There are two main source categories that can distort or deform medical images and create problems and challenges for accurate alignment/coregistration of two different image sets. One is due to physical factors (including mathematical reconstruction of the images) in the imaging device/instrument. The second category is due to anatomical/biological characteristics of patients. In this chapter, we will go over a few of these factors in these two categories. The physical factors, although we only focus on those of position mission tomography (PET), are similar for single photon emission computed tomography (SPECT). We will also discuss some correction methods to illustrate some general approaches to address the problems.

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