Zhao Chen

Jiwen Yu, Yinhuai Wang, Chen Zhao et al.

Recently, conditional diffusion models have gained popularity in numerous applications due to their exceptional generation ability. However, many existing methods are training-required. They need to train a time-dependent classifier or a condition-dependent score estimator, which increases the cost of constructing conditional diffusion models and is inconvenient to transfer across different conditions. Some current works aim to overcome this limitation by proposing training-free solutions, but most can only be applied to a specific category of tasks and not to more general conditions. In this work, we propose a training-Free conditional Diffusion Model (FreeDoM) used for various conditions. Specifically, we leverage off-the-shelf pre-trained networks, such as a face detection model, to construct time-independent energy functions, which guide the generation process without requiring training. Furthermore, because the construction of the energy function is very flexible and adaptable to various conditions, our proposed FreeDoM has a broader range of applications than existing training-free methods. FreeDoM is advantageous in its simplicity, effectiveness, and low cost. Experiments demonstrate that FreeDoM is effective for various conditions and suitable for diffusion models of diverse data domains, including image and latent code domains.

Xuewei Cao, Joyce H Keyak, Sigurdur Sigurdsson et al.

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient specific finite element analysis (FEA) computes the force (fracture load) to break the proximal femur in a particular loading condition. It provides different structural information about the proximal femur that can influence a subject overall fracture risk. To obtain a more robust measure of fracture risk, we used principal component analysis (PCA) to develop a global FEA computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies to failure in four loading conditions (single-limb stance and impact from a fall onto the posterior, posterolateral, and lateral aspects of the greater trochanter) of 110 hip fracture subjects and 235 age and sex matched control subjects from the AGES-Reykjavik study. We found that the first PC (PC1) of the FE parameters was the only significant predictor of hip fracture. Using a logistic regression model, we determined if prediction performance for hip fracture using PC1 differed from that using FE parameters combined by stratified random resampling with respect to hip fracture status. The results showed that the average of the area under the receive operating characteristic curve (AUC) using PC1 was always higher than that using all FE parameters combined in the male subjects. The AUC of PC1 and AUC of the FE parameters combined were not significantly different than that in the female subjects or in all subjects

Haocheng Yuan, Chen Zhao, Shichao Fan et al.

Semantic 3D keypoints are category-level semantic consistent points on 3D objects. Detecting 3D semantic keypoints is a foundation for a number of 3D vision tasks but remains challenging, due to the ambiguity of semantic information, especially when the objects are represented by unordered 3D point clouds. Existing unsupervised methods tend to generate category-level keypoints in implicit manners, making it difficult to extract high-level information, such as semantic labels and topology. From a novel mutual reconstruction perspective, we present an unsupervised method to generate consistent semantic keypoints from point clouds explicitly. To achieve this, the proposed model predicts keypoints that not only reconstruct the object itself but also reconstruct other instances in the same category. To the best of our knowledge, the proposed method is the first to mine 3D semantic consistent keypoints from a mutual reconstruction view. Experiments under various evaluation metrics as well as comparisons with the state-of-the-arts demonstrate the efficacy of our new solution to mining semantic consistent keypoints with mutual reconstruction.

Chen Zhao, Anqi Liu, Xiao Zhang et al.

Integration of heterogeneous and high-dimensional multi-omics data is becoming increasingly important in understanding genetic data. Each omics technique only provides a limited view of the underlying biological process and integrating heterogeneous omics layers simultaneously would lead to a more comprehensive and detailed understanding of diseases and phenotypes. However, one obstacle faced when performing multi-omics data integration is the existence of unpaired multi-omics data due to instrument sensitivity and cost. Studies may fail if certain aspects of the subjects are missing or incomplete. In this paper, we propose a deep learning method for multi-omics integration with incomplete data by Cross-omics Linked unified embedding with Contrastive Learning and Self Attention (CLCLSA). Utilizing complete multi-omics data as supervision, the model employs cross-omics autoencoders to learn the feature representation across different types of biological data. The multi-omics contrastive learning, which is used to maximize the mutual information between different types of omics, is employed before latent feature concatenation. In addition, the feature-level self-attention and omics-level self-attention are employed to dynamically identify the most informative features for multi-omics data integration. Extensive experiments were conducted on four public multi-omics datasets. The experimental results indicated that the proposed CLCLSA outperformed the state-of-the-art approaches for multi-omics data classification using incomplete multi-omics data.

Chen Zhao, Zhihui Xu, Jingfeng Jiang et al.

Semantic labeling of coronary arterial segments in invasive coronary angiography (ICA) is important for automated assessment and report generation of coronary artery stenosis in the computer-aided diagnosis of coronary artery disease (CAD). Inspired by the training procedure of interventional cardiologists for interpreting the structure of coronary arteries, we propose an association graph-based graph matching network (AGMN) for coronary arterial semantic labeling. We first extract the vascular tree from invasive coronary angiography (ICA) and convert it into multiple individual graphs. Then, an association graph is constructed from two individual graphs where each vertex represents the relationship between two arterial segments. Using the association graph, the AGMN extracts the vertex features by the embedding module, aggregates the features from adjacent vertices and edges by graph convolution network, and decodes the features to generate the semantic mappings between arteries. By learning the mapping of arterial branches between two individual graphs, the unlabeled arterial segments are classified by the labeled segments to achieve semantic labeling. A dataset containing 263 ICAs was employed to train and validate the proposed model, and a five-fold cross-validation scheme was performed. Our AGMN model achieved an average accuracy of 0.8264, an average precision of 0.8276, an average recall of 0.8264, and an average F1-score of 0.8262, which significantly outperformed existing coronary artery semantic labeling methods. In conclusion, we have developed and validated a new algorithm with high accuracy, interpretability, and robustness for coronary artery semantic labeling on ICAs.

Kristoffer Larsen, Chen Zhao, Joyce Keyak et al.

Aims. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Methods. 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6+-1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. Results. The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0+-11.8, and LVEF of 27.7+-11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. Conclusions. By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without sacrificing performance.

Chen Zhao, Joyce H Keyak, Xuewei Cao et al.

The aim of this paper is to design a deep learning-based model to predict proximal femoral strength using multi-view information fusion. Method: We developed new models using multi-view variational autoencoder (MVAE) for feature representation learning and a product of expert (PoE) model for multi-view information fusion. We applied the proposed models to an in-house Louisiana Osteoporosis Study (LOS) cohort with 931 male subjects, including 345 African Americans and 586 Caucasians. With an analytical solution of the product of Gaussian distribution, we adopted variational inference to train the designed MVAE-PoE model to perform common latent feature extraction. We performed genome-wide association studies (GWAS) to select 256 genetic variants with the lowest p-values for each proximal femoral strength and integrated whole genome sequence (WGS) features and DXA-derived imaging features to predict proximal femoral strength. Results: The best prediction model for fall fracture load was acquired by integrating WGS features and DXA-derived imaging features. The designed models achieved the mean absolute percentage error of 18.04%, 6.84% and 7.95% for predicting proximal femoral fracture loads using linear models of fall loading, nonlinear models of fall loading, and nonlinear models of stance loading, respectively. Compared to existing multi-view information fusion methods, the proposed MVAE-PoE achieved the best performance. Conclusion: The proposed models are capable of predicting proximal femoral strength using WGS features and DXA-derived imaging features. Though this tool is not a substitute for FEA using QCT images, it would make improved assessment of hip fracture risk more widely available while avoiding the increased radiation dosage and clinical costs from QCT.

Fubao Zhu, Jinyu Zhao, Chen Zhao et al.

Background: The assessment of left ventricular (LV) function by myocardial perfusion SPECT (MPS) relies on accurate myocardial segmentation. The purpose of this paper is to develop and validate a new method incorporating deep learning with shape priors to accurately extract the LV myocardium for automatic measurement of LV functional parameters. Methods: A segmentation architecture that integrates a three-dimensional (3D) V-Net with a shape deformation module was developed. Using the shape priors generated by a dynamic programming (DP) algorithm, the model output was then constrained and guided during the model training for quick convergence and improved performance. A stratified 5-fold cross-validation was used to train and validate our models. Results: Results of our proposed method agree well with those from the ground truth. Our proposed model achieved a Dice similarity coefficient (DSC) of 0.9573(0.0244), 0.9821(0.0137), and 0.9903(0.0041), a Hausdorff distances (HD) of 6.7529(2.7334) mm, 7.2507(3.1952) mm, and 7.6121(3.0134) mm in extracting the endocardium, myocardium, and epicardium, respectively. Conclusion: Our proposed method achieved a high accuracy in extracting LV myocardial contours and assessing LV function.

Yinghui Meng, Zhenglong Du, Chen Zhao et al.

Accurate extraction of coronary arteries from invasive coronary angiography (ICA) is important in clinical decision-making for the diagnosis and risk stratification of coronary artery disease (CAD). In this study, we develop a method using deep learning to automatically extract the coronary artery lumen. Methods. A deep learning model U-Net 3+, which incorporates the full-scale skip connections and deep supervisions, was proposed for automatic extraction of coronary arteries from ICAs. Transfer learning and a hybrid loss function were employed in this novel coronary artery extraction framework. Results. A data set containing 616 ICAs obtained from 210 patients was used. In the technical evaluation, the U-Net 3+ achieved a Dice score of 0.8942 and a sensitivity of 0.8735, which is higher than U-Net ++ (Dice score: 0.8814, the sensitivity of 0.8331) and U-net (Dice score: 0.8799, the sensitivity of 0.8305). Conclusion. Our study demonstrates that the U-Net 3+ is superior to other segmentation frameworks for the automatic extraction of the coronary arteries from ICAs. This result suggests great promise for clinical use.

Chen Zhao, Kuan-Jui Su, Chong Wu et al.

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R^2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.

Chen Zhao, Michele Esposito, Zhihui Xu et al.

Coronary artery disease (CAD) is one of the primary causes leading to death worldwide. Accurate extraction of individual arterial branches on invasive coronary angiograms (ICA) is important for stenosis detection and CAD diagnosis. However, deep learning-based models face challenges in generating semantic segmentation for coronary arteries due to the morphological similarity among different types of coronary arteries. To address this challenge, we propose an innovative approach using the hyper association graph-matching neural network with uncertainty quantification (HAGMN-UQ) for coronary artery semantic labeling on ICAs. The graph-matching procedure maps the arterial branches between two individual graphs, so that the unlabeled arterial segments are classified by the labeled segments, and the coronary artery semantic labeling is achieved. By incorporating the anatomical structural loss and uncertainty, our model achieved an accuracy of 0.9345 for coronary artery semantic labeling with a fast inference speed, leading to an effective and efficient prediction in real-time clinical decision-making scenarios.

Ni Yao, Yanhui Tian, Daniel Gama das Neves et al.

Epicardial adipose tissue (EAT) is known for its pro-inflammatory properties and association with Coronavirus Disease 2019 (COVID-19) severity. However, current EAT segmentation methods do not consider positional information. Additionally, the detection of COVID-19 severity lacks consideration for EAT radiomics features, which limits interpretability. This study investigates the use of radiomics features from EAT and lungs to detect the severity of COVID-19 infections. A retrospective analysis of 515 patients with COVID-19 (Cohort1: 415, Cohort2: 100) was conducted using a proposed three-stage deep learning approach for EAT extraction. Lung segmentation was achieved using a published method. A hybrid model for detecting the severity of COVID-19 was built in a derivation cohort, and its performance and uncertainty were evaluated in internal (125, Cohort1) and external (100, Cohort2) validation cohorts. For EAT extraction, the Dice similarity coefficients (DSC) of the two centers were 0.972 (+-0.011) and 0.968 (+-0.005), respectively. For severity detection, the hybrid model with radiomics features of both lungs and EAT showed improvements in AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) compared to the model with only lung radiomics features. The hybrid model exhibited an increase of 0.1 (p<0.001), 19.3%, and 18.0% respectively, in the internal validation cohort and an increase of 0.09 (p<0.001), 18.0%, and 18.0%, respectively, in the external validation cohort while outperforming existing detection methods. Uncertainty quantification and radiomics features analysis confirmed the interpretability of case prediction after inclusion of EAT features.

Rochak Dhakal, Chen Zhao, Zixin Shi et al.

Quantitative computed tomography (QCT) plays a crucial role in assessing bone strength and fracture risk by enabling volumetric analysis of bone density distribution in the proximal femur. However, deploying automated segmentation models in practice remains difficult because deep networks trained on one dataset often fail when applied to another. This failure stems from domain shift, where scanners, reconstruction settings, and patient demographics vary across institutions, leading to unstable predictions and unreliable quantitative metrics. Overcoming this barrier is essential for multi-center osteoporosis research and for ensuring that radiomics and structural finite element analysis results remain reproducible across sites. In this work, we developed a domain-adaptive transformer segmentation framework tailored for multi-institutional QCT. Our model is trained and validated on one of the largest hip fracture related research cohorts to date, comprising 1,024 QCT images scans from Tulane University and 384 scans from Rochester, Minnesota for proximal femur segmentation. To address domain shift, we integrate two complementary strategies within a 3D TransUNet backbone: adversarial alignment via Gradient Reversal Layer (GRL), which discourages the network from encoding site-specific cues, and statistical alignment via Maximum Mean Discrepancy (MMD), which explicitly reduces distributional mismatches between institutions. This dual mechanism balances invariance and fine-grained alignment, enabling scanner-agnostic feature learning while preserving anatomical detail.

Ni Yao, Hang Hu, Kaicong Chen et al.

Objectives To develop and validate a deep learning-based diagnostic model incorporating uncertainty estimation so as to facilitate radiologists in the preoperative differentiation of the pathological subtypes of renal cell carcinoma (RCC) based on CT images. Methods Data from 668 consecutive patients, pathologically proven RCC, were retrospectively collected from Center 1. By using five-fold cross-validation, a deep learning model incorporating uncertainty estimation was developed to classify RCC subtypes into clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). An external validation set of 78 patients from Center 2 further evaluated the model's performance. Results In the five-fold cross-validation, the model's area under the receiver operating characteristic curve (AUC) for the classification of ccRCC, pRCC, and chRCC was 0.868 (95% CI: 0.826-0.923), 0.846 (95% CI: 0.812-0.886), and 0.839 (95% CI: 0.802-0.88), respectively. In the external validation set, the AUCs were 0.856 (95% CI: 0.838-0.882), 0.787 (95% CI: 0.757-0.818), and 0.793 (95% CI: 0.758-0.831) for ccRCC, pRCC, and chRCC, respectively. Conclusions The developed deep learning model demonstrated robust performance in predicting the pathological subtypes of RCC, while the incorporated uncertainty emphasized the importance of understanding model confidence, which is crucial for assisting clinical decision-making for patients with renal tumors. Clinical relevance statement Our deep learning approach, integrated with uncertainty estimation, offers clinicians a dual advantage: accurate RCC subtype predictions complemented by diagnostic confidence references, promoting informed decision-making for patients with RCC.

Rene Lisasi, Michele Esposito, Chen Zhao

Computational fluid dynamics (CFD) based simulation of coronary blood flow provides valuable hemodynamic markers, such as pressure gradients, for diagnosing coronary artery disease (CAD). However, CFD is computationally expensive, time-consuming, and difficult to integrate into large-scale clinical workflows. These limitations restrict the availability of labeled hemodynamic data for training AI models and hinder broad adoption of non-invasive, physiology based CAD assessment. To address these challenges, we develop an end to end pipeline that automates coronary geometry extraction from coronary computed tomography angiography (CCTA), streamlines simulation data generation, and enables efficient learning of coronary blood pressure distributions. The pipeline reduces the manual burden associated with traditional CFD workflows while producing consistent training data. We further introduce a diffusion-based regression model designed to predict coronary blood pressure directly from CCTA derived features, bypassing the need for slow CFD computation during inference. Evaluated on a dataset of simulated coronary hemodynamics, the proposed model achieves state of the art performance, with an R2 of 64.42%, a root mean squared error of 0.0974, and a normalized RMSE of 0.154, outperforming several baseline approaches. This work provides a scalable and accessible framework for rapid, non-invasive blood pressure prediction to support CAD diagnosis.

Haoliang Wang, Chen Zhao, Feng Chen

Real-world machine learning applications often face simultaneous covariate and semantic shifts, challenging traditional domain generalization and out-of-distribution (OOD) detection methods. We introduce Meta-learned Across Domain Out-of-distribution Detection (MADOD), a novel framework designed to address both shifts concurrently. MADOD leverages meta-learning and G-invariance to enhance model generalizability and OOD detection in unseen domains. Our key innovation lies in task construction: we randomly designate in-distribution classes as pseudo-OODs within each meta-learning task, simulating OOD scenarios using existing data. This approach, combined with energy-based regularization, enables the learning of robust, domain-invariant features while calibrating decision boundaries for effective OOD detection. Operating in a test domain-agnostic setting, MADOD eliminates the need for adaptation during inference, making it suitable for scenarios where test data is unavailable. Extensive experiments on real-world and synthetic datasets demonstrate MADOD's superior performance in semantic OOD detection across unseen domains, achieving an AUPR improvement of 8.48% to 20.81%, while maintaining competitive in-distribution classification accuracy, representing a significant advancement in handling both covariate and semantic shifts.

Hongjun Liu, Yinghao Zhu, Yuhui Wang et al.

Recent progress in multimodal large language models (MLLMs) has demonstrated promising performance on medical benchmarks and in preliminary trials as clinical assistants. Yet, our pilot audit of diagnostic cases uncovers a critical failure mode: instability in early evidence interpretation precedes hallucination, creating branching reasoning trajectories that cascade into globally inconsistent conclusions. This highlights the need for clinical reasoning agents that constrain stochasticity and hallucination while producing auditable decision flows. We introduce MedMMV, a controllable multimodal multi-agent framework for reliable and verifiable clinical reasoning. MedMMV stabilizes reasoning through diversified short rollouts, grounds intermediate steps in a structured evidence graph under the supervision of a Hallucination Detector, and aggregates candidate paths with a Combined Uncertainty scorer. On six medical benchmarks, MedMMV improves accuracy by up to 12.7% and, more critically, demonstrates superior reliability. Blind physician evaluations confirm that MedMMV substantially increases reasoning truthfulness without sacrificing informational content. By controlling instability through a verifiable, multi-agent process, our framework provides a robust path toward deploying trustworthy AI systems in high-stakes domains like clinical decision support.

Chen Zhao, Anjum Shaik, Joyce H. Keyak et al.

Hip fractures represent a major health concern, particularly among the elderly, often leading decreased mobility and increased mortality. Early and accurate detection of at risk individuals is crucial for effective intervention. In this study, we propose Iterative Cross Graph Matching for Hip Fracture Risk Assessment (ICGM-FRAX), a novel approach for predicting hip fractures using Dual-energy X-ray Absorptiometry (DXA) images. ICGM-FRAX involves iteratively comparing a test (subject) graph with multiple template graphs representing the characteristics of hip fracture subjects to assess the similarity and accurately to predict hip fracture risk. These graphs are obtained as follows. The DXA images are separated into multiple regions of interest (RoIs), such as the femoral head, shaft, and lesser trochanter. Radiomic features are then calculated for each RoI, with the central coordinates used as nodes in a graph. The connectivity between nodes is established according to the Euclidean distance between these coordinates. This process transforms each DXA image into a graph, where each node represents a RoI, and edges derived by the centroids of RoIs capture the spatial relationships between them. If the test graph closely matches a set of template graphs representing subjects with incident hip fractures, it is classified as indicating high hip fracture risk. We evaluated our method using 547 subjects from the UK Biobank dataset, and experimental results show that ICGM-FRAX achieved a sensitivity of 0.9869, demonstrating high accuracy in predicting hip fractures.

Shuo Sun, Meiling Zhou, Chen Zhao et al.

Hip fractures are a major cause of disability, mortality, and healthcare burden in older adults, underscoring the need for early risk assessment. However, commonly used tools such as the DXA T-score and FRAX often lack sensitivity and miss individuals at high risk, particularly those without prior fractures or with osteopenia. To address this limitation, we propose a sequential two-stage model that integrates clinical and imaging information to improve prediction accuracy. Using data from the Osteoporotic Fractures in Men Study (MrOS), the Study of Osteoporotic Fractures (SOF), and the UK Biobank, Stage 1 (Screening) employs clinical, demographic, and functional variables to estimate baseline risk, while Stage 2 (Imaging) incorporates DXA-derived features for refinement. The model was rigorously validated through internal and external testing, showing consistent performance and adaptability across cohorts. Compared to T-score and FRAX, the two-stage framework achieved higher sensitivity and reduced missed cases, offering a cost-effective and personalized approach for early hip fracture risk assessment. Keywords: Hip Fracture, Two-Stage Model, Risk Prediction, Sensitivity, DXA, FRAX

Nan Mu, Ruiqi Song, Zhihui Xu et al.

Background: Coronary Artery Disease (CAD) is one of the leading causes of death worldwide. Invasive Coronary Angiography (ICA), regarded as the gold standard for CAD diagnosis, necessitates precise vessel segmentation and stenosis detection. However, ICA images are typically characterized by low contrast, high noise levels, and complex, fine-grained vascular structures, which pose significant challenges to the clinical adoption of existing segmentation and detection methods. Objective: This study aims to improve the accuracy of coronary artery segmentation and stenosis detection in ICA images by integrating multi-scale structural priors, state-space-based long-range dependency modeling, and frequency-domain detail enhancement strategies. Methods: We propose SFD-Mamba2Net, an end-to-end framework tailored for ICA-based vascular segmentation and stenosis detection. In the encoder, a Curvature-Aware Structural Enhancement (CASE) module is embedded to leverage multi-scale responses for highlighting slender tubular vascular structures, suppressing background interference, and directing attention toward vascular regions. In the decoder, we introduce a Progressive High-Frequency Perception (PHFP) module that employs multi-level wavelet decomposition to progressively refine high-frequency details while integrating low-frequency global structures. Results and Conclusions: SFD-Mamba2Net consistently outperformed state-of-the-art methods across eight segmentation metrics, and achieved the highest true positive rate and positive predictive value in stenosis detection.

Nan Mu, Hongbo Yang, Chen Zhao

Background and Objective: High-throughput multi-omics technologies have proven invaluable for elucidating disease mechanisms and enabling early diagnosis. However, the high cost of multi-omics profiling imposes a significant economic burden, with over reliance on full omics data potentially leading to unnecessary resource consumption. To address these issues, we propose an uncertainty-aware, multi-view dynamic decision framework for omics data classification that aims to achieve high diagnostic accuracy while minimizing testing costs. Methodology: At the single-omics level, we refine the activation functions of neural networks to generate Dirichlet distribution parameters, utilizing subjective logic to quantify both the belief masses and uncertainty mass of classification results. Belief mass reflects the support of a specific omics modality for a disease class, while the uncertainty parameter captures limitations in data quality and model discriminability, providing a more trustworthy basis for decision-making. At the multi omics level, we employ a fusion strategy based on Dempster-Shafer theory to integrate heterogeneous modalities, leveraging their complementarity to boost diagnostic accuracy and robustness. A dynamic decision mechanism is then applied that omics data are incrementally introduced for each patient until either all data sources are utilized or the model confidence exceeds a predefined threshold, potentially before all data sources are utilized. Results and Conclusion: We evaluate our approach on four benchmark multi-omics datasets, ROSMAP, LGG, BRCA, and KIPAN. In three datasets, over 50% of cases achieved accurate classification using a single omics modality, effectively reducing redundant testing. Meanwhile, our method maintains diagnostic performance comparable to full-omics models and preserves essential biological insights.

Nan Mu, Ruiqi Song, Xiaoning Li et al.

Background: Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide. Precise segmentation of coronary arteries from invasive coronary angiography (ICA) is critical for effective clinical decision-making. Objective: This study aims to propose a novel deep learning model based on frequency-domain analysis to enhance the accuracy of coronary artery segmentation and stenosis detection in ICA, thereby offering robust support for the stenosis detection and treatment of CAD. Methods: We propose the Frequency-Domain Attention-Guided Diffusion Network (FAD-Net), which integrates a frequency-domain-based attention mechanism and a cascading diffusion strategy to fully exploit frequency-domain information for improved segmentation accuracy. Specifically, FAD-Net employs a Multi-Level Self-Attention (MLSA) mechanism in the frequency domain, computing the similarity between queries and keys across high- and low-frequency components in ICAs. Furthermore, a Low-Frequency Diffusion Module (LFDM) is incorporated to decompose ICAs into low- and high-frequency components via multi-level wavelet transformation. Subsequently, it refines fine-grained arterial branches and edges by reintegrating high-frequency details via inverse fusion, enabling continuous enhancement of anatomical precision. Results and Conclusions: Extensive experiments demonstrate that FAD-Net achieves a mean Dice coefficient of 0.8717 in coronary artery segmentation, outperforming existing state-of-the-art methods. In addition, it attains a true positive rate of 0.6140 and a positive predictive value of 0.6398 in stenosis detection, underscoring its clinical applicability. These findings suggest that FAD-Net holds significant potential to assist in the accurate diagnosis and treatment planning of CAD.

Yehong Huang, Chen Zhao, Rochak Dhakal et al.

Background and Purpose: Functional assessment of the left ventricle using gated myocardial perfusion (MPS) single-photon emission computed tomography relies on the precise extraction of the left ventricular contours while simultaneously ensuring the security of patient data. Methods: In this paper, we introduce the integration of Federated Domain Adaptation with TimeSformer, named 'FedDA-TSformer' for left ventricle segmentation using MPS. FedDA-TSformer captures spatial and temporal features in gated MPS images, leveraging spatial attention, temporal attention, and federated learning for improved domain adaptation while ensuring patient data security. In detail, we employed Divide-Space-Time-Attention mechanism to extract spatio-temporal correlations from the multi-centered MPS datasets, ensuring that predictions are spatio-temporally consistent. To achieve domain adaptation, we align the model output on MPS from three different centers using local maximum mean discrepancy (LMMD) loss. This approach effectively addresses the dual requirements of federated learning and domain adaptation, enhancing the model's performance during training with multi-site datasets while ensuring the protection of data from different hospitals. Results: Our FedDA-TSformer was trained and evaluated using MPS datasets collected from three hospitals, comprising a total of 150 subjects. Each subject's cardiac cycle was divided into eight gates. The model achieved Dice Similarity Coefficients (DSC) of 0.842 and 0.907 for left ventricular (LV) endocardium and epicardium segmentation, respectively. Conclusion: Our proposed FedDA-TSformer model addresses the challenge of multi-center generalization, ensures patient data privacy protection, and demonstrates effectiveness in left ventricular (LV) segmentation.

Chen Zhao, Zhihui Xu, Guang-Uei Hung et al.

Coronary artery disease (CAD) is one of the primary causes leading deaths worldwide. The presence of atherosclerotic lesions in coronary arteries is the underlying pathophysiological basis of CAD, and accurate extraction of individual arterial branches using invasive coronary angiography (ICA) is crucial for stenosis detection and CAD diagnosis. We propose an innovative approach called the Edge Attention Graph Matching Network (EAGMN) for coronary artery semantic labeling. By converting the coronary artery semantic segmentation task into a graph node similarity comparison task, identifying the node-to-node correspondence would assign semantic labels for each arterial branch. More specifically, The EAGMN utilizes the association graph constructed from the two individual graphs as input. Experimental results indicate the EAGMN achieved a weighted accuracy of 0.8653, a weighted precision of 0.8656, a weighted recall of 0.8653 and a weighted F1-score of 0.8643. Furthermore, we employ ZORRO to provide interpretability and explainability of the graph matching for artery semantic labeling. These findings highlight the potential of the EAGMN for accurate and efficient coronary artery semantic labeling using ICAs. By leveraging the inherent characteristics of ICAs and incorporating graph matching techniques, our proposed model provides a promising solution for improving CAD diagnosis and treatment

Kristoffer Larsena, Zhuo He, Chen Zhao et al.

Background. Clinical parameters measured from gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) have value in predicting cardiac resynchronization therapy (CRT) patient outcomes, but still show limitations. The purpose of this study is to combine clinical variables, features from electrocardiogram (ECG), and parameters from assessment of cardiac function with polarmaps from gated SPECT MPI through deep learning (DL) to predict CRT response. Methods. 218 patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6-month follow up. A DL model was constructed by combining a pre-trained VGG16 module and a multilayer perceptron. Two modalities of data were input to the model: polarmap images from SPECT MPI and tabular data from clinical features and ECG parameters. Gradient-weighted Class Activation Mapping (Grad-CAM) was applied to the VGG16 module to provide explainability for the polarmaps. For comparison, four machine learning (ML) models were trained using only the tabular features. Results. Modeling was performed on 218 patients who underwent CRT implantation with a response rate of 55.5% (n = 121). The DL model demonstrated average AUC (0.83), accuracy (0.73), sensitivity (0.76), and specificity (0.69) surpassing the ML models and guideline criteria. Guideline recommendations presented accuracy (0.53), sensitivity (0.75), and specificity (0.26). Conclusions. The DL model outperformed the ML models, showcasing the additional predictive benefit of utilizing SPECT MPI polarmaps. Incorporating additional patient data directly in the form of medical imagery can improve CRT response prediction.

Chen Zhao, Shi Shi, Zhuo He et al.

Background. Functional assessment of right ventricle (RV) using gated myocardial perfusion single-photon emission computed tomography (MPS) heavily relies on the precise extraction of right ventricular contours. In this paper, we present a new deep-learning-based model integrating both the spatial and temporal features in gated MPS images to perform the segmentation of the RV epicardium and endocardium. Methods. By integrating the spatial features from each cardiac frame of the gated MPS and the temporal features from the sequential cardiac frames of the gated MPS, we developed a Spatial-Temporal V-Net (ST-VNet) for automatic extraction of RV endocardial and epicardial contours. In the ST-VNet, a V-Net is employed to hierarchically extract spatial features, and convolutional long-term short-term memory (ConvLSTM) units are added to the skip-connection pathway to extract the temporal features. The input of the ST-VNet is ECG-gated sequential frames of the MPS images and the output is the probability map of the epicardial or endocardial masks. A Dice similarity coefficient (DSC) loss which penalizes the discrepancy between the model prediction and the ground truth was adopted to optimize the segmentation model. Results. Our segmentation model was trained and validated on a retrospective dataset with 45 subjects, and the cardiac cycle of each subject was divided into 8 gates. The proposed ST-VNet achieved a DSC of 0.8914 and 0.8157 for the RV epicardium and endocardium segmentation, respectively. The mean absolute error, the mean squared error, and the Pearson correlation coefficient of the RV ejection fraction (RVEF) between the ground truth and the model prediction were 0.0609, 0.0830, and 0.6985. Conclusion. Our proposed ST-VNet is an effective model for RV segmentation. It has great promise for clinical use in RV functional assessment.

Yinghui Meng, Minghao Dong, Xumin Dai et al.

Automatic identification of proper image frames at the end-diastolic (ED) and end-systolic (ES) frames during the review of invasive coronary angiograms (ICA) is important to assess blood flow during a cardiac cycle, reconstruct the 3D arterial anatomy from bi-planar views, and generate the complementary fusion map with myocardial images. The current identification method primarily relies on visual interpretation, making it not only time-consuming but also less reproducible. In this paper, we propose a new method to automatically identify angiographic image frames associated with the ED and ES cardiac phases by using the trajectories of key vessel points (i.e. landmarks). More specifically, a detection algorithm is first used to detect the key points of coronary arteries, and then an optical flow method is employed to track the trajectories of the selected key points. The ED and ES frames are identified based on all these trajectories. Our method was tested with 62 ICA videos from two separate medical centers (22 and 9 patients in sites 1 and 2, respectively). Comparing consensus interpretations by two human expert readers, excellent agreement was achieved by the proposed algorithm: the agreement rates within a one-frame range were 92.99% and 92.73% for the automatic identification of the ED and ES image frames, respectively. In conclusion, the proposed automated method showed great potential for being an integral part of automated ICA image analysis.

Zhuo He, Xinwei Zhang, Chen Zhao et al.

Background. Studies have shown that the conventional left ventricular mechanical dyssynchrony (LVMD) parameters have their own statistical limitations. The purpose of this study is to extract new LVMD parameters from the phase analysis of gated SPECT MPI by deep learning to help CRT patient selection. Methods. One hundred and three patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) >= 15% at 6 +- 1 month follow up. Autoencoder (AE), an unsupervised deep learning method, was trained by the raw LV systolic phase polar maps to extract new LVMD parameters, called AE-based LVMD parameters. Correlation analysis was used to explain the relationships between new parameters with conventional LVMD parameters. Univariate and multivariate analyses were used to establish a multivariate model for predicting CRT response. Results. Complete data were obtained in 102 patients, 44.1% of them were classified as CRT responders. AE-based LVMD parameter was significant in the univariate (OR 1.24, 95% CI 1.07 - 1.44, P = 0.006) and multivariate analyses (OR 1.03, 95% CI 1.01 - 1.06, P = 0.006). Moreover, it had incremental value over PSD (AUC 0.72 vs. 0.63, LH 8.06, P = 0.005) and PBW (AUC 0.72 vs. 0.64, LH 7.87, P = 0.005), combined with significant clinic characteristics, including LVEF and gender. Conclusions. The new LVMD parameters extracted by autoencoder from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Fubao Zhu, Zhengyuan Gao, Chen Zhao et al.

Intravascular ultrasound (IVUS) imaging allows direct visualization of the coronary vessel wall and is suitable for the assessment of atherosclerosis and the degree of stenosis. Accurate segmentation and measurements of lumen and median-adventitia (MA) from IVUS are essential for such a successful clinical evaluation. However, current segmentation relies on manual operations, which is time-consuming and user-dependent. In this paper, we aim to develop a deep learning-based method using an encoder-decoder deep architecture to automatically extract both lumen and MA border. Our method named IVUS-U-Net++ is an extension of the well-known U-Net++ model. More specifically, a feature pyramid network was added to the U-Net++ model, enabling the utilization of feature maps at different scales. As a result, the accuracy of the probability map and subsequent segmentation have been improved We collected 1746 IVUS images from 18 patients in this study. The whole dataset was split into a training dataset (1572 images) for the 10-fold cross-validation and a test dataset (174 images) for evaluating the performance of models. Our IVUS-U-Net++ segmentation model achieved a Jaccard measure (JM) of 0.9412, a Hausdorff distance (HD) of 0.0639 mm for the lumen border, and a JM of 0.9509, an HD of 0.0867 mm for the MA border, respectively. Moreover, the Pearson correlation and Bland-Altman analyses were performed to evaluate the correlations of 12 clinical parameters measured from our segmentation results and the ground truth, and automatic measurements agreed well with those from the ground truth (all Ps<0.01). In conclusion, our preliminary results demonstrate that the proposed IVUS-U-Net++ model has great promise for clinical use.

Yu Deng, Ling Wang, Chen Zhao et al.

Automatic CT segmentation of proximal femur is crucial for the diagnosis and risk stratification of orthopedic diseases; however, current methods for the femur CT segmentation mainly rely on manual interactive segmentation, which is time-consuming and has limitations in both accuracy and reproducibility. In this study, we proposed an approach based on deep learning for the automatic extraction of the periosteal and endosteal contours of proximal femur in order to differentiate cortical and trabecular bone compartments. A three-dimensional (3D) end-to-end fully convolutional neural network, which can better combine the information between neighbor slices and get more accurate segmentation results, was developed for our segmentation task. 100 subjects aged from 50 to 87 years with 24,399 slices of proximal femur CT images were enrolled in this study. The separation of cortical and trabecular bone derived from the QCT software MIAF-Femur was used as the segmentation reference. We randomly divided the whole dataset into a training set with 85 subjects for 10-fold cross-validation and a test set with 15 subjects for evaluating the performance of models. Two models with the same network structures were trained and they achieved a dice similarity coefficient (DSC) of 97.87% and 96.49% for the periosteal and endosteal contours, respectively. To verify the excellent performance of our model for femoral segmentation, we measured the volume of different parts of the femur and compared it with the ground truth and the relative errors between predicted result and ground truth are all less than 5%. It demonstrated a strong potential for clinical use, including the hip fracture risk prediction and finite element analysis.

Chen Zhao, Haipeng Tang, Daniel McGonigle et al.

In stable coronary artery disease (CAD), reduction in mortality and/or myocardial infarction with revascularization over medical therapy has not been reliably achieved. Coronary arteries are usually extracted to perform stenosis detection. We aim to develop an automatic algorithm by deep learning to extract coronary arteries from ICAs.In this study, a multi-input and multi-scale (MIMS) U-Net with a two-stage recurrent training strategy was proposed for the automatic vessel segmentation. Incorporating features such as the Inception residual module with depth-wise separable convolutional layers, the proposed model generated a refined prediction map with the following two training stages: (i) Stage I coarsely segmented the major coronary arteries from pre-processed single-channel ICAs and generated the probability map of vessels; (ii) during the Stage II, a three-channel image consisting of the original preprocessed image, a generated probability map, and an edge-enhanced image generated from the preprocessed image was fed to the proposed MIMS U-Net to produce the final segmentation probability map. During the training stage, the probability maps were iteratively and recurrently updated by feeding into the neural network. After segmentation, an arterial stenosis detection algorithm was developed to extract vascular centerlines and calculate arterial diameters to evaluate stenotic level. Experimental results demonstrated that the proposed method achieved an average Dice score of 0.8329, an average sensitivity of 0.8281, and an average specificity of 0.9979 in our dataset with 294 ICAs obtained from 73 patient. Moreover, our stenosis detection algorithm achieved a true positive rate of 0.6668 and a positive predictive value of 0.7043.

Chen Zhao, Joyce H. Keyak, Jinshan Tang et al.

Purpose: Proximal femur image analyses based on quantitative computed tomography (QCT) provide a method to quantify the bone density and evaluate osteoporosis and risk of fracture. We aim to develop a deep-learning-based method for automatic proximal femur segmentation. Methods and Materials: We developed a 3D image segmentation method based on V-Net, an end-to-end fully convolutional neural network (CNN), to extract the proximal femur QCT images automatically. The proposed V-net methodology adopts a compound loss function, which includes a Dice loss and a L2 regularizer. We performed experiments to evaluate the effectiveness of the proposed segmentation method. In the experiments, a QCT dataset which included 397 QCT subjects was used. For the QCT image of each subject, the ground truth for the proximal femur was delineated by a well-trained scientist. During the experiments for the entire cohort then for male and female subjects separately, 90% of the subjects were used in 10-fold cross-validation for training and internal validation, and to select the optimal parameters of the proposed models; the rest of the subjects were used to evaluate the performance of models. Results: Visual comparison demonstrated high agreement between the model prediction and ground truth contours of the proximal femur portion of the QCT images. In the entire cohort, the proposed model achieved a Dice score of 0.9815, a sensitivity of 0.9852 and a specificity of 0.9992. In addition, an R2 score of 0.9956 (p<0.001) was obtained when comparing the volumes measured by our model prediction with the ground truth. Conclusion: This method shows a great promise for clinical application to QCT and QCT-based finite element analysis of the proximal femur for evaluating osteoporosis and hip fracture risk.