arXiv subjects

Muhammad Khalid Khan Niazi

Publications and source records attributed to Muhammad Khalid Khan Niazi.

17 recordsLinked to original sources

arXiv2026

Morphology-aware deep learning predicts colorectal cancer survival from whole-slide images

Background: Five-year survival prediction from hematoxylin-and-eosin whole-slide images could support risk stratification, but the task is weakly supervised, and the tissue morphologies carrying prognostic information remain incompletely characterized. Methods: We conducted a retrospective secondary analysis using TCGA-COAD/READ (n=562) for morphology-specific analysis, Alliance/ CALGB 89803 (n=424) for model development, and SurGen (n=218) for external evaluation. We propose MorphContrast, a morphology-aware contrastive multiple-instance learning framework that uses tissue labels as structural supervision for five-year survival prediction. MorphContrast combines gated-attention pooling with three auxiliary objectives: patch-level morphology labels define within-patient contrasts, outcome concordance or discordance defines cross-patient contrasts within matched morphologies, and diversity regularization discourages representational collapse. Morphology-matched patches from patients with discordant outcomes serve as hard negatives, encouraging prognostic discrimination within comparable histologic contexts. Results: Morphology-specific models show weak but distributed prognostic discrimination: adipose tissue achieves an area under the receiver operating characteristic curve (AUC) of 0.622, stroma achieves 0.604, and both perform comparably to tumor epithelium (0.601-0.605). On Alliance/CALGB 89803, the single model achieves an AUC of 0.642, while the post hoc ensemble reaches a pooled out-of-fold AUC of 0.70 and a risk-group hazard ratio of 3.79 (95% confidence interval: 2.55-5.63). On the external SurGen colon cancer cohort (n=218), the single model and ensemble achieve AUCs of 0.669 and 0.678, respectively. Conclusions: These findings support tissue morphology as structural supervision for outcome-aware representation learning in colorectal cancer prognosis.

cs.CV↗

arXiv2026

Streamline pathology foundation model by cross-magnification distillation

Foundation models (FM) have transformed computational pathology but remain computationally prohibitive for clinical deployment due to their massive parameter counts and high-magnification processing requirements. Here, we introduce XMAG, a lightweight FM developed through corss-magnification distillation that transfers knowledge from state-of-the-art 20x magnification teacher to an efficient 5x magnification student architecture. XMAG employs a compact backbone and operates entirely at 5x, requiring 11.3 times fewer patches per whole slide image (WSI) compared to existing approaches. Our Novel distillation framework incorporates dual-level knowledge transfer, aligning both global image representations and local spatial token mapping. We trained XMAG on 3.49 million images curated from publicly available datasets and evaluated performance across six clinically relevant histopathology analysis tasks spanning multiple cancer types. XMAG achieved diagnostic accuracy within 1% of substantially larger foundation models while delivering 30-fold processing acceleration, reaching 8.8 WSIs per minute processing speed. Our cross-institutional validation confirmed robust generalization. Further, we developed an end-to-end training strategy to further boost our model's performance to approach the larger FMs' performance. These results establish cross-magnification distillation as a viable approach for deploying FM capabilities in resource-constrained clinical environments, potentially enabling real-time pathology AI integration.

cs.CV↗

arXiv2026

Dino-NestedUNet: Unlocking Foundation Vision Encoders for Pathology Tumor Bulk Segmentation via Dense Decoding

Vision foundation models (VFMs), such as DINOv3, provide rich semantic representations that are promising for computational pathology. However, many current adaptations pair frozen VFMs with lightweight decoders, creating a capacity mismatch that often limits boundary fidelity for infiltrative tumor bulk segmentation. This paper presents Dino-NestedUNet, a framework that couples a pre-trained DINOv3 encoder with a Nested Dense Decoder. Instead of sparse skip connections and linear upsampling, the proposed decoder forms a dense grid of intermediate pathways to enable continuous feature reuse and multi-scale recalibration, aligning high-level semantics with low-level morphological textures during reconstruction. We evaluate Dino-NestedUNet on three histopathology cohorts (multi-center CHTN, institutional OSU, and CAMELYON16) and observe consistent improvements over UNet++ and standard Dino-UNet variants, particularly under cross-domain shift. To further assess external generalization, we perform zero-shot evaluation by training on CHTN and directly testing on unseen TIGER WSIBULK and OSU CRC cohorts without fine-tuning. These results suggest that dense decoding is a key ingredient for unlocking foundation encoders in boundary-sensitive pathology segmentation.

cs.CV↗

arXiv2026

Unified Multi-Foundation-Model Slide Representation for Pan-Cancer Recognition and Text-Guided Tumor Localization

The expanding ecosystem of pathology foundation models has produced powerful but fragmented tile-level representations, limiting their use in clinical tasks that require unified slide-level reasoning and interpretable linkage to clinically meaningful information. We present ASTRA, a pan-cancer framework that integrates heterogeneous foundation-model representations into a shared slide-level representation space and semantically grounds that space using structured pathology annotation fields, including classification category, cancer type, and anatomic site. ASTRA combines sparse mixture-of-experts contextualization, masked multi-model reconstruction, and contrastive alignment to structured pathology prompts to learn slide representations that support 4-category classification, 3-class solid tumor typing, 16-class cancer typing, and text-guided tumor localization without pixel-level supervision. Developed on a CHTN cohort of 10,359 whole-slide images (WSIs) spanning 16 tumor types, ASTRA consistently improves pan-cancer classification across four pathology foundation-model backbones, achieving up to 97.8% macro-AUC for 4-category classification, 99.7% for 3-class solid tumor typing, and 99.2% for 16-class cancer typing. For tumor localization, ASTRA achieves a mean Dice of 0.897 on an annotated in-domain CHTN subset (n = 380) spanning 16 cancer types and 0.738 on an external TCGA cohort (n = 1,686) spanning four cancer types. These results demonstrate that minimal structured pathology annotation fields derived from slide-level metadata can provide effective semantic supervision for unified slide representation learning, enabling both pan-cancer prediction and weakly supervised tumor localization within a single framework.

cs.CV↗

arXiv2026

MorphDistill: Distilling Unified Morphological Knowledge from Pathology Foundation Models for Colorectal Cancer Survival Prediction

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Accurate survival prediction is essential for treatment stratification, yet existing pathology foundation models often overlook organ-specific features critical for CRC prognostication. Methods: We propose MorphDistill, a two-stage framework that distills complementary knowledge from multiple pathology foundation models into a compact CRC-specific encoder. In Stage I, a student encoder is trained using dimension-agnostic multi-teacher relational distillation with supervised contrastive regularization on large-scale colorectal datasets. This preserves inter-sample relationships from ten foundation models without explicit feature alignment. In Stage II, the encoder extracts patch-level features from whole-slide images, which are aggregated via attention-based multiple instance learning to predict five-year survival. Results: On the Alliance/CALGB 89803 cohort (n=424, stage III CRC), MorphDistill achieves an AUC of 0.68 (SD 0.08), an approximately 8% relative improvement over the strongest baseline (AUC 0.63). It also attains a C-index of 0.661 and a hazard ratio of 2.52 (95% CI: 1.73-3.65), outperforming all baselines. On an external TCGA cohort (n=562), it achieves a C-index of 0.628, demonstrating strong generalization across datasets and robustness across clinical subgroups. Conclusion: MorphDistill enables task-specific representation learning by integrating knowledge from multiple foundation models into a unified encoder. This approach provides an efficient strategy for prognostic modeling in computational pathology, with potential for broader oncology applications. Further validation across additional cohorts and disease stages is warranted.

cs.CV↗

arXiv2026

Weakly Supervised Teacher-Student Framework with Progressive Pseudo-mask Refinement for Gland Segmentation

Background and objectives: Colorectal cancer histopathological grading depends on accurate segmentation of glandular structures. Current deep learning approaches rely on large scale pixel level annotations that are labor intensive and difficult to obtain in routine clinical practice. Weakly supervised semantic segmentation offers a promising alternative. However, class activation map based methods often produce incomplete pseudo masks that emphasize highly discriminative regions and fail to supervise unannotated glandular structures. We propose a weakly supervised teacher student framework that leverages sparse pathologist annotations and an Exponential Moving Average stabilized teacher network to generate refined pseudo masks. Methods: The framework integrates confidence based filtering, adaptive fusion of teacher predictions with limited ground truth, and curriculum guided refinement to progressively segment unannotated glandular regions. The method was evaluated on an institutional colorectal cancer cohort from The Ohio State University Wexner Medical Center consisting of 60 hematoxylin and eosin stained whole slide images and on public datasets including the Gland Segmentation dataset, TCGA COAD, TCGA READ, and SPIDER. Results: On the Gland Segmentation dataset the framework achieved a mean Intersection over Union of 80.10 and a mean Dice coefficient of 89.10. Cross cohort evaluation demonstrated robust generalization on TCGA COAD and TCGA READ without additional annotations, while reduced performance on SPIDER reflected domain shift. Conclusions: The proposed framework provides an annotation efficient and generalizable approach for gland segmentation in colorectal histopathology.

cs.CV↗

arXiv2026

Inferring Clinically Relevant Molecular Subtypes of Pancreatic Cancer from Routine Histopathology Using Deep Learning

Molecular subtyping of PDAC into basal-like and classical has established prognostic and predictive value. However, its use in clinical practice is limited by cost, turnaround time, and tissue requirements, thereby restricting its application in the management of PDAC. We introduce PanSubNet, an interpretable deep learning framework that predicts therapy-relevant molecular subtypes directly from standard H&E-stained WSIs. PanSubNet was developed using data from 1,055 patients across two multi-institutional cohorts (PANCAN, n=846; TCGA, n=209) with paired histology and RNA-seq data. Ground-truth labels were derived using the validated Moffitt 50-gene signature refined by GATA6 expression. The model employs dual-scale architecture that fuses cellular-level morphology with tissue-level architecture, leveraging attention mechanisms for multi-scale representation learning and transparent feature attribution. On internal validation within PANCAN using five-fold cross-validation, PanSubNet achieved mean AUC of 88.5% with balanced sensitivity and specificity. External validation on the independent TCGA cohort without fine-tuning demonstrated robust generalizability (AUC 84.0%). PanSubNet preserved and, in metastatic disease, strengthened prognostic stratification compared to RNA-seq based labels. Prediction uncertainty linked to intermediate transcriptional states, not classification noise. Model predictions are aligned with established transcriptomic programs, differentiation markers, and DNA damage repair signatures. By enabling rapid, cost-effective molecular stratification from routine H&E-stained slides, PanSubNet offers a clinically deployable and interpretable tool for genetic subtyping. We are gathering data from two institutions to validate and assess real-world performance, supporting integration into digital pathology workflows and advancing precision oncology for PDAC.

cs.LG↗

arXiv2026

PathoScribe: Transforming Pathology Data into a Living Library with a Unified LLM-Driven Framework for Semantic Retrieval and Clinical Integration

Pathology underpins modern diagnosis and cancer care, yet its most valuable asset, the accumulated experience encoded in millions of narrative reports, remains largely inaccessible. Although institutions are rapidly digitizing pathology workflows, storing data without effective mechanisms for retrieval and reasoning risks transforming archives into a passive data repository, where institutional knowledge exists but cannot meaningfully inform patient care. True progress requires not only digitization, but the ability for pathologists to interrogate prior similar cases in real time while evaluating a new diagnostic dilemma. We present PathoScribe, a unified retrieval-augmented large language model (LLM) framework designed to transform static pathology archives into a searchable, reasoning-enabled living library. PathoScribe enables natural language case exploration, automated cohort construction, clinical question answering, immunohistochemistry (IHC) panel recommendation, and prompt-controlled report transformation within a single architecture. Evaluated on 70,000 multi-institutional surgical pathology reports, PathoScribe achieved perfect Recall@10 for natural language case retrieval and demonstrated high-quality retrieval-grounded reasoning (mean reviewer score 4.56/5). Critically, the system operationalized automated cohort construction from free-text eligibility criteria, assembling research-ready cohorts in minutes (mean 9.2 minutes) with 91.3% agreement to human reviewers and no eligible cases incorrectly excluded, representing orders-of-magnitude reductions in time and cost compared to traditional manual chart review. This work establishes a scalable foundation for converting digital pathology archives from passive storage systems into active clinical intelligence platforms.

cs.CV↗

arXiv2026

RANGER: Sparsely-Gated Mixture-of-Experts with Adaptive Retrieval Re-ranking for Pathology Report Generation

Pathology report generation remains a relatively under-explored downstream task, primarily due to the gigapixel scale and complex morphological heterogeneity of Whole Slide Images (WSIs). Existing pathology report generation frameworks typically employ transformer architectures, relying on a homogeneous decoder architecture and static knowledge retrieval integration. Such architectures limit generative specialization and may introduce noisy external guidance during the report generation process. To address these limitations, we propose RANGER, a sparsely-gated Mixture-of-Experts (MoE) framework with adaptive retrieval re-ranking for pathology report generation. Specifically, we integrate a sparsely gated MoE into the decoder, along with noisy top-$k$ routing and load-balancing regularization, to enable dynamic expert specialization across various diagnostic patterns. Additionally, we introduce an adaptive retrieval re-ranking module that selectively refines retrieved memory from a knowledge base before integration, reducing noise and improving semantic alignment based on visual feature representations. We perform extensive experiments on the PathText-BRCA dataset and demonstrate consistent improvements over existing approaches across standard natural language generation metrics. Our full RANGER model achieves optimal performance on PathText dataset, reaching BLEU-1 to BLEU-4 scores of 0.4598, 0.3044, 0.2036, and 0.1435, respectively, with METEOR of 0.1883, and ROUGE-L of 0.3038, validating the effectiveness of dynamic expert routing and adaptive knowledge refinement for semantically grounded pathology report generation.

cs.CV↗

arXiv2026

Learning the Language of Histopathology Images reveals Prognostic Subgroups in Invasive Lung Adenocarcinoma Patients

Recurrence remains a major clinical challenge in surgically resected invasive lung adenocarcinoma, where existing grading and staging systems fail to capture the cellular complexity that underlies tumor aggressiveness. We present PathRosetta, a novel AI model that conceptualizes histopathology as a language, where cells serve as words, spatial neighborhoods form syntactic structures, and tissue architecture composes sentences. By learning this language of histopathology, PathRosetta predicts five-year recurrence directly from hematoxylin-and-eosin (H&E) slides, treating them as documents representing the state of the disease. In a multi-cohort dataset of 289 patients (600 slides), PathRosetta achieved an area under the curve (AUC) of 0.78 +- 0.04 on the internal cohort, significantly outperforming IASLC grading (AUC:0.71), AJCC staging (AUC:0.64), and other state-of-the-art AI models (AUC:0.62-0.67). It yielded a hazard ratio of 9.54 and a concordance index of 0.70, generalized robustly to external TCGA (AUC:0.75) and CPTAC (AUC:0.76) cohorts, and performed consistently across demographic and clinical subgroups. Beyond whole-slide prediction, PathRosetta uncovered prognostic subgroups within individual cell types, revealing that even within benign epithelial, stromal, or other cells, distinct morpho-spatial phenotypes correspond to divergent outcomes. Moreover, because the model explicitly understands what it is looking at, including cell types, cellular neighborhoods, and higher-order tissue morphology, it is inherently interpretable and can articulate the rationale behind its predictions. These findings establish that representing histopathology as a language enables interpretable and generalizable prognostication from routine histology.

cs.CV↗

arXiv2025

Progressive Translation of H&E to IHC with Enhanced Structural Fidelity

Compared to hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC) not only maintains the structural features of tissue samples, but also provides high-resolution protein localization, which is essential for aiding in pathology diagnosis. Despite its diagnostic value, IHC remains a costly and labor-intensive technique. Its limited scalability and constraints in multiplexing further hinder widespread adoption, especially in resource-limited settings. Consequently, researchers are increasingly exploring computational stain translation techniques to synthesize IHC-equivalent images from H&E-stained slides, aiming to extract protein-level information more efficiently and cost-effectively. However, most existing stain translation techniques rely on a linearly weighted summation of multiple loss terms within a single objective function, strategy that often overlooks the interdepedence among these components-resulting in suboptimal image quality and an inability to simultaneously preserve structural authenticity and color fidelity. To address this limitation, we propose a novel network architecture that follows a progressive structure, incorporating color and cell border generation logic, which enables each visual aspect to be optimized in a stage-wise and decoupled manner. To validate the effectiveness of our proposed network architecture, we build upon the Adaptive Supervised PatchNCE (ASP) framework as our baseline. We introduce additional loss functions based on 3,3'-diaminobenzidine (DAB) chromogen concentration and image gradient, enhancing color fidelity and cell boundary clarity in the generated IHC images. By reconstructing the generation pipeline using our structure-color-cell boundary progressive mechanism, experiments on HER2 and ER datasets demonstrated that the model significantly improved visual quality and achieved finer structural details.

cs.CV↗

arXiv2025

Hyperparameter Optimization and Reproducibility in Deep Learning Model Training

Reproducibility remains a critical challenge in foundation model training for histopathology, often hindered by software randomness, hardware non-determinism, and inconsistent hyperparameter reporting. To investigate these issues, we trained a CLIP model on the QUILT-1M dataset and systematically evaluated the impact of different hyperparameter settings and augmentation strategies across three downstream histopathology datasets (PatchCamelyon, LC25000-Lung, and LC25000-Colon). Despite variability across runs, we identified clear trends: RandomResizedCrop values of 0.7-0.8 outperformed more aggressive (0.6) or conservative (0.9) settings, distributed training without local loss improved stability, and learning rates below 5.0e-5 consistently degraded performance across all datasets. The LC25000 (Colon) dataset consistently provided the most reproducible benchmark. These findings highlight that reproducibility in computational pathology depends not only on transparent documentation but also on carefully chosen experimental configurations, and we provide practical rules to guide future efforts in developing reproducible foundation models for digital pathology.

cs.CV↗

arXiv2025

Morphology-Aware Prognostic model for Five-Year Survival Prediction in Colorectal Cancer from H&E Whole Slide Images

Colorectal cancer (CRC) remains the third most prevalent malignancy globally, with approximately 154,000 new cases and 54,000 projected deaths anticipated for 2025. The recent advancement of foundation models in computational pathology has been largely propelled by task agnostic methodologies that can overlook organ-specific crucial morphological patterns that represent distinct biological processes that can fundamentally influence tumor behavior, therapeutic response, and patient outcomes. The aim of this study is to develop a novel, interpretable AI model, PRISM (Prognostic Representation of Integrated Spatial Morphology), that incorporates a continuous variability spectrum within each distinct morphology to characterize phenotypic diversity and reflecting the principle that malignant transformation occurs through incremental evolutionary processes rather than abrupt phenotypic shifts. PRISM is trained on 8.74 million histological images extracted from surgical resection specimens of 424 patients with stage III CRC. PRISM achieved superior prognostic performance for five-year OS (AUC = 0.70 +- 0.04; accuracy = 68.37% +- 4.75%; HR = 3.34, 95% CI = 2.28-4.90; p < 0.0001), outperforming existing CRC-specific methods by 15% and AI foundation models by ~23% accuracy. It showed sex-agnostic robustness (AUC delta = 0.02; accuracy delta = 0.15%) and stable performance across clinicopathological subgroups, with minimal accuracy fluctuation (delta = 1.44%) between 5FU/LV and CPT-11/5FU/LV regimens, replicating the Alliance cohort finding of no survival difference between treatments.

cs.CV↗

arXiv2025

Predicting Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancer Using Pre-Treatment Histopathologic Images

Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive behavior and lack of targeted therapies. Accurate early prediction of response to neoadjuvant chemotherapy (NACT) is essential for guiding personalized treatment strategies and improving patient outcomes. In this study, we present an attention-based multiple instance learning (MIL) framework designed to predict pathologic complete response (pCR) directly from pre-treatment hematoxylin and eosin (H&E)-stained biopsy slides. The model was trained on a retrospective in-house cohort of 174 TNBC patients and externally validated on an independent cohort (n = 30). It achieved a mean area under the curve (AUC) of 0.85 during five-fold cross-validation and 0.78 on external testing, demonstrating robust predictive performance and generalizability. To enhance model interpretability, attention maps were spatially co-registered with multiplex immuno-histochemistry (mIHC) data stained for PD-L1, CD8+ T cells, and CD163+ macrophages. The attention regions exhibited moderate spatial overlap with immune-enriched areas, with mean Intersection over Union (IoU) scores of 0.47 for PD-L1, 0.45 for CD8+ T cells, and 0.46 for CD163+ macrophages. The presence of these biomarkers in high-attention regions supports their biological relevance to NACT response in TNBC. This not only improves model interpretability but may also inform future efforts to identify clinically actionable histological biomarkers directly from H&E-stained biopsy slides, further supporting the utility of this approach for accurate NACT response prediction and advancing precision oncology in TNBC.

q-bio.QM↗

arXiv2024

Machine Learning-Based Analysis of Ebola Virus' Impact on Gene Expression in Nonhuman Primates

This study introduces the Supervised Magnitude-Altitude Scoring (SMAS) methodology, a machine learning-based approach, for analyzing gene expression data obtained from nonhuman primates (NHPs) infected with Ebola virus (EBOV). We utilize a comprehensive dataset of NanoString gene expression profiles from Ebola-infected NHPs, deploying the SMAS system for nuanced host-pathogen interaction analysis. SMAS effectively combines gene selection based on statistical significance and expression changes, employing linear classifiers such as logistic regression to accurately differentiate between RT-qPCR positive and negative NHP samples. A key finding of our research is the identification of IFI6 and IFI27 as critical biomarkers, demonstrating exceptional predictive performance with 100% accuracy and Area Under the Curve (AUC) metrics in classifying various stages of Ebola infection. Alongside IFI6 and IFI27, genes, including MX1, OAS1, and ISG15, were significantly upregulated, highlighting their essential roles in the immune response to EBOV. Our results underscore the efficacy of the SMAS method in revealing complex genetic interactions and response mechanisms during EBOV infection. This research provides valuable insights into EBOV pathogenesis and aids in developing more precise diagnostic tools and therapeutic strategies to address EBOV infection in particular and viral infection in general.

q-bio.GN↗

arXiv2023

Attention2Minority: A salient instance inference-based multiple instance learning for classifying small lesions in whole slide images

Multiple instance learning (MIL) models have achieved remarkable success in analyzing whole slide images (WSIs) for disease classification problems. However, with regard to gigapixel WSI classification problems, current MIL models are often incapable of differentiating a WSI with extremely small tumor lesions. This minute tumor-to-normal area ratio in a MIL bag inhibits the attention mechanism from properly weighting the areas corresponding to minor tumor lesions. To overcome this challenge, we propose salient instance inference MIL (SiiMIL), a weakly-supervised MIL model for WSI classification. Our method initially learns representations of normal WSIs, and it then compares the normal WSIs representations with all the input patches to infer the salient instances of the input WSI. Finally, it employs attention-based MIL to perform the slide-level classification based on the selected patches of the WSI. Our experiments imply that SiiMIL can accurately identify tumor instances, which could only take up less than 1% of a WSI, so that the ratio of tumor to normal instances within a bag can increase by two to four times. It is worth mentioning that it performs equally well for large tumor lesions. As a result, SiiMIL achieves a significant improvement in performance over the state-of-the-art MIL methods.

cs.CV↗

arXiv2023

Cross-attention-based saliency inference for predicting cancer metastasis on whole slide images

Although multiple instance learning (MIL) methods are widely used for automatic tumor detection on whole slide images (WSI), they suffer from the extreme class imbalance within the small tumor WSIs. This occurs when the tumor comprises only a few isolated cells. For early detection, it is of utmost importance that MIL algorithms can identify small tumors, even when they are less than 1% of the size of the WSI. Existing studies have attempted to address this issue using attention-based architectures and instance selection-based methodologies, but have not yielded significant improvements. This paper proposes cross-attention-based salient instance inference MIL (CASiiMIL), which involves a novel saliency-informed attention mechanism, to identify breast cancer lymph node micro-metastasis on WSIs without the need for any annotations. Apart from this new attention mechanism, we introduce a negative representation learning algorithm to facilitate the learning of saliency-informed attention weights for improved sensitivity on tumor WSIs. The proposed model outperforms the state-of-the-art MIL methods on two popular tumor metastasis detection datasets, and demonstrates great cross-center generalizability. In addition, it exhibits excellent accuracy in classifying WSIs with small tumor lesions. Moreover, we show that the proposed model has excellent interpretability attributed to the saliency-informed attention weights. We strongly believe that the proposed method will pave the way for training algorithms for early tumor detection on large datasets where acquiring fine-grained annotations is practically impossible.

cs.CV↗