Hai Shu

Heng Li, Haofeng Liu, Huazhu Fu et al.

Fundus photography is a routine examination in clinics to diagnose and monitor ocular diseases. However, for cataract patients, the fundus image always suffers quality degradation caused by the clouding lens. The degradation prevents reliable diagnosis by ophthalmologists or computer-aided systems. To improve the certainty in clinical diagnosis, restoration algorithms have been proposed to enhance the quality of fundus images. Unfortunately, challenges remain in the deployment of these algorithms, such as collecting sufficient training data and preserving retinal structures. In this paper, to circumvent the strict deployment requirement, a structure-consistent restoration network (SCR-Net) for cataract fundus images is developed from synthesized data that shares an identical structure. A cataract simulation model is firstly designed to collect synthesized cataract sets (SCS) formed by cataract fundus images sharing identical structures. Then high-frequency components (HFCs) are extracted from the SCS to constrain structure consistency such that the structure preservation in SCR-Net is enforced. The experiments demonstrate the effectiveness of SCR-Net in the comparison with state-of-the-art methods and the follow-up clinical applications. The code is available at https://github.com/liamheng/ArcNet-Medical-Image-Enhancement.

Yuyu Chen, Taehyo Kim, Hai Shu et al.

Missing data imputation in large-scale surveys faces two challenges that are not well handled by current tabular diffusion methods. First, \emph{structural skips}, cells made inapplicable by questionnaire design, should not be imputed but are often conflated with item nonresponse. Second, \emph{ordinal} responses encode ordered categories, yet most pipelines treat them as nominal levels through one-hot or analog-bit encodings. We introduce \textbf{TabSODA} (\textbf{Tab}ular diffusion with \textbf{S}kip pattern detection and \textbf{O}r\textbf{d}inal \textbf{A}wareness), an Expectation-Maximization (EM)-based diffusion imputer built on the Elucidated Diffusion Model (EDM) framework. TabSODA propagates structural skips through the denoising loss and reverse-time sampler, and represents ordinal variables with cumulative-probit scalar latents while retaining analog-bit encodings for nominal variables. When a codebook skip mask is available, TabSODA uses it directly; otherwise, the TabSODA+SKIP variant estimates the mask from raw responses and questionnaire order using a CART-based skip-pattern miner. On Population Assessment of Tobacco and Health (PATH) study and the National Survey on Drug Use and Health (NSDUH), two nationally representative U.S.\ surveys, TabSODA reduces ordinal MACE by up to $23.7\%$ and improves categorical accuracy by up to $9\%$ over the strongest baseline across MCAR, MAR, and MNAR masking. The skip miner achieves near-perfect precision on both datasets, allowing TabSODA+SKIP to closely track the codebook-mask variant.

Yuchen Dang, Ziqi Chen, Heng Li et al.

Solar activity has significant impacts on human activities and health. One most commonly used measure of solar activity is the sunspot number. This paper compares three important non-deep learning models, four popular deep learning models, and their five ensemble models in forecasting sunspot numbers. In particular, we propose an ensemble model called XGBoost-DL, which uses XGBoost as a two-level nonlinear ensemble method to combine the deep learning models. Our XGBoost-DL achieves the best forecasting performance (RMSE = 25.70 and MAE = 19.82) in the comparison, outperforming the best non-deep learning model SARIMA (RMSE = 54.11 and MAE = 45.51), the best deep learning model Informer (RMSE = 29.90 and MAE = 22.35) and the NASA's forecast (RMSE = 48.38 and MAE = 38.45). Our XGBoost-DL forecasts a peak sunspot number of 133.47 in May 2025 for Solar Cycle 25 and 164.62 in November 2035 for Solar Cycle 26, similar to but later than the NASA's at 137.7 in October 2024 and 161.2 in December 2034. An open-source Python package of our XGBoost-DL for the sunspot number prediction is available at https://github.com/yd1008/ts_ensemble_sunspot.

Rong Wu, Ziqi Chen, Liming Zhong et al.

Existing segmentation models trained on a single medical imaging dataset often lack robustness when encountering unseen organs or tumors. Developing a robust model capable of identifying rare or novel tumor categories not present during training is crucial for advancing medical imaging applications. We propose DSM, a novel framework that leverages diffusion and state space models to segment unseen tumor categories beyond the training data. DSM utilizes two sets of object queries trained within modified attention decoders to enhance classification accuracy. Initially, the model learns organ queries using an object-aware feature grouping strategy to capture organ-level visual features. It then refines tumor queries by focusing on diffusion-based visual prompts, enabling precise segmentation of previously unseen tumors. Furthermore, we incorporate diffusion-guided feature fusion to improve semantic segmentation performance. By integrating CLIP text embeddings, DSM captures category-sensitive classes to improve linguistic transfer knowledge, thereby enhancing the model's robustness across diverse scenarios and multi-label tasks. Extensive experiments demonstrate the superior performance of DSM in various tumor segmentation tasks. Code is available at https://github.com/Rows21/k-Means_Mask_Mamba.

Yanbing Chen, Tianze Tang, Taehyo Kim et al.

Background: Gliomas are among the most common malignant brain tumors and exhibit substantial heterogeneity, complicating accurate detection and segmentation. Although multi-modal MRI is the clinical standard for glioma imaging, variability across modalities and high computational demands hamper effective automated segmentation. Methods: We propose UKAN-EP, a novel 3D extension of the original 2D U-KAN model for multi-modal MRI brain tumor segmentation. While U-KAN integrates Kolmogorov-Arnold Network (KAN) layers into a U-Net backbone, UKAN-EP further incorporates Efficient Channel Attention (ECA) and Pyramid Feature Aggregation (PFA) modules to enhance inter-modality feature fusion and multi-scale feature representation. We also introduce a dynamic loss weighting strategy that adaptively balances cross-entropy and Dice losses during training. Results: On the 2024 BraTS-GLI dataset, UKAN-EP achieves superior segmentation performance (e.g., Dice = 0.9001 $\pm$ 0.0127 and IoU = 0.8257 $\pm$ 0.0186 for the whole tumor) while requiring substantially fewer computational resources (223.57 GFLOPs and 11.30M parameters) compared to strong baselines including U-Net, Attention U-Net, Swin UNETR, VT-Unet, TransBTS, and 3D U-KAN. An extensive ablation study further confirms the effectiveness of ECA and PFA and shows the limited utility of self-attention and spatial attention alternatives. Conclusion: UKAN-EP demonstrates that combining the expressive power of KAN layers with lightweight channel-wise attention and multi-scale feature aggregation improves the accuracy and efficiency of brain tumor segmentation.

Qiran Jia, Hai Shu

Convolutional neural networks (CNNs) have achieved remarkable success in automatically segmenting organs or lesions on 3D medical images. Recently, vision transformer networks have exhibited exceptional performance in 2D image classification tasks. Compared with CNNs, transformer networks have an appealing advantage of extracting long-range features due to their self-attention algorithm. Therefore, we propose a CNN-Transformer combined model, called BiTr-Unet, with specific modifications for brain tumor segmentation on multi-modal MRI scans. Our BiTr-Unet achieves good performance on the BraTS2021 validation dataset with median Dice score 0.9335, 0.9304 and 0.8899, and median Hausdorff distance 2.8284, 2.2361 and 1.4142 for the whole tumor, tumor core, and enhancing tumor, respectively. On the BraTS2021 testing dataset, the corresponding results are 0.9257, 0.9350 and 0.8874 for Dice score, and 3, 2.2361 and 1.4142 for Hausdorff distance. The code is publicly available at https://github.com/JustaTinyDot/BiTr-Unet.

Chenggang Lyu, Hai Shu

Automatic MRI brain tumor segmentation is of vital importance for the disease diagnosis, monitoring, and treatment planning. In this paper, we propose a two-stage encoder-decoder based model for brain tumor subregional segmentation. Variational autoencoder regularization is utilized in both stages to prevent the overfitting issue. The second-stage network adopts attention gates and is trained additionally using an expanded dataset formed by the first-stage outputs. On the BraTS 2020 validation dataset, the proposed method achieves the mean Dice score of 0.9041, 0.8350, and 0.7958, and Hausdorff distance (95%) of 4.953, 6.299, and 23.608 for the whole tumor, tumor core, and enhancing tumor, respectively. The corresponding results on the BraTS 2020 testing dataset are 0.8729, 0.8357, and 0.8205 for Dice score, and 11.4288, 19.9690, and 15.6711 for Hausdorff distance. The code is publicly available at https://github.com/shu-hai/two-stage-VAE-Attention-gate-BraTS2020.

Taehyo Kim, Hai Shu, Qiran Jia et al.

Voxel-based multiple testing is widely used in neuroimaging data analysis. Traditional false discovery rate (FDR) control methods often ignore the spatial dependence among the voxel-based tests and thus suffer from substantial loss of testing power. While recent spatial FDR control methods have emerged, their validity and optimality remain questionable when handling the complex spatial dependencies of the brain. Concurrently, deep learning methods have revolutionized image segmentation, a task closely related to voxel-based multiple testing. In this paper, we propose DeepFDR, a novel spatial FDR control method that leverages unsupervised deep learning-based image segmentation to address the voxel-based multiple testing problem. Numerical studies, including comprehensive simulations and Alzheimer's disease FDG-PET image analysis, demonstrate DeepFDR's superiority over existing methods. DeepFDR not only excels in FDR control and effectively diminishes the false nondiscovery rate, but also boasts exceptional computational efficiency highly suited for tackling large-scale neuroimaging data.

Yanfeng Yang, Shuai Li, Yingjie Zhang et al.

Conditional independence (CI) testing is a fundamental task in modern statistics and machine learning. The conditional randomization test (CRT) was recently introduced to test whether two random variables, $X$ and $Y$, are conditionally independent given a potentially high-dimensional set of random variables, $Z$. The CRT operates exceptionally well under the assumption that the conditional distribution $X|Z$ is known. However, since this distribution is typically unknown in practice, accurately approximating it becomes crucial. In this paper, we propose using conditional diffusion models (CDMs) to learn the distribution of $X|Z$. Theoretically and empirically, it is shown that CDMs closely approximate the true conditional distribution. Furthermore, CDMs offer a more accurate approximation of $X|Z$ compared to GANs, potentially leading to a CRT that performs better than those based on GANs. To accommodate complex dependency structures, we utilize a computationally efficient classifier-based conditional mutual information (CMI) estimator as our test statistic. The proposed testing procedure performs effectively without requiring assumptions about specific distribution forms or feature dependencies, and is capable of handling mixed-type conditioning sets that include both continuous and discrete variables. Theoretical analysis shows that our proposed test achieves a valid control of the type I error. A series of experiments on synthetic data demonstrates that our new test effectively controls both type-I and type-II errors, even in high dimensional scenarios.

Taehyo Kim, Qiran Jia, Mony J. de Leon et al.

False discovery rate (FDR) control methods are essential for voxel-wise multiple testing in neuroimaging data analysis, where hundreds of thousands or even millions of tests are conducted to detect brain regions associated with disease-related changes. Classical FDR control methods (e.g., BH, q-value, and LocalFDR) assume independence among tests and often lead to high false non-discovery rates (FNR). Although various spatial FDR control methods have been developed to improve power, they still fall short of jointly addressing three major challenges in neuroimaging applications: capturing complex spatial dependencies, maintaining low variability in both false discovery proportion (FDP) and false non-discovery proportion (FNP) across replications, and achieving computational scalability for high-resolution data. To address these challenges, we propose fcHMRF-LIS, a powerful, stable, and scalable spatial FDR control method for voxel-wise multiple testing. It integrates the local index of significance (LIS)-based testing procedure with a novel fully connected hidden Markov random field (fcHMRF) designed to model complex spatial structures using a parsimonious parameterization. We develop an efficient expectation-maximization algorithm incorporating mean-field approximation, the Conditional Random Fields as Recurrent Neural Networks (CRF-RNN) technique, and permutohedral lattice filtering, reducing the time complexity from quadratic to linear in the number of tests. Extensive simulations demonstrate that fcHMRF-LIS achieves accurate FDR control, lower FNR, reduced variability in FDP and FNP, and a higher number of true positives compared to existing methods. Applied to an FDG-PET dataset from the Alzheimer's Disease Neuroimaging Initiative, fcHMRF-LIS identifies neurobiologically relevant brain regions and offers notable advantages in computational efficiency.

Rong Wu, Ziqi Chen, Gen Li et al.

Motivation: Biomedical studies increasingly produce multi-view high-dimensional datasets (e.g., multi-omics) that demand integrative analysis. Existing canonical correlation analysis (CCA) and generalized CCA methods address at most two of the following three key aspects simultaneously: (i) nonlinear dependence, (ii) sparsity for variable selection, and (iii) generalization to more than two data views. There is a pressing need for CCA methods that integrate all three aspects to effectively analyze multi-view high-dimensional data. Results: We propose three nonlinear, sparse, generalized CCA methods, HSIC-SGCCA, SA-KGCCA, and TS-KGCCA, for variable selection in multi-view high-dimensional data. These methods extend existing SCCA-HSIC, SA-KCCA, and TS-KCCA from two-view to multi-view settings. While SA-KGCCA and TS-KGCCA yield multi-convex optimization problems solved via block coordinate descent, HSIC-SGCCA introduces a necessary unit-variance constraint previously ignored in SCCA-HSIC, resulting in a nonconvex, non-multiconvex problem. We efficiently address this challenge by integrating the block prox-linear method with the linearized alternating direction method of multipliers. Simulations and TCGA-BRCA data analysis demonstrate that HSIC-SGCCA outperforms competing methods in multi-view variable selection.

Zhaoyang Zhang, Hongtu Zhu, Ziqi Chen et al.

In this paper, we aim to address a significant challenge in the field of missing data imputation: identifying and leveraging the interdependencies among features to enhance missing data imputation for tabular data. We introduce a novel framework named the Bipartite and Complete Directed Graph Neural Network (BCGNN). Within BCGNN, observations and features are differentiated as two distinct node types, and the values of observed features are converted into attributed edges linking them. The bipartite segment of our framework inductively learns embedding representations for nodes, efficiently utilizing the comprehensive information encapsulated in the attributed edges. In parallel, the complete directed graph segment adeptly outlines and communicates the complex interdependencies among features. When compared to contemporary leading imputation methodologies, BCGNN consistently outperforms them, achieving a noteworthy average reduction of 15% in mean absolute error for feature imputation tasks under different missing mechanisms. Our extensive experimental investigation confirms that an in-depth grasp of the interdependence structure substantially enhances the model's feature embedding ability. We also highlight the model's superior performance in label prediction tasks involving missing data, and its formidable ability to generalize to unseen data points.

Hai Shu

A typical approach to the joint analysis of multiple high-dimensional data views is to decompose each view's data matrix into three parts: a low-rank common-source matrix generated by common latent factors of all data views, a low-rank distinctive-source matrix generated by distinctive latent factors of the corresponding data view, and an additive noise matrix. Existing decomposition methods often focus on the uncorrelatedness between the common latent factors and distinctive latent factors, but inadequately address the equally necessary uncorrelatedness between distinctive latent factors from different data views. We propose a novel decomposition method, called Decomposition of Common and Distinctive Latent Factors (D-CDLF), to effectively achieve both types of uncorrelatedness for two-view data. We also discuss the estimation of the D-CDLF under high-dimensional settings.

Hai Shu, Ronghua Shi, Qiran Jia et al.

Deep neural networks (DNNs) have achieved great success in image classification, but can be very vulnerable to adversarial attacks with small perturbations to images. To improve adversarial image generation for DNNs, we develop a novel method, called mFI-PSO, which utilizes a Manifold-based First-order Influence measure for vulnerable image and pixel selection and the Particle Swarm Optimization for various objective functions. Our mFI-PSO can thus effectively design adversarial images with flexible, customized options on the number of perturbed pixels, the misclassification probability, and the targeted incorrect class. Experiments demonstrate the flexibility and effectiveness of our mFI-PSO in adversarial attacks and its appealing advantages over some popular methods.

Hai Shu, Zhe Qu, Hongtu Zhu

Modern biomedical studies often collect multi-view data, that is, multiple types of data measured on the same set of objects. A popular model in high-dimensional multi-view data analysis is to decompose each view's data matrix into a low-rank common-source matrix generated by latent factors common across all data views, a low-rank distinctive-source matrix corresponding to each view, and an additive noise matrix. We propose a novel decomposition method for this model, called decomposition-based generalized canonical correlation analysis (D-GCCA). The D-GCCA rigorously defines the decomposition on the L2 space of random variables in contrast to the Euclidean dot product space used by most existing methods, thereby being able to provide the estimation consistency for the low-rank matrix recovery. Moreover, to well calibrate common latent factors, we impose a desirable orthogonality constraint on distinctive latent factors. Existing methods, however, inadequately consider such orthogonality and may thus suffer from substantial loss of undetected common-source variation. Our D-GCCA takes one step further than generalized canonical correlation analysis by separating common and distinctive components among canonical variables, while enjoying an appealing interpretation from the perspective of principal component analysis. Furthermore, we propose to use the variable-level proportion of signal variance explained by common or distinctive latent factors for selecting the variables most influenced. Consistent estimators of our D-GCCA method are established with good finite-sample numerical performance, and have closed-form expressions leading to efficient computation especially for large-scale data. The superiority of D-GCCA over state-of-the-art methods is also corroborated in simulations and real-world data examples.

Hai Shu, Zhe Qu

A representative model in integrative analysis of two high-dimensional correlated datasets is to decompose each data matrix into a low-rank common matrix generated by latent factors shared across datasets, a low-rank distinctive matrix corresponding to each dataset, and an additive noise matrix. Existing decomposition methods claim that their common matrices capture the common pattern of the two datasets. However, their so-called common pattern only denotes the common latent factors but ignores the common pattern between the two coefficient matrices of these common latent factors. We propose a new unsupervised learning method, called the common and distinctive pattern analysis (CDPA), which appropriately defines the two types of data patterns by further incorporating the common and distinctive patterns of the coefficient matrices. A consistent estimation approach is developed for high-dimensional settings, and shows reasonably good finite-sample performance in simulations. Our simulation studies and real data analysis corroborate that the proposed CDPA can provide better characterization of common and distinctive patterns and thereby benefit data mining.

Hai Shu, Hongtu Zhu

Deep neural networks (DNNs) have achieved superior performance in various prediction tasks, but can be very vulnerable to adversarial examples or perturbations. Therefore, it is crucial to measure the sensitivity of DNNs to various forms of perturbations in real applications. We introduce a novel perturbation manifold and its associated influence measure to quantify the effects of various perturbations on DNN classifiers. Such perturbations include various external and internal perturbations to input samples and network parameters. The proposed measure is motivated by information geometry and provides desirable invariance properties. We demonstrate that our influence measure is useful for four model building tasks: detecting potential 'outliers', analyzing the sensitivity of model architectures, comparing network sensitivity between training and test sets, and locating vulnerable areas. Experiments show reasonably good performance of the proposed measure for the popular DNN models ResNet50 and DenseNet121 on CIFAR10 and MNIST datasets.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Hai Shu, Bin Nan

We consider the estimation of large covariance and precision matrices from high-dimensional sub-Gaussian or heavier-tailed observations with slowly decaying temporal dependence. The temporal dependence is allowed to be long-range so with longer memory than those considered in the current literature. We show that several commonly used methods for independent observations can be applied to the temporally dependent data. In particular, the rates of convergence are obtained for the generalized thresholding estimation of covariance and correlation matrices, and for the constrained $\ell_1$ minimization and the $\ell_1$ penalized likelihood estimation of precision matrix. Properties of sparsistency and sign-consistency are also established. A gap-block cross-validation method is proposed for the tuning parameter selection, which performs well in simulations. As a motivating example, we study the brain functional connectivity using resting-state fMRI time series data with long-range temporal dependence.

Hai Shu, Bin Nan, Robert Koeppe

Traditional voxel-level multiple testing procedures in neuroimaging, mostly $p$-value based, often ignore the spatial correlations among neighboring voxels and thus suffer from substantial loss of power. We extend the local-significance-index based procedure originally developed for the hidden Markov chain models, which aims to minimize the false nondiscovery rate subject to a constraint on the false discovery rate, to three-dimensional neuroimaging data using a hidden Markov random field model. A generalized expectation-maximization algorithm for maximizing the penalized likelihood is proposed for estimating the model parameters. Extensive simulations show that the proposed approach is more powerful than conventional false discovery rate procedures. We apply the method to the comparison between mild cognitive impairment, a disease status with increased risk of developing Alzheimer's or another dementia, and normal controls in the FDG-PET imaging study of the Alzheimer's Disease Neuroimaging Initiative.