Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has the potential to identify lipid pools within rupture-prone arterial plaques and serve as a valuable supplement to current IVUS systems in diagnosing acute coronary syndromes. The major challenge for in vivo application of TSI will be cardiac motion, including bulk motion and tissue deformation. Simulations based on an artery model, including a lipid-filled plaque, demonstrate that effective bulk motion compensation can be achieved within a certain motion range using spatial interpolation. We also propose a practical imaging scheme to minimize mechanical strains caused by tissue deformation based on a linear least squares fitting strategy. This scheme was tested on clinical data by artificially superimposing thermal displacements corresponding to different temperature rises. Results suggest a 1-2 degrees C temperature rise is required to detect lipids in an atherosclerotic plaque in vivo.