张和破裂。我们将在共聚焦显微镜下使用定制设计的微双轴装置研究应力介导的弱化。先前的研究已经表明，材料特性以及动脉瘤壁中的胶原蛋白含量和方向发生了显著变化。特别是，壁的变形能力似乎与其强度有关，变形的局部增加可能有助于识别破裂风险升高的区域。然而，这样的信息不能用当前的临床成像模式非侵入性地导出。基于我们的初步结果与光流检测壁变形，我们将开发一个软件套件，以获得在体内地图的变形和局部材料性能。一旦估计出局部材料特性，我们将采用多尺度方法来充分表征组织的体内机械状态。这是评估破裂可能性的重要信息。提出的新方法允许估计个性化的患者特定数据（患者间变异性）的指数，同时还考虑到胸段内的众所周知的区域异质性（患者内变异性）。该技术将用于识别基于工程的主动脉瘤加速生长和夹层指数，并提供早期可靠的干预指征。最终结果将是一个工程软件工具，通过体内力学评估提供对应力介导的软组织退化的估计。该技术可应用于其他软组织，包括左心房壁以识别房颤复发，以及软骨和肌腱。

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.