Accurately registered images of complementary biomedicalimaging devices, for example images representing tissuefunction (PET or SPECT) registered with structural/anatomical images obtained with CT or MRI, are of crucialimportance for research, diagnosis and patient treatment.Several multi-modal tomography approaches have alreadyproven to significantly enhance accuracy of diagnosis andpatient management. The main reason for this is thatmolecular processes that show up at the site of (for example)atumourorinfectionprocesscanbeaccuratelylocalisedinananatomical framework and attributed to a specific tissue ororgan. Such combination of modalities presents addeddiagnosticinformationcomparedwitheitheroftheemployedmodalitiesusedinisolation.Furthermore,thereispotentialtoenhance reconstruction and improve quantification utilisingthe combined information from multiple modalities.Until recently, pure software-based methods based oneither rigid body or non-rigid algorithms were used forimage registration. There are several comprehensivereviews available covering both intra-modality and inter-modality registration [1–3]. In general, however, whenapplied to multi-modal studies involving emission tomog-raphy, these methods have been unable to deliver suffi-ciently robust registration for general clinical imagingpractice. For many parts of the body the registration iscomplicated, for instance because changes in the patient’sposition cause organs and tissues to shift relative to eachother, necessitating computationally slow, sometimes ill-defined, non-rigid approaches. More importantly forSPECT, some of the applications where registration hasmost clinical potential involve the localisation of specificuptake where there often is insufficient information outsidethe target tissue to permit accurate multi-modal registration.In addition, the logistics of retrieving data from multiplesites is seldom straightforward.The recognition of this problem led to the introduction ofcombined molecular and structural imaging devices: PET/CT [4, 5] and SPECT/CT [6, 7]. SPECT/CT, originallysuggested by Hasegawa and co-workers, predated PET/CTas an attempt to improve on the low-cost transmissionscanning that was developed for cardiac attenuationcorrection (whose commercial implementation proved tobe problematic [see 8]). Both PET/CT and SPECT/CT canbe very successful in eliminating the organ shift problem.In 2000, the modern PET/CT scanner, as proposed byTownsend and Nutt, was named by TIME Magazine as themedical invention of the year, and indeed it has maintaineda significant impact on clinical practice. Today, sales inPET involve almost exclusively PET/CT systems. This isnot the case yet with SPECT/CT scanners although theinstalled base is rapidly growing. One reason for the sloweracceptance of SPECT/CT is the relative cost of CT andSPECT, especially considering the relatively low percent-age of studies where SPECT/CT imaging is indicated. Asa consequence there was an initial trend to offer slow,
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