Certain embodiments provide a computer system for determining a registration mapping between a novel medical image and a reference medical image, the computer system comprising: a storage system adapted to store data representing the novel medical image and the reference medical image and variance data for a plurality of different locations in the reference medical image representing a statistical variation for corresponding locations identified in a plurality of training medical images; and a processor unit operable to execute machine readable instructions to determine a registration mapping between the novel medical image and the reference medical image in a manner that takes account of the variance data for the plurality of different locations in the reference medical image.