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Background  By providing estimates of tumor glucose metabolism,  18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) can potentially characterize the response of breast tumors to treatment. To assess therapy response, serial measurements of FDG-PET parameters (derived from static and/or dynamic images) can be obtained at different time points during the course of treatment. However, most studies track the changes in average parameter values obtained from the whole tumor, thereby discarding all spatial information manifested in tumor heterogeneity. Here, we propose a method whereby serially acquired FDG-PET breast data sets can be spatially co-registered to enable the spatial comparison of parameter maps at the voxel level.    Methods  The goal is to optimally register normal tissues while simultaneously preventing tumor distortion. In order to accomplish this, we constructed a PET support device to enable PET/CT imaging of the breasts of ten patients in the prone position and applied a mutual information-based rigid body registration followed by a non-rigid registration. The non-rigid registration algorithm extended the adaptive bases algorithm (ABA) by incorporating a tumor volume-preserving constraint, which computed the Jacobian determinant over the tumor regions as outlined on the PET/CT images, into the cost function. We tested this approach on ten breast cancer patients undergoing neoadjuvant chemotherapy.    Results  By both qualitative and quantitative evaluation, our constrained algorithm yielded significantly less tumor distortion than the unconstrained algorithm: considering the tumor volume determined from standard uptake value maps, the post-registration median tumor volume changes, and the 25th and 75th quantiles were 3.42% (0%, 13.39%) and 16.93% (9.21%, 49.93%) for the constrained and unconstrained algorithms, respectively ( p  = 0.002), while the bending energy (a measure of the smoothness of the deformation) was 0.0015 (0.0005, 0.012) and 0.017 (0.005, 0.044), respectively ( p  = 0.005).    Conclusion  The results indicate that the constrained ABA algorithm can accurately align prone breast FDG-PET images acquired at different time points while keeping the tumor from being substantially compressed or distorted.    Trial registration  NCT00474604

An algorithm for longitudinal registration of PET/CT images acquired during neoadjuvant chemotherapy in breast cancer: preliminary results