AbstractChronic infusion of angiotensin-II in atheroprone (ApoE^−/−) mice provides a reproducible model of dissection in the suprarenal abdominal aorta, often with a false lumen and intramural thrombus that thickens the wall. Such lesions exhibit complex morphologies, with different regions characterized by localized changes in wall composition, microstructure, and properties. We sought to quantify the multiaxial mechanical properties of murine dissecting aneurysm samples by combining in vitro extension-distension data with full-field multimodality measurements of wall strain and thickness to inform an inverse material characterization using the virtual fields method. A key advance is the use of a digital volume correlation approach that allows for characterization of properties not only along and around the lesion, but also across its wall. Specifically, deformations are measured at the adventitial surface by tracking motions of a speckle pattern using a custom panoramic digital image correlation technique while deformations throughout the wall and thrombus are inferred from optical coherence tomography. These measurements are registered and combined in 3D to reconstruct the reference geometry and compute the 3D finite strain fields in response to pressurization. Results reveal dramatic regional variations in material stiffness and strain energy, which reflect local changes in constituent area fractions obtained from histology but emphasize the complexity of lesion morphology and damage within the dissected wall. This is the first point-wise biomechanical characterization of such complex, heterogeneous arterial segments. Because matrix remodeling is critical to the formation and growth of these lesions, we submit that quantification of regional material properties will increase the understanding of pathological mechanical mechanisms underlying aortic dissection.