Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.11.23.624680

Versatile Stain Transfer in Histopathology Using a Unified Diffusion Framework

Abstract

Histological staining is vital in clinical pathology for visualizing tissue structures. However, these techniques are laborious and time-consuming. Digital virtual staining offers a promising solution, but existing methods typically rely on Generative Adversarial Networks (GANs), which may suffer from artifacts and mode collapse. Motivated by the success of diffusion models, we present DUST, a novel Diffusion-based Unified framework for versatile Stain Transfer in histopathology. To enhance domain awareness and task-specific performance, we propose a dual encoding strategy that integrates the stain types of both the source and target domains. Additionally, we introduce a dynamic dual-output head to address the unstable intensity issue encountered with conventional DDPM implementations. Validated on a curated fourstain kidney histopathological dataset (H&E, MT, PAS, and PASM), DUST demonstrates superior versatile stain transfer capabilities. Our research highlights the potential of diffusion models to advance virtual staining, paving the way for more efficient digital pathology analyses.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yan, X., Yuan, M., Lu, Y., Zhang, Y., Chen, Z., Bao, P., Li, Z., Dong, B., Yang, L., Zhang, L., Zhou, F.. 2024-11-23. Versatile Stain Transfer in Histopathology Using a Unified Diffusion Framework. https://doi.org/10.1101/2024.11.23.624680

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

Loss of the Coronary Artery Disease Risk Gene Leiomodin1 in Vascular Smooth Muscle Cells Triggers Rapid Onset Coronary Atherosclerosis

BackgroundAtherosclerosis is the primary underlying cause of coronary artery disease (CAD). Leiomodin1 is a vascular smooth muscle cell (VSMC)-restricted CAD risk gene whose role in coronary artery pathophysiology is unknown. Global loss of Leiomodin1 causes lethal neonatal visceral myopathy, requiring unique approaches for study in VSMCs. MethodsSeveral distinct Leiomodin1 mutant mouse models were generated by clustered regularly interspaced short palindromic repeats (CRISPR). Control (Lmod1WT) and VSMC-restricted Lmod1 knockout (Lmod1SMKO) mice were subjected to various atherogenic regimens. Atherosclerosis and LMOD1 expression in mouse and human coronary arteries were assessed by histopathology and confocal immunofluorescence microscopy. Coronary arteries from Lmod1WT and Lmod1SMKO mice were analyzed with assorted stains and antibodies, immunogold lineage tracing, spatial metabolomics/transcriptomics, and single-cell RNA sequencing (scRNA-seq). Mouse aortic SMCs from Lmod1WT and Lmod1SMKO mice were subjected to lipid loading with lentiviruses expressing wild-type Lmod1, a nucleation deficient Leiomodin1 (Lmod1ND), or a short hairpin RNA (shRNA) targeting Thrombospondin (Thbs1). ResultsUnder atherogenic conditions, Lmod1SMKO mice displayed unremarkable vessels in several organs but developed diffuse and occlusive coronary atherosclerosis. No such disease was observed in Lmod1WT mice. Time-course studies documented lipid insudation and VSMC foam cell formation in the coronary arteries of Lmod1SMKO mice as early as six days post-regimen. Immunogold lineage tracing demonstrated 46% of coronary plaque cells being of VSMC origin, with most showing evidence of lipid uptake. An intronic deletion of Lmod1, containing a conserved region where the single nucleotide variant associated with CAD exists, showed attenuated LMOD1 expression; heterozygous Lmod1SMKO mice, with a similar reduction in LMOD1, showed no CAD. Spatial metabolomics uncovered multiple lipid species within coronary atheromata of Lmod1SMKO mice, and spatial/scRNA-seq of similar coronary lesions disclosed altered lipid pathways with a consistent elevation in Thbs1. In vitro mechanistic studies revealed lipid accumulation in Lmod1SMKO VSMCs that was rescued by Lmod1WT, Lmod1ND, and Thbs1 shRNA. VSMC-restricted expression of Lmod1ND in mice resulted in negligible coronary atherosclerosis. ConclusionsUnder proatherogenic conditions, Lmod1SMKO mice present with rapidly manifesting coronary atherosclerosis that appears to be independent of the actin nucleation function of LMOD1. Targeting Thbs1 represents a viable strategy to mitigate VSMC foam cell formation. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIVascular smooth muscle cell (VSMC) loss of Leiomodin1 (Lmod1) causes diffuse and occlusive coronary atherosclerosis in mice, with little or no such disease in other vascular beds. C_LIO_LIA novel immunogold lineage tracing assay shows VSMC migration to the intima as early as six days following an atherogenic regimen, and quantitative studies demonstrate that 46% of coronary plaque cells are of SMC origin. C_LIO_LIThe coronary phenotype appears to be independent of LMOD1s actin nucleation activity, but VSMC lipid uptake is thrombospondin-dependent. C_LI What are the clinical implications?O_LILMOD1 is an annotated smooth muscle cell-restricted risk allele for human coronary artery disease (CAD), offering new insight into the role of smooth muscle cells in atherogenesis. C_LIO_LIThe rapidly manifesting CAD phenotype in Lmod1 knockout mice enables expedited testing of novel therapeutics to mitigate disease progression. C_LIO_LINew insight into LMOD1 pathobiology will help inform further SNV interrogation of the LMOD1 locus for CAD risk in patients. C_LI

pathology↗

Value-Based Evidence Accumulation as a Transdiagnostic Marker of General Distress

General distress cuts across psychiatric symptom domains, yet its computational correlates remain poorly defined. We examined whether drift rate--a core parameter indexing the efficiency of evidence accumulation--is more strongly associated with general distress than with domain-specific symptoms. In a cross-sectional online sample of 441 adults from the general population, participants completed a perceptual and value-based decision-making task, symptom assessments, and cognitive testing. Drift rates were estimated using hierarchical drift-diffusion modeling. Individuals with severe symptom elevations showed robust reductions in drift rate, particularly for value-based decisions. Mixed-effects models demonstrated that general distress, indexed by the Positive Symptom Distress Index, was more strongly associated with value-based than perceptual drift rate, even after accounting for all symptom domains. Value-based drift rate also explained variance in general distress beyond that accounted for by elevated symptoms across domains and selectively attenuated associations with somatization and paranoid symptoms. These findings suggest that value-based evidence accumulation captures a transdiagnostic component of distress-related impairment that is not reducible to symptom burden alone.

pathology↗