A system for obtaining serial biochemical, anatomical or physiological in vivo measurements of disease from one or more medical images of a patient before, during and after treatment, and measuring extent and severity of the disease is provided. First anatomical and functional image data sets are acquired, and form a first co-registered composite image data set. At least a volume of interest (VOI) within the first co-registered composite image data set is identified. The first co-registered composite image data set including the VOI is qualitatively and quantitatively analyzed to determine extent and severity of the disease. Second anatomical and functional image data sets are acquired, and form a second co-registered composite image data set. A global, rigid registration is performed on the first and second anatomical image data sets, such that the first and second functional image data sets are also globally registered.