Hanqing Chao

Hanqing Chao, Jiajin Zhang, Pingkun Yan

Regression plays an essential role in many medical imaging applications for estimating various clinical risk or measurement scores. While training strategies and loss functions have been studied for the deep neural networks in medical image classification tasks, options for regression tasks are very limited. One of the key challenges is that the high-dimensional feature representation learned by existing popular loss functions like Mean Squared Error or L1 loss is hard to interpret. In this paper, we propose a novel Regression Metric Loss (RM-Loss), which endows the representation space with the semantic meaning of the label space by finding a representation manifold that is isometric to the label space. Experiments on two regression tasks, i.e. coronary artery calcium score estimation and bone age assessment, show that RM-Loss is superior to the existing popular regression losses on both performance and interpretability. Code is available at https://github.com/DIAL-RPI/Regression-Metric-Loss.

Jiajin Zhang, Hanqing Chao, Amit Dhurandhar et al.

Domain generalization (DG) aims to train a model to perform well in unseen domains under different distributions. This paper considers a more realistic yet more challenging scenario,namely Single Domain Generalization (Single-DG), where only a single source domain is available for training. To tackle this challenge, we first try to understand when neural networks fail to generalize? We empirically ascertain a property of a model that correlates strongly with its generalization that we coin as "model sensitivity". Based on our analysis, we propose a novel strategy of Spectral Adversarial Data Augmentation (SADA) to generate augmented images targeted at the highly sensitive frequencies. Models trained with these hard-to-learn samples can effectively suppress the sensitivity in the frequency space, which leads to improved generalization performance. Extensive experiments on multiple public datasets demonstrate the superiority of our approach, which surpasses the state-of-the-art single-DG methods.

Bokai Zhao, Yiyang Zhang, Yuanchi Zhu et al.

Pathology foundation models (PFMs) have emerged as a core approach for learning transferable representations from whole slide images (WSIs), and they are typically benchmarked through downstream clinical endpoints. While such task level evaluations are indispensable, they offer limited insight into what the representations themselves encode, particularly whether PFM embeddings can distinguish meaningful tissue regions and capture their spatial relationships. We present SpaPath-Bench, a representation level benchmark designed to diagnose spatial representation capability in PFMs. SpaPath-Bench formulates spatial domain identification (SDI) on paired whole slide image and spatial transcriptomics (ST) data as a diagnostic task. It curates 42 public paired WSI and ST slides, enables large scale evaluation across 19 encoders and seven SDI methods, and measures partition quality using three complementary criteria: unsupervised spatial coherence, transcriptomics referenced agreement, and expert referenced agreement. Across 83K runs, SpaPath-Bench reveals that different pretraining paradigms capture distinct aspects of tissue spatial architecture, and it provides practical guidance for building the next generation of spatially aware computational pathology models. Code and data pipelines are publicly available at https://bokai-zhao.github.io/SpaPath-benchboard/.

Zijiang Yang, Hanqing Chao, Bokai Zhao et al.

Nucleus detection and classification (NDC) in histopathology analysis is a fundamental task that underpins a wide range of high-level pathology applications. However, existing methods heavily rely on labor-intensive nucleus-level annotations and struggle to fully exploit large-scale unlabeled data for learning discriminative nucleus representations. In this work, we propose MUSE (MUlti-scale denSE self-distillation), a novel self-supervised learning method tailored for NDC. At its core is NuLo (Nucleus-based Local self-distillation), a coordinate-guided mechanism that enables flexible local self-distillation based on predicted nucleus positions. By removing the need for strict spatial alignment between augmented views, NuLo allows critical cross-scale alignment, thus unlocking the capacity of models for fine-grained nucleus-level representation. To support MUSE, we design a simple yet effective encoder-decoder architecture and a large field-of-view semi-supervised fine-tuning strategy that together maximize the value of unlabeled pathology images. Extensive experiments on three widely used benchmarks demonstrate that MUSE effectively addresses the core challenges of histopathological NDC. The resulting models not only surpass state-of-the-art supervised baselines but also outperform generic pathology foundation models.

Bokai Zhao, Weiyang Shi, Hanqing Chao et al.

Spatial proteomics maps protein distributions in tissues, providing transformative insights for life sciences. However, current sequencing-based technologies suffer from low spatial resolution, and substantial inter-tissue variability in protein expression further compromises the performance of existing molecular data prediction methods. In this work, we introduce the novel task of spatial super-resolution for sequencing-based spatial proteomics (seq-SP) and, to the best of our knowledge, propose the first deep learning model for this task--Neural Proteomics Fields (NPF). NPF formulates seq-SP as a protein reconstruction problem in continuous space by training a dedicated network for each tissue. The model comprises a Spatial Modeling Module, which learns tissue-specific protein spatial distributions, and a Morphology Modeling Module, which extracts tissue-specific morphological features. Furthermore, to facilitate rigorous evaluation, we establish an open-source benchmark dataset, Pseudo-Visium SP, for this task. Experimental results demonstrate that NPF achieves state-of-the-art performance with fewer learnable parameters, underscoring its potential for advancing spatial proteomics research. Our code and dataset are publicly available at https://github.com/Bokai-Zhao/NPF.

Xinrui Song, Hengtao Guo, Xuanang Xu et al.

Prostate cancer biopsy benefits from accurate fusion of transrectal ultrasound (TRUS) and magnetic resonance (MR) images. In the past few years, convolutional neural networks (CNNs) have been proved powerful in extracting image features crucial for image registration. However, challenging applications and recent advances in computer vision suggest that CNNs are quite limited in its ability to understand spatial correspondence between features, a task in which the self-attention mechanism excels. This paper aims to develop a self-attention mechanism specifically for cross-modal image registration. Our proposed cross-modal attention block effectively maps each of the features in one volume to all features in the corresponding volume. Our experimental results demonstrate that a CNN network designed with the cross-modal attention block embedded outperforms an advanced CNN network 10 times of its size. We also incorporated visualization techniques to improve the interpretability of our network. The source code of our work is available at https://github.com/DIAL-RPI/Attention-Reg .

Hanqing Chao, Kun Wang, Yiwei He et al.

Gait is a unique biometric feature that can be recognized at a distance; thus, it has broad applications in crime prevention, forensic identification, and social security. To portray a gait, existing gait recognition methods utilize either a gait template which makes it difficult to preserve temporal information, or a gait sequence that maintains unnecessary sequential constraints and thus loses the flexibility of gait recognition. In this paper, we present a novel perspective that utilizes gait as a deep set, which means that a set of gait frames are integrated by a global-local fused deep network inspired by the way our left- and right-hemisphere processes information to learn information that can be used in identification. Based on this deep set perspective, our method is immune to frame permutations, and can naturally integrate frames from different videos that have been acquired under different scenarios, such as diverse viewing angles, different clothes, or different item-carrying conditions. Experiments show that under normal walking conditions, our single-model method achieves an average rank-1 accuracy of 96.1% on the CASIA-B gait dataset and an accuracy of 87.9% on the OU-MVLP gait dataset. Under various complex scenarios, our model also exhibits a high level of robustness. It achieves accuracies of 90.8% and 70.3% on CASIA-B under bag-carrying and coat-wearing walking conditions respectively, significantly outperforming the best existing methods. Moreover, the proposed method maintains a satisfactory accuracy even when only small numbers of frames are available in the test samples; for example, it achieves 85.0% on CASIA-B even when using only 7 frames. The source code has been released at https://github.com/AbnerHqC/GaitSet.

Hanqing Chao, Xi Fang, Jiajin Zhang et al.

While image analysis of chest computed tomography (CT) for COVID-19 diagnosis has been intensively studied, little work has been performed for image-based patient outcome prediction. Management of high-risk patients with early intervention is a key to lower the fatality rate of COVID-19 pneumonia, as a majority of patients recover naturally. Therefore, an accurate prediction of disease progression with baseline imaging at the time of the initial presentation can help in patient management. In lieu of only size and volume information of pulmonary abnormalities and features through deep learning based image segmentation, here we combine radiomics of lung opacities and non-imaging features from demographic data, vital signs, and laboratory findings to predict need for intensive care unit (ICU) admission. To our knowledge, this is the first study that uses holistic information of a patient including both imaging and non-imaging data for outcome prediction. The proposed methods were thoroughly evaluated on datasets separately collected from three hospitals, one in the United States, one in Iran, and another in Italy, with a total 295 patients with reverse transcription polymerase chain reaction (RT-PCR) assay positive COVID-19 pneumonia. Our experimental results demonstrate that adding non-imaging features can significantly improve the performance of prediction to achieve AUC up to 0.884 and sensitivity as high as 96.1%, which can be valuable to provide clinical decision support in managing COVID-19 patients. Our methods may also be applied to other lung diseases including but not limited to community acquired pneumonia. The source code of our work is available at https://github.com/DIAL-RPI/COVID19-ICUPrediction.

Hanqing Chao, Yiwei He, Junping Zhang et al.

As a unique biometric feature that can be recognized at a distance, gait has broad applications in crime prevention, forensic identification and social security. To portray a gait, existing gait recognition methods utilize either a gait template, where temporal information is hard to preserve, or a gait sequence, which must keep unnecessary sequential constraints and thus loses the flexibility of gait recognition. In this paper we present a novel perspective, where a gait is regarded as a set consisting of independent frames. We propose a new network named GaitSet to learn identity information from the set. Based on the set perspective, our method is immune to permutation of frames, and can naturally integrate frames from different videos which have been filmed under different scenarios, such as diverse viewing angles, different clothes/carrying conditions. Experiments show that under normal walking conditions, our single-model method achieves an average rank-1 accuracy of 95.0% on the CASIA-B gait dataset and an 87.1% accuracy on the OU-MVLP gait dataset. These results represent new state-of-the-art recognition accuracy. On various complex scenarios, our model exhibits a significant level of robustness. It achieves accuracies of 87.2% and 70.4% on CASIA-B under bag-carrying and coat-wearing walking conditions, respectively. These outperform the existing best methods by a large margin. The method presented can also achieve a satisfactory accuracy with a small number of frames in a test sample, e.g., 82.5% on CASIA-B with only 7 frames. The source code has been released at https://github.com/AbnerHqC/GaitSet.

Diego Machado Reyes, Hanqing Chao, Juergen Hahn et al.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease; yet its currently available treatments are limited to stopping disease progression. Moreover, effectiveness of these treatments is not guaranteed due to the heterogenetiy of the disease. Therefore, it is essential to be able to identify the disease subtypes at a very early stage. Current data driven approaches are able to classify the subtypes at later stages of AD or related disorders, but struggle when predicting at the asymptomatic or prodromal stage. Moreover, most existing models either lack explainability behind the classification or only use a single modality for the assessment, limiting scope of its analysis. Thus, we propose a multimodal framework that uses early-stage indicators such as imaging, genetics and clinical assessments to classify AD patients into subtypes at early stages. Similarly, we build prompts and use large language models, such as ChatGPT, to interpret the findings of our model. In our framework, we propose a tri-modal co-attention mechanism (Tri-COAT) to explicitly learn the cross-modal feature associations. Our proposed model outperforms baseline models and provides insight into key cross-modal feature associations supported by known biological mechanisms.

Zhongwei Qiu, Hanqing Chao, Tiancheng Lin et al.

Histopathology plays a critical role in medical diagnostics, with whole slide images (WSIs) offering valuable insights that directly influence clinical decision-making. However, the large size and complexity of WSIs may pose significant challenges for deep learning models, in both computational efficiency and effective representation learning. In this work, we introduce Pixel-Mamba, a novel deep learning architecture designed to efficiently handle gigapixel WSIs. Pixel-Mamba leverages the Mamba module, a state-space model (SSM) with linear memory complexity, and incorporates local inductive biases through progressively expanding tokens, akin to convolutional neural networks. This enables Pixel-Mamba to hierarchically combine both local and global information while efficiently addressing computational challenges. Remarkably, Pixel-Mamba achieves or even surpasses the quantitative performance of state-of-the-art (SOTA) foundation models that were pretrained on millions of WSIs or WSI-text pairs, in a range of tumor staging and survival analysis tasks, {\bf even without requiring any pathology-specific pretraining}. Extensive experiments demonstrate the efficacy of Pixel-Mamba as a powerful and efficient framework for end-to-end WSI analysis.

Zijiang Yang, Zhongwei Qiu, Tiancheng Lin et al.

It is clinically crucial and potentially very beneficial to be able to analyze and model directly the spatial distributions of cells in histopathology whole slide images (WSI). However, most existing WSI datasets lack cell-level annotations, owing to the extremely high cost over giga-pixel images. Thus, it remains an open question whether deep learning models can directly and effectively analyze WSIs from the semantic aspect of cell distributions. In this work, we construct a large-scale WSI dataset with more than 5 billion cell-level annotations, termed WSI-Cell5B, and a novel hierarchical Cell Cloud Transformer (CCFormer) to tackle these challenges. WSI-Cell5B is based on 6,998 WSIs of 11 cancers from The Cancer Genome Atlas Program, and all WSIs are annotated per cell by coordinates and types. To the best of our knowledge, WSI-Cell5B is the first WSI-level large-scale dataset integrating cell-level annotations. On the other hand, CCFormer formulates the collection of cells in each WSI as a cell cloud and models cell spatial distribution. Specifically, Neighboring Information Embedding (NIE) is proposed to characterize the distribution of cells within the neighborhood of each cell, and a novel Hierarchical Spatial Perception (HSP) module is proposed to learn the spatial relationship among cells in a bottom-up manner. The clinical analysis indicates that WSI-Cell5B can be used to design clinical evaluation metrics based on counting cells that effectively assess the survival risk of patients. Extensive experiments on survival prediction and cancer staging show that learning from cell spatial distribution alone can already achieve state-of-the-art (SOTA) performance, i.e., CCFormer strongly outperforms other competing methods.

Minfeng Xu, Chen-Chen Fan, Yan-Jie Zhou et al.

Cardiovascular diseases (CVD) remain a leading health concern and contribute significantly to global mortality rates. While clinical advancements have led to a decline in CVD mortality, accurately identifying individuals who could benefit from preventive interventions remains an unsolved challenge in preventive cardiology. Current CVD risk prediction models, recommended by guidelines, are based on limited traditional risk factors or use CT imaging to acquire quantitative biomarkers, and still have limitations in predictive accuracy and applicability. On the other hand, end-to-end trained CVD risk prediction methods leveraging deep learning on CT images often fail to provide transparent and explainable decision grounds for assisting physicians. In this work, we proposed a novel joint representation that integrates discrete quantitative biomarkers and continuous deep features extracted from chest CT scans. Our approach initiated with a deep CVD risk classification model by capturing comprehensive continuous deep learning features while jointly obtaining currently clinical-established quantitative biomarkers via segmentation models. In the feature joint representation stage, we use an instance-wise feature-gated mechanism to align the continuous and discrete features, followed by a soft instance-wise feature interaction mechanism fostering independent and effective feature interaction for the final CVD risk prediction. Our method substantially improves CVD risk predictive performance and offers individual contribution analysis of each biomarker, which is important in assisting physicians' decision-making processes. We validated our method on a public chest low-dose CT dataset and a private external chest standard-dose CT patient cohort of 17,207 CT volumes from 6,393 unique subjects, and demonstrated superior predictive performance, achieving AUCs of 0.875 and 0.843, respectively.

Jiajin Zhang, Hanqing Chao, Amit Dhurandhar et al.

Domain shift is a common problem in clinical applications, where the training images (source domain) and the test images (target domain) are under different distributions. Unsupervised Domain Adaptation (UDA) techniques have been proposed to adapt models trained in the source domain to the target domain. However, those methods require a large number of images from the target domain for model training. In this paper, we propose a novel method for Few-Shot Unsupervised Domain Adaptation (FSUDA), where only a limited number of unlabeled target domain samples are available for training. To accomplish this challenging task, first, a spectral sensitivity map is introduced to characterize the generalization weaknesses of models in the frequency domain. We then developed a Sensitivity-guided Spectral Adversarial MixUp (SAMix) method to generate target-style images to effectively suppresses the model sensitivity, which leads to improved model generalizability in the target domain. We demonstrated the proposed method and rigorously evaluated its performance on multiple tasks using several public datasets.

Nkechinyere N. Agu, Joy T. Wu, Hanqing Chao et al.

Radiologists usually observe anatomical regions of chest X-ray images as well as the overall image before making a decision. However, most existing deep learning models only look at the entire X-ray image for classification, failing to utilize important anatomical information. In this paper, we propose a novel multi-label chest X-ray classification model that accurately classifies the image finding and also localizes the findings to their correct anatomical regions. Specifically, our model consists of two modules, the detection module and the anatomical dependency module. The latter utilizes graph convolutional networks, which enable our model to learn not only the label dependency but also the relationship between the anatomical regions in the chest X-ray. We further utilize a method to efficiently create an adjacency matrix for the anatomical regions using the correlation of the label across the different regions. Detailed experiments and analysis of our results show the effectiveness of our method when compared to the current state-of-the-art multi-label chest X-ray image classification methods while also providing accurate location information.

Jiajin Zhang, Hanqing Chao, Xuanang Xu et al.

The extensive use of medical CT has raised a public concern over the radiation dose to the patient. Reducing the radiation dose leads to increased CT image noise and artifacts, which can adversely affect not only the radiologists judgement but also the performance of downstream medical image analysis tasks. Various low-dose CT denoising methods, especially the recent deep learning based approaches, have produced impressive results. However, the existing denoising methods are all downstream-task-agnostic and neglect the diverse needs of the downstream applications. In this paper, we introduce a novel Task-Oriented Denoising Network (TOD-Net) with a task-oriented loss leveraging knowledge from the downstream tasks. Comprehensive empirical analysis shows that the task-oriented loss complements other task agnostic losses by steering the denoiser to enhance the image quality in the task related regions of interest. Such enhancement in turn brings general boosts on the performance of various methods for the downstream task. The presented work may shed light on the future development of context-aware image denoising methods.

Jiajin Zhang, Hanqing Chao, Pingkun Yan

Unsupervised domain adaptation (UDA) is widely used to transfer knowledge from a labeled source domain to an unlabeled target domain with different data distribution. While extensive studies attested that deep learning models are vulnerable to adversarial attacks, the adversarial robustness of models in domain adaptation application has largely been overlooked. This paper points out that the inevitable domain distribution deviation in UDA is a critical barrier to model robustness on the target domain. To address the problem, we propose a novel Class-consistent Unsupervised Robust Domain Adaptation (CURDA) framework for training robust UDA models. With the introduced contrastive robust training and source anchored adversarial contrastive losses, our proposed CURDA framework can effectively robustify UDA models by simultaneously minimizing the data distribution deviation and the distance between target domain clean-adversarial pairs without creating classification confusion. Experiments on several public benchmarks show that CURDA can significantly improve model robustness in the target domain with only minor cost of accuracy on the clean samples.

Hanqing Chao, Hongming Shan, Fatemeh Homayounieh et al.

Cancer patients have a higher risk of cardiovascular disease (CVD) mortality than the general population. Low dose computed tomography (LDCT) for lung cancer screening offers an opportunity for simultaneous CVD risk estimation in at-risk patients. Our deep learning CVD risk prediction model, trained with 30,286 LDCTs from the National Lung Cancer Screening Trial, achieved an area under the curve (AUC) of 0.871 on a separate test set of 2,085 subjects and identified patients with high CVD mortality risks (AUC of 0.768). We validated our model against ECG-gated cardiac CT based markers, including coronary artery calcification (CAC) score, CAD-RADS score, and MESA 10-year risk score from an independent dataset of 335 subjects. Our work shows that, in high-risk patients, deep learning can convert LDCT for lung cancer screening into a dual-screening quantitative tool for CVD risk estimation.

Xiaoyang Xu, Yiqun Liu, Hanqing Chao et al.

With broad applications in various public services like aviation management and urban disaster warning, numerical precipitation prediction plays a crucial role in weather forecast. However, constrained by the limitation of observation and conventional meteorological models, the numerical precipitation predictions are often highly biased. To correct this bias, classical correction methods heavily depend on profound experts who have knowledge in aerodynamics, thermodynamics and meteorology. As precipitation can be influenced by countless factors, however, the performances of these expert-driven methods can drop drastically when some un-modeled factors change. To address this issue, this paper presents a data-driven deep learning model which mainly includes two blocks, i.e. a Denoising Autoencoder Block and an Ordinal Regression Block. To the best of our knowledge, it is the first expert-free models for bias correction. The proposed model can effectively correct the numerical precipitation prediction based on 37 basic meteorological data from European Centre for Medium-Range Weather Forecasts (ECMWF). Experiments indicate that compared with several classical machine learning algorithms and deep learning models, our method achieves the best correcting performance and meteorological index, namely the threat scores (TS), obtaining satisfactory visualization effect.