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Effective connectivity estimation plays a crucial role in understanding the interactions and information flow between different brain regions. However, the functional time series used for estimating effective connectivity is derived from certain software, which may lead to large computing errors because of different parameter settings and degrade the ability to model complex causal relationships between brain regions. In this paper, a brain diffuser with hierarchical transformer (BDHT) is proposed to estimate effective connectivity for mild cognitive impairment (MCI) analysis. To our best knowledge, the proposed brain diffuser is the first generative model to apply diffusion models to the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages structural connectivity to guide the reverse processes in an efficient way. It makes the denoising process more reliable and guarantees effective connectivity estimation accuracy. To improve denoising quality, the hierarchical denoising transformer is designed to learn multi-scale features in topological space. By stacking the multi-head attention and graph convolutional network, the graph convolutional transformer (GraphConformer) module is devised to enhance structure-function complementarity and improve the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The proposed model achieves superior performance in terms of accuracy and robustness compared to existing approaches. Moreover, the proposed model can identify altered directional connections and provide a comprehensive understanding of parthenogenesis for MCI treatment., Comment: 13pages, 14 figures

Integrating the brain structural and functional connectivity features is of great significance in both exploring brain science and analyzing cognitive impairment clinically. However, it remains a challenge to effectively fuse structural and functional features in exploring the brain network. In this paper, a novel brain structure-function fusing-representation learning (BSFL) model is proposed to effectively learn fused representation from diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) for mild cognitive impairment (MCI) analysis. Specifically, the decomposition-fusion framework is developed to first decompose the feature space into the union of the uniform and the unique spaces for each modality, and then adaptively fuse the decomposed features to learn MCI-related representation. Moreover, a knowledge-aware transformer module is designed to automatically capture local and global connectivity features throughout the brain. Also, a uniform-unique contrastive loss is further devised to make the decomposition more effective and enhance the complementarity of structural and functional features. The extensive experiments demonstrate that the proposed model achieves better performance than other competitive methods in predicting and analyzing MCI. More importantly, the proposed model could be a potential tool for reconstructing unified brain networks and predicting abnormal connections during the degenerative processes in MCI.

In minimally-invasive brain surgeries with indirect and narrow operating environments, 3D brain reconstruction is crucial. However, as requirements of accuracy for some new minimally-invasive surgeries (such as brain-computer interface surgery) are higher and higher, the outputs of conventional 3D reconstruction, such as point cloud (PC), are facing the challenges that sample points are too sparse and the precision is insufficient. On the other hand, there is a scarcity of high-density point cloud datasets, which makes it challenging to train models for direct reconstruction of high-density brain point clouds. In this work, a novel model named stereoscopic-aware graph generative adversarial network (SG-GAN) with two stages is proposed to generate fine high-density PC conditioned on a single image. The Stage-I GAN sketches the primitive shape and basic structure of the organ based on the given image, yielding Stage-I point clouds. The Stage-II GAN takes the results from Stage-I and generates high-density point clouds with detailed features. The Stage-II GAN is capable of correcting defects and restoring the detailed features of the region of interest (ROI) through the up-sampling process. Furthermore, a parameter-free-attention-based free-transforming module is developed to learn the efficient features of input, while upholding a promising performance. Comparing with the existing methods, the SG-GAN model shows superior performance in terms of visual quality, objective measurements, and performance in classification, as demonstrated by comprehensive results measured by several evaluation metrics including PC-to-PC error and Chamfer distance.

Brain network analysis is essential for diagnosing and intervention for Alzheimer's disease (AD). However, previous research relied primarily on specific time-consuming and subjective toolkits. Only few tools can obtain the structural brain networks from brain diffusion tensor images (DTI). In this paper, we propose a diffusion based end-to-end brain network generative model Brain Diffuser that directly shapes the structural brain networks from DTI. Compared to existing toolkits, Brain Diffuser exploits more structural connectivity features and disease-related information by analyzing disparities in structural brain networks across subjects. For the case of Alzheimer's disease, the proposed model performs better than the results from existing toolkits on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

There are still many challenges of emotion recognition using physiological data despite the substantial progress made recently. In this paper, we attempted to address two major challenges. First, in order to deal with the sparsely-labeled physiological data, we first decomposed the raw physiological data using signal spectrum analysis, based on which we extracted both complexity and energy features. Such a procedure helped reduce noise and improve feature extraction effectiveness. Second, in order to improve the explainability of the machine learning models in emotion recognition with physiological data, we proposed Light Gradient Boosting Machine (LightGBM) and SHapley Additive exPlanations (SHAP) for emotion prediction and model explanation, respectively. The LightGBM model outperformed the eXtreme Gradient Boosting (XGBoost) model on the public Database for Emotion Analysis using Physiological signals (DEAP) with f1-scores of 0.814, 0.823, and 0.860 for binary classification of valence, arousal, and liking, respectively, with cross-subject validation using eight peripheral physiological signals. Furthermore, the SHAP model was able to identify the most important features in emotion recognition, and revealed the relationships between the predictor variables and the response variables in terms of their main effects and interaction effects. Therefore, the results of the proposed model not only had good performance using peripheral physiological data, but also gave more insights into the underlying mechanisms in recognizing emotions.

With the rapid development of artificial intelligence (AI) in medical image processing, deep learning in color fundus photography (CFP) analysis is also evolving. Although there are some open-source, labeled datasets of CFPs in the ophthalmology community, large-scale datasets for screening only have labels of disease categories, and datasets with annotations of fundus structures are usually small in size. In addition, labeling standards are not uniform across datasets, and there is no clear information on the acquisition device. Here we release a multi-annotation, multi-quality, and multi-device color fundus image dataset for glaucoma analysis on an original challenge -- Retinal Fundus Glaucoma Challenge 2nd Edition (REFUGE2). The REFUGE2 dataset contains 2000 color fundus images with annotations of glaucoma classification, optic disc/cup segmentation, as well as fovea localization. Meanwhile, the REFUGE2 challenge sets three sub-tasks of automatic glaucoma diagnosis and fundus structure analysis and provides an online evaluation framework. Based on the characteristics of multi-device and multi-quality data, some methods with strong generalizations are provided in the challenge to make the predictions more robust. This shows that REFUGE2 brings attention to the characteristics of real-world multi-domain data, bridging the gap between scientific research and clinical application., Comment: 29 pages, 21 figures

Age-related macular degeneration (AMD) is the leading cause of visual impairment among elderly in the world. Early detection of AMD is of great importance, as the vision loss caused by this disease is irreversible and permanent. Color fundus photography is the most cost-effective imaging modality to screen for retinal disorders. Cutting edge deep learning based algorithms have been recently developed for automatically detecting AMD from fundus images. However, there are still lack of a comprehensive annotated dataset and standard evaluation benchmarks. To deal with this issue, we set up the Automatic Detection challenge on Age-related Macular degeneration (ADAM), which was held as a satellite event of the ISBI 2020 conference. The ADAM challenge consisted of four tasks which cover the main aspects of detecting and characterizing AMD from fundus images, including detection of AMD, detection and segmentation of optic disc, localization of fovea, and detection and segmentation of lesions. As part of the challenge, we have released a comprehensive dataset of 1200 fundus images with AMD diagnostic labels, pixel-wise segmentation masks for both optic disc and AMD-related lesions (drusen, exudates, hemorrhages and scars, among others), as well as the coordinates corresponding to the location of the macular fovea. A uniform evaluation framework has been built to make a fair comparison of different models using this dataset. During the challenge, 610 results were submitted for online evaluation, with 11 teams finally participating in the onsite challenge. This paper introduces the challenge, the dataset and the evaluation methods, as well as summarizes the participating methods and analyzes their results for each task. In particular, we observed that the ensembling strategy and the incorporation of clinical domain knowledge were the key to improve the performance of the deep learning models., Comment: 31 pages, 17 figures

The diagnosis of early stages of Alzheimer's disease (AD) is essential for timely treatment to slow further deterioration. Visualizing the morphological features for the early stages of AD is of great clinical value. In this work, a novel Multidirectional Perception Generative Adversarial Network (MP-GAN) is proposed to visualize the morphological features indicating the severity of AD for patients of different stages. Specifically, by introducing a novel multidirectional mapping mechanism into the model, the proposed MP-GAN can capture the salient global features efficiently. Thus, by utilizing the class-discriminative map from the generator, the proposed model can clearly delineate the subtle lesions via MR image transformations between the source domain and the pre-defined target domain. Besides, by integrating the adversarial loss, classification loss, cycle consistency loss and \emph{L}1 penalty, a single generator in MP-GAN can learn the class-discriminative maps for multiple-classes. Extensive experimental results on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate that MP-GAN achieves superior performance compared with the existing methods. The lesions visualized by MP-GAN are also consistent with what clinicians observe.

Alzheimer's disease is characterized by alterations of the brain's structural and functional connectivity during its progressive degenerative processes. Existing auxiliary diagnostic methods have accomplished the classification task, but few of them can accurately evaluate the changing characteristics of brain connectivity. In this work, a prior guided adversarial representation learning and hypergraph perceptual network (PGARL-HPN) is proposed to predict abnormal brain connections using triple-modality medical images. Concretely, a prior distribution from the anatomical knowledge is estimated to guide multimodal representation learning using an adversarial strategy. Also, the pairwise collaborative discriminator structure is further utilized to narrow the difference of representation distribution. Moreover, the hypergraph perceptual network is developed to effectively fuse the learned representations while establishing high-order relations within and between multimodal images. Experimental results demonstrate that the proposed model outperforms other related methods in analyzing and predicting Alzheimer's disease progression. More importantly, the identified abnormal connections are partly consistent with the previous neuroscience discoveries. The proposed model can evaluate characteristics of abnormal brain connections at different stages of Alzheimer's disease, which is helpful for cognitive disease study and early treatment.

One of the main reasons for Alzheimer's disease (AD) is the disorder of some neural circuits. Existing methods for AD prediction have achieved great success, however, detecting abnormal neural circuits from the perspective of brain networks is still a big challenge. In this work, a novel decoupling generative adversarial network (DecGAN) is proposed to detect abnormal neural circuits for AD. Concretely, a decoupling module is designed to decompose a brain network into two parts: one part is composed of a few sparse graphs which represent the neural circuits largely determining the development of AD; the other part is a supplement graph, whose influence on AD can be ignored. Furthermore, the adversarial strategy is utilized to guide the decoupling module to extract the feature more related to AD. Meanwhile, by encoding the detected neural circuits to hypergraph data, an analytic module associated with the hyperedge neurons algorithm is designed to identify the neural circuits. More importantly, a novel sparse capacity loss based on the spatial-spectral hypergraph similarity is developed to minimize the intrinsic topological distribution of neural circuits, which can significantly improve the accuracy and robustness of the proposed model. Experimental results demonstrate that the proposed model can effectively detect the abnormal neural circuits at different stages of AD, which is helpful for pathological study and early treatment.

3D shape reconstruction is essential in the navigation of minimally-invasive and auto robot-guided surgeries whose operating environments are indirect and narrow, and there have been some works that focused on reconstructing the 3D shape of the surgical organ through limited 2D information available. However, the lack and incompleteness of such information caused by intraoperative emergencies (such as bleeding) and risk control conditions have not been considered. In this paper, a novel hierarchical shape-perception network (HSPN) is proposed to reconstruct the 3D point clouds (PCs) of specific brains from one single incomplete image with low latency. A branching predictor and several hierarchical attention pipelines are constructed to generate point clouds that accurately describe the incomplete images and then complete these point clouds with high quality. Meanwhile, attention gate blocks (AGBs) are designed to efficiently aggregate geometric local features of incomplete PCs transmitted by hierarchical attention pipelines and internal features of reconstructing point clouds. With the proposed HSPN, 3D shape perception and completion can be achieved spontaneously. Comprehensive results measured by Chamfer distance and PC-to-PC error demonstrate that the performance of the proposed HSPN outperforms other competitive methods in terms of qualitative displays, quantitative experiment, and classification evaluation.

Using multimodal neuroimaging data to characterize brain network is currently an advanced technique for Alzheimer's disease(AD) Analysis. Over recent years the neuroimaging community has made tremendous progress in the study of resting-state functional magnetic resonance imaging (rs-fMRI) derived from blood-oxygen-level-dependent (BOLD) signals and Diffusion Tensor Imaging (DTI) derived from white matter fiber tractography. However, Due to the heterogeneity and complexity between BOLD signals and fiber tractography, Most existing multimodal data fusion algorithms can not sufficiently take advantage of the complementary information between rs-fMRI and DTI. To overcome this problem, a novel Hypergraph Generative Adversarial Networks(HGGAN) is proposed in this paper, which utilizes Interactive Hyperedge Neurons module (IHEN) and Optimal Hypergraph Homomorphism algorithm(OHGH) to generate multimodal connectivity of Brain Network from rs-fMRI combination with DTI. To evaluate the performance of this model, We use publicly available data from the ADNI database to demonstrate that the proposed model not only can identify discriminative brain regions of AD but also can effectively improve classification performance.

Multimodal neuroimage can provide complementary information about the dementia, but small size of complete multimodal data limits the ability in representation learning. Moreover, the data distribution inconsistency from different modalities may lead to ineffective fusion, which fails to sufficiently explore the intra-modal and inter-modal interactions and compromises the disease diagnosis performance. To solve these problems, we proposed a novel multimodal representation learning and adversarial hypergraph fusion (MRL-AHF) framework for Alzheimer's disease diagnosis using complete trimodal images. First, adversarial strategy and pre-trained model are incorporated into the MRL to extract latent representations from multimodal data. Then two hypergraphs are constructed from the latent representations and the adversarial network based on graph convolution is employed to narrow the distribution difference of hyperedge features. Finally, the hyperedge-invariant features are fused for disease prediction by hyperedge convolution. Experiments on the public Alzheimer's Disease Neuroimaging Initiative(ADNI) database demonstrate that our model achieves superior performance on Alzheimer's disease detection compared with other related models and provides a possible way to understand the underlying mechanisms of disorder's progression by analyzing the abnormal brain connections., Comment: 13 pages, 3 figures

Fusing medical images and the corresponding 3D shape representation can provide complementary information and microstructure details to improve the operational performance and accuracy in brain surgery. However, compared to the substantial image data, it is almost impossible to obtain the intraoperative 3D shape information by using physical methods such as sensor scanning, especially in minimally invasive surgery and robot-guided surgery. In this paper, a general generative adversarial network (GAN) architecture based on graph convolutional networks is proposed to reconstruct the 3D point clouds (PCs) of brains by using one single 2D image, thus relieving the limitation of acquiring 3D shape data during surgery. Specifically, a tree-structured generative mechanism is constructed to use the latent vector effectively and transfer features between hidden layers accurately. With the proposed generative model, a spontaneous image-to-PC conversion is finished in real-time. Competitive qualitative and quantitative experimental results have been achieved on our model. In multiple evaluation methods, the proposed model outperforms another common point cloud generative model PointOutNet.

In large studies involving multi protocol Magnetic Resonance Imaging (MRI), it can occur to miss one or more sub-modalities for a given patient owing to poor quality (e.g. imaging artifacts), failed acquisitions, or hallway interrupted imaging examinations. In some cases, certain protocols are unavailable due to limited scan time or to retrospectively harmonise the imaging protocols of two independent studies. Missing image modalities pose a challenge to segmentation frameworks as complementary information contributed by the missing scans is then lost. In this paper, we propose a novel model, Multi-modal Gaussian Process Prior Variational Autoencoder (MGP-VAE), to impute one or more missing sub-modalities for a patient scan. MGP-VAE can leverage the Gaussian Process (GP) prior on the Variational Autoencoder (VAE) to utilize the subjects/patients and sub-modalities correlations. Instead of designing one network for each possible subset of present sub-modalities or using frameworks to mix feature maps, missing data can be generated from a single model based on all the available samples. We show the applicability of MGP-VAE on brain tumor segmentation where either, two, or three of four sub-modalities may be missing. Our experiments against competitive segmentation baselines with missing sub-modality on BraTS'19 dataset indicate the effectiveness of the MGP-VAE model for segmentation tasks., Comment: Accepted in MICCAI 2021

In this paper, we first present an arc based algorithm for fan-beam computed tomography (CT) reconstruction via applying Katsevich's helical CT formula to 2D fan-beam CT reconstruction. Then, we propose a new weighting function to deal with the redundant projection data. By extending the weighted arc based fan-beam algorithm to circle cone-beam geometry, we also obtain a new FDK-similar algorithm for circle cone-beam CT reconstruction. Experiments show that our methods can obtain higher PSNR and SSIM compared to the Parker-weighted conventional fan-beam algorithm and the FDK algorithm for super-short-scan trajectories.

Magnetic resonance imaging plays an important role in computer-aided diagnosis and brain exploration. However, limited by hardware, scanning time and cost, it's challenging to acquire high-resolution (HR) magnetic resonance (MR) image clinically. In this paper, fine perceptive generative adversarial networks (FP-GANs) is proposed to produce HR MR images from low-resolution counterparts. It can cope with the detail insensitive problem of the existing super-resolution model in a divide-and-conquer manner. Specifically, FP-GANs firstly divides an MR image into low-frequency global approximation and high-frequency anatomical texture in wavelet domain. Then each sub-band generative adversarial network (sub-band GAN) conquers the super-resolution procedure of each single sub-band image. Meanwhile, sub-band attention is deployed to tune focus between global and texture information. It can focus on sub-band images instead of feature maps to further enhance the anatomical reconstruction ability of FP-GANs. In addition, inverse discrete wavelet transformation (IDWT) is integrated into model for taking the reconstruction of whole image into account. Experiments on MultiRes_7T dataset demonstrate that FP-GANs outperforms the competing methods quantitatively and qualitatively., Comment: 9 pages, 11figures

Structural magnetic resonance imaging (MRI) has been widely utilized for analysis and diagnosis of brain diseases. Automatic segmentation of brain tumors is a challenging task for computer-aided diagnosis due to low-tissue contrast in the tumor subregions. To overcome this, we devise a novel pixel-wise segmentation framework through a convolutional 3D to 2D MR patch conversion model to predict class labels of the central pixel in the input sliding patches. Precisely, we first extract 3D patches from each modality to calibrate slices through the squeeze and excitation (SE) block. Then, the output of the SE block is fed directly into subsequent bottleneck layers to reduce the number of channels. Finally, the calibrated 2D slices are concatenated to obtain multimodal features through a 2D convolutional neural network (CNN) for prediction of the central pixel. In our architecture, both local inter-slice and global intra-slice features are jointly exploited to predict class label of the central voxel in a given patch through the 2D CNN classifier. We implicitly apply all modalities through trainable parameters to assign weights to the contributions of each sequence for segmentation. Experimental results on the segmentation of brain tumors in multimodal MRI scans (BraTS'19) demonstrate that our proposed method can efficiently segment the tumor regions.

The state-of-the-art deep learning methods have demonstrated impressive performance in segmentation tasks. However, the success of these methods depends on a large amount of manually labeled masks, which are expensive and time-consuming to be collected. In this work, a novel Consistent PerceptionGenerative Adversarial Network (CPGAN) is proposed for semi-supervised stroke lesion segmentation. The proposed CPGAN can reduce the reliance on fully labeled samples. Specifically, A similarity connection module (SCM) is designed to capture the information of multi-scale features. The proposed SCM can selectively aggregate the features at each position by a weighted sum. Moreover, a consistent perception strategy is introduced into the proposed model to enhance the effect of brain stroke lesion prediction for the unlabeled data. Furthermore, an assistant network is constructed to encourage the discriminator to learn meaningful feature representations which are often forgotten during training stage. The assistant network and the discriminator are employed to jointly decide whether the segmentation results are real or fake. The CPGAN was evaluated on the Anatomical Tracings of Lesions After Stroke (ATLAS). The experimental results demonstrate that the proposed network achieves superior segmentation performance. In semi-supervised segmentation task, the proposed CPGAN using only two-fifths of labeled samples outperforms some approaches using full labeled samples., Comment: 11 pages, 10 figures

In this paper, we first propose a variational model for the limited-angle computed tomography (CT) image reconstruction and then convert the model into an end-to-end deep network.We use the penalty method to solve the model and divide it into three iterative subproblems, where the first subproblem completes the sinograms by utilizing the prior information of sinograms in the frequency domain and the second refines the CT images by using the prior information of CT images in the spatial domain, and the last merges the outputs of the first two subproblems. In each iteration, we use the convolutional neural networks (CNNs) to approxiamte the solutions of the first two subproblems and, thus, obtain an end-to-end deep network for the limited-angle CT image reconstruction. Our network tackles both the sinograms and the CT images, and can simultaneously suppress the artifacts caused by the incomplete data and recover fine structural information in the CT images. Experimental results show that our method outperforms the existing algorithms for the limited-angle CT image reconstruction.

Fusing multi-modality medical images, such as MR and PET, can provide various anatomical or functional information about human body. But PET data is always unavailable due to different reasons such as cost, radiation, or other limitations. In this paper, we propose a 3D end-to-end synthesis network, called Bidirectional Mapping Generative Adversarial Networks (BMGAN), where image contexts and latent vector are effectively used and jointly optimized for brain MR-to-PET synthesis. Concretely, a bidirectional mapping mechanism is designed to embed the semantic information of PET images into the high dimensional latent space. And the 3D DenseU-Net generator architecture and the extensive objective functions are further utilized to improve the visual quality of synthetic results. The most appealing part is that the proposed method can synthesize the perceptually realistic PET images while preserving the diverse brain structures of different subjects. Experimental results demonstrate that the performance of the proposed method outperforms other competitive cross-modality synthesis methods in terms of quantitative measures, qualitative displays, and classification evaluation., Comment: 12pages, 10 figures

It is of great significance to apply deep learning for the early diagnosis of Alzheimer's Disease (AD). In this work, a novel tensorizing GAN with high-order pooling is proposed to assess Mild Cognitive Impairment (MCI) and AD. By tensorizing a three-player cooperative game based framework, the proposed model can benefit from the structural information of the brain. By incorporating the high-order pooling scheme into the classifier, the proposed model can make full use of the second-order statistics of the holistic Magnetic Resonance Imaging (MRI) images. To the best of our knowledge, the proposed Tensor-train, High-pooling and Semi-supervised learning based GAN (THS-GAN) is the first work to deal with classification on MRI images for AD diagnosis. Extensive experimental results on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset are reported to demonstrate that the proposed THS-GAN achieves superior performance compared with existing methods, and to show that both tensor-train and high-order pooling can enhance classification performance. The visualization of generated samples also shows that the proposed model can generate plausible samples for semi-supervised learning purpose., Comment: 15 pages, 20 figures

Amid the ongoing COVID-19 pandemic, whether COVID-19 patients with high risks can be recovered or not depends, to a large extent, on how early they will be treated appropriately before irreversible consequences are caused to the patients by the virus. In this research, we reported an explainable, intuitive, and accurate machine learning model based on logistic regression to predict the fatality rate of COVID-19 patients using only three important blood biomarkers, including lactic dehydrogenase, lymphocyte (%) and high-sensitivity C-reactive protein, and their interactions. We found that when the fatality probability produced by the logistic regression model was over 0.8, the model had the optimal performance in that it was able to predict patient fatalities more than 11.30 days on average with maximally 34.91 days in advance, an accumulative f1-score of 93.76% and and an accumulative accuracy score of 93.92%. Such a model can be used to identify COVID-19 patients with high risks with three blood biomarkers and help the medical systems around the world plan critical medical resources amid this pandemic.