FetusMapV2: Enhanced Fetal Pose Estimation in 3D Ultrasound

Fetal pose estimation in 3D ultrasound (US) involves identifying a set of associated fetal anatomical landmarks. Its primary objective is to provide comprehensive information about the fetus through landmark connections, thus benefiting various critical applications, such as biometric measurements, plane localization, and fetal movement monitoring. However, accurately estimating the 3D fetal pose in US volume has several challenges, including poor image quality, limited GPU memory for tackling high dimensional data, symmetrical or ambiguous anatomical structures, and considerable variations in fetal poses. In this study, we propose a novel 3D fetal pose estimation framework (called FetusMapV2) to overcome the above challenges. Our contribution is three-fold. First, we propose a heuristic scheme that explores the complementary network structure-unconstrained and activation-unreserved GPU memory management approaches, which can enlarge the input image resolution for better results under limited GPU memory. Second, we design a novel Pair Loss to mitigate confusion caused by symmetrical and similar anatomical structures. It separates the hidden classification task from the landmark localization task and thus progressively eases model learning. Last, we propose a shape priors-based self-supervised learning by selecting the relatively stable landmarks to refine the pose online. Extensive experiments and diverse applications on a large-scale fetal US dataset including 1000 volumes with 22 landmarks per volume demonstrate that our method outperforms other strong competitors.

SESNet: sequence-structure feature-integrated deep learning method for data-efficient protein engineering

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (<50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.

A Ligand-and-structure Dual-driven Deep Learning Method for the Discovery of Highly Potent GnRH1R Antagonist to treat Uterine Diseases

Gonadotrophin-releasing hormone receptor (GnRH1R) is a promising therapeutic target for the treatment of uterine diseases. To date, several GnRH1R antagonists are available in clinical investigation without satisfying multiple property constraints. To fill this gap, we aim to develop a deep learning-based framework to facilitate the effective and efficient discovery of a new orally active small-molecule drug targeting GnRH1R with desirable properties. In the present work, a ligand-and-structure combined model, namely LS-MolGen, was firstly proposed for molecular generation by fully utilizing the information on the known active compounds and the structure of the target protein, which was demonstrated by its superior performance than ligand- or structure-based methods separately. Then, a in silico screening including activity prediction, ADMET evaluation, molecular docking and FEP calculation was conducted, where ~30,000 generated novel molecules were narrowed down to 8 for experimental synthesis and validation. In vitro and in vivo experiments showed that three of them exhibited potent inhibition activities (compound 5 IC50 = 0.856 nM, compound 6 IC50 = 0.901 nM, compound 7 IC50 = 2.54 nM) against GnRH1R, and compound 5 performed well in fundamental PK properties, such as half-life, oral bioavailability, and PPB, etc. We believed that the proposed ligand-and-structure combined molecular generative model and the whole computer-aided workflow can potentially be extended to similar tasks for de novo drug design or lead optimization.

Weakly-supervised High-fidelity Ultrasound Video Synthesis with Feature Decoupling

Ultrasound (US) is widely used for its advantages of real-time imaging, radiation-free and portability. In clinical practice, analysis and diagnosis often rely on US sequences rather than a single image to obtain dynamic anatomical information. This is challenging for novices to learn because practicing with adequate videos from patients is clinically unpractical. In this paper, we propose a novel framework to synthesize high-fidelity US videos. Specifically, the synthesis videos are generated by animating source content images based on the motion of given driving videos. Our highlights are three-fold. First, leveraging the advantages of self- and fully-supervised learning, our proposed system is trained in weakly-supervised manner for keypoint detection. These keypoints then provide vital information for handling complex high dynamic motions in US videos. Second, we decouple content and texture learning using the dual decoders to effectively reduce the model learning difficulty. Last, we adopt the adversarial training strategy with GAN losses for further improving the sharpness of the generated videos, narrowing the gap between real and synthesis videos. We validate our method on a large in-house pelvic dataset with high dynamic motion. Extensive evaluation metrics and user study prove the effectiveness of our proposed method.

Fine-grained Correlation Loss for Regression

Regression learning is classic and fundamental for medical image analysis. It provides the continuous mapping for many critical applications, like the attribute estimation, object detection, segmentation and non-rigid registration. However, previous studies mainly took the case-wise criteria, like the mean square errors, as the optimization objectives. They ignored the very important population-wise correlation criterion, which is exactly the final evaluation metric in many tasks. In this work, we propose to revisit the classic regression tasks with novel investigations on directly optimizing the fine-grained correlation losses. We mainly explore two complementary correlation indexes as learnable losses: Pearson linear correlation (PLC) and Spearman rank correlation (SRC). The contributions of this paper are two folds. First, for the PLC on global level, we propose a strategy to make it robust against the outliers and regularize the key distribution factors. These efforts significantly stabilize the learning and magnify the efficacy of PLC. Second, for the SRC on local level, we propose a coarse-to-fine scheme to ease the learning of the exact ranking order among samples. Specifically, we convert the learning for the ranking of samples into the learning of similarity relationships among samples. We extensively validate our method on two typical ultrasound image regression tasks, including the image quality assessment and bio-metric measurement. Experiments prove that, with the fine-grained guidance in directly optimizing the correlation, the regression performances are significantly improved. Our proposed correlation losses are general and can be extended to more important applications.

Statistical Dependency Guided Contrastive Learning for Multiple Labeling in Prenatal Ultrasound

Standard plane recognition plays an important role in prenatal ultrasound (US) screening. Automatically recognizing the standard plane along with the corresponding anatomical structures in US image can not only facilitate US image interpretation but also improve diagnostic efficiency. In this study, we build a novel multi-label learning (MLL) scheme to identify multiple standard planes and corresponding anatomical structures of fetus simultaneously. Our contribution is three-fold. First, we represent the class correlation by word embeddings to capture the fine-grained semantic and latent statistical concurrency. Second, we equip the MLL with a graph convolutional network to explore the inner and outer relationship among categories. Third, we propose a novel cluster relabel-based contrastive learning algorithm to encourage the divergence among ambiguous classes. Extensive validation was performed on our large in-house dataset. Our approach reports the highest accuracy as 90.25% for standard planes labeling, 85.59% for planes and structures labeling and mAP as 94.63%. The proposed MLL scheme provides a novel perspective for standard plane recognition and can be easily extended to other medical image classification tasks.

Debiasing Samples from Online Learning Using Bootstrap

It has been recently shown in the literature that the sample averages from online learning experiments are biased when used to estimate the mean reward. To correct the bias, off-policy evaluation methods, including importance sampling and doubly robust estimators, typically calculate the propensity score, which is unavailable in this setting due to unknown reward distribution and the adaptive policy. This paper provides a procedure to debias the samples using bootstrap, which doesn't require the knowledge of the reward distribution at all. Numerical experiments demonstrate the effective bias reduction for samples generated by popular multi-armed bandit algorithms such as Explore-Then-Commit (ETC), UCB, Thompson sampling and $\epsilon$-greedy. We also analyze and provide theoretical justifications for the procedure under the ETC algorithm, including the asymptotic convergence of the bias decay rate in the real and bootstrap worlds.

Sublinear Regret for Learning POMDPs

We study the model-based undiscounted reinforcement learning for partially observable Markov decision processes (POMDPs). The oracle we consider is the optimal policy of the POMDP with a known environment in terms of the average reward over an infinite horizon. We propose a learning algorithm for this problem, building on spectral method-of-moments estimations for hidden Markov models, the belief error control in POMDPs and upper-confidence-bound methods for online learning. We establish a regret bound of $O(T^{2/3}\sqrt{\log T})$ for the proposed learning algorithm where $T$ is the learning horizon. This is, to the best of our knowledge, the first algorithm achieving sublinear regret with respect to our oracle for learning general POMDPs.

Searching Collaborative Agents for Multi-plane Localization in 3D Ultrasound

3D ultrasound (US) has become prevalent due to its rich spatial and diagnostic information not contained in 2D US. Moreover, 3D US can contain multiple standard planes (SPs) in one shot. Thus, automatically localizing SPs in 3D US has the potential to improve user-independence and scanning-efficiency. However, manual SP localization in 3D US is challenging because of the low image quality, huge search space and large anatomical variability. In this work, we propose a novel multi-agent reinforcement learning (MARL) framework to simultaneously localize multiple SPs in 3D US. Our contribution is four-fold. First, our proposed method is general and it can accurately localize multiple SPs in different challenging US datasets. Second, we equip the MARL system with a recurrent neural network (RNN) based collaborative module, which can strengthen the communication among agents and learn the spatial relationship among planes effectively. Third, we explore to adopt the neural architecture search (NAS) to automatically design the network architecture of both the agents and the collaborative module. Last, we believe we are the first to realize automatic SP localization in pelvic US volumes, and note that our approach can handle both normal and abnormal uterus cases. Extensively validated on two challenging datasets of the uterus and fetal brain, our proposed method achieves the average localization accuracy of 7.03 degrees/1.59mm and 9.75 degrees/1.19mm. Experimental results show that our light-weight MARL model has higher accuracy than state-of-the-art methods.