RegWSI: Whole slide image registration using combined deep feature- and intensity-based methods: Winner of the ACROBAT 2023 challenge.

Background And Objective: The automatic registration of differently stained whole slide images (WSIs) is crucial for improving diagnosis and prognosis by fusing complementary information emerging from different visible structures. It is also useful to quickly transfer annotations between consecutive or restained slides, thus significantly reducing the annotation time and associated costs. Nevertheless, the slide preparation is different for each stain and the tissue undergoes complex and large deformations. Therefore, a robust, efficient, and accurate registration method is highly desired by the scientific community and hospitals specializing in digital pathology.

Methods: We propose a two-step hybrid method consisting of (i) deep learning- and feature-based initial alignment algorithm, and (ii) intensity-based nonrigid registration using the instance optimization. The proposed method does not require any fine-tuning to a particular dataset and can be used directly for any desired tissue type and stain. The registration time is low, allowing one to perform efficient registration even for large datasets. The method was proposed for the ACROBAT 2023 challenge organized during the MICCAI 2023 conference and scored 1st place. The method is released as open-source software.

Results: The proposed method is evaluated using three open datasets: (i) Automatic Nonrigid Histological Image Registration Dataset (ANHIR), (ii) Automatic Registration of Breast Cancer Tissue Dataset (ACROBAT), and (iii) Hybrid Restained and Consecutive Histological Serial Sections Dataset (HyReCo). The target registration error (TRE) is used as the evaluation metric. We compare the proposed algorithm to other state-of-the-art solutions, showing considerable improvement. Additionally, we perform several ablation studies concerning the resolution used for registration and the initial alignment robustness and stability. The method achieves the most accurate results for the ACROBAT dataset, the cell-level registration accuracy for the restained slides from the HyReCo dataset, and is among the best methods evaluated on the ANHIR dataset.

Conclusions: The article presents an automatic and robust registration method that outperforms other state-of-the-art solutions. The method does not require any fine-tuning to a particular dataset and can be used out-of-the-box for numerous types of microscopic images. The method is incorporated into the DeeperHistReg framework, allowing others to directly use it to register, transform, and save the WSIs at any desired pyramid level (resolution up to 220k x 220k). We provide free access to the software. The results are fully and easily reproducible. The proposed method is a significant contribution to improving the WSI registration quality, thus advancing the field of digital pathology.