The dataset describing an entity in a first modality and of a first, high resolution is used to enhance the resolution of a dataset describing the same entity in a second modality of a lower resolution. The two data sets of different modalities are spatially registered to each other. From this information, a joint histogram of the values in the two datasets is computed to provide a raw analysis of how the intensities in the first dataset correspond to intensities in the second dataset. This is converted into a joint probability of possible intensities for the missing pixels in the low resolution dataset as a function of the intensities of the corresponding pixels in the high-resolution dataset to provide a very rough estimate of the intensities of the missing pixels in the low resolution dataset. Then, an objective function is defined over the set of possible new values that gives preference to datasets consistent with (1) the joint probability distributions, (2) the existing values in the low resolution dataset, and (3) smoothness throughout the data set. Finally, an annealing or similar iterative method is used to minimize the objective function and find an optimal solution over the entire dataset.