Accurate compensation of brain deformation is critical for reliable image-guided neurosurgery. Surgical manipulation and tumor resection induce tissue motion, causing preoperative planning images to become misaligned with the intraoperative anatomy. In this review, we examine data-driven methods developed between 2020 and 2025 for brain deformation registration and modeling, with a particular focus on learning-based approaches. A comprehensive literature search was conducted in PubMed, IEEE Xplore, Scopus, and Web of Science using predefined inclusion and exclusion criteria for computational methods addressing brain deformation in neurosurgical imaging, resulting in 46 eligible studies. We provide a unified analysis of methodological strategies, including deep learning-based image registration, direct deformation field regression, synthesis-driven multimodal alignment, resection-aware architectures for handling missing correspondences, and hybrid models integrating biomechanical priors. We also examine dataset utilization, evaluation metrics, validation protocols, and the assessment of uncertainty and generalization across studies. While learning-based methods demonstrate promising accuracy and computational efficiency, current approaches remain limited by out-of-distribution robustness, standardized benchmarking, interpretability, and readiness for clinical deployment. Our review highlights these gaps and outlines future directions toward more robust, generalizable, and clinically translatable solutions for neurosurgical guidance. By organizing recent advances and critically assessing evaluation practices, this work provides a comprehensive reference for researchers and clinicians working on data-driven registration and modeling of brain deformation.

Spatial Transcriptomics (ST) reveals the spatial distribution of gene expression in tissues, offering critical insights into biological processes and disease mechanisms. However, the high cost, limited coverage, and technical complexity of current ST technologies restrict their widespread use in clinical and research settings, making obtaining high-resolution transcriptomic profiles across large tissue areas challenging. Predicting ST from H&E-stained histology images has emerged as a promising alternative to address these limitations but remains challenging due to the heterogeneous relationship between histomorphology and gene expression, which is affected by substantial variability across patients and tissue sections. In response, we propose PH2ST, a prompt-guided hypergraph learning framework, which leverages limited ST signals to guide multi-scale histological representation learning for accurate and robust spatial gene expression prediction. Extensive evaluations on two public ST datasets and multiple prompt sampling strategies simulating real-world scenarios demonstrate that PH2ST not only outperforms existing state-of-the-art methods, but also shows strong potential for practical applications such as imputing missing spots, ST super-resolution, and local-to-global prediction, highlighting its value for scalable and cost-effective spatial gene expression mapping in biomedical contexts.

Retrieval-Augmented Generation (RAG) offers a promising solution to the limitations of static knowledge and hallucinations in Large Language Models (LLMs). While prior research has introduced numerous enhancements to RAG systems, a significant challenge remains under-explored: the potential conflict between external retrievals and LLMs' internal priors, which can undermine the quality of generated outputs. To tackle this issue, we present theEpitome-AugmentedGeneration (EAG) framework, which strategically aligns queries, external retrievals, and internal priors to produce high-quality LLM generations by selecting fuzzy inputs. EAG employs two novel lightweight modules, Criticism and Distillation, allowing traditional RAGs to be upgraded to EAGs without the need for specialized training data. Extensive experiments on five datasets across general and medical domains, including both open-ended and closed-ended tasks, validate the effectiveness of EAG. Our framework achieves substantial F1 score improvements: 7.03%, 23.35%, and 21.58% over baseline RAGs in medical QA tasks, 11.80% in law domain, 7.95% in finance domain, and 4.13% and 5.16% in general domain. Beyond performance gains, our study delves into the interplay between LLMs' internal priors and external retrievals, uncovering key principles that govern generation quality and providing valuable insights for future retrieval-augmented frameworks.

Interactive segmentation offers greater clinical potential in computational pathology compared to traditional automatic segmentation. By incorporating interactive input, it addresses the limitations of fully automatic segmentation models, which often fail to meet pathologists' requirements and rely heavily on large-scale, pixel-level annotated datasets. However, current interactive segmentation methods struggle to balance interaction cost and segmentation performance, and they fail to adapt effectively to slide-level segmentation, a task that is even more crucial in routine pathology analysis. In this study, we propose a Prototype-Guided Interactive Segmentation (ProGIS) framework for pathological image segmentation, designed to deliver precise segmentation results efficiently with minimal interaction signals. ProGIS identifies all same-type tissue connected components in a single interaction and supports multi-class segmentation without predefined categories during inference. Moreover, ProGIS can be easily adapted for slide-level interactive segmentation. Specifically, ProGIS consists of three modules: Prototype Initialization, Prototype Navigation, and Local Refinement. First, the Prototype Initialization module identifies categorical prototypes, which are then utilized in the Prototype Navigation module to identify all tissue connected components belonging to the same type. The local refinement module further refines the segmentation results using detailed correction signals to ensure the accuracy of challenging-to-distinguish regions. We evaluate our framework on two regions of interest level and two slide-level pathological segmentation datasets, achieving new state-of-the-art performance with fewer interactions than existing methods. Our code is available at https://github.com/JSGe-AI/ProGIS.

Whole Slide Images (WSIs) are the digital version of pathology slides, central to computational pathology. The WSI pyramid makes it can offer a wide range of diagnostic information, from global tissue structures to detailed cellular features. However, current multi-instance and graph representation learning methods struggle to create a unified framework that effectively captures both local spatial awareness and global WSI representation, limiting their performance in critical tasks such as tumor staging. To this end, we propose a Prototypeaware Heterogeneous Graph ATtention (PHGAT) network that enables each region within a WSI to perceive the representations of its diverse heterogeneous neighbors. This, in turn, guides the learning of WSI-level heterogeneous embedding through multilevel prototypes. Specifically, we introduce three node relations (i.e., local, non-local, and hierarchical) into WSI heterogeneous graph construction and design a novel Heterogeneous Calibration Graph ATtention (HC-GAT) module to propagate the various heterogeneous neighbor node representations within graphs. Then, a Level-aware Prototype Attention module is proposed to obtain prototypes from different levels by aggregating the node representations via a set of trainable query embeddings. Lastly, based on these learned prototypes, a prototype-aware hierarchical pooling module is designed to generate the final heterogeneous embedding of each WSI. Extensive experiments on six diverse datasets across three cancer types and two specific diagnostic tasks show that the proposed framework significantly outperforms the state-of-the-art tumor staging methods and performs comparably in cancer subtyping.

Medical AI has achieved strong predictive performance, yet most systems remain limited by shallow reasoning, poor transparency, and weak generalisation in safety-critical settings. Neurosymbolic AI offers a path beyond these constraints by combining neural models' ability to learn from complex clinical data with the explicit structure, logic, and domain knowledge of symbolic methods. This article examines how neurosymbolic approaches can address core challenges in healthcare AI through five key areas: hybrid reasoning that unifies learning and logic; symbol grounding that links internal representations to clinically meaningful concepts; clinical interpretability that exposes reasoning steps; human-integrated decision-making that keeps clinicians in control; and knowledge-driven diagnosis that incorporates guidelines, ontologies, and causal understanding. Together, these elements outline how neurosymbolic AI can support systems that are not only accurate but also transparent, clinically aligned, and robust in complex or data-sparse scenarios. Advancing this paradigm will require collaboration across AI research, clinical practice, and knowledge engineering, as well as governance mechanisms that ensure fairness and accountability. Neurosymbolic AI thus represents a promising direction for building trustworthy, knowledge-rich intelligence in healthcare.

MOTIVATION: Survival analysis is a branch of statistics that is crucial in medicine for modeling the time to critical events such as death or relapse, in order to improve treatment strategies and patient outcomes. Selecting survival models often involves a trade-off between performance and interpretability; deep learning models offer high performance but lack the transparency of more traditional approaches. This poses a significant issue in medicine, where practitioners are reluctant to use black-box models for critical patient decisions. RESULTS: We introduce CoxKAN, a Cox proportional hazards Kolmogorov-Arnold Network for interpretable, high-performance survival analysis. Kolmogorov-Arnold Networks (KANs) were recently proposed as an interpretable and accurate alternative to multi-layer perceptrons. We evaluated CoxKAN on four synthetic and nine real datasets, including five cohorts with clinical data and four with genomics biomarkers. In synthetic experiments, CoxKAN accurately recovered interpretable hazard function formulae and excelled in automatic feature selection. Evaluations on real datasets showed that CoxKAN consistently outperformed the traditional Cox proportional hazards model (by up to 4% in C-index) and matched or surpassed the performance of deep learning-based models. Importantly, CoxKAN revealed complex interactions between predictor variables and uncovered symbolic formulae, which are key capabilities that other survival analysis methods lack, to provide clear insights into the impact of key biomarkers on patient risk. AVAILABILITY AND IMPLEMENTATION: CoxKAN is available at GitHub and Zenodo.

Accurate histopathological image segmentation is crucial for precise disease diagnosis and prognosis. Yet, challenges like staining variations, imaging conditions, and tissue diversity impede model generalization across domains, such as different institutes or organs. Traditional domain generalization (DG) techniques, such as data augmentation and feature alignment, excel in classification tasks but face challenges in segmentation tasks due to their dense prediction requirements. These tasks are particularly computationally demanding, and are complicated due to the fine-grained feature variability that arises from the domain differences in histopathological images. To tackle this, we propose the Shallow-Deep Synergy (SDS) approach for the U-Net-based segmentation framework, which capitalizes on the distinctive characteristics of both shallow and deep layers of the U-Net. Specifically, we introduce the fine-grained domain variations in image intensities and textures for shallow layers, while focusing on aligning the pixel-level classification decision boundaries in deep layers by adjusting the optimization trajectory through class-wise gradient and feature alignment. Moreover, the SDS is equipped with a big-batch strategy further boosting alignment efficiency, achieving high accuracy without substantial GPU memory. Extensive experiments conducted on two histopathological segmentation datasets, each representing different domain types, demonstrate that the proposed SDS achieves superior generalization performance compared to existing domain generalization methods, even being competitive with intra-domain models in some cases.

MOTIVATION: Artificially making clinical decisions for patients with multi-morbidity has long been considered a thorny problem due to the complexity of the disease. Drug recommendations can assist doctors in automatically providing effective and safe drug combinations conducive to treatment and reducing adverse reactions. However, the existing drug recommendation works ignored two critical information. (i) Different types of medical information and their interrelationships in the patient's visit history can be used to construct a comprehensive patient representation. (ii) Patients with similar disease characteristics and their corresponding medication information can be used as a reference for predicting drug combinations. RESULTS: To address these limitations, we propose DAPSNet, which encodes multi-type medical codes into patient representations through code- and visit-level attention mechanisms, while integrating drug information corresponding to similar patient states to improve the performance of drug recommendation. Specifically, our DAPSNet is enlightened by the decision-making process of human doctors. Given a patient, DAPSNet first learns the importance of patient history records between diagnosis, procedure and drug in different visits, then retrieves the drug information corresponding to similar patient disease states for assisting drug combination prediction. Moreover, in the training stage, we introduce a novel information constraint loss function based on the information bottleneck principle to constrain the learned representation and enhance the robustness of DAPSNet. We evaluate the proposed DAPSNet on the public MIMIC-III dataset, our model achieves relative improvements of 1.33%, 1.20% and 2.03% in Jaccard, F1 and PR-AUC scores, respectively, compared to state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The source code is available at the github repository: https://github.com/andylun96/DAPSNet.

Leukemia classification relies on a detailed cytomorphological examination of Bone Marrow (BM) smear. However, applying existing deep-learning methods to it is facing two significant limitations. Firstly, these methods require large-scale datasets with expert annotations at the cell level for good results and typically suffer from poor generalization. Secondly, they simply treat the BM cytomorphological examination as a multi-class cell classification task, thus failing to exploit the correlation among leukemia subtypes over different hierarchies. Therefore, BM cytomorphological estimation as a time-consuming and repetitive process still needs to be done manually by experienced cytologists. Recently, Multi-Instance Learning (MIL) has achieved much progress in data-efficient medical image processing, which only requires patient-level labels (which can be extracted from the clinical reports). In this paper, we propose a hierarchical MIL framework and equip it with Information Bottleneck (IB) to tackle the above limitations. First, to handle the patient-level label, our hierarchical MIL framework uses attention-based learning to identify cells with high diagnostic values for leukemia classification in different hierarchies. Then, following the information bottleneck principle, we propose a hierarchical IB to constrain and refine the representations of different hierarchies for better accuracy and generalization. By applying our framework to a large-scale childhood acute leukemia dataset with corresponding BM smear images and clinical reports, we show that it can identify diagnostic-related cells without the need for cell-level annotations and outperforms other comparison methods. Furthermore, the evaluation conducted on an independent test cohort demonstrates the high generalizability of our framework.

Multiple instance learning (MIL)-based methods have become the mainstream for processing the megapixel-sized whole slide image (WSI) with pyramid structure in the field of digital pathology. The current MIL-based methods usually crop a large number of patches from WSI at the highest magnification, resulting in a lot of redundancy in the input and feature space. Moreover, the spatial relations between patches can not be sufficiently modeled, which may weaken the model's discriminative ability on fine-grained features. To solve the above limitations, we propose a Multi-scale Graph Transformer (MG-Trans) with information bottleneck for whole slide image classification. MG-Trans is composed of three modules: patch anchoring module (PAM), dynamic structure information learning module (SILM), and multi-scale information bottleneck module (MIBM). Specifically, PAM utilizes the class attention map generated from the multi-head self-attention of vision Transformer to identify and sample the informative patches. SILM explicitly introduces the local tissue structure information into the Transformer block to sufficiently model the spatial relations between patches. MIBM effectively fuses the multi-scale patch features by utilizing the principle of information bottleneck to generate a robust and compact bag-level representation. Besides, we also propose a semantic consistency loss to stabilize the training of the whole model. Extensive studies on three subtyping datasets and seven gene mutation detection datasets demonstrate the superiority of MG-Trans.

Pathological primary tumor (pT) stage focuses on the infiltration degree of the primary tumor to surrounding tissues, which relates to the prognosis and treatment choices. The pT staging relies on the field-of-views from multiple magnifications in the gigapixel images, which makes pixel-level annotation difficult. Therefore, this task is usually formulated as a weakly supervised whole slide image (WSI) classification task with the slide-level label. Existing weakly-supervised classification methods mainly follow the multiple instance learning paradigm, which takes the patches from single magnification as the instances and extracts their morphological features independently. However, they cannot progressively represent the contextual information from multiple magnifications, which is critical for pT staging. Therefore, we propose a structure-aware hierarchical graph-based multi-instance learning framework (SGMF) inspired by the diagnostic process of pathologists. Specifically, a novel graph-based instance organization method is proposed, namely structure-aware hierarchical graph (SAHG), to represent the WSI. Based on that, we design a novel hierarchical attention-based graph representation (HAGR) network to capture the critical patterns for pT staging by learning cross-scale spatial features. Finally, the top nodes of SAHG are aggregated by a global attention layer for bag-level representation. Extensive studies on three large-scale multi-center pT staging datasets with two different cancer types demonstrate the effectiveness of SGMF, which outperforms state-of-the-art up to 5.6% in the F1 score.

Computational Pathology (CPATH) offers the possibility for highly accurate and low-cost automated pathological diagnosis. However, the high time cost of model inference is one of the main issues limiting the application of CPATH methods. Due to the large size of Whole-Slide Image (WSI), commonly used CPATH methods divided a WSI into a large number of image patches at relatively high magnification, then predicted each image patch individually, which is time-consuming. In this paper, we propose a novel Uncertainty-based Model Acceleration (UMA) method for reducing the time cost of model inference, thereby relieving the deployment burden of CPATH applications. Enlightened by the slide-viewing process of pathologists, only a few high-uncertain regions are regarded as “suspicious” regions that need to be predicted at high magnification, and most of the regions in WSI are predicted at low magnification, thereby reducing the times of image patch extraction and prediction. Meanwhile, uncertainty estimation ensures prediction accuracy at low magnification. We take two fundamental CPATH classification tasks (i.e., cancer region detection and subtyping) as examples. Extensive experiments on two large-scale renal cell carcinoma classification datasets demonstrate that our UMA can significantly reduce the time cost of model inference while maintaining competitive classification performance.

Predicting drug combinations according to patients' electronic health records is an essential task in intelligent healthcare systems, which can assist clinicians in ordering safe and effective prescriptions. However, existing work either missed/underutilized the important information lying in the drug molecule structure in drug encoding or has insufficient control over Drug-Drug Interactions (DDIs) rates within the predictions. To address these limitations, we propose CSEDrug, which enhances the drug encoding and DDIs controlling by leveraging multi-faceted drug knowledge, including molecule structures of drugs, Synergistic DDIs (SDDIs), and Antagonistic DDIs (ADDIs). We integrate these types of knowledge into CSEDrug by a graph-based drug encoder and multiple loss functions, including a novel triplet learning loss and a comprehensive DDI controllable loss. We evaluate the performance of CSEDrug in terms of accuracy, effectiveness, and safety on the public MIMIC-III dataset. The experimental results demonstrate that CSEDrug outperforms several state-of-the-art methods and achieves a 2.93% and a 2.77% increase in the Jaccard similarity scores and F1 scores, meanwhile, a 0.68% reduction of the ADDI rate (safer drug combinations), and 0.69% improvement of the SDDI rate (more effective drug combinations).

Patient similarity measurement is an essential step in discovering clinically meaningful subgroups and building case retrieval systems. Most existing studies implement this procedure using similarity measurement algorithms on the multivariate clinical time-series (input space) or the low-dimensional patient representation (representation space) learned by a representation learning model. However, they either suffer from the adverse effects of irrelevant variables in the data or fail to assess the fine-grained similarity underneath the disease progress. In this paper, we propose a method to measure more fine-grained patient similarity in the state space, where each patient is represented by a series of state representations that reveal the dynamic health status. We discuss three desiderata, including stability, personality, and interpretability, for the state representations, and on this basis, develop a supervised predictive model that learns good state representations for identifying similar patients and predicting patient outcomes. Experimental results on the publicly available dataset MIMIC-III show that our method offers a promising direction for precisely identifying similar patients at the state trajectory level, as well as accurately predicting outcomes.

Tissue segmentation is an essential task in computational pathology. However, relevant datasets for such a pixel-level classification task are hard to obtain due to the difficulty of annotation, bringing obstacles for training a deep learning-based segmentation model. Recently, contrastive learning has provided a feasible solution for mitigating the heavy reliance of deep learning models on annotation. Nevertheless, applying contrastive loss to the most abstract image representations, existing contrastive learning frameworks focus on global features, therefore, are less capable of encoding finer-grained features (e.g., pixel-level discrimination) for the tissue segmentation task. Enlightened by domain knowledge, we design three contrastive learning tasks with multi-granularity views (from global to local) for encoding necessary features into representations without accessing annotations. Specifically, we construct: (1) an image-level task to capture the difference between tissue components, i.e., encoding the component discrimination; (2) a superpixel-level task to learn discriminative representations of local regions with different tissue components, i.e., encoding the prototype discrimination; (3) a pixel-level task to encourage similar representations of different tissue components within a local region, i.e., encoding the spatial smoothness. Through our global-to-local pre-training strategy, the learned representations can reasonably capture the domain-specific and fine-grained patterns, making them easily transferable to various tissue segmentation tasks in histopathological images. We conduct extensive experiments on two tissue segmentation datasets, while considering two real-world scenarios with limited or sparse annotations. The experimental results demonstrate that our framework is superior to existing contrastive learning methods and can be easily combined with weakly supervised and semi-supervised segmentation methods.

Pathological diagnosis is the gold standard for cancer diagnosis, but it is labor-intensive, in which tasks such as cell detection, classification, a nd c ounting a re particularly prominent. A common solution for automating these tasks is using nucleus segmentation technology. However, it is hard to train a robust nucleus segmentation model, due to several challenging problems,i.e., the nucleus adhesion, stacking, and excessive fusion with the background. Recently, some researchers proposed a series of automatic nucleus segmentation methods based on point annotation, which can significant i mprove t he m odel performance. Nevertheless, the point annotation needs to be marked by experienced pathologists. In order to take advantage of segmentation methods based on point annotation, further alleviate the manual workload, and make cancer diagnosis more efficient and accurate, it is necessary to develop an automatic nucleus detection algorithm, which can automatically and efficiently l ocate the position of the nucleus in the pathological image and extract valuable information for pathologists. In this paper, we propose a W-shaped network for automatic nucleus detection. Different from the traditional U-Net based method, mapping the original pathology image to the target mask directly, our proposed method split the detection task into two sub-tasks. The first sub-task maps the original pathology image to the binary mask, then the binary mask is mapped to the density mask in the second subtask. After the task is split, the task's difficulty i s significantly reduced, and the network's overall performance is improved. Our proposed network can automatic identify the center of each nucleus. Combined with the NuClick, a semi-supervised recognition model based on point annotation, we implement a fully automatic nucleus annotation framework.

Nuclei segmentation is a fundamental task in digital pathology analysis and can be automated by deep learning-based methods. However, the development of such an automated method requires a large amount of data with precisely annotated masks which is hard to obtain. Training with weakly labeled data is a popular solution for reducing the workload of annotation. In this paper, we propose a novel meta-learning-based nuclei segmentation method which follows the label correction paradigm to leverage data with noisy masks. Specifically, we design a fully conventional meta-model that can correct noisy masks using a small amount of clean meta-data. Then the corrected masks can be used to supervise the training of the segmentation model. Meanwhile, a bi-level optimization method is adopted to alternately update the parameters of the main segmentation model and the meta-model in an end-to-end way. Extensive experimental results on two nuclear segmentation datasets show that our method achieves the state-of-the-art result. It even achieves comparable performance with the model training on supervised data in some noisy settings.

Digital pathology plays a crucial role in the development of artificial intelligence in the medical field. The digital pathology platform can make the pathological resources digital and networked, and realize the permanent storage of visual data and the synchronous browsing processing without the limitation of time and space. It has been widely used in various fields of pathology. However, there is still a lack of an open and universal digital pathology platform to assist doctors in the management and analysis of digital pathological sections, as well as the management and structured description of relevant patient information. Most platforms cannot integrate image viewing, annotation and analysis, and text information management. To solve the above problems, we propose a comprehensive and extensible platform, PIMIP (Pathology Information Management & Integration Platform). PIMIP has developed the image annotation functions based on the visualization of digital pathological sections. Our annotation functions support multi-user collaborative annotation and multi-device annotation, and realize the automation of some annotation tasks. In the annotation task, we invited a professional pathologist for guidance. We introduce a machine learning module for image analysis. The data we collected included public data from local hospitals and clinical examples. Our platform is more clinical and suitable for clinical use. In addition to image data, we also structured the management and display of text information. So our platform is comprehensive. The platform framework is built in a modular way to support users to add machine learning modules independently, which makes our platform extensible.

Diagnostic pathology, which is the basis and gold standard of cancer diagnosis, provides essential information on the prognosis of the disease and vital evidence for clinical treatment. However, pathological diagnosis is subjective, and differences in observation and diagnosis between pathologists are common. This phenomenon is more evident in hospitals with insufficient medical resources. Deep learning (DL) can be used to identify and classify structures in digital pathology. In order to solve the above difficulties, in this work, we propose a DL framework for generating pathological diagnosis by analyzing histopathological images of renal cell carcinoma. A deep neural network is trained on a large high-quality annotated dataset for accurate tumor area detection, subtyping, and grading. The results show that our framework has achieved pathologist-level accuracy in diagnosis, can generate pathology reports with tumor indicators, and provide pathologists with interpretable auxiliary diagnoses

Clinical time-series is receiving long-term attention in data mining and machine learning communities and has boosted a variety of data-driven applications. Identifying similar patients or subgroups from clinical time-series is an essential step to design tailored treatments in clinical practice. However, most of the existing methods are either purely unsupervised that tend to neglect the patient outcome information or cannot generate personalized patient representation through supervised learning, thus may fail to identify ‘truly similar patients’ (i.e., patients who similar in both outcomes and individual outcome-related clinical variables). To tackle these limitations, we propose a novel predictive clinical time-series analysis framework. Specifically, our framework uses task-specific information to rule out the task-irrelevant factors in each patient data individually and generates the contribution scores that reveal the factors’ importance for the patient outcome. Then a patient representation construction method is proposed to generate task-related and personalized representations by combining remained factors and their contribution scores. At last, similarity measurement or cluster analysis can be conducted. We evaluate our framework on three real-world clinical time-series datasets, empirically demonstrate that our framework achieves improvements in prediction performance, similarity measurement, and clustering, thus potentially benefiting patient-similarity-based precision medicine applications.

Transition from conventional to digital pathology requires a new category of biomedical informatic infrastructure which could facilitate delicate pathological routine. Pathological diagnoses are sensitive to many external factors and is known to be subjective. Only systems that can meet strict requirements in pathology would be able to run along pathological routines and eventually digitized the area, and the developed platform should comply with existing pathological routines and international standards. Currently, there are a number of available software tools which can perform histopathological tasks including virtual slide viewing, annotating, and basic image analysis, however, none of them can serve as a digital platform for pathology. Here we describe OpenHI2, an enhanced version Open Histopathological Image platform which is capable of supporting all basic pathological tasks and file formats; ready to be deployed in medical institutions on a standard server environment or cloud computing infrastructure. In this paper, we also describe the development decisions for the platform and propose solutions to overcome technical challenges including responsive region retrieval and viewing, virtual slide magnification, recording of diagnostic areas. These factors would promote OpenHI2 be used as a platform for histopathological images in real-world clinical settings. Furthermore, in research, OpenHI2 inherited the annotation functionality from the previous version, thus acquired annotations can be directly utilized by the newly added machine learning module which include popular machine learning models to perform tasks such as histology image classification and segmentation in the same environment. Addition can be made to the platform since each component is modularized and fully documented. OpenHI2 is free, open-source, and available at https://gitlab.com/BioAI/OpenHI.

Pathological is crucial to cancer diagnosis. Usually, Pathologists draw their conclusion based on observed cell and tissue structure on histology slides. Rapid development in machine learning, especially deep learning have established robust and accurate classifiers. They are being used to analyze histopathological slides and assist pathologists in diagnosis. Most machine learning systems rely heavily on annotated data sets to gain experiences and knowledge to correctly and accurately perform various tasks such as classification and segmentation. Generally, annotations made in pathology-related datasets have inherited annotation methods from natural scene images. This work investigates different granularity of annotations in histopathological data set including image-wise, bounding box, ellipse-wise, and pixel-wise to verify the influence of annotation in pathological slide on deep learning models. We design corresponding experiments to test classification and segmentation performance of deep learning models based on annotations with different annotation granularity. In classification, state-of-the-art deep learning-based classifiers perform better when trained by pixel-wise annotation dataset. On average, precision, recall and F1-score improves by 7.87%, 8.83% and 7.85% respectively. Thus, it is suggested that finer granularity annotations are better utilized by deep learning algorithms in classification tasks. Similarly, semantic segmentation algorithms can achieve 8.33% better segmentation accuracy when trained by pixel-wise annotations. Our study shows not only that finer-grained annotation can improve the performance of deep learning models, but also help they extract more accurate phenotypic information from histopathological slides. The accurate and spatially precise acquisitions of phenotypic information can improve the reliability of the model prediction. Intelligence systems trained on granular annotations may help pathologists inspecting certain regions and features in the slide that were mainly used to calculate the prediction. The compartmentalized prediction approach similar to this work may contribute to phenotype and genotype association studies.

Hyperspectral images (HSIs) provide invaluable information in both spectral and spatial domains for image classification tasks. In this paper, we use semantic representation as a middle-level feature to describe image pixels' characteristics. Deriving effective semantic representation is critical for achieving good classification performance. Since different image descriptors depict characteristics from different perspectives, combining multiple features in the same semantic space makes semantic representation more meaningful. First, a probabilistic support vector machine is used to generate semantic representation-based multifeatures. In order to derive better semantic representation, we introduce a new adaptive spatial regularizer that well exploits the local spatial information, while a nonlocal regularizer is also used to search for global patch-pair similarities in the whole image. We combine multiple features with local and nonlocal spatial constraints using an extended Markov random field model in the semantic space. Experimental results on three hyperspectral data sets show that the proposed method provides better performance than several state-of-the-art techniques in terms of region uniformity, overall accuracy, average accuracy, and Kappa statistics.

This paper presents a novel method for hyperspectral classification combining multiple features and exploiting spatial information at the same time. We proposed a supervised classification method under the Markov random field (MRF)-based framework. Firstly using the probability SVM to map multiple features from different low-level subspace to the same semantic space (probability space), then integrating these features in semantic space with MRF-based model to enforce a smooth and accurate representation, in addition the manifold distance has been used in MRF-based model to measure the similarity of two point. To further improve the classification accuracy, a new approach of building the adaptive neighborhood has been proposed and used in our method. As our model is a derivable and convex problem, gradient descent can be used to solve this problem with less computational and time cost. Experimental results on real hyperspectral dataset shows that the proposed method provides improved classification accuracy in terms of the overall accuracy, average accuracy and kappa statistic.