An image data subtraction system enhances visualization of vessels subject to movement using an imaging system. The imaging system acquires data representing first and second anatomical image sets comprising multiple temporally sequential individual mask (without contrast agent) and fill images (with contrast agent) of vessels respectively, during multiple heart cycles. An image data processor automatically identifies temporally corresponding pairs of images comprising a mask image and a contrast enhanced image and for the corresponding pairs, automatically determines a shift of a contrast enhanced image relative to a mask image to compensate for motion induced image mis-alignment. The image data processor automatically shifts a contrast enhanced image relative to a mask image in response to the determined shift. The image data processor subtracts data representing a mask image of a corresponding pair from a shifted contrast enhanced image of the corresponding pair, to provide multiple subtracted images showing enhanced visualization of vessels.