Recent growth of genetic disease models in swine has presented the opportunity to advance translation of developed imaging protocols, while characterizing the genotype to phenotype relationship. Repeated imaging with multiple clinical modalities provides non-invasive detection, diagnosis, and monitoring of disease to accomplish these goals; however, longitudinal scanning requires repeatable and reproducible positioning of the animals. A modular positioning unit was designed to provide a fixed, stable base for the anesthetized animal through transit and imaging. Post ventilation and sedation, animals were placed supine in the unit and monitored for consistent vitals. Comprehensive imaging was performed with a computed tomography (CT) chest-abdomen-pelvis scan at each screening time point. Longitudinal images were rigidly registered, accounting for rotation, translation, and anisotropic scaling, and the skeleton was isolated using a basic thresholding algorithm. Assessment of alignment was quantified via eleven pairs of corresponding points on the skeleton with the first time point as the reference. Results were obtained with five animals over five screening time points. The developed unit aided in skeletal alignment within an average of 13.13 ± 6.7 mm for all five subjects providing a strong foundation for developing qualitative and quantitative methods of disease tracking.