Systems and methods for generating a medical image of a subject that includes functional information. First, two medical images are acquired. One is weighted based on functional information reflecting physiological functions of the subject and the other weighted based on anatomic information of the subject. A difference image between the two images are generated. By subjecting the difference image and the second image to a localized kernel, a local similarity image is generated. Using the local similarity image, an improved difference image is generated. Lastly, by subtracting the improved difference image from the first image, an enhanced medical image that retains the functional information reflecting physiological functions of the subject is generated.