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Prostate Cancer is one of the most frequently occurring cancers in men, with a low survival rate if not early diagnosed. PI-RADS reading has a high false positive rate, thus increasing the diagnostic incurred costs and patient discomfort. Deep learning (DL) models achieve a high segmentation performance, although require a large model size and complexity. Also, DL models lack of feature interpretability and are perceived as "black-boxes" in the medical field. PCa-RadHop pipeline is proposed in this work, aiming to provide a more transparent feature extraction process using a linear model. It adopts the recently introduced Green Learning (GL) paradigm, which offers a small model size and low complexity. PCa-RadHop consists of two stages: Stage-1 extracts data-driven radiomics features from the bi-parametric Magnetic Resonance Imaging (bp-MRI) input and predicts an initial heatmap. To reduce the false positive rate, a subsequent stage-2 is introduced to refine the predictions by including more contextual information and radiomics features from each already detected Region of Interest (ROI). Experiments on the largest publicly available dataset, PI-CAI, show a competitive performance standing of the proposed method among other deep DL models, achieving an area under the curve (AUC) of 0.807 among a cohort of 1,000 patients. Moreover, PCa-RadHop maintains orders of magnitude smaller model size and complexity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The off-the-shelf model for unsupervised domain adaptation (OSUDA) has been introduced to protect patient data privacy and intellectual property of the source domain without access to the labeled source domain data. Yet, an off-the-shelf diagnosis model, deliberately compromised by backdoor attacks during the source domain training phase, can function as a parasite-host, disseminating the backdoor to the target domain model during the OSUDA stage. Because of limitations in accessing or controlling the source domain training data, OSUDA can make the target domain model highly vulnerable and susceptible to prominent attacks. To sidestep this issue, we propose to quantify the channel-wise backdoor sensitivity via a Lipschitz constant and, explicitly, eliminate the backdoor infection by overwriting the backdoor-related channel kernels with random initialization. Furthermore, we propose to employ an auxiliary model with a full source model to ensure accurate pseudo-labeling, taking into account the controllable, clean target training data in OSUDA. We validate our framework using a multi-center, multi-vendor, and multi-disease (M&M) cardiac dataset. Our findings suggest that the target model is susceptible to backdoor attacks during OSUDA, and our defense mechanism effectively mitigates the infection of target domain victims.

In this work, we aim to predict the survival time (ST) of glioblastoma (GBM) patients undergoing different treatments based on preoperative magnetic resonance (MR) scans. The personalized and precise treatment planning can be achieved by comparing the ST of different treatments. It is well established that both the current status of the patient (as represented by the MR scans) and the choice of treatment are the cause of ST. While previous related MR-based glioblastoma ST studies have focused only on the direct mapping of MR scans to ST, they have not included the underlying causal relationship between treatments and ST. To address this limitation, we propose a treatment-conditioned regression model for glioblastoma ST that incorporates treatment information in addition to MR scans. Our approach allows us to effectively utilize the data from all of the treatments in a unified manner, rather than having to train separate models for each of the treatments. Furthermore, treatment can be effectively injected into each convolutional layer through the adaptive instance normalization we employ. We evaluate our framework on the BraTS20 ST prediction task. Three treatment options are considered: Gross Total Resection (GTR), Subtotal Resection (STR), and no resection. The evaluation results demonstrate the effectiveness of injecting the treatment for estimating GBM survival.

The multilayer perceptron (MLP) neural network is interpreted from the geometrical viewpoint in this work, that is, an MLP partition an input feature space into multiple nonoverlapping subspaces using a set of hyperplanes, where the great majority of samples in a subspace belongs to one object class. Based on this high-level idea, we propose a three-layer feedforward MLP (FF-MLP) architecture for its implementation. In the first layer, the input feature space is split into multiple subspaces by a set of partitioning hyperplanes and rectified linear unit (ReLU) activation, which is implemented by the classical two-class linear discriminant analysis (LDA). In the second layer, each neuron activates one of the subspaces formed by the partitioning hyperplanes with specially designed weights. In the third layer, all subspaces of the same class are connected to an output node that represents the object class. The proposed design determines all MLP parameters in a feedforward one-pass fashion analytically without backpropagation. Experiments are conducted to compare the performance of the traditional backpropagation-based MLP (BP-MLP) and the new FF-MLP. It is observed that the FF-MLP outperforms the BP-MLP in terms of design time, training time, and classification performance in several benchmarking datasets. Our source code is available at https://colab.research.google.com/drive/1Gz0L8AnT4ijrUchrhEXXsnaacrFdenn?usp = sharing.

Unsupervised domain adaptation (UDA) has been successfully applied to transfer knowledge from a labeled source domain to target domains without their labels. Recently introduced transferable prototypical networks (TPNs) further address class-wise conditional alignment. In TPN, while the closeness of class centers between source and target domains is explicitly enforced in a latent space, the underlying fine-grained subtype structure and the cross-domain within-class compactness have not been fully investigated. To counter this, we propose a new approach to adaptively perform a fine-grained subtype-aware alignment to improve the performance in the target domain without the subtype label in both domains. The insight of our approach is that the unlabeled subtypes in a class have the local proximity within a subtype while exhibiting disparate characteristics because of different conditional and label shifts. Specifically, we propose to simultaneously enforce subtype-wise compactness and class-wise separation, by utilizing intermediate pseudo-labels. In addition, we systematically investigate various scenarios with and without prior knowledge of subtype numbers and propose to exploit the underlying subtype structure. Furthermore, a dynamic queue framework is developed to evolve the subtype cluster centroids steadily using an alternative processing scheme. Experimental results, carried out with multiview congenital heart disease data and VisDA and DomainNet, show the effectiveness and validity of our subtype-aware UDA, compared with state-of-the-art UDA methods.

Learning low-dimensional representations of bipartite graphs enables e-commerce applications, such as recommendation, classification, and link prediction. A layerwise-trained bipartite graph neural network (L-BGNN) embedding method, which is unsupervised, efficient, and scalable, is proposed in this work. To aggregate the information across and within two partitions of a bipartite graph, a customized interdomain message passing (IDMP) operation and an intradomain alignment (IDA) operation are adopted by the proposed L-BGNN method. Furthermore, we develop a layerwise training algorithm for L-BGNN to capture the multihop relationship of large bipartite networks and improve training efficiency. We conduct extensive experiments on several datasets and downstream tasks of various scales to demonstrate the effectiveness and efficiency of the L-BGNN method as compared with state-of-the-art methods. Our codes are publicly available at https://github.com/TianXieUSC/L-BGNN.

An enhanced label propagation (LP) method called GraphHop was proposed recently. It outperforms graph convolutional networks (GCNs) in the semi-supervised node classification task on various networks. Although the performance of GraphHop was explained intuitively with joint node attribute and label signal smoothening, its rigorous mathematical treatment is lacking. In this paper, we propose a label efficient regularization and propagation (LERP) framework for graph node classification, and present an alternate optimization procedure for its solution. Furthermore, we show that GraphHop only offers an approximate solution to this framework and has two drawbacks. First, it includes all nodes in the classifier training without taking the reliability of pseudo-labeled nodes into account in the label update step. Second, it provides a rough approximation to the optimum of a subproblem in the label aggregation step. Based on the LERP framework, we propose a new method, named the LERP method, to solve these two shortcomings. LERP determines reliable pseudo-labels adaptively during the alternate optimization and provides a better approximation to the optimum with computational efficiency. Theoretical convergence of LERP is guaranteed. Extensive experiments are conducted to demonstrate the effectiveness and efficiency of LERP. That is, LERP outperforms all benchmarking methods, including GraphHop, consistently on five common test datasets, two large-scale networks, and an object recognition task at extremely low label rates (i.e., 1, 2, 4, 8, 16, and 20 labeled samples per class).

A scalable semisupervised node classification method on graph-structured data, called GraphHop, is proposed in this work. The graph contains all nodes' attributes and link connections but labels of only a subset of nodes. Graph convolutional networks (GCNs) have provided superior performance in node label classification over the traditional label propagation (LP) methods for this problem. Nevertheless, current GCN algorithms suffer from a considerable amount of labels for training because of high model complexity or cannot be easily generalized to large-scale graphs due to the expensive cost of loading the entire graph and node embeddings. Besides, nonlinearity makes the optimization process a mystery. To this end, an enhanced LP method, called GraphHop, is proposed to tackle these problems. GraphHop can be viewed as a smoothening LP algorithm, in which each propagation alternates between two steps: label aggregation and label update. In the label aggregation step, multihop neighbor embeddings are aggregated to the center node. In the label update step, new embeddings are learned and predicted for each node based on aggregated results from the previous step. The two-step iteration improves the graph signal smoothening capacity. Furthermore, to encode attributes, links, and labels on graphs effectively under one framework, we adopt a two-stage training process, i.e., the initialization stage and the iteration stage. Thus, the smooth attribute information extracted from the initialization stage is consistently imposed in the propagation process in the iteration stage. Experimental results show that GraphHop outperforms state-of-the-art graph learning methods on a wide range of tasks in graphs of various sizes (e.g., multilabel and multiclass classification on citation networks, social graphs, and commodity consumption graphs).

Cardiac cine magnetic resonance imaging (MRI) has been used to characterize cardiovascular diseases (CVD), often providing a noninvasive phenotyping tool. While recently flourished deep learning based approaches using cine MRI yield accurate characterization results, the performance is often degraded by small training samples. In addition, many deep learning models are deemed a "black box," for which models remain largely elusive in how models yield a prediction and how reliable they are. To alleviate this, this work proposes a lightweight successive subspace learning (SSL) framework for CVD classification, based on an interpretable feedforward design, in conjunction with a cardiac atlas. Specifically, our hierarchical SSL model is based on (i) neighborhood voxel expansion, (ii) unsupervised subspace approximation, (iii) supervised regression, and (iv) multi-level feature integration. In addition, using two-phase 3D deformation fields, including end-diastolic and end-systolic phases, derived between the atlas and individual subjects as input offers objective means of assessing CVD, even with small training samples. We evaluate our framework on the ACDC2017 database, comprising one healthy group and four disease groups. Compared with 3D CNN-based approaches, our framework achieves superior classification performance with 140× fewer parameters, which supports its potential value in clinical use.

Dynamic point cloud is a volumetric visual data representing realistic 3D scenes for virtual reality and augmented reality applications. However, its large data volume has been the bottleneck of data processing, transmission, and storage, which requires effective compression. In this paper, we propose a Perceptually Weighted Rate-Distortion Optimization (PWRDO) scheme for Video-based Point Cloud Compression (V-PCC), which aims to minimize the perceptual distortion of reconstructed point cloud at the given bit rate. Firstly, we propose a general framework of perceptually optimized V-PCC to exploit visual redundancies in point clouds. Secondly, a multi-scale Projection based Point Cloud quality Metric (PPCM) is proposed to measure the perceptual quality of 3D point cloud. The PPCM model comprises 3D-to-2D patch projection, multi-scale structural distortion measurement, and fusion model. Approximations and simplifications of the proposed PPCM are also presented for both V-PCC integration and low complexity. Thirdly, based on the simplified PPCM model, we propose a PWRDO scheme with Lagrange multiplier adaptation, which is incorporated into the V-PCC to enhance the coding efficiency. Experimental results show that the proposed PPCM models can be used as standalone quality metrics, and they are able to achieve higher consistency with the human subjective scores than the state-of-the-art objective visual quality metrics. Also, compared with the latest V-PCC reference model, the proposed PWRDO-based V-PCC scheme achieves an average bit rate reduction of 13.52%, 8.16%, 10.56% and 9.54%, respectively, in terms of four objective visual quality metrics for point clouds. It is significantly superior to the state-of-the-art coding algorithms. The computational complexity of the proposed PWRDO increases by 1.71% and 0.05% on average to the V-PCC encoder and decoder, respectively, which is negligible. The source codes of the PPCM and PWRDO schemes are available at https://github.com/VVCodec/PPCM-PWRDO.

Unsupervised domain adaptation (UDA) has been vastly explored to alleviate domain shifts between source and target domains, by applying a well-performed model in an unlabeled target domain via supervision of a labeled source domain. Recent literature, however, has indicated that the performance is still far from satisfactory in the presence of significant domain shifts. Nonetheless, delineating a few target samples is usually manageable and particularly worthwhile, due to the substantial performance gain. Inspired by this, we aim to develop semi-supervised domain adaptation (SSDA) for medical image segmentation, which is largely underexplored. We, thus, propose to exploit both labeled source and target domain data, in addition to unlabeled target data in a unified manner. Specifically, we present a novel asymmetric co-training (ACT) framework to integrate these subsets and avoid the domination of the source domain data. Following a divide-and-conquer strategy, we explicitly decouple the label supervisions in SSDA into two asymmetric sub-tasks, including semi-supervised learning (SSL) and UDA, and leverage different knowledge from two segmentors to take into account the distinction between the source and target label supervisions. The knowledge learned in the two modules is then adaptively integrated with ACT, by iteratively teaching each other, based on the confidence-aware pseudo-label. In addition, pseudo label noise is well-controlled with an exponential MixUp decay scheme for smooth propagation. Experiments on cross-modality brain tumor MRI segmentation tasks using the BraTS18 database showed, even with limited labeled target samples, ACT yielded marked improvements over UDA and state-of-the-art SSDA methods and approached an "upper bound" of supervised joint training.

Deep learning recognition approaches can potentially perform better if we can extract a discriminative representation that controllably separates nuisance factors. In this paper, we propose a novel approach to explicitly enforce the extracted discriminative representation d, extracted latent variation l (e,g., background, unlabeled nuisance attributes), and semantic variation label vector s (e.g., labeled expressions/pose) to be independent and complementary to each other. We can cast this problem as an adversarial game in the latent space of an auto-encoder. Specifically, with the to-be-disentangled s, we propose to equip an end-to-end conditional adversarial network with the ability to decompose an input sample into d and l. However, we argue that maximizing the cross-entropy loss of semantic variation prediction from d is not sufficient to remove the impact of s from d, and that the uniform-target and entropy regularization are necessary. A collaborative mutual information regularization framework is further proposed to avoid unstable adversarial training. It is able to minimize the differentiable mutual information between the variables to enforce independence. The proposed discriminative representation inherits the desired tolerance property guided by prior knowledge of the task. Our proposed framework achieves top performance on diverse recognition tasks, including digits classification, large-scale face recognition on LFW and IJB-A datasets, and face recognition tolerant to changes in lighting, makeup, disguise, etc.

Vision-and-language (V&L) models take image and text as input and learn to capture the associations between them. These models can potentially deal with the tasks that involve understanding medical images along with their associated text. However, applying V&L models in the medical domain is challenging due to the expensiveness of data annotations and the requirements of domain knowledge. In this paper, we identify that the visual representation in general V&L models is not suitable for processing medical data. To overcome this limitation, we propose BERTHop, a transformer-based model based on PixelHop++ and VisualBERT for better capturing the associations between clinical notes and medical images. Experiments on the OpenI dataset, a commonly used thoracic disease diagnosis benchmark, show that BERTHop achieves an average Area Under the Curve (AUC) of 98.12% which is 1.62% higher than state-of-the-art while it is trained on a 9× smaller dataset.

Modeling statistical properties of anatomical structures using magnetic resonance imaging is essential for revealing common information of a target population and unique properties of specific subjects. In brain imaging, a statistical brain atlas is often constructed using a number of healthy subjects. When tumors are present, however, it is difficult to either provide a common space for various subjects or align their imaging data due to the unpredictable distribution of lesions. Here we propose a deep learning-based image inpainting method to replace the tumor regions with normal tissue intensities using only a patient population. Our framework has three major innovations: 1) incompletely distributed datasets with random tumor locations can be used for training; 2) irregularly-shaped tumor regions are properly learned, identified, and corrected; and 3) a symmetry constraint between the two brain hemispheres is applied to regularize inpainted regions. Henceforth, regular atlas construction and image registration methods can be applied using inpainted data to obtain tissue deformation, thereby achieving group-specific statistical atlases and patient-to-atlas registration. Our framework was tested using the public database from the Multimodal Brain Tumor Segmentation challenge. Results showed increased similarity scores as well as reduced reconstruction errors compared with three existing image inpainting methods. Patient-to-atlas registration also yielded better results with improved normalized cross-correlation and mutual information and a reduced amount of deformation over the tumor regions.

Unsupervised domain adaptation (UDA) is an emerging technique that enables the transfer of domain knowledge learned from a labeled source domain to unlabeled target domains, providing a way of coping with the difficulty of labeling in new domains. The majority of prior work has relied on both source and target domain data for adaptation. However, because of privacy concerns about potential leaks in sensitive information contained in patient data, it is often challenging to share the data and labels in the source domain and trained model parameters in cross-center collaborations. To address this issue, we propose a practical framework for UDA with a black-box segmentation model trained in the source domain only, without relying on source data or a white-box source model in which the network parameters are accessible. In particular, we propose a knowledge distillation scheme to gradually learn target-specific representations. Additionally, we regularize the confidence of the labels in the target domain via unsupervised entropy minimization, leading to performance gain over UDA without entropy minimization. We extensively validated our framework on a few datasets and deep learning backbones, demonstrating the potential for our framework to be applied in challenging yet realistic clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yoo, Xing, Kuo, El Fakhri, Kang and Woo.)

Unsupervised domain adaptation (UDA) has been widely used to transfer knowledge from a labeled source domain to an unlabeled target domain to counter the difficulty of labeling in a new domain. The training of conventional solutions usually relies on the existence of both source and target domain data. However, privacy of the large-scale and well-labeled data in the source domain and trained model parameters can become the major concern of cross center/domain collaborations. In this work, to address this, we propose a practical solution to UDA for segmentation with a black-box segmentation model trained in the source domain only, rather than original source data or a white-box source model. Specifically, we resort to a knowledge distillation scheme with exponential mixup decay (EMD) to gradually learn target-specific representations. In addition, unsupervised entropy minimization is further applied to regularization of the target domain confidence. We evaluated our framework on the BraTS 2018 database, achieving performance on par with white-box source model adaptation approaches.

Inspired by the recent PointHop classification method, an unsupervised 3D point cloud registration method, called R-PointHop, is proposed in this work. R-PointHop first determines a local reference frame (LRF) for every point using its nearest neighbors and finds local attributes. Next, R-PointHop obtains local-to-global hierarchical features by point downsampling, neighborhood expansion, attribute construction and dimensionality reduction steps. Thus, point correspondences are built in hierarchical feature space using the nearest neighbor rule. Afterwards, a subset of salient points with good correspondence is selected to estimate the 3D transformation. The use of the LRF allows for invariance of the hierarchical features of points with respect to rotation and translation, thus making R-PointHop more robust at building point correspondence, even when the rotation angles are large. Experiments are conducted on the 3DMatch, ModelNet40, and Stanford Bunny datasets, which demonstrate the effectiveness of R-PointHop for 3D point cloud registration. R-PointHop's model size and training time are an order of magnitude smaller than those of deep learning methods, and its registration errors are smaller, making it a green and accurate solution. Our codes are available on GitHub (https://github.com/pranavkdm/R-PointHop).

Assessment of cardiovascular disease (CVD) with cine magnetic resonance imaging (MRI) has been used to non-invasively evaluate detailed cardiac structure and function. Accurate segmentation of cardiac structures from cine MRI is a crucial step for early diagnosis and prognosis of CVD, and has been greatly improved with convolutional neural networks (CNN). There, however, are a number of limitations identified in CNN models, such as limited interpretability and high complexity, thus limiting their use in clinical practice. In this work, to address the limitations, we propose a lightweight and interpretable machine learning model, successive subspace learning with the subspace approximation with adjusted bias (Saab) transform, for accurate and efficient segmentation from cine MRI. Specifically, our segmentation framework is comprised of the following steps: (1) sequential expansion of near-to-far neighborhood at different resolutions; (2) channel-wise subspace approximation using the Saab transform for unsupervised dimension reduction; (3) class-wise entropy guided feature selection for supervised dimension reduction; (4) concatenation of features and pixel-wise classification with gradient boost; and (5) conditional random field for post-processing. Experimental results on the ACDC 2017 segmentation database, showed that our framework performed better than state-of-the-art U-Net models with 200× fewer parameters in delineating the left ventricle, right ventricle, and myocardium, thus showing its potential to be used in clinical practice.Clinical relevance- Delineation of the left ventricular cavity, myocardium, and right ventricle from cardiac MR images is a common clinical task to establish diagnosis and prognosis of CVD.

Viewing various stereo images under different viewing conditions has escalated the need for effective object-level remapping techniques. In this paper, we propose a new object spatial mapping scheme, which adjusts the depth and size of the selected object to match user preference and viewing conditions. Existing warping-based methods often distort the shape of important objects or cannot faithfully adjust the depth/size of the selected object due to improper warping such as local rotations. In this paper, by explicitly reducing the transformation freedom degree of warping, we propose an optimization model based on axis-aligned warping for object spatial remapping. The proposed axis-aligned warping based optimization model can simultaneously adjust the depths and sizes of selected objects to their target values without introducing severe shape distortions. Moreover, we propose object consistency constraints to ensure the size/shape of parts inside a selected object to be consistently adjusted. Such constraints improve the size/shape adjustment performance while remaining robust to some extent to incomplete object extraction. Experimental results demonstrate that the proposed method achieves high flexibility and effectiveness in adjusting the size and depth of objects compared with existing methods.

It has been recognized that videos have to be encoded in a rate-distortion optimized manner for high coding performance. Therefore, operational coding methods have been developed for conventional distortion metrics such as Sum of Squared Error (SSE). Nowadays, with the rapid development of machine learning, the state-of-the-art learning based metric Video Multimethod Assessment Fusion (VMAF) has been proven to outperform conventional ones in terms of the correlation with human perception, and thus deserves integration into the coding framework. However, unlike conventional metrics, VMAF has no specific computational formulas and may be frequently updated by new training data, which invalidates the existing coding methods and makes it highly desired to develop a rate-distortion optimized method for VMAF. Moreover, VMAF is designed to operate at the frame level, which leads to further difficulties in its application to today's block based coding. In this paper, we propose a VMAF oriented perceptual coding method based on piecewise metric coupling. Firstly, we explore the correlation between VMAF and SSE in the neighborhood of a benchmark distortion. Then a rate-distortion optimization model is formulated based on the correlation, and an optimized block based coding method is presented for VMAF. Experimental results show that 3.61% and 2.67% bit saving on average can be achieved for VMAF under the low_delay_p and the random_access_main configurations of HEVC coding respectively.

Objective: Recent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a challenge., Methods: We hereby employed "subspace approximation with augmented kernels (Saak) transform" for accurate and efficient quantification of the light-sheet image stacks following chemotherapy-treatment. We established a machine learning framework with augmented kernels based on the Karhunen-Loeve Transform (KLT) to preserve linearity and reversibility of rectification., Results: The Saak transform-based machine learning enhances computational efficiency and obviates iterative optimization of cost function needed for neural networks, minimizing the number of training datasets for segmentation in our scenario. The integration of forward and inverse Saak transforms can also serve as a light-weight module to filter adversarial perturbations and reconstruct estimated images, salvaging robustness of existing classification methods. The accuracy and robustness of the Saak transform are evident following the tests of dice similarity coefficients and various adversary perturbation algorithms, respectively. The addition of edge detection further allows for quantifying the surface area to volume ratio (SVR) of the myocardium in response to chemotherapy-induced cardiac remodeling., Conclusion: The combination of Saak transform, random forest, and edge detection augments segmentation efficiency by 20-fold as compared to manual processing., Significance: This new methodology establishes a robust framework for post light-sheet imaging processing, and creating a data-driven machine learning for automated quantification of cardiac ultra-structure.

Image compression has always been an important topic in the last decades due to the explosive increase of images. The popular image compression formats are based on different transforms which convert images from the spatial domain into compact frequency domain to remove the spatial correlation. In this paper, we focus on the exploration of data-driven transform, Karhunen-Loéve transform (KLT), the kernels of which are derived from specific images via Principal Component Analysis (PCA), and design a high efficient KLT based image compression algorithm with variable transform sizes. To explore the optimal compression performance, the multiple transform sizes and categories are utilized and determined adaptively according to their rate-distortion (RD) costs. Moreover, comprehensive analyses on the transform coefficients are provided and a band-adaptive quantization scheme is proposed based on the coefficient RD performance. Extensive experiments are performed on several class-specific images as well as general images, and the proposed method achieves significant coding gain over the popular image compression standards including JPEG, JPEG 2000, and the state-of-the-art dictionary learning based methods.

Stereo video retargeting aims at minimizing shape and depth distortions with temporal coherence in resizing a stereo video content to a desired size. Existing methods extend stereo image retargeting schemes to stereo video retargeting by adding additional temporal constraints that demand temporal coherence in all corresponding regions. However, such a straightforward extension incurs conflicts among multiple requirements (i.e., shape and depth preservation and their temporal coherence), thus failing to meet one or more of these requirements satisfactorily. To mitigate conflicts among depth, shape, and temporal constraints and avoid degrading temporal coherence perceptually, we relax temporal constraints for non-paired regions at frame boundaries, derive new temporal constraints to improve human viewing experience of a 3D scene, and propose an efficient grid-based implementation for stereo video retargeting. Experimental results demonstrate that our method achieves superior visual quality over existing methods.

With explosive increase of internet video services, perceptual modeling for video quality has attracted more attentions to provide high quality-of-experience (QoE) for end-users subject to bandwidth constraints, especially for compressed video quality. In this paper, a novel perceptual model for satisfied-user-ratio (SUR) on compressed video quality is proposed by exploiting compressed video bitrate changes and spatial-temporal statistical characteristics extracted from both uncompressed original video and reference video. In the proposed method, an efficient video feature set is explored and established to model SUR curves against bitrate variations by leveraging the Gaussian Processes Regression (GPR) framework. In particular, the proposed model is based on the recently released large-scale video quality dataset, VideoSet, and takes both spatial and temporal masking effects into consideration. To make it more practical, we further optimize the proposed method from three aspects including feature source simplification, computation complexity reduction and video codec adaption. Based on experimental results on VideoSet, the proposed method can accurately model SUR curves for various video contents and predict their required bitrates at given SUR values. Subjective experiments are conducted to further verify the generalization ability of the proposed SUR model.

Image translation between two domains is a class of problems aiming to learn mapping from an input image in the source domain to an output image in the target domain. It has been applied to numerous applications, such as data augmentation, domain adaptation, and unsupervised training. When paired training data is not accessible, image translation becomes an ill-posed problem. We constrain the problem with the assumption that the translated image needs to be perceptually similar to the original image and also appears to be drawn from the new domain, and propose a simple yet effective image translation model consisting of a single generator trained with a self-regularization term and an adversarial term. We further notice that the existing image translation techniques are agnostic to the subjects of interest and often introduce unwanted changes or artifacts to the input. Thus, we propose to add an attention module to predict an attention map to guide the image translation process. The module learns to attend to key parts of the image while keeping everything else unaltered, essentially avoiding undesired artifacts or changes. Extensive experiments and evaluations show that our model while being simpler, achieves significantly better performance than existing image translation methods.

Picture Wise Just Noticeable Difference (PW-JND), which accounts for the minimum difference of a picture that human visual system can perceive, can be widely used in perception-oriented image and video processing. However, the conventional Just Noticeable Difference (JND) models calculate the JND threshold for each pixel or sub-band separately, which may not reflect the total masking effect of a picture accurately. In this paper, we propose a deep learning based PW-JND prediction model for image compression. Firstly, we formulate the task of predicting PW-JND as a multi-class classification problem, and propose a framework to transform the multi-class classification problem to a binary classification problem solved by just one binary classifier. Secondly, we construct a deep learning based binary classifier named perceptually lossy/lossless predictor which can predict whether an image is perceptually lossy to another or not. Finally, we propose a sliding window based search strategy to predict PW-JND based on the prediction results of the perceptually lossy/lossless predictor. Experimental results show that the mean accuracy of the perceptually lossy/lossless predictor reaches 92%, and the absolute prediction error of the proposed PW-JND model is 0.79 dB on average, which shows the superiority of the proposed PW-JND model to the conventional JND models.

While virtual reality (VR) has potential in enhancing cardiovascular diagnosis and treatment, prerequisite labor-intensive image segmentation remains an obstacle for seamlessly simulating 4-dimensional (4-D, 3-D + time) imaging data in an immersive, physiological VR environment. We applied deformable image registration (DIR) in conjunction with 3-D reconstruction and VR implementation to recapitulate developmental cardiac contractile function from light-sheet fluorescence microscopy (LSFM). This method addressed inconsistencies that would arise from independent segmentations of time-dependent data, thereby enabling the creation of a VR environment that fluently simulates cardiac morphological changes. By analyzing myocardial deformation at high spatiotemporal resolution, we interfaced quantitative computations with 4-D VR. We demonstrated that our LSFM-captured images, followed by DIR, yielded average dice similarity coefficients of 0.92 ± 0.05 (n = 510) and 0.93 ± 0.06 (n = 240) when compared to ground truth images obtained from Otsu thresholding and manual segmentation, respectively. The resulting VR environment simulates a wide-angle zoomed-in view of motion in live embryonic zebrafish hearts, in which the cardiac chambers are undergoing structural deformation throughout the cardiac cycle. Thus, this technique allows for an interactive micro-scale VR visualization of developmental cardiac morphology to enable high resolution simulation for both basic and clinical science.

Textual data such as tags, sentence descriptions are combined with visual cues to reduce the semantic gap for image retrieval applications in today's Multimodal Image Retrieval (MIR) systems. However, all tags are treated as equally important in these systems, which may result in misalignment between visual and textual modalities during MIR training. This will further lead to degenerated retrieval performance at query time. To address this issue, we investigate the problem of tag importance prediction, where the goal is to automatically predict the tag importance and use it in image retrieval. To achieve this, we first propose a method to measure the relative importance of object and scene tags from image sentence descriptions. Using this as the ground truth, we present a tag importance prediction model to jointly exploit visual, semantic and context cues. The Structural Support Vector Machine (SSVM) formulation is adopted to ensure efficient training of the prediction model. Then, the Canonical Correlation Analysis (CCA) is employed to learn the relation between the image visual feature and tag importance to obtain robust retrieval performance. Experimental results on three real-world datasets show a significant performance improvement of the proposed MIR with Tag Importance Prediction (MIR/TIP) system over other MIR systems.

Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present a novel computational framework to simulate cardiac hemodynamics in developing zebrafish embryos by coupling 4-D light sheet imaging with a stabilized finite element flow solver, and extract time-dependent mechanical stimuli data. We employ deformable image registration methods to segment the motion of the ventricle from high resolution 4-D light sheet image data. This results in a robust and efficient workflow, as segmentation need only be performed at one cardiac phase, while wall position in the other cardiac phases is found by image registration. Ventricular hemodynamics are then quantified by numerically solving the Navier-Stokes equations in the moving wall domain with our validated flow solver. We demonstrate the applicability of the workflow in wild type zebrafish and three treated fish types that disrupt trabeculation: (a) chemical treatment using AG1478, an ErbB2 signaling inhibitor that inhibits proliferation and differentiation of cardiac trabeculation; (b) injection of gata1a morpholino oligomer (gata1aMO) suppressing hematopoiesis and resulting in attenuated trabeculation; (c) weak-atriumm58 mutant (wea) with inhibited atrial contraction leading to a highly undeveloped ventricle and poor cardiac function. Our simulations reveal elevated wall shear stress (WSS) in wild type and AG1478 compared to gata1aMO and wea. High oscillatory shear index (OSI) in the grooves between trabeculae, compared to lower values on the ridges, in the wild type suggest oscillatory forces as a possible regulatory mechanism of cardiac trabeculation development. The framework has broad applicability for future cardiac developmental studies focused on quantitatively investigating the role of hemodynamic forces and mechanotransduction during morphogenesis.

The just noticeable difference (JND) in an image, which reveals the visibility limitation of the human visual system (HVS), is widely used for visual redundancy estimation in signal processing. To determine the JND threshold with the current schemes, the spatial masking effect is estimated as the contrast masking, and this cannot accurately account for the complicated interaction among visual contents. Research on cognitive science indicates that the HVS is highly adapted to extract the repeated patterns for visual content representation. Inspired by this, we formulate the pattern complexity as another factor to determine the total masking effect: the interaction is relatively straightforward with a limited masking effect in a regular pattern, and is complicated with a strong masking effect in an irregular pattern. From the orientation selectivity mechanism in the primary visual cortex, the response of each local receptive field can be considered as a pattern; therefore, in this paper, the orientation that each pixel presents is regarded as the fundamental element of a pattern, and the pattern complexity is calculated as the diversity of the orientation in a local region. Finally, considering both pattern complexity and luminance contrast, a novel spatial masking estimation function is deduced, and an improved JND estimation model is built. Experimental results on comparing with the latest JND models demonstrate the effectiveness of the proposed model, which performs highly consistent with the human perception. The source code of the proposed model is publicly available at http://web.xidian.edu.cn/wjj/en/index.html.

An ensemble method for full-reference image quality assessment (IQA) based on the parallel boosting (ParaBoost) idea is proposed in this paper. We first extract features from existing image quality metrics and train them to form basic image quality scorers (BIQSs). Then, we select additional features to address specific distortion types and train them to construct auxiliary image quality scorers (AIQSs). Both BIQSs and AIQSs are trained on small image subsets of certain distortion types and, as a result, they are weak performers with respect to a wide variety of distortions. Finally, we adopt the ParaBoost framework, which is a statistical scorer selection scheme for support vector regression (SVR), to fuse the scores of BIQSs and AIQSs to evaluate the images containing a wide range of distortion types. This ParaBoost methodology can be easily extended to images of new distortion types. Extensive experiments are conducted to demonstrate the superior performance of the ParaBoost method, which outperforms existing IQA methods by a significant margin. Specifically, the Spearman rank order correlation coefficients (SROCCs) of the ParaBoost method with respect to the LIVE, CSIQ, TID2008, and TID2013 image quality databases are 0.98, 0.97, 0.98, and 0.96, respectively.

Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via gata1a morpholino oligonucleotides (MO) reduced shear stress, resulting in downregulation of Notch signaling and attenuation of trabeculation. Arrest of cardiomyocyte contraction either by troponin T type 2a (tnnt2a) MO or in weak atriumm58 (wea) mutants resulted in reduced shear stress and downregulation of Notch signaling and trabeculation. Integrating 4D SPIM imaging with synchronization algorithm demonstrated that coinjection of neuregulin1 mRNA with gata1 MO rescued trabeculation to restore contractile function in association with upregulation of Notch-related genes. Crossbreeding of Tg(flk:mCherry) fish, which allows visualization of the vascular system with the Tg(tp1:gfp) Notch reporter line, revealed that shear stress-mediated Notch activation localizes to the endocardium. Deleting endocardium via the clochesk4 mutants downregulated Notch signaling, resulting in nontrabeculated ventricle. Subjecting endothelial cells to pulsatile flow in the presence of the ADAM10 inhibitor corroborated shear stress-activated Notch signaling to modulate trabeculation.

Light Sheet Fluorescence Microscopy (LSFM) enables multi-dimensional and multi-scale imaging via illuminating specimens with a separate thin sheet of laser. It allows rapid plane illumination for reduced photo-damage and superior axial resolution and contrast. We hereby demonstrate cardiac LSFM (c-LSFM) imaging to assess the functional architecture of zebrafish embryos with a retrospective cardiac synchronization algorithm for four-dimensional reconstruction (3-D space + time). By combining our approach with tissue clearing techniques, we reveal the entire cardiac structures and hypertrabeculation of adult zebrafish hearts in response to doxorubicin treatment. By integrating the resolution enhancement technique with c-LSFM to increase the resolving power under a large field-of-view, we demonstrate the use of low power objective to resolve the entire architecture of large-scale neonatal mouse hearts, revealing the helical orientation of individual myocardial fibers. Therefore, our c-LSFM imaging approach provides multi-scale visualization of architecture and function to drive cardiovascular research with translational implication in congenital heart diseases.

Effective feature selection plays a vital role in anterior segment imaging for determining the mechanism involved in angle-closure glaucoma (ACG) diagnosis. This research focuses on the use of redundant features for complex disease diagnosis such as ACG using anterior segment optical coherence tomography images. Both supervised [minimum redundancy maximum relevance (MRMR)] and unsupervised [Laplacian score (L-score)] feature selection algorithms have been cross-examined with different ACG mechanisms. An AdaBoost machine learning classifier is then used for classifying the five various classes of ACG mechanism such as iris roll, lens, pupil block, plateau iris, and no mechanism using both feature selection methods. The overall accuracy has shown that the usefulness of redundant features by L-score method in improved ACG diagnosis compared to minimum redundant features by MRMR method.

The quality assessment for synthesized video with texture/depth compression distortion is important for the design, optimization, and evaluation of the multi-view video plus depth (MVD)-based 3D video system. In this paper, the subjective and objective studies for synthesized view assessment are both conducted. First, a synthesized video quality database with texture/depth compression distortion is presented with subjective scores given by 56 subjects. The 140 videos are synthesized from ten MVD sequences with different texture/depth quantization combinations. Second, a full reference objective video quality assessment (VQA) method is proposed concerning about the annoying temporal flicker distortion and the change of spatio-temporal activity in the synthesized video. The proposed VQA algorithm has a good performance evaluated on the entire synthesized video quality database, and is particularly prominent on the subsets which have significant temporal flicker distortion induced by depth compression and view synthesis process.

Objective quality assessment for compressed images is critical to various image compression systems that are essential in image delivery and storage. Although the mean squared error (MSE) is computationally simple, it may not be accurate to reflect the perceptual quality of compressed images, which is also affected dramatically by the characteristics of human visual system (HVS), such as masking effect. In this paper, an image quality metric (IQM) is proposed based on perceptually weighted distortion in terms of the MSE. To capture the characteristics of HVS, a randomness map is proposed to measure the masking effect and a preprocessing scheme is proposed to simulate the processing that occurs in the initial part of HVS. Since the masking effect highly depends on the structural randomness, the prediction error from neighborhood with a statistical model is used to measure the significance of masking. Meanwhile, the imperceptible signal with high frequency could be removed by preprocessing with low-pass filters. The relation is investigated between the distortions before and after masking effect, and a masking modulation model is proposed to simulate the masking effect after preprocessing. The performance of the proposed IQM is validated on six image databases with various compression distortions. The experimental results show that the proposed algorithm outperforms other benchmark IQMs.

Motivation: The deconvolution of isoform expression from RNA-seq remains challenging because of non-uniform read sampling and subtle differences among isoforms., Results: We present a weighted-log-likelihood expectation maximization method on isoform quantification (WemIQ). WemIQ integrates an effective bias removal with a weighted expectation maximization (EM) algorithm to distribute reads among isoforms efficiently. The weight represents the oversampling or undersampling of sequence reads and is estimated through a generalized Poisson model without any presumption on the bias sources and formats. WemIQ significantly improves the quantification of isoform and gene expression as well as the derived exon inclusion rates. It provides robust expression estimates across different laboratories and protocols, which is valuable for the integrative analysis of RNA-seq. For the recent single-cell RNA-seq data, WemIQ also provides the opportunity to distinguish bias heterogeneity from true biological heterogeneity and uncovers smaller cell-to-cell expression variability., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Visual identification of coronary arterial lesion from three-dimensional coronary computed tomography angiography (CTA) remains challenging. We aimed to develop a robust automated algorithm for computer detection of coronary artery lesions by machine learning techniques. A structured learning technique is proposed to detect all coronary arterial lesions with stenosis [Formula: see text]. Our algorithm consists of two stages: (1) two independent base decisions indicating the existence of lesions in each arterial segment and (b) the final decision made by combining the base decisions. One of the base decisions is the support vector machine (SVM) based learning algorithm, which divides each artery into small volume patches and integrates several quantitative geometric and shape features for arterial lesions in each small volume patch by SVM algorithm. The other base decision is the formula-based analytic method. The final decision in the first stage applies SVM-based decision fusion to combine the two base decisions in the second stage. The proposed algorithm was applied to 42 CTA patient datasets, acquired with dual-source CT, where 21 datasets had 45 lesions with stenosis [Formula: see text]. Visual identification of lesions with stenosis [Formula: see text] by three expert readers, using consensus reading, was considered as a reference standard. Our method performed with high sensitivity (93%), specificity (95%), and accuracy (94%), with receiver operator characteristic area under the curve of 0.94. The proposed algorithm shows promising results in the automated detection of obstructive and nonobstructive lesions from CTA.

In this paper, we present a compressed-domain video retargeting solution that operates without compromising the resizing quality. Existing video retargeting methods operate in the spatial (or pixel) domain. Such a solution is not practical if it is implemented in mobile devices due to its large memory requirement. In the proposed solution, each component of the retargeting system is designed to exploit the low-level compressed domain features extracted from the coded bit stream. For example, motion information is obtained directly from motion vectors. An efficient column shape mesh deformation is employed to solve the difficulty of sophisticated quad-shape mesh deformation in the compressed domain. The proposed solution achieves comparable (or slightly better) visual quality performance as compared with several state-of-the-art pixel-domain retargeting methods at lower computational and memory costs, making content-aware video resizing both scalable and practical in real-world applications.

In this paper, we propose a view synthesis distortion model (VSDM) that establishes the relationship between depth distortion and view synthesis distortion for the regions with different characteristics: color texture area corresponding depth (CTAD) region and color smooth area corresponding depth (CSAD), respectively. With this VSDM, we propose regional bit allocation (RBA) and rate distortion optimization (RDO) algorithms for multiview depth video coding (MDVC) by allocating more bits on CTAD for rendering quality and fewer bits on CSAD for compression efficiency. Experimental results show that the proposed VSDM based RBA and RDO can improve the coding efficiency significantly for the test sequences. In addition, for the proposed overall MDVC algorithm that integrates VSDM based RBA and RDO, it achieves 9.99% and 14.51% bit rate reduction on average for the high and low bit rate, respectively. It can improve virtual view image quality 0.22 and 0.24 dB on average at the high and low bit rate, respectively, when compared with the original joint multiview video coding model. The RD performance comparisons using five different metrics also validate the effectiveness of the proposed overall algorithm. In addition, the proposed algorithms can be applied to both INTRA and INTER frames.

In this paper, we propose a cascaded sparse/DCT (S/DCT) two-layer representation of prediction residuals, and implement this idea on top of the state-of-the-art high efficiency video coding (HEVC) standard. First, a dictionary is adaptively trained to contain featured patterns of residual signals so that a high portion of energy in a structured residual can be efficiently coded via sparse coding. It is observed that the sparse representation alone is less effective in the R-D performance due to the side information overhead at higher bit rates. To overcome this problem, the DCT representation is cascaded at the second stage. It is applied to the remaining signal to improve coding efficiency. The two representations successfully complement each other. It is demonstrated by experimental results that the proposed algorithm outperforms the HEVC reference codec HM5.0 in the Common Test Condition.

A new methodology for objective image quality assessment (IQA) with multi-method fusion (MMF) is presented in this paper. The research is motivated by the observation that there is no single method that can give the best performance in all situations. To achieve MMF, we adopt a regression approach. The new MMF score is set to be the nonlinear combination of scores from multiple methods with suitable weights obtained by a training process. In order to improve the regression results further, we divide distorted images into three to five groups based on the distortion types and perform regression within each group, which is called "context-dependent MMF" (CD-MMF). One task in CD-MMF is to determine the context automatically, which is achieved by a machine learning approach. To further reduce the complexity of MMF, we perform algorithms to select a small subset from the candidate method set. The result is very good even if only three quality assessment methods are included in the fusion process. The proposed MMF method using support vector regression is shown to outperform a large number of existing IQA methods by a significant margin when being tested in six representative databases.

In a generic decision process, optimal stopping theory aims to achieve a good tradeoff between decision performance and time consumed, with the advantages of theoretical decision-making and predictable decision performance. In this paper, optimal stopping theory is employed to develop an effective hybrid model for the mode decision problem, which aims to theoretically achieve a good tradeoff between the two interrelated measurements in mode decision, as computational complexity reduction and rate-distortion degradation. The proposed hybrid model is implemented and examined with a multiview encoder. To support the model and further promote coding performance, the multiview coding mode characteristics, including predicted mode probability and estimated coding time, are jointly investigated with inter-view correlations. Exhaustive experimental results with a wide range of video resolutions reveal the efficiency and robustness of our method, with high decision accuracy, negligible computational overhead, and almost intact rate-distortion performance compared to the original encoder.

Purpose: Visual analysis of three-dimensional (3D) coronary computed tomography angiography (CCTA) remains challenging due to large number of image slices and tortuous character of the vessels. The authors aimed to develop a robust, automated algorithm for unsupervised computer detection of coronary artery lesions., Methods: The authors' knowledge-based algorithm consists of centerline extraction, vessel classification, vessel linearization, lumen segmentation with scan-specific lumen attenuation ranges, and lesion location detection. Presence and location of lesions are identified using a multi-pass algorithm which considers expected or "normal" vessel tapering and luminal stenosis from the segmented vessel. Expected luminal diameter is derived from the scan by automated piecewise least squares line fitting over proximal and mid segments (67%) of the coronary artery considering the locations of the small branches attached to the main coronary arteries., Results: The authors applied this algorithm to 42 CCTA patient datasets, acquired with dual-source CT, where 21 datasets had 45 lesions with stenosis ≥ 25%. The reference standard was provided by visual and quantitative identification of lesions with any stenosis ≥ 25% by three expert readers using consensus reading. The authors algorithm identified 42 lesions (93%) confirmed by the expert readers. There were 46 additional lesions detected; 23 out of 39 (59%) of these were less-stenosed lesions. When the artery was divided into 15 coronary segments according to standard cardiology reporting guidelines, per-segment basis, sensitivity was 93% and per-segment specificity was 81% using 10-fold cross-validation., Conclusions: The authors' algorithm shows promising results in the detection of both obstructive and nonobstructive CCTA lesions.

In this paper, a novel rate control scheme with optimized bits allocation for the 3-D video coding is proposed. First, we investigate the R-D characteristics of the texture and depth map of the coded view, as well as the quality dependency between the virtual view and the coded view. Second, an optimal bit allocation scheme is developed to allocate target bits for both the texture and depth maps of different views. Meanwhile, a simplified model parameter estimation scheme is adopted to speed up the coding process. Finally, the experimental results on various 3-D video sequences demonstrate that the proposed algorithm achieves excellent R-D efficiency and bit rate accuracy compared to benchmark algorithms.

Identification of splicing regulatory elements (SREs) deserves special attention because these cis-acting short sequences are vital parts of splicing code. The fact that a variety of other biological signals cooperatively govern the splicing pattern indicates the necessity of developing novel tools to incorporate information from multiple sources to improve splicing factor binding sites prediction. Under this context, we proposed a Varying Effect Regression for Splicing Elements (VERSE) to discover intronic SREs in the proximity of exon junctions by integrating other biological features. As a result, 1562 intronic SREs were identified in 16 human tissues, many of which overlapped with experimentally verified binding motifs for several well-known splicing factors, including FOX-1, PTB, hnRNP A/B, hnRNP F/H, and so on. The discovered tissue, region, and conservation preferences of the putative motifs demonstrate that splice site selection is a complicated process that needs subtle and delicate regulation. VERSE may serve as a powerful tool to not only discover SREs by incorporating additional informative signals but also precisely quantify their varying contribution under different biological contexts.

Fast mode decision algorithms have been widely used in the video encoder implementation to reduce encoding complexity yet without much sacrifice in the coding performance. Optimal stopping theory, which addresses early termination for a generic class of decision problems, is adopted in this paper to achieve fast mode decision for the H.264/Scalable Video Coding standard. A constrained model is developed with optimal stopping, and the solutions to this model are employed to initialize the candidate mode list and predict the early termination. Comprehensive simulation results are conducted to demonstrate that the proposed method strikes a good balance between low encoding complexity and high coding efficiency.

Background: Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens), mice (Mus musculus), fruit flies (Drosophila melanogaster), and nematodes (Caenorhabditis elegans) to further investigate this phenomenon., Results: We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures., Conclusion: All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.