Automatic lesion segmentation is important for assisting doctors in the diagnostic process. Recent deep learning approaches heavily rely on large-scale datasets, which are difficult to obtain in many clinical applications. Leveraging external labelled datasets is an effective solution to tackle the problem of insufficient training data. In this paper, we propose a new framework, namely LatenTrans, to utilize existing datasets for boosting the performance of lesion segmentation in extremely low data regimes. LatenTrans translates non-target lesions into target-like lesions and expands the training dataset with target-like data for better performance. Images are first projected to the latent space via aligned style-based generative models, and rich lesion semantics are encoded using the latent codes. A novel consistency-aware latent code manipulation module is proposed to enable high-quality local style transfer from non-target lesions to target-like lesions while preserving other parts. Moreover, we propose a new metric, Normalized Latent Distance, to solve the question of how to select an adequate one from various existing datasets for knowledge transfer. Extensive experiments are conducted on segmenting lung and brain lesions, and the experimental results demonstrate that our proposed LatenTrans is superior to existing methods for cross-disease lesion segmentation.

Automatic liver tumor segmentation is of great importance for assisting doctors in liver cancer diagnosis and treatment planning. Recently, deep learning approaches trained with pixel-level annotations have contributed many breakthroughs in image segmentation. However, acquiring such accurate dense annotations is time-consuming and labor-intensive, which limits the performance of deep neural networks for medical image segmentation. We note that Couinaud segment is widely used by radiologists when recording liver cancer-related findings in the reports, since it is well-suited for describing the localization of tumors. In this paper, we propose a novel approach to train convolutional networks for liver tumor segmentation using Couinaud segment annotations. Couinaud segment annotations are image-level labels with values ranging from 1 to 8, indicating a specific region of the liver. Our proposed model, namely CouinaudNet, can estimate pseudo tumor masks from the Couinaud segment annotations as pixel-wise supervision for training a fully supervised tumor segmentation model, and it is composed of two components: 1) an inpainting network with Couinaud segment masks which can effectively remove tumors for pathological images by filling the tumor regions with plausible healthy-looking intensities; 2) a difference spotting network for segmenting the tumors, which is trained with healthy-pathological pairs generated by an effective tumor synthesis strategy. The proposed method is extensively evaluated on two liver tumor segmentation datasets. The experimental results demonstrate that our method can achieve competitive performance compared to the fully supervised counterpart and the state-of-the-art methods while requiring significantly less annotation effort.

Automatic liver tumor segmentation could offer assistance to radiologists in liver tumor diagnosis, and its performance has been significantly improved by recent deep learning based methods. These methods rely on large-scale well-annotated training datasets, but collecting such datasets is time-consuming and labor-intensive, which could hinder their performance in practical situations. Learning from synthetic data is an encouraging solution to address this problem. In our task, synthetic tumors can be injected to healthy images to form training pairs. However, directly applying the model trained using the synthetic tumor images on real test images performs poorly due to the domain shift problem. In this paper, we propose a novel approach, namely Synthetic-to-Real Test-Time Training (SR-TTT), to reduce the domain gap between synthetic training images and real test images. Specifically, we add a self-supervised auxiliary task, i.e., two-step reconstruction, which takes the output of the main segmentation task as its input to build an explicit connection between these two tasks. Moreover, we design a scheduled mixture strategy to avoid error accumulation and bias explosion in the training process. During test time, we adapt the segmentation model to each test image with self-supervision from the auxiliary task so as to improve the inference performance. The proposed method is extensively evaluated on two public datasets for liver tumor segmentation. The experimental results demonstrate that our proposed SR-TTT can effectively mitigate the synthetic-to-real domain shift problem in the liver tumor segmentation task, and is superior to existing state-of-the-art approaches.

OBJECTIVE: Accurate risk prediction is important for evaluating early medical treatment effects and improving health care quality. Existing methods are usually designed for dynamic medical data, which require long-term observations. Meanwhile, important personalized static information is ignored due to the underlying uncertainty and unquantifiable ambiguity. It is urgent to develop an early risk prediction method that can adaptively integrate both static and dynamic health data. MATERIALS AND METHODS: Data were from 6367 patients with Peptic Ulcer Bleeding between 2007 and 2016. This article develops a novel End-to-end Importance-Aware Personalized Deep Learning Approach (eiPDLA) to achieve accurate early clinical risk prediction. Specifically, eiPDLA introduces a long short-term memory with temporal attention to learn sequential dependencies from time-stamped records and simultaneously incorporating a residual network with correlation attention to capture their influencing relationship with static medical data. Furthermore, a new multi-residual multi-scale network with the importance-aware mechanism is designed to adaptively fuse the learned multisource features, automatically assigning larger weights to important features while weakening the influence of less important features. RESULTS: Extensive experimental results on a real-world dataset illustrate that our method significantly outperforms the state-of-the-arts for early risk prediction under various settings (eg, achieving an AUC score of 0.944 at 1 year ahead of risk prediction). Case studies indicate that the achieved prediction results are highly interpretable. CONCLUSION: These results reflect the importance of combining static and dynamic health data, mining their influencing relationship, and incorporating the importance-aware mechanism to automatically identify important features. The achieved accurate early risk prediction results save precious time for doctors to timely design effective treatments and improve clinical outcomes.

Influenced by the dynamic changes in the severity of illness, patients usually take examinations in hospitals irregularly, producing a large volume of irregular medical time-series data. Performing diagnosis prediction from the irregular medical time series is challenging because the intervals between consecutive records significantly vary along time. Existing methods often handle this problem by generating regular time series from the irregular medical records without considering the uncertainty in the generated data, induced by the varying intervals. Thus, a novel Uncertainty-Aware Convolutional Recurrent Neural Network (UA-CRNN) is proposed in this article, which introduces the uncertainty information in the generated data to boost the risk prediction. To tackle the complex medical time series with subseries of different frequencies, the uncertainty information is further incorporated into the subseries level rather than the whole sequence to seamlessly adjust different time intervals. Specifically, a hierarchical uncertainty-aware decomposition layer (UADL) is designed to adaptively decompose time series into different subseries and assign them proper weights in accordance with their reliabilities. Meanwhile, an Explainable UA-CRNN (eUA-CRNN) is proposed to exploit filters with different passbands to ensure the unity of components in each subseries and the diversity of components in different subseries. Furthermore, eUA-CRNN incorporates with an uncertainty-aware attention module to learn attention weights from the uncertainty information, providing the explainable prediction results. The extensive experimental results on three real-world medical data sets illustrate the superiority of the proposed method compared with the state-of-the-art methods.

Due to the discrepancy of diseases and symptoms, patients usually visit hospitals irregularly and different physiological variables are examined at each visit, producing large amounts of irregular multivariate time series (IMTS) data with missing values and varying intervals. Existing methods process IMTS into regular data so that standard machine learning models can be employed. However, time intervals are usually determined by the status of patients, while missing values are caused by changes in symptoms. Therefore, we propose a novel end-to-end Dual-Attention Time-Aware Gated Recurrent Unit (DATA-GRU) for IMTS to predict the mortality risk of patients. In particular, DATA-GRU is able to: 1) preserve the informative varying intervals by introducing a time-aware structure to directly adjust the influence of the previous status in coordination with the elapsed time, and 2) tackle missing values by proposing a novel dual-attention structure to jointly consider data-quality and medical-knowledge. A novel unreliability-aware attention mechanism is designed to handle the diversity in the reliability of different data, while a new symptom-aware attention mechanism is proposed to extract medical reasons from original clinical records. Extensive experimental results on two real-world datasets demonstrate that DATA-GRU can significantly outperform state-of-the-art methods and provide meaningful clinical interpretation.

Accurate prediction of mortality risk is important for evaluating early treatments, detecting high-risk patients and improving healthcare outcomes. Predicting mortality risk from the irregular clinical time series data is challenging due to the varying time intervals in the consecutive records. Existing methods usually solve this issue by generating regular time series data from the original irregular data without considering the uncertainty in the generated data, caused by varying time intervals. In this paper, we propose a novel Uncertainty-Aware Convolutional Recurrent Neural Network (UA-CRNN), which incorporates the uncertainty information in the generated data to improve the mortality risk prediction performance. To handle the complex clinical time series data with sub-series of different frequencies, we propose to incorporate the uncertainty information into the sub-series level rather than the whole time series data. Specifically, we design a novel hierarchical uncertainty-aware decomposition layer (UADL) to adaptively decompose time series into different sub-series and assign them proper weights according to their reliabilities. Experimental results on two real-world clinical datasets demonstrate that the proposed UA-CRNN method significantly outperforms state-of-the-art methods in both short-term and long-term mortality risk predictions.