The widespread use of screening mammography has resulted in a remarkable rise in the diagnosis of Ductal Carcinoma In Situ (DCIS). A resultant challenge is the early screening of these patients to identify those with concurrent invasive breast cancer (IBC), as one in five DCIS at biopsy, are upgraded to IBC following surgery. Both x-ray mammography and multi-parametric Magnetic Resonance Imaging (MRI) lack the ability to distinguish DCIS from IBC reliably. Our robust methodology for 3D alignment of histopathology images and MRI provides a unique opportunity to spatially map digitized histopathology slides on pre-surgical MRI which is particularly important in the tumors where DCIS and IBC co-occur as well as for the study of tumor heterogeneity. In this proof-of-concept study, we developed and evaluated a methodological framework for the 3D spatial alignment of MRI and histopathology slices, using x-ray radiographs as intermediate modality. Our methodology involves (1) the co-registration of 2D x-ray radiographs showing macrosections and corresponding 2D histology slices, (2) the 3D reconstruction of the ex vivo specimen based on the x-ray images, and aligned histology slices, and (3) the registration of the 3D reconstructed ex vivo specimen with the 3D MRI. The spatially co-registered MRI and histopathology images may enable the identification of MRI features that distinguish aggressive from indolent disease on in vivo MRI.
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