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Digital Breast Tomosynthesis (DBT) provides an insight into the fine details of normal fibroglandular tissues and abnormal lesions by reconstructing a pseudo-3D image of the breast. In this respect, DBT overcomes a major limitation of conventional X-ray mammography by reducing the confounding effects caused by the superposition of breast tissue. In a breast cancer screening or diagnostic context, a radiologist is interested in detecting change, which might be indicative of malignant disease. To help automate this task image registration is required to establish spatial correspondence between time points. Typically, images, such as MRI or CT, are first reconstructed and then registered. This approach can be effective if reconstructing using a complete set of data. However, for ill-posed, limited-angle problems such as DBT, estimating the deformation is complicated by the significant artefacts associated with the reconstruction, leading to severe inaccuracies in the registration. This paper presents a mathematical framework, which couples the two tasks and jointly estimates both image intensities and the parameters of a transformation. We evaluate our methods using various computational digital phantoms, uncompressed breast MR images, and in-vivo DBT simulations. Firstly, we compare both iterative and simultaneous methods to the conventional, sequential method using an affine transformation model. We show that jointly estimating image intensities and parametric transformations gives superior results with respect to reconstruction fidelity and registration accuracy. Also, we incorporate a non-rigid B-spline transformation model into our simultaneous method. The results demonstrate a visually plausible recovery of the deformation with preservation of the reconstruction fidelity., Comment: 29 pages, 22 figures; The Annals of the British Machine Vision Association and Society for Pattern Recognition (BMVA) 2013