Carney, John2024-08-222024-08-222024https://hdl.handle.net/11299/265189University of Minnesota Ph.D. dissertation. 2024. Major: Biomedical Informatics and Computational Biology. Advisors: Paul Iaizzo, Richard Bianco. 1 computer file (PDF); vii, 169 pages.The development of catheter-based cardiac valve replacement devices, or transcatheter valves, has ushered in a new era in the treatment of patients with valvular disease. Prior to clinical study, regulators require comprehensive in vivo safety studies of novel cardiac devices in large animal models. The domestic sheep model has been widely used to evaluate predicate surgically implanted valves, therefore its use to assess valve durability, thromboembolic complications and biocompatibility is well documented and understood. However, the model’s cardiac valvular anatomy and hemodynamics both pre- and postoperatively remains largely unstudied to date, presenting a gap in the knowledge and understanding of the model and the translation of preclinical device findings to clinical use. The purpose of this thesis was to characterize, propose and standardize methods for the use of cardiac computed tomography (CT), echocardiography (echo) and four-dimensional flow magnetic resonance imaging (4D MRI) in assessing naïve and implanted prosthetic valves in the sheep model. Resulting anatomic and hemodynamic data was analyzed statistically and reported to create the first cardiac valve reference intervals for sheep, to be used as comparator data in future studies of next-generation cardiac valve devices in the model. Looking to the future of preclinical in vivo studies, we demonstrate the use of machine learning algorithms and their potential predictive role in determining cardiac anatomy of the sheep model, as well as in-life outcomes to help investigators better assess, interpret, and translate preclinical study outcomes to clinical use. Finally, we present a number of articles documenting our use of the sheep model in next generation cardiac valve replacement studies and background pathology of the model to be used to more effectively interpret study findings. We envision this thesis improving future preclinical research studies of novel cardiac device technology in the sheep through understanding of the model, refinements in animal use, and ultimately interpretation of future study results.enCardiacComputed TomographyEchocardiographyHeart valvesPreclinicalSheepThesis or Dissertation