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

这项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上。然而，生成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的永久性和局限性扩张，通常没有症状。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，伴有破裂或夹层，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，哪些容易出现危及生命的并发症。这种紧迫性进一步加剧，因为治疗可能会有自己的并发症，并保留给破裂风险最高的动脉瘤。 主动脉瘤的挑战：该研究计划集中于基于生物力学的指标的确定，这些指标可以帮助澄清局部机械应力和病理性主动脉壁变弱程度之间的相互作用。在最初的损伤(这可能是遗传、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，改变其成分的合成和降解的平衡。在早期阶段，平衡被转移到更高的胶原蛋白产生。然而，随着病理的进展，炎症过程占主导地位，生长/重塑平衡转向结构成分的进行性退化，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。 以前的研究表明，动脉瘤的材料特性以及壁上胶原含量和方向都发生了显着变化。特别是，墙体的变形性似乎与其强度有关，局部变形的增加可能有助于识别破裂风险较高的区域。然而，这样的信息不能用目前的临床成像方式非侵入性地获得。基于我们对墙体变形的光流检测的初步结果，我们将开发一套软件来获得活体变形图和局部材料属性图。一旦评估了局部材料的特性，我们将使用多尺度方法来充分描述组织的体内机械状态。这是评估破裂可能性的基本信息。 提出的新方法允许估计针对患者特定数据的个性化指数(患者间变异性)，同时也考虑到胸段内众所周知的区域异质性(患者内变异性)。这项技术将被应用于确定主动脉瘤加速生长和夹层的工程学指标，并为干预提供早期可靠的指征。 最终的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。这项技术也可以应用于其他软组织，包括左心房壁，以识别房颤的复发，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.