Pinaki Sarder

Harishwar Reddy Kasireddy, Patricio S. La Rosa, Akshita Gupta et al.

Histopathology foundation models (HFMs), pretrained on large-scale cancer datasets, have advanced computational pathology. However, their applicability to non-cancerous chronic kidney disease remains underexplored, despite coexistence of renal pathology with malignancies such as renal cell and urothelial carcinoma. We systematically evaluate 11 publicly available HFMs across 11 kidney-specific downstream tasks spanning multiple stains (PAS, H&E, PASM, and IHC), spatial scales (tile and slide-level), task types (classification, regression, and copy detection), and clinical objectives, including detection, diagnosis, and prognosis. Tile-level performance is assessed using repeated stratified group cross-validation, while slide-level tasks are evaluated using repeated nested stratified cross-validation. Statistical significance is examined using Friedman test followed by pairwise Wilcoxon signed-rank testing with Holm-Bonferroni correction and compact letter display visualization. To promote reproducibility, we release an open-source Python package, kidney-hfm-eval, available at https://pypi.org/project/kidney-hfm-eval/ , that reproduces the evaluation pipelines. Results show moderate to strong performance on tasks driven by coarse meso-scale renal morphology, including diagnostic classification and detection of prominent structural alterations. In contrast, performance consistently declines for tasks requiring fine-grained microstructural discrimination, complex biological phenotypes, or slide-level prognostic inference, largely independent of stain type. Overall, current HFMs appear to encode predominantly static meso-scale representations and may have limited capacity to capture subtle renal pathology or prognosis-related signals. Our results highlight the need for kidney-specific, multi-stain, and multimodal foundation models to support clinically reliable decision-making in nephrology.

Ruining Deng, Yihe Yang, David J. Pisapia et al.

Multi-class cell segmentation in high-resolution gigapixel whole slide images (WSIs) is crucial for various clinical applications. However, training such models typically requires labor-intensive, pixel-wise annotations by domain experts. Recent efforts have democratized this process by involving lay annotators without medical expertise. However, conventional non-corrective approaches struggle to handle annotation noise adaptively because they lack mechanisms to mitigate false positives (FP) and false negatives (FN) at both the image-feature and pixel levels. In this paper, we propose a consensus-aware self-corrective AI agent that leverages the Consensus Matrix to guide its learning process. The Consensus Matrix defines regions where both the AI and annotators agree on cell and non-cell annotations, which are prioritized with stronger supervision. Conversely, areas of disagreement are adaptively weighted based on their feature similarity to high-confidence consensus regions, with more similar regions receiving greater attention. Additionally, contrastive learning is employed to separate features of noisy regions from those of reliable consensus regions by maximizing their dissimilarity. This paradigm enables the model to iteratively refine noisy labels, enhancing its robustness. Validated on one real-world lay-annotated cell dataset and two reasoning-guided simulated noisy datasets, our method demonstrates improved segmentation performance, effectively correcting FP and FN errors and showcasing its potential for training robust models on noisy datasets. The official implementation and cell annotations are publicly available at https://github.com/ddrrnn123/CASC-AI.

Mahesh Bhosale, Abdul Wasi, Yuanhao Zhai et al.

Diffusion-based generative models have shown promise in synthesizing histopathology images to address data scarcity caused by privacy constraints. Diagnostic text reports provide high-level semantic descriptions, and masks offer fine-grained spatial structures essential for representing distinct morphological regions. However, public datasets lack paired text and mask data for the same histopathological images, limiting their joint use in image generation. This constraint restricts the ability to fully exploit the benefits of combining both modalities for enhanced control over semantics and spatial details. To overcome this, we propose PathDiff, a diffusion framework that effectively learns from unpaired mask-text data by integrating both modalities into a unified conditioning space. PathDiff allows precise control over structural and contextual features, generating high-quality, semantically accurate images. PathDiff also improves image fidelity, text-image alignment, and faithfulness, enhancing data augmentation for downstream tasks like nuclei segmentation and classification. Extensive experiments demonstrate its superiority over existing methods.

Brendon Lutnick, Leema Krishna Murali, Brandon Ginley et al.

We created a custom pipeline (histo-fetch) to efficiently extract random patches and labels from pathology whole slide images (WSIs) for input to a neural network on-the-fly. We prefetch these patches as needed during network training, avoiding the need for WSI preparation such as chopping/tiling. We demonstrate the utility of this pipeline to perform artificial stain transfer and image generation using the popular networks CycleGAN and ProGAN, respectively.

Brandon Ginley, Kuang-Yu Jen, Avi Rosenberg et al.

Glomerulosclerosis, interstitial fibrosis, and tubular atrophy (IFTA) are histologic indicators of irrecoverable kidney injury. In standard clinical practice, the renal pathologist visually assesses, under the microscope, the percentage of sclerotic glomeruli and the percentage of renal cortical involvement by IFTA. Estimation of IFTA is a subjective process due to a varied spectrum and definition of morphological manifestations. Modern artificial intelligence and computer vision algorithms have the ability to reduce inter-observer variability through rigorous quantitation. In this work, we apply convolutional neural networks for the segmentation of glomerulosclerosis and IFTA in periodic acid-Schiff stained renal biopsies. The convolutional network approach achieves high performance in intra-institutional holdout data, and achieves moderate performance in inter-intuitional holdout data, which the network had never seen in training. The convolutional approach demonstrated interesting properties, such as learning to predict regions better than the provided ground truth as well as developing its own conceptualization of segmental sclerosis. Subsequent estimations of IFTA and glomerulosclerosis percentages showed high correlation with ground truth.

Brendon Lutnick, Wen Dong, Zohar Nussinov et al.

Unsupervised segmentation of large images using a Potts model Hamiltonian is unique in that segmentation is governed by a resolution parameter which scales the sensitivity to small clusters. Here, the input image is first modeled as a graph, which is then segmented by minimizing a Hamiltonian cost function defined on the graph and the respective segments. However, there exists no closed form solution of this optimization, and using previous iterative algorithmic solution techniques, the problem scales quadratically in the Input Length. Therefore, while Potts model segmentation gives accurate segmentation, it is grossly underutilized as an unsupervised learning technique. We propose a fast statistical down-sampling of input image pixels based on the respective color features, and a new iterative method to minimize the Potts model energy considering pixel to segment relationship. This method is generalizable and can be extended for image pixel texture features as well as spatial features. We demonstrate that this new method is highly efficient, and outperforms existing methods for Potts model based image segmentation. We demonstrate the application of our method in medical microscopy image segmentation; particularly, in segmenting renal glomerular micro-environment in renal pathology. Our method is not limited to image segmentation, and can be extended to any image/data segmentation/clustering task for arbitrary datasets with discrete features.

Brendon Lutnick, Brandon Ginley, Darshana Govind et al.

Neural networks promise to bring robust, quantitative analysis to medical fields, but adoption is limited by the technicalities of training these networks. To address this translation gap between medical researchers and neural networks in the field of pathology, we have created an intuitive interface which utilizes the commonly used whole slide image (WSI) viewer, Aperio ImageScope (Leica Biosystems Imaging, Inc.), for the annotation and display of neural network predictions on WSIs. Leveraging this, we propose the use of a human-in-the-loop strategy to reduce the burden of WSI annotation. We track network performance improvements as a function of iteration and quantify the use of this pipeline for the segmentation of renal histologic findings on WSIs. More specifically, we present network performance when applied to segmentation of renal micro compartments, and demonstrate multi-class segmentation in human and mouse renal tissue slides. Finally, to show the adaptability of this technique to other medical imaging fields, we demonstrate its ability to iteratively segment human prostate glands from radiology imaging data.

Dandan Hu, Pinaki Sarder, Peter Ronhovde et al.

We have developed an automatic method for segmenting fluorescence lifetime (FLT) imaging microscopy (FLIM) images of cells inspired by a multi-resolution community detection (MCD) based network segmentation method. The image processing problem is framed as identifying segments with respective average FLTs against a background in FLIM images. The proposed method segments a FLIM image for a given resolution of the network composed using image pixels as the nodes and similarity between the pixels as the edges. In the resulting segmentation, low network resolution leads to larger segments and high network resolution leads to smaller segments. Further, the mean-square error (MSE) in estimating the FLT segments in a FLIM image using the proposed method was found to be consistently decreasing with increasing resolution of the corresponding network. The proposed MCD method outperformed a popular spectral clustering based method in performing FLIM image segmentation. The spectral segmentation method introduced noisy segments in its output at high resolution. It was unable to offer a consistent decrease in MSE with increasing resolution.