Spatially registered positron emission tomography (PET), computed tomograph
y (CT), and magnetic resonance (MR) images of the same small animal offer p
otential advantages over PET alone: CT images should allow accurate, nearly
noise-free correction of the PET image data for attenuation; the CT or MR
images should permit more certain identification of structures evident in t
he PET images; and CT images provide a priori anatomical information that m
ay be of use with resolution-improving image-reconstruction algorithms that
model the PET imaging process. However, image registration algorithms effe
ctive in human studies have not been characterized in the small-animal sett
ing. Accordingly, we evaluated the ability of the automated image registrat
ion (AIR) and mutual information (MI) algorithms to register PET images of
the rat skull and brain to CT or MR images of the same animal. External fid
ucial marks visible in all three modalities were used to estimate residual
errors after registration. The AIR algorithm registered PET bone-to-CT bone
images with a maximum error of less than 1.0 mm. The registration errors f
or PET brain-to-CT brain images, however, were greater, and considerable us
er intervention was required prior to registration. The AIR algorithm eithe
r failed or required excessive user intervention to register PET and MR bra
in images. In contrast, the MI algorithm yielded smaller registration error
s in all scenarios with little user intervention. The MI algorithm thus app
ears to be a more robust method for registering PET, CT, and MR images of t
he rat head.