Abstract: Medical imaging simulation is a powerful tool for characterizing, evaluating, and optimizing medical imaging devices and techniques. A vital aspect of simulation is to have a realistic phantom or model of the subject's anatomy. Four-dimensional mouse whole-body phantoms provide realistic models of the mouse anatomy and physiology for imaging studies. When combined with accurate models for the imaging process, are capable of providing a wealth of realistic imaging data from subjects with various anatomies and motions(cardiac and respiratory)in health and disease. With this ability, the four-dimensional mouse whole-body phantoms have enormous potential to study the effects of anatomical, physiological and physical factors on medical and small animal imaging and to research new instrumentation, image acquisition strategies, image processing, reconstruction methods, image visualization and interpretation techniques.