Sidong Liu

Soham Rohit Chitnis, Sidong Liu, Tirtharaj Dash et al.

Whole Slide Images (WSIs) or histopathology images are used in digital pathology. WSIs pose great challenges to deep learning models for clinical diagnosis, owing to their size and lack of pixel-level annotations. With the recent advancements in computational pathology, newer multiple-instance learning-based models have been proposed. Multiple-instance learning for WSIs necessitates creating patches and uses the encoding of these patches for diagnosis. These models use generic pre-trained models (ResNet-50 pre-trained on ImageNet) for patch encoding. The recently proposed KimiaNet, a DenseNet121 model pre-trained on TCGA slides, is a domain-specific pre-trained model. This paper shows the effect of domain-specific pre-training on WSI classification. To investigate the effect of domain-specific pre-training, we considered the current state-of-the-art multiple-instance learning models, 1) CLAM, an attention-based model, and 2) TransMIL, a self-attention-based model, and evaluated the models' confidence and predictive performance in detecting primary brain tumors - gliomas. Domain-specific pre-training improves the confidence of the models and also achieves a new state-of-the-art performance of WSI-based glioma subtype classification, showing a high clinical applicability in assisting glioma diagnosis. We will publicly share our code and experimental results at https://github.com/soham-chitnis10/WSI-domain-specific.

David Black, Declan Byrne, Anna Walke et al.

Complete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores' emission spectra in most human brain tumors. In this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8). Four machine learning models were trained to classify tumor type, grade, glioma margins and IDH mutation. Using random forests and multi-layer perceptrons, the classifiers achieved average test accuracies of 84-87%, 96%, 86%, and 93% respectively. All five fluorophore abundances varied between tumor margin types and tumor grades (p < 0.01). For tissue type, at least four of the five fluorophore abundances were found to be significantly different (p < 0.01) between all classes. These results demonstrate the fluorophores' differing abundances in different tissue classes, as well as the value of the five fluorophores as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Yizhi Zhang, Lei Fan, Zhulin Tao et al.

Universal, transferable whole-slide image (WSI) representations are central to computational pathology. Incorporating multiple markers (e.g., immunohistochemistry, IHC) alongside H&E enriches H&E-based features with diverse, biologically meaningful information. However, progress is limited by the scarcity of well-aligned multi-stain datasets. Inter-stain misalignment shifts corresponding tissue across slides, hindering consistent patch-level features and degrading slide-level embeddings. To address this, we curated a slide-level aligned, five-stain dataset (H&E, HER2, KI67, ER, PGR) to enable paired H&E-IHC learning and robust cross-stain representation. Leveraging this dataset, we propose Cross-Stain Contrastive Learning (CSCL), a two-stage pretraining framework with a lightweight adapter trained using patch-wise contrastive alignment to improve the compatibility of H&E features with corresponding IHC-derived contextual cues, and slide-level representation learning with Multiple Instance Learning (MIL), which uses a cross-stain attention fusion module to integrate stain-specific patch features and a cross-stain global alignment module to enforce consistency among slide-level embeddings across different stains. Experiments on cancer subtype classification, IHC biomarker status classification, and survival prediction show consistent gains, yielding high-quality, transferable H&E slide-level representations. The code and data are available at https://github.com/lily-zyz/CSCL.

Cong Cong, Shiyu Xuan, Sidong Liu et al.

Deep neural networks (DNNs) have exhibited remarkable success in the field of histopathology image analysis. On the other hand, the contemporary trend of employing large models and extensive datasets has underscored the significance of dataset distillation, which involves compressing large-scale datasets into a condensed set of synthetic samples, offering distinct advantages in improving training efficiency and streamlining downstream applications. In this work, we introduce a novel dataset distillation algorithm tailored for histopathology image datasets (Histo-DD), which integrates stain normalisation and model augmentation into the distillation progress. Such integration can substantially enhance the compatibility with histopathology images that are often characterised by high colour heterogeneity. We conduct a comprehensive evaluation of the effectiveness of the proposed algorithm and the generated histopathology samples in both patch-level and slide-level classification tasks. The experimental results, carried out on three publicly available WSI datasets, including Camelyon16, TCGA-IDH, and UniToPath, demonstrate that the proposed Histo-DD can generate more informative synthetic patches than previous coreset selection and patch sampling methods. Moreover, the synthetic samples can preserve discriminative information, substantially reduce training efforts, and exhibit architecture-agnostic properties. These advantages indicate that synthetic samples can serve as an alternative to large-scale datasets.

Harshvardhan Mestha, Karan Bania, Shreyas V Sathyanarayana et al. · cmu

Our interest is in the design of software systems involving a human-expert interacting -- using natural language -- with a large language model (LLM) on data analysis tasks. For complex problems, it is possible that LLMs can harness human expertise and creativity to find solutions that were otherwise elusive. On one level, this interaction takes place through multiple turns of prompts from the human and responses from the LLM. Here we investigate a more structured approach based on an abstract protocol described in [3] for interaction between agents. The protocol is motivated by a notion of "two-way intelligibility" and is modelled by a pair of communicating finite-state machines. We provide an implementation of the protocol, and provide empirical evidence of using the implementation to mediate interactions between an LLM and a human-agent in two areas of scientific interest (radiology and drug design). We conduct controlled experiments with a human proxy (a database), and uncontrolled experiments with human subjects. The results provide evidence in support of the protocol's capability of capturing one- and two-way intelligibility in human-LLM interaction; and for the utility of two-way intelligibility in the design of human-machine systems. Our code is available at https://github.com/karannb/interact.

Junze Wang, Lei Fan, Dezheng Zhang et al.

Visual Prompt Tuning (VPT) adapts a frozen Vision Transformer (ViT) to downstream tasks by inserting a small number of learnable prompt tokens into the token sequence at each layer. However, we observe that existing VPT variants often suffer from unstable training dynamics, characterized by gradient oscillations. A layer-wise analysis reveals that shallow-layer prompts tend to stagnate early, while deeper-layer prompts exhibit high-variance oscillations, leading to cross-layer mismatch. These issues slow convergence and degrade final performance. To address these challenges, we propose Prompt-Agnostic Evolution ($\mathtt{PAE}$), which strengthens vision prompt tuning by explicitly modeling prompt dynamics. From a frequency-domain perspective, we initialize prompts in a task-aware direction by uncovering and propagating frequency shortcut patterns that the backbone inherently exploits for recognition. To ensure coherent evolution across layers, we employ a shared Koopman operator that imposes a global linear transformation instead of uncoordinated, layer-specific updates. Finally, inspired by Lyapunov stability theory, we introduce a regularizer that constrains error amplification during evolution. Extensive experiments show that $\mathtt{PAE}$ accelerates convergence with an average $1.41\times$ speedup and improves accuracy by 1--3% on 25 datasets across multiple downstream tasks. Beyond performance, $\mathtt{PAE}$ is prompt-agnostic and lightweight, and it integrates seamlessly with diverse VPT variants without backbone modification or inference-time changes.

Junze Wang, Lei Fan, Weipeng Jing et al.

Existing methods for multimodal MRI segmentation with missing modalities typically assume that all MRI modalities are available during training. However, in clinical practice, some modalities may be missing due to the sequential nature of MRI acquisition, leading to performance degradation. Furthermore, retraining models to accommodate newly available modalities can be inefficient and may cause overfitting, potentially compromising previously learned knowledge. To address these challenges, we propose Replay-based Hypergraph Domain Incremental Learning (ReHyDIL) for brain tumor segmentation with missing modalities. ReHyDIL leverages Domain Incremental Learning (DIL) to enable the segmentation model to learn from newly acquired MRI modalities without forgetting previously learned information. To enhance segmentation performance across diverse patient scenarios, we introduce the Cross-Patient Hypergraph Segmentation Network (CHSNet), which utilizes hypergraphs to capture high-order associations between patients. Additionally, we incorporate Tversky-Aware Contrastive (TAC) loss to effectively mitigate information imbalance both across and within different modalities. Extensive experiments on the BraTS2019 dataset demonstrate that ReHyDIL outperforms state-of-the-art methods, achieving an improvement of over 2% in the Dice Similarity Coefficient across various tumor regions. Our code is available at https://github.com/reeive/ReHyDIL.

Litao Yang, Deval Mehta, Sidong Liu et al.

Digital pathology based on whole slide images (WSIs) plays a key role in cancer diagnosis and clinical practice. Due to the high resolution of the WSI and the unavailability of patch-level annotations, WSI classification is usually formulated as a weakly supervised problem, which relies on multiple instance learning (MIL) based on patches of a WSI. In this paper, we aim to learn an optimal patch-level feature space by integrating prototype learning with MIL. To this end, we develop a Trainable Prototype enhanced deep MIL (TPMIL) framework for weakly supervised WSI classification. In contrast to the conventional methods which rely on a certain number of selected patches for feature space refinement, we softly cluster all the instances by allocating them to their corresponding prototypes. Additionally, our method is able to reveal the correlations between different tumor subtypes through distances between corresponding trained prototypes. More importantly, TPMIL also enables to provide a more accurate interpretability based on the distance of the instances from the trained prototypes which serves as an alternative to the conventional attention score-based interpretability. We test our method on two WSI datasets and it achieves a new SOTA. GitHub repository: https://github.com/LitaoYang-Jet/TPMIL

Sahar Moradizeyveh, Mehnaz Tabassum, Sidong Liu et al.

Eye-gaze tracking research offers significant promise in enhancing various healthcare-related tasks, above all in medical image analysis and interpretation. Eye tracking, a technology that monitors and records the movement of the eyes, provides valuable insights into human visual attention patterns. This technology can transform how healthcare professionals and medical specialists engage with and analyze diagnostic images, offering a more insightful and efficient approach to medical diagnostics. Hence, extracting meaningful features and insights from medical images by leveraging eye-gaze data improves our understanding of how radiologists and other medical experts monitor, interpret, and understand images for diagnostic purposes. Eye-tracking data, with intricate human visual attention patterns embedded, provides a bridge to integrating artificial intelligence (AI) development and human cognition. This integration allows novel methods to incorporate domain knowledge into machine learning (ML) and deep learning (DL) approaches to enhance their alignment with human-like perception and decision-making. Moreover, extensive collections of eye-tracking data have also enabled novel ML/DL methods to analyze human visual patterns, paving the way to a better understanding of human vision, attention, and cognition. This systematic review investigates eye-gaze tracking applications and methodologies for enhancing ML/DL algorithms for medical image analysis in depth.

Syed Talal Ahmad, Haohui Lu, Sidong Liu et al.

Recent advancements in Large Language Models (LLMs) have significantly improved text generation capabilities. However, they also present challenges, particularly in generating vaccine-related misinformation, which poses risks to public health. Despite research on human-authored misinformation, a notable gap remains in understanding how LLMs contribute to vaccine misinformation and how best to detect it. Existing benchmarks often overlook vaccine-specific misinformation and the diverse roles of misinformation spreaders. This paper introduces VaxGuard, a novel dataset designed to address these challenges. VaxGuard includes vaccine-related misinformation generated by multiple LLMs and provides a comprehensive framework for detecting misinformation across various roles. Our findings show that GPT-3.5 and GPT-4o consistently outperform other LLMs in detecting misinformation, especially when dealing with subtle or emotionally charged narratives. On the other hand, PHI3 and Mistral show lower performance, struggling with precision and recall in fear-driven contexts. Additionally, detection performance tends to decline as input text length increases, indicating the need for improved methods to handle larger content. These results highlight the importance of role-specific detection strategies and suggest that VaxGuard can serve as a key resource for improving the detection of LLM-generated vaccine misinformation.

Somayeh Farahani, Marjaneh Hejazi, Antonio Di Ieva et al.

Accurate, noninvasive glioma characterization is crucial for effective clinical management. Traditional methods, dependent on invasive tissue sampling, often fail to capture the spatial heterogeneity of the tumor. While deep learning has improved segmentation and molecular profiling, few approaches simultaneously integrate tumor morphology and molecular features. Foundation deep learning models, which learn robust, task-agnostic representations from large-scale datasets, hold great promise but remain underutilized in glioma imaging biomarkers. We propose the Multi-Task SWIN-UNETR (MTS-UNET) model, a novel foundation-based framework built on the BrainSegFounder model, pretrained on large-scale neuroimaging data. MTS-UNET simultaneously performs glioma segmentation, histological grading, and molecular subtyping (IDH mutation and 1p/19q co-deletion). It incorporates two key modules: Tumor-Aware Feature Encoding (TAFE) for multi-scale, tumor-focused feature extraction and Cross-Modality Differential (CMD) for highlighting subtle T2-FLAIR mismatch signals associated with IDH mutation. The model was trained and validated on a diverse, multi-center cohort of 2,249 glioma patients from seven public datasets. MTS-UNET achieved a mean Dice score of 84% for segmentation, along with AUCs of 90.58% for IDH mutation, 69.22% for 1p/19q co-deletion prediction, and 87.54% for grading, significantly outperforming baseline models (p<=0.05). Ablation studies validated the essential contributions of the TAFE and CMD modules and demonstrated the robustness of the framework. The foundation-based MTS-UNET model effectively integrates tumor segmentation with multi-level classification, exhibiting strong generalizability across diverse MRI datasets. This framework shows significant potential for advancing noninvasive, personalized glioma management by improving predictive accuracy and interpretability.

Somayeh Farahani, Marjaneh Hejazi, Antonio Di Ieva et al.

Accurate, noninvasive detection of isocitrate dehydrogenase (IDH) mutation is essential for effective glioma management. Traditional methods rely on invasive tissue sampling, which may fail to capture a tumor's spatial heterogeneity. While deep learning models have shown promise in molecular profiling, their performance is often limited by scarce annotated data. In contrast, foundation deep learning models offer a more generalizable approach for glioma imaging biomarkers. We propose a Foundation-based Biomarker Network (FoundBioNet) that utilizes a SWIN-UNETR-based architecture to noninvasively predict IDH mutation status from multi-parametric MRI. Two key modules are incorporated: Tumor-Aware Feature Encoding (TAFE) for extracting multi-scale, tumor-focused features, and Cross-Modality Differential (CMD) for highlighting subtle T2-FLAIR mismatch signals associated with IDH mutation. The model was trained and validated on a diverse, multi-center cohort of 1705 glioma patients from six public datasets. Our model achieved AUCs of 90.58%, 88.08%, 65.41%, and 80.31% on independent test sets from EGD, TCGA, Ivy GAP, RHUH, and UPenn, consistently outperforming baseline approaches (p <= 0.05). Ablation studies confirmed that both the TAFE and CMD modules are essential for improving predictive accuracy. By integrating large-scale pretraining and task-specific fine-tuning, FoundBioNet enables generalizable glioma characterization. This approach enhances diagnostic accuracy and interpretability, with the potential to enable more personalized patient care.

Somayeh Farahani, Marjaneh Hejazi, Mehnaz Tabassum et al.

Objectives We aimed to evaluate the diagnostic performance of deep learning (DL)-based radiomics models for the noninvasive prediction of isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status in glioma patients using MRI sequences, and to identify methodological factors influencing accuracy and generalizability. Materials and methods Following PRISMA guidelines, we systematically searched major databases (PubMed, Scopus, Embase, Web of Science, and Google Scholar) up to March 2025, screening studies that utilized DL to predict IDH and 1p/19q co-deletion status from MRI data. We assessed study quality and risk of bias using the Radiomics Quality Score and the QUADAS-2 tool. Our meta-analysis employed a bivariate model to compute pooled sensitivity and specificity, and meta-regression to assess interstudy heterogeneity. Results Among the 1517 unique publications, 104 were included in the qualitative synthesis, and 72 underwent meta-analysis. Pooled estimates for IDH prediction in test cohorts yielded a sensitivity of 0.80 and specificity of 0.85. For 1p/19q co-deletion, sensitivity was 0.75 and specificity was 0.82. Meta-regression identified the tumor segmentation method and the extent of DL integration into the radiomics pipeline as significant contributors to interstudy variability. Conclusion Although DL models demonstrate strong potential for noninvasive molecular classification of gliomas, clinical translation requires several critical steps: harmonization of multi-center MRI data using techniques such as histogram matching and DL-based style transfer; adoption of standardized and automated segmentation protocols; extensive multi-center external validation; and prospective clinical validation.

Carlo Russo, Sidong Liu, Antonio Di Ieva

Pre-processing and Data Augmentation play an important role in Deep Convolutional Neural Networks (DCNN). Whereby several methods aim for standardization and augmentation of the dataset, we here propose a novel method aimed to feed DCNN with spherical space transformed input data that could better facilitate feature learning compared to standard Cartesian space images and volumes. In this work, the spherical coordinates transformation has been applied as a preprocessing method that, used in conjunction with normal MRI volumes, improves the accuracy of brain tumor segmentation and patient overall survival (OS) prediction on Brain Tumor Segmentation (BraTS) Challenge 2020 dataset. The LesionEncoder framework has been then applied to automatically extract features from DCNN models, achieving 0.586 accuracy of OS prediction on the validation data set, which is one of the best results according to BraTS 2020 leaderboard.

Carlo Russo, Sidong Liu, Antonio Di Ieva

Magnetic Resonance Imaging (MRI) is used in everyday clinical practice to assess brain tumors. Several automatic or semi-automatic segmentation algorithms have been introduced to segment brain tumors and achieve an expert-like accuracy. Deep Convolutional Neural Networks (DCNN) have recently shown very promising results, however, DCNN models are still far from achieving clinically meaningful results mainly because of the lack of generalization of the models. DCNN models need large annotated datasets to achieve good performance. Models are often optimized on the domain dataset on which they have been trained, and then fail the task when the same model is applied to different datasets from different institutions. One of the reasons is due to the lack of data standardization to adjust for different models and MR machines. In this work, a 3D Spherical coordinates transform during the pre-processing phase has been hypothesized to improve DCNN models' accuracy and to allow more generalizable results even when the model is trained on small and heterogeneous datasets and translated into different domains. Indeed, the spherical coordinate system avoids several standardization issues since it works independently of resolution and imaging settings. Both Cartesian and spherical volumes were evaluated in two DCNN models with the same network structure using the BraTS 2019 dataset. The model trained on spherical transform pre-processed inputs resulted in superior performance over the Cartesian-input trained model on predicting gliomas' segmentation on tumor core and enhancing tumor classes (increase of 0.011 and 0.014 respectively on the validation dataset), achieving a further improvement in accuracy by merging the two models together. Furthermore, the spherical transform is not resolution-dependent and achieve same results on different input resolution.

Lelin Zhang, Xi Nan, Eva Huang et al.

Social media platforms now serve billions of users by providing convenient means of communication, content sharing and even payment between different users. Due to such convenient and anarchic nature, they have also been used rampantly to promote and conduct business activities between unregistered market participants without paying taxes. Tax authorities worldwide face difficulties in regulating these hidden economy activities by traditional regulatory means. This paper presents a machine learning based Regtech tool for international tax authorities to detect transaction-based tax evasion activities on social media platforms. To build such a tool, we collected a dataset of 58,660 Instagram posts and manually labelled 2,081 sampled posts with multiple properties related to transaction-based tax evasion activities. Based on the dataset, we developed a multi-modal deep neural network to automatically detect suspicious posts. The proposed model combines comments, hashtags and image modalities to produce the final output. As shown by our experiments, the combined model achieved an AUC of 0.808 and F1 score of 0.762, outperforming any single modality models. This tool could help tax authorities to identify audit targets in an efficient and effective manner, and combat social e-commerce tax evasion in scale.

Siqi Liu, Sidong Liu, Sonia Pujol et al.

We present a longitudinal MR simulation framework which simulates the future neurodegenerative progression by outputting the predicted follow-up MR image and the voxel-based morphometry (VBM) map. This framework expects the patients to have at least 2 historical MR images available. The longitudinal and cross-sectional VBM maps are extracted to measure the affinity between the target subject and the template subjects collected for simulation. Then the follow-up simulation is performed by resampling the latest available target MR image with a weighted sum of non-linear transformations derived from the best-matched templates. The leave-one-out strategy was used to compare different simulation methods. Compared to the state-of-the-art voxel-based method, our proposed morphometry-based simulation achieves better accuracy in most cases.