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Representation learning is all about discovering the hidden modular attributes that generate the data faithfully. We explore the potential of Denoising Diffusion Probabilistic Model (DM) in unsupervised learning of the modular attributes. We build a theoretical framework that connects the diffusion time-steps and the hidden attributes, which serves as an effective inductive bias for unsupervised learning. Specifically, the forward diffusion process incrementally adds Gaussian noise to samples at each time-step, which essentially collapses different samples into similar ones by losing attributes, e.g., fine-grained attributes such as texture are lost with less noise added (i.e., early time-steps), while coarse-grained ones such as shape are lost by adding more noise (i.e., late time-steps). To disentangle the modular attributes, at each time-step t, we learn a t-specific feature to compensate for the newly lost attribute, and the set of all 1,...,t-specific features, corresponding to the cumulative set of lost attributes, are trained to make up for the reconstruction error of a pre-trained DM at time-step t. On CelebA, FFHQ, and Bedroom datasets, the learned feature significantly improves attribute classification and enables faithful counterfactual generation, e.g., interpolating only one specified attribute between two images, validating the disentanglement quality. Codes are in https://github.com/yue-zhongqi/diti., Comment: Accepted by ICLR 2024

Electronic Health Records (EHRs), which contain patients' medical histories in various multi-modal formats, often overlook the potential for joint reasoning across imaging and table modalities underexplored in current EHR Question Answering (QA) systems. In this paper, we introduce EHRXQA, a novel multi-modal question answering dataset combining structured EHRs and chest X-ray images. To develop our dataset, we first construct two uni-modal resources: 1) The MIMIC-CXR-VQA dataset, our newly created medical visual question answering (VQA) benchmark, specifically designed to augment the imaging modality in EHR QA, and 2) EHRSQL (MIMIC-IV), a refashioned version of a previously established table-based EHR QA dataset. By integrating these two uni-modal resources, we successfully construct a multi-modal EHR QA dataset that necessitates both uni-modal and cross-modal reasoning. To address the unique challenges of multi-modal questions within EHRs, we propose a NeuralSQL-based strategy equipped with an external VQA API. This pioneering endeavor enhances engagement with multi-modal EHR sources and we believe that our dataset can catalyze advances in real-world medical scenarios such as clinical decision-making and research. EHRXQA is available at https://github.com/baeseongsu/ehrxqa., Comment: Accepted at NeurIPS 2023 Datasets and Benchmarks Track (10 pages for main text, 4 pages for references, 39 pages for supplementary materials)

Potential radioactive hazards in full-dose positron emission tomography (PET) imaging remain a concern, whereas the quality of low-dose images is never desirable for clinical use. So it is of great interest to translate low-dose PET images into full-dose. Previous studies based on deep learning methods usually directly extract hierarchical features for reconstruction. We notice that the importance of each feature is different and they should be weighted dissimilarly so that tiny information can be captured by the neural network. Furthermore, the synthesis on some regions of interest is important in some applications. Here we propose a novel segmentation guided style-based generative adversarial network (SGSGAN) for PET synthesis. (1) We put forward a style-based generator employing style modulation, which specifically controls the hierarchical features in the translation process, to generate images with more realistic textures. (2) We adopt a task-driven strategy that couples a segmentation task with a generative adversarial network (GAN) framework to improve the translation performance. Extensive experiments show the superiority of our overall framework in PET synthesis, especially on those regions of interest., Comment: This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/TMI.2022.3156614, IEEE Transactions on Medical Imaging

Hispathological image segmentation algorithms play a critical role in computer aided diagnosis technology. The development of weakly supervised segmentation algorithm alleviates the problem of medical image annotation that it is time-consuming and labor-intensive. As a subset of weakly supervised learning, Multiple Instance Learning (MIL) has been proven to be effective in segmentation. However, there is a lack of related information between instances in MIL, which limits the further improvement of segmentation performance. In this paper, we propose a novel weakly supervised method for pixel-level segmentation in histopathology images, which introduces Transformer into the MIL framework to capture global or long-range dependencies. The multi-head self-attention in the Transformer establishes the relationship between instances, which solves the shortcoming that instances are independent of each other in MIL. In addition, deep supervision is introduced to overcome the limitation of annotations in weakly supervised methods and make the better utilization of hierarchical information. The state-of-the-art results on the colon cancer dataset demonstrate the superiority of the proposed method compared with other weakly supervised methods. It is worth believing that there is a potential of our approach for various applications in medical images., Comment: Provisional accepted for MICCAI 2022

Whole brain segmentation is an important neuroimaging task that segments the whole brain volume into anatomically labeled regions-of-interest. Convolutional neural networks have demonstrated good performance in this task. Existing solutions, usually segment the brain image by classifying the voxels, or labeling the slices or the sub-volumes separately. Their representation learning is based on parts of the whole volume whereas their labeling result is produced by aggregation of partial segmentation. Learning and inference with incomplete information could lead to sub-optimal final segmentation result. To address these issues, we propose to adopt a full volume framework, which feeds the full volume brain image into the segmentation network and directly outputs the segmentation result for the whole brain volume. The framework makes use of complete information in each volume and can be implemented easily. An effective instance in this framework is given subsequently. We adopt the $3$D high-resolution network (HRNet) for learning spatially fine-grained representations and the mixed precision training scheme for memory-efficient training. Extensive experiment results on a publicly available $3$D MRI brain dataset show that our proposed model advances the state-of-the-art methods in terms of segmentation performance. Source code is publicly available at https://github.com/microsoft/VoxHRNet., Comment: Accepted to CMIG

Numerous task-specific variants of conditional generative adversarial networks have been developed for image completion. Yet, a serious limitation remains that all existing algorithms tend to fail when handling large-scale missing regions. To overcome this challenge, we propose a generic new approach that bridges the gap between image-conditional and recent modulated unconditional generative architectures via co-modulation of both conditional and stochastic style representations. Also, due to the lack of good quantitative metrics for image completion, we propose the new Paired/Unpaired Inception Discriminative Score (P-IDS/U-IDS), which robustly measures the perceptual fidelity of inpainted images compared to real images via linear separability in a feature space. Experiments demonstrate superior performance in terms of both quality and diversity over state-of-the-art methods in free-form image completion and easy generalization to image-to-image translation. Code is available at https://github.com/zsyzzsoft/co-mod-gan., Comment: ICLR 2021 (Spotlight). Code: https://github.com/zsyzzsoft/co-mod-gan Demo: https://comodgan.ml/

Fine-grained classification of microscopic image data with limited samples is an open problem in computer vision and biomedical imaging. Deep learning based vision systems mostly deal with high number of low-resolution images, whereas subtle detail in biomedical images require higher resolution. To bridge this gap, we propose a simple yet effective deep network that performs two tasks simultaneously in an end-to-end manner. First, it utilises a gated attention module that can focus on multiple key instances at high resolution without extra annotations or region proposals. Second, the global structural features and local instance features are fused for final image level classification. The result is a robust but lightweight end-to-end trainable deep network that yields state-of-the-art results in two separate fine-grained multi-instance biomedical image classification tasks: a benchmark breast cancer histology dataset and our new fungi species mycology dataset. In addition, we demonstrate the interpretability of the proposed model by visualising the concordance of the learned features with clinically relevant features.

Feature warping is a core technique in optical flow estimation; however, the ambiguity caused by occluded areas during warping is a major problem that remains unsolved. In this paper, we propose an asymmetric occlusion-aware feature matching module, which can learn a rough occlusion mask that filters useless (occluded) areas immediately after feature warping without any explicit supervision. The proposed module can be easily integrated into end-to-end network architectures and enjoys performance gains while introducing negligible computational cost. The learned occlusion mask can be further fed into a subsequent network cascade with dual feature pyramids with which we achieve state-of-the-art performance. At the time of submission, our method, called MaskFlownet, surpasses all published optical flow methods on the MPI Sintel, KITTI 2012 and 2015 benchmarks. Code is available at https://github.com/microsoft/MaskFlownet., Comment: CVPR 2020 (Oral)

We present recursive cascaded networks, a general architecture that enables learning deep cascades, for deformable image registration. The proposed architecture is simple in design and can be built on any base network. The moving image is warped successively by each cascade and finally aligned to the fixed image; this procedure is recursive in a way that every cascade learns to perform a progressive deformation for the current warped image. The entire system is end-to-end and jointly trained in an unsupervised manner. In addition, enabled by the recursive architecture, one cascade can be iteratively applied for multiple times during testing, which approaches a better fit between each of the image pairs. We evaluate our method on 3D medical images, where deformable registration is most commonly applied. We demonstrate that recursive cascaded networks achieve consistent, significant gains and outperform state-of-the-art methods. The performance reveals an increasing trend as long as more cascades are trained, while the limit is not observed. Code is available at https://github.com/microsoft/Recursive-Cascaded-Networks., Comment: Accepted to ICCV 2019

3D medical image registration is of great clinical importance. However, supervised learning methods require a large amount of accurately annotated corresponding control points (or morphing), which are very difficult to obtain. Unsupervised learning methods ease the burden of manual annotation by exploiting unlabeled data without supervision. In this paper, we propose a new unsupervised learning method using convolutional neural networks under an end-to-end framework, Volume Tweening Network (VTN), for 3D medical image registration. We propose three innovative technical components: (1) An end-to-end cascading scheme that resolves large displacement; (2) An efficient integration of affine registration network; and (3) An additional invertibility loss that encourages backward consistency. Experiments demonstrate that our algorithm is 880x faster (or 3.3x faster without GPU acceleration) than traditional optimization-based methods and achieves state-of-theart performance in medical image registration., Comment: Journal of Biomedical and Health Informatics

Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is highly subjective and labor-intensive task. Previous efforts to automate tumor proliferation assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohen's kappa score of $\kappa$ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearman's correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labelled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task., Comment: Overview paper of the TUPAC16 challenge: http://tupac.tue-image.nl/

We present a cross-modality generation framework that learns to generate translated modalities from given modalities in MR images without real acquisition. Our proposed method performs NeuroImage-to-NeuroImage translation (abbreviated as N2N) by means of a deep learning model that leverages conditional generative adversarial networks (cGANs). Our framework jointly exploits the low-level features (pixel-wise information) and high-level representations (e.g. brain tumors, brain structure like gray matter, etc.) between cross modalities which are important for resolving the challenging complexity in brain structures. Our framework can serve as an auxiliary method in clinical diagnosis and has great application potential. Based on our proposed framework, we first propose a method for cross-modality registration by fusing the deformation fields to adopt the cross-modality information from translated modalities. Second, we propose an approach for MRI segmentation, translated multichannel segmentation (TMS), where given modalities, along with translated modalities, are segmented by fully convolutional networks (FCN) in a multichannel manner. Both of these two methods successfully adopt the cross-modality information to improve the performance without adding any extra data. Experiments demonstrate that our proposed framework advances the state-of-the-art on five brain MRI datasets. We also observe encouraging results in cross-modality registration and segmentation on some widely adopted brain datasets. Overall, our work can serve as an auxiliary method in clinical diagnosis and be applied to various tasks in medical fields. Keywords: image-to-image, cross-modality, registration, segmentation, brain MRI, Comment: 46 pages, 16 figures

The visual attributes of cells, such as the nuclear morphology and chromatin openness, are critical for histopathology image analysis. By learning cell-level visual representation, we can obtain a rich mix of features that are highly reusable for various tasks, such as cell-level classification, nuclei segmentation, and cell counting. In this paper, we propose a unified generative adversarial networks architecture with a new formulation of loss to perform robust cell-level visual representation learning in an unsupervised setting. Our model is not only label-free and easily trained but also capable of cell-level unsupervised classification with interpretable visualization, which achieves promising results in the unsupervised classification of bone marrow cellular components. Based on the proposed cell-level visual representation learning, we further develop a pipeline that exploits the varieties of cellular elements to perform histopathology image classification, the advantages of which are demonstrated on bone marrow datasets., Comment: Accepted for publication in IEEE Journal of Biomedical and Health Informatics

We propose a registration algorithm for 2D CT/MRI medical images with a new unsupervised end-to-end strategy using convolutional neural networks. The contributions of our algorithm are threefold: (1) We transplant traditional image registration algorithms to an end-to-end convolutional neural network framework, while maintaining the unsupervised nature of image registration problems. The image-to-image integrated framework can simultaneously learn both image features and transformation matrix for registration. (2) Training with additional data without any label can further improve the registration performance by approximately 10 %. (3) The registration speed is 100x faster than traditional methods. The proposed network is easy to implement and can be trained efficiently. Experiments demonstrate that our system achieves state-of-the-art results on 2D brain registration and achieves comparable results on 2D liver registration. It can be extended to register other organs beyond liver and brain such as kidney, lung, and heart.

This paper proposes a practical approach for automatic sleep stage classification based on a multi-level feature learning framework and Recurrent Neural Network (RNN) classifier using heart rate and wrist actigraphy derived from a wearable device. The feature learning framework is designed to extract low- and mid-level features. Low-level features capture temporal and frequency domain properties and mid-level features learn compositions and structural information of signals. Since sleep staging is a sequential problem with long-term dependencies, we take advantage of RNNs with Bidirectional Long Short-Term Memory (BLSTM) architectures for sequence data learning. To simulate the actual situation of daily sleep, experiments are conducted with a resting group in which sleep is recorded in resting state, and a comprehensive group in which both resting sleep and non-resting sleep are included.We evaluate the algorithm based on an eight-fold cross validation to classify five sleep stages (W, N1, N2, N3, and REM). The proposed algorithm achieves weighted precision, recall and F1 score of 58.0%, 60.3%, and 58.2% in the resting group and 58.5%, 61.1%, and 58.5% in the comprehensive group, respectively. Various comparison experiments demonstrate the effectiveness of feature learning and BLSTM. We further explore the influence of depth and width of RNNs on performance. Our method is specially proposed for wearable devices and is expected to be applicable for long-term sleep monitoring at home. Without using too much prior domain knowledge, our method has the potential to generalize sleep disorder detection., Comment: 11 pages, 10 figures

In this paper, we develop a new weakly-supervised learning algorithm to learn to segment cancerous regions in histopathology images. Our work is under a multiple instance learning framework (MIL) with a new formulation, deep weak supervision (DWS); we also propose an effective way to introduce constraints to our neural networks to assist the learning process. The contributions of our algorithm are threefold: (1) We build an end-to-end learning system that segments cancerous regions with fully convolutional networks (FCN) in which image-to-image weakly-supervised learning is performed. (2) We develop a deep week supervision formulation to exploit multi-scale learning under weak supervision within fully convolutional networks. (3) Constraints about positive instances are introduced in our approach to effectively explore additional weakly-supervised information that is easy to obtain and enjoys a significant boost to the learning process. The proposed algorithm, abbreviated as DWS-MIL, is easy to implement and can be trained efficiently. Our system demonstrates state-of-the-art results on large-scale histopathology image datasets and can be applied to various applications in medical imaging beyond histopathology images such as MRI, CT, and ultrasound images.

This paper proposes a multi-level feature learning framework for human action recognition using a single body-worn inertial sensor. The framework consists of three phases, respectively designed to analyze signal-based (low-level), components (mid-level) and semantic (high-level) information. Low-level features capture the time and frequency domain property while mid-level representations learn the composition of the action. The Max-margin Latent Pattern Learning (MLPL) method is proposed to learn high-level semantic descriptions of latent action patterns as the output of our framework. The proposed method achieves the state-of-the-art performances, 88.7%, 98.8% and 72.6% (weighted F1 score) respectively, on Skoda, WISDM and OPP datasets., Comment: 26 pages, 23 figures

Objective: A new image instance segmentation method is proposed to segment individual glands (instances) in colon histology images. This process is challenging since the glands not only need to be segmented from a complex background, they must also be individually identified. Methods: We leverage the idea of image-to-image prediction in recent deep learning by designing an algorithm that automatically exploits and fuses complex multichannel information - regional, location, and boundary cues - in gland histology images. Our proposed algorithm, a deep multichannel framework, alleviates heavy feature design due to the use of convolutional neural networks and is able to meet multifarious requirements by altering channels. Results: Compared with methods reported in the 2015 MICCAI Gland Segmentation Challenge and other currently prevalent instance segmentation methods, we observe state-of-the-art results based on the evaluation metrics. Conclusion: The proposed deep multichannel algorithm is an effective method for gland instance segmentation. Significance: The generalization ability of our model not only enable the algorithm to solve gland instance segmentation problems, but the channel is also alternative that can be replaced for a specific task., Comment: arXiv admin note: substantial text overlap with arXiv:1607.04889

In this paper, we propose an innovative end-to-end subtitle detection and recognition system for videos in East Asian languages. Our end-to-end system consists of multiple stages. Subtitles are firstly detected by a novel image operator based on the sequence information of consecutive video frames. Then, an ensemble of Convolutional Neural Networks (CNNs) trained on synthetic data is adopted for detecting and recognizing East Asian characters. Finally, a dynamic programming approach leveraging language models is applied to constitute results of the entire body of text lines. The proposed system achieves average end-to-end accuracies of 98.2% and 98.3% on 40 videos in Simplified Chinese and 40 videos in Traditional Chinese respectively, which is a significant outperformance of other existing methods. The near-perfect accuracy of our system dramatically narrows the gap between human cognitive ability and state-of-the-art algorithms used for such a task., Comment: 35 pages

In this paper, we propose a new image instance segmentation method that segments individual glands (instances) in colon histology images. This is a task called instance segmentation that has recently become increasingly important. The problem is challenging since not only do the glands need to be segmented from the complex background, they are also required to be individually identified. Here we leverage the idea of image-to-image prediction in recent deep learning by building a framework that automatically exploits and fuses complex multichannel information, regional, location and boundary patterns in gland histology images. Our proposed system, deep multichannel framework, alleviates heavy feature design due to the use of convolutional neural networks and is able to meet multifarious requirement by altering channels. Compared to methods reported in the 2015 MICCAI Gland Segmentation Challenge and other currently prevalent methods of instance segmentation, we observe state-of-the-art results based on a number of evaluation metrics.

In this paper, we propose a new image instance segmentation method that segments individual glands (instances) in colon histology images. This is a task called instance segmentation that has recently become increasingly important. The problem is challenging since not only do the glands need to be segmented from the complex background, they are also required to be individually identified. Here we leverage the idea of image-to-image prediction in recent deep learning by building a framework that automatically exploits and fuses complex multichannel information, regional and boundary patterns, with side supervision (deep supervision on side responses) in gland histology images. Our proposed system, deep multichannel side supervision (DMCS), alleviates heavy feature design due to the use of convolutional neural networks guided by side supervision. Compared to methods reported in the 2015 MICCAI Gland Segmentation Challenge, we observe state-of-the-art results based on a number of evaluation metrics., Comment: conditionally accepted at MICCAI 2016