Advancing Aortic Aneurysm Strength Predictions: A Novel Density-Driven Strength Assessment Tool - Project Summary Thoracic aortic aneurysms (TAA) are irreversible focal dilatations of the aorta. Unrepaired TAAs can lead to death following dissection or rupture, which represent the catastrophic biomechanical failure of the aneurysm where the pressure-induced wall stress surpasses the wall strength. Reliable assessment of both the wall strength and wall stress in patient-specific TAA could be a powerful tool for predicting TAA failure and, hence, assessing rupture or dissection potential. As a TAA progresses, the stress acting on it generally increases, and the wall strength decreases due to breakdown and damage to the extracellular matrix. While non-invasive estimation of wall stress in TAA through computational finite element analysis and, more recently, artificial intelligence is well-established, accurate non-invasive assessment of tissue strength for direct comparison to stress has been elusive. Studies have established the tensile strength of TAA as a general population compared to non-aneurysmal aorta, and between different cohorts of patient pathologies or demographics. However, to date, no means of estimation of the tensile strength for individual (patient-specific) TAA exists, nor does the ability to predict spatial distribution of tissue strength within a given TAA. We recently introduced and validated the concept of the tensile strength of porcine aortic tissue being directly related to its tissue mass density. This proposal aims to extend this concept to human TAA tissue and utilize state-of-the-art imaging to estimate tissue mass density. Specifically, we will conduct the following specific aims: Aim 1A) Assess the ability of bulk tissue density to serve as a predictor of local tissue strength in human TAA; Aim 1B) Evaluate the viability of diffusion tensor magnetic resonance imaging (DT MRI) for measuring local TAA tissue density; and Aim 2) Demonstrate that regions of reduced tissue mass density in TAA tissue coincide with regions of tissue weakness and, subsequently, with the initiation of biomechanical tissue failure. This aim will also provide novel information on TAA tissue failure by using high-speed imaging of tissue specimens under loading until failure. Our multidisciplinary team will address this critical gap in TAA patient management using innovative and novel methods. If successful, the proposed work can lead to a paradigm-shifting tool for the estimation of patient- specific TAA tissue strength distribution for direct comparison to companion wall stress distribution maps. By evaluating both strength and stress distributions we may identify not only which TAA patients are prone to rupture or dissection, but where that failure might occur in their aneurysm.
