A standard treatment protocol for breast cancer entails administering neoadjuvant therapy followed by surgical removal of the tumor and surrounding tissue. Pathologists typically rely on cabinet X-ray radiographs, known as Faxitron, to examine the excised breast tissue and diagnose the extent of residual disease. However, accurately determining the location, size, and focality of residual cancer can be challenging, and incorrect assessments can lead to clinical consequences. The utilization of automated methods can improve the histopathology process, allowing pathologists to choose regions for sampling more effectively and precisely. Despite the recognized necessity, there are currently no such methods available. Training such automated detection models require accurate ground truth labels on ex-vivo radiology images, which can be acquired through registering Faxitron and histopathology images and mapping the extent of cancer from histopathology to x-ray images. This study introduces a deep learning-based image registration approach trained on mono-modal synthetic image pairs. The models were trained using data from 50 women who received neoadjuvant chemotherapy and underwent surgery. The results demonstrate that our method is faster and yields significantly lower average landmark error ($2.1\pm1.96$ mm) over the state-of-the-art iterative ($4.43\pm4.1$ mm) and deep learning ($4.02\pm3.15$ mm) approaches. Improved performance of our approach in integrating radiology and pathology information facilitates generating large datasets, which allows training models for more accurate breast cancer detection.
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