Why don't high-resolution simulations and images match?

Computer simulations have been used for many years to understand experimental high-resolution electron microscope images in a qualitative fashion, but the trend nowadays has been to attempt more quantitative image matching. This has led to the discovery that the contrast in experimental images is much less than in simulated images, typically by a factor of about three, There are many possible causes for this discrepancy, ranging from the mechanisms of scattering of electrons by the specimen through the calculations of the diffracted beam intensities and their focusing by the objective lens to the point spread function of the recording device. No single cause can explain all of the experimental contrast loss, although a combination of many factors could.