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

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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.