An open-source framework (TIRL) and a novel 3-stage pipeline are presented to automate the registration between sparsely sampled small histology sections and 3-D MRI data for validating imaging biomarkers. In addition to affine registration, deformable slice-to-volume registration is employed to compensate for both in-plane and through-plane distortions of the histology sections. Each stage of the pipeline is shown to achieve submillimetre precise alignments, surpassing the accuracy of previous methods. With photographic intermediaries the pipeline is fully automatic and does not depend on serial histological sectioning or specialist cutting and stain automation hardware. The tools are provided as part of FSL.
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