Beatrice S. Knudsen

Xiaoya Tang, Bodong Zhang, Beatrice S. Knudsen et al.

We here propose a novel hierarchical transformer model that adeptly integrates the feature extraction capabilities of Convolutional Neural Networks (CNNs) with the advanced representational potential of Vision Transformers (ViTs). Addressing the lack of inductive biases and dependence on extensive training datasets in ViTs, our model employs a CNN backbone to generate hierarchical visual representations. These representations are then adapted for transformer input through an innovative patch tokenization. We also introduce a 'scale attention' mechanism that captures cross-scale dependencies, complementing patch attention to enhance spatial understanding and preserve global perception. Our approach significantly outperforms baseline models on small and medium-sized medical datasets, demonstrating its efficiency and generalizability. The components are designed as plug-and-play for different CNN architectures and can be adapted for multiple applications. The code is available at https://github.com/xiaoyatang/DuoFormer.git.

Bodong Zhang, Xiwen Li, Hamid Manoochehri et al.

Digital histopathology whole slide images (WSIs) provide gigapixel-scale high-resolution images that are highly useful for disease diagnosis. However, digital histopathology image analysis faces significant challenges due to the limited training labels, since manually annotating specific regions or small patches cropped from large WSIs requires substantial time and effort. Weakly supervised multiple instance learning (MIL) offers a practical and efficient solution by requiring only bag-level (slide-level) labels, while each bag typically contains multiple instances (patches). Most MIL methods directly use frozen image patch features generated by various image encoders as inputs and primarily focus on feature aggregation. However, feature representation learning for encoder pretraining in MIL settings has largely been neglected. In our work, we propose a novel feature representation learning framework called weakly supervised contrastive learning (WeakSupCon) that incorporates bag-level label information during training. Our method does not rely on instance-level pseudo-labeling, yet it effectively separates patches with different labels in the feature space. Experimental results demonstrate that the image features generated by our WeakSupCon method lead to improved downstream MIL performance compared to self-supervised contrastive learning approaches in three datasets. Our related code is available at github.com/BzhangURU/Paper_WeakSupCon_for_MIL

Tushar Kataria, Shikha Dubey, Mary Bronner et al.

Deep learning models can generate virtual immunohistochemistry (IHC) stains from hematoxylin and eosin (H&E) images, offering a scalable and low-cost alternative to laboratory IHC. However, reliable evaluation of image quality remains a challenge as current texture- and distribution-based metrics quantify image fidelity rather than the accuracy of IHC staining. Here, we introduce an automated and accuracy grounded framework to determine image quality across sixteen paired or unpaired image translation models. Using color deconvolution, we generate masks of pixels stained brown (i.e., IHC-positive) as predicted by each virtual IHC model. We use the segmented masks of real and virtual IHC to compute stain accuracy metrics (Dice, IoU, Hausdorff distance) that directly quantify correct pixel - level labeling without needing expert manual annotations. Our results demonstrate that conventional image fidelity metrics, including Frechet Inception Distance (FID), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM), correlate poorly with stain accuracy and pathologist assessment. Paired models such as PyramidPix2Pix and AdaptiveNCE achieve the highest stain accuracy, whereas unpaired diffusion- and GAN-based models are less reliable in providing accurate IHC positive pixel labels. Moreover, whole-slide images (WSI) reveal performance declines that are invisible in patch-based evaluations, emphasizing the need for WSI-level benchmarks. Together, this framework defines a reproducible approach for assessing the quality of virtual IHC models, a critical step to accelerate translation towards routine use by pathologists.

Bodong Zhang, Hamid Manoochehri, Man Minh Ho et al.

Histopathological image classification is an important task in medical image analysis. Recent approaches generally rely on weakly supervised learning due to the ease of acquiring case-level labels from pathology reports. However, patch-level classification is preferable in applications where only a limited number of cases are available or when local prediction accuracy is critical. On the other hand, acquiring extensive datasets with localized labels for training is not feasible. In this paper, we propose a semi-supervised patch-level histopathological image classification model, named CLASS-M, that does not require extensively labeled datasets. CLASS-M is formed by two main parts: a contrastive learning module that uses separated Hematoxylin and Eosin images generated through an adaptive stain separation process, and a module with pseudo-labels using MixUp. We compare our model with other state-of-the-art models on two clear cell renal cell carcinoma datasets. We demonstrate that our CLASS-M model has the best performance on both datasets. Our code is available at github.com/BzhangURU/Paper_CLASS-M/tree/main

Bodong Zhang, Hamid Manoochehri, Xiwen Li et al.

Weakly supervised multiple instance learning (MIL) is a challenging task given that only bag-level labels are provided, while each bag typically contains multiple instances. This topic has been extensively studied in histopathological image analysis, where labels are usually available only at the whole slide image (WSI) level, while each WSI could be divided into thousands of small image patches for training. The dominant MIL approaches focus on feature aggregation and take fixed patch features as inputs. However, weakly supervised feature representation learning in MIL settings is always neglected. Those features used to be generated by self-supervised learning methods that do not utilize weak labels, or by foundation encoders pre-trained on other large datasets. In this paper, we propose a novel weakly supervised feature representation learning method called Weakly Supervised Contrastive Learning (WeakSupCon) that utilizes bag-level labels. In our method, we employ multi-task learning and define distinct contrastive losses for samples with different bag labels. Our experiments demonstrate that the features generated using WeakSupCon with limited computing resources significantly enhance MIL classification performance compared to self-supervised approaches across three datasets. Our WeakSupCon code is available at github.com/BzhangURU/Paper_WeakSupCon

Xiaoya Tang, Bodong Zhang, Man Minh Ho et al.

Despite the widespread adoption of transformers in medical applications, the exploration of multi-scale learning through transformers remains limited, while hierarchical representations are considered advantageous for computer-aided medical diagnosis. We propose a novel hierarchical transformer model that adeptly integrates the feature extraction capabilities of Convolutional Neural Networks (CNNs) with the advanced representational potential of Vision Transformers (ViTs). Addressing the lack of inductive biases and dependence on extensive training datasets in ViTs, our model employs a CNN backbone to generate hierarchical visual representations. These representations are adapted for transformer input through an innovative patch tokenization process, preserving the inherited multi-scale inductive biases. We also introduce a scale-wise attention mechanism that directly captures intra-scale and inter-scale associations. This mechanism complements patch-wise attention by enhancing spatial understanding and preserving global perception, which we refer to as local and global attention, respectively. Our model significantly outperforms baseline models in terms of classification accuracy, demonstrating its efficiency in bridging the gap between Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs). The components are designed as plug-and-play for different CNN architectures and can be adapted for multiple applications. The code is available at https://github.com/xiaoyatang/DuoFormer.git.

Hamid Manoochehri, Bodong Zhang, Beatrice S. Knudsen et al.

Self-supervised learning has become a cornerstone in various areas, particularly histopathological image analysis. Image augmentation plays a crucial role in self-supervised learning, as it generates variations in image samples. However, traditional image augmentation techniques often overlook the unique characteristics of histopathological images. In this paper, we propose a new histopathology-specific image augmentation method called stain reconstruction augmentation (SRA). We integrate our SRA with MoCo v3, a leading model in self-supervised contrastive learning, along with our additional contrastive loss terms, and call the new model SRA-MoCo v3. We demonstrate that our SRA-MoCo v3 always outperforms the standard MoCo v3 across various downstream tasks and achieves comparable or superior performance to other foundation models pre-trained on significantly larger histopathology datasets.

Jiayun Li, Wenyuan Li, Arkadiusz Gertych et al.

Histology review is often used as the `gold standard' for disease diagnosis. Computer aided diagnosis tools can potentially help improve current pathology workflows by reducing examination time and interobserver variability. Previous work in cancer grading has focused mainly on classifying pre-defined regions of interest (ROIs), or relied on large amounts of fine-grained labels. In this paper, we propose a two-stage attention-based multiple instance learning model for slide-level cancer grading and weakly-supervised ROI detection and demonstrate its use in prostate cancer. Compared with existing Gleason classification models, our model goes a step further by utilizing visualized saliency maps to select informative tiles for fine-grained grade classification. The model was primarily developed on a large-scale whole slide dataset consisting of 3,521 prostate biopsy slides with only slide-level labels from 718 patients. The model achieved state-of-the-art performance for prostate cancer grading with an accuracy of 85.11\% for classifying benign, low-grade (Gleason grade 3+3 or 3+4), and high-grade (Gleason grade 4+3 or higher) slides on an independent test set.