PViT-AIR: Puzzling vision transformer-based affine image registration for multi histopathology and faxitron images of breast tissue

Breast cancer is a significant global public health concern, with various treatment options available based on tumor characteristics. Pathological examination of excision specimens after surgery provides essential information for treatment decisions. However, the manual selection of representative sections for histological examination is laborious and subjective, leading to potential sampling errors and variability, especially in carcinomas that have been previously treated with chemotherapy. Furthermore, the accurate identification of residual tumors presents significant challenges, emphasizing the need for systematic or assisted methods to address this issue. In order to enable the development of deep-learning algorithms for automated cancer detection on radiology images, it is crucial to perform radiology-pathology registration, which ensures the generation of accurately labeled ground truth data. The alignment of radiology and histopathology images plays a critical role in establishing reliable cancer labels for training deep-learning algorithms on radiology images. However, aligning these images is challenging due to their content and resolution differences, tissue deformation, artifacts, and imprecise correspondence. We present a novel deep learning-based pipeline for the affine registration of faxitron images, the x-ray representations of macrosections of ex-vivo breast tissue, and their corresponding histopathology images of tissue segments. The proposed model combines convolutional neural networks and vision transformers, allowing it to effectively capture both local and global information from the entire tissue macrosection as well as its segments. This integrated approach enables simultaneous registration and stitching of image segments, facilitating segment-to-macrosection registration through a puzzling-based mechanism. To address the limitations of multi-modal ground truth data, we tackle the problem by training the model using synthetic mono-modal data in a weakly supervised manner. The trained model demonstrated successful performance in multi-modal registration, yielding registration results with an average landmark error of 1.51 mm $(\pm 2.40)$, and stitching distance of 1.15 mm $(\pm 0.94)$. The results indicate that the model performs significantly better than existing baselines, including both deep learning-based and iterative models, and it is also approximately 200 times faster than the iterative approach. This work bridges the gap in the current research and clinical workflow and has the potential to improve efficiency and accuracy in breast cancer evaluation and streamline pathology workflow.