Haoran Dou

Shaokun Lan, Haoran Dou, Jinghan Huang et al.

In-silico trials of medical devices require the generation of virtual populations of anatomies. In cardiovascular applications, virtual anatomy is typically represented as a 3D+t mesh sampled from a generative model. However, most existing mesh generators focus on static anatomy, while sequence models often lack explicit periodicity. To this end, we propose 4D F-MeshLDM, a conditional generative framework comprising a convolutional mesh VAE to encode meshes, a structural latent space that parameterises motion using a truncated Fourier series, and a diffusion prior that learns the latent distribution over Fourier coefficient tokens. By conditioning the diffusion process on clinical covariates via affine modulation, we enable controllable synthesis. Sampling tokens and performing inverse Fourier synthesis yield cycle-consistent latent trajectories, which can be decoded into 3D+t cardiac mesh sequences. Experiments on 5,000 UK Biobank subjects demonstrate that 4D F-MeshLDM outperforms state-of-the-art baselines in anatomical fidelity and achieves near-zero cycle closure error. Furthermore, the generated cohorts accurately preserve clinical functional indices, highlighting the potential of our framework for reliable in-silico cardiac trials.

Luyi Han, Tianyu Zhang, Yunzhi Huang et al.

Multi-sequence MRI is valuable in clinical settings for reliable diagnosis and treatment prognosis, but some sequences may be unusable or missing for various reasons. To address this issue, MRI synthesis is a potential solution. Recent deep learning-based methods have achieved good performance in combining multiple available sequences for missing sequence synthesis. Despite their success, these methods lack the ability to quantify the contributions of different input sequences and estimate the quality of generated images, making it hard to be practical. Hence, we propose an explainable task-specific synthesis network, which adapts weights automatically for specific sequence generation tasks and provides interpretability and reliability from two sides: (1) visualize the contribution of each input sequence in the fusion stage by a trainable task-specific weighted average module; (2) highlight the area the network tried to refine during synthesizing by a task-specific attention module. We conduct experiments on the BraTS2021 dataset of 1251 subjects, and results on arbitrary sequence synthesis indicate that the proposed method achieves better performance than the state-of-the-art methods. Our code is available at \url{https://github.com/fiy2W/mri_seq2seq}.

Yuxin Zou, Haoran Dou, Yuhao Huang et al.

Standard plane (SP) localization is essential in routine clinical ultrasound (US) diagnosis. Compared to 2D US, 3D US can acquire multiple view planes in one scan and provide complete anatomy with the addition of coronal plane. However, manually navigating SPs in 3D US is laborious and biased due to the orientation variability and huge search space. In this study, we introduce a novel reinforcement learning (RL) framework for automatic SP localization in 3D US. Our contribution is three-fold. First, we formulate SP localization in 3D US as a tangent-point-based problem in RL to restructure the action space and significantly reduce the search space. Second, we design an auxiliary task learning strategy to enhance the model's ability to recognize subtle differences crossing Non-SPs and SPs in plane search. Finally, we propose a spatial-anatomical reward to effectively guide learning trajectories by exploiting spatial and anatomical information simultaneously. We explore the efficacy of our approach on localizing four SPs on uterus and fetal brain datasets. The experiments indicate that our approach achieves a high localization accuracy as well as robust performance.

Haoran Dou, Ning Bi, Luyi Han et al.

Deep learning-based deformable registration methods have been widely investigated in diverse medical applications. Learning-based deformable registration relies on weighted objective functions trading off registration accuracy and smoothness of the deformation field. Therefore, they inevitably require tuning the hyperparameter for optimal registration performance. Tuning the hyperparameters is highly computationally expensive and introduces undesired dependencies on domain knowledge. In this study, we construct a registration model based on the gradient surgery mechanism, named GSMorph, to achieve a hyperparameter-free balance on multiple losses. In GSMorph, we reformulate the optimization procedure by projecting the gradient of similarity loss orthogonally to the plane associated with the smoothness constraint, rather than additionally introducing a hyperparameter to balance these two competing terms. Furthermore, our method is model-agnostic and can be merged into any deep registration network without introducing extra parameters or slowing down inference. In this study, We compared our method with state-of-the-art (SOTA) deformable registration approaches over two publicly available cardiac MRI datasets. GSMorph proves superior to five SOTA learning-based registration models and two conventional registration techniques, SyN and Demons, on both registration accuracy and smoothness.

Yash Deo, Haoran Dou, Nishant Ravikumar et al.

The Circle of Willis (CoW) is the part of cerebral vasculature responsible for delivering blood to the brain. Understanding the diverse anatomical variations and configurations of the CoW is paramount to advance research on cerebrovascular diseases and refine clinical interventions. However, comprehensive investigation of less prevalent CoW variations remains challenging because of the dominance of a few commonly occurring configurations. We propose a novel generative approach utilising a conditional latent diffusion model with shape and anatomical guidance to generate realistic 3D CoW segmentations, including different phenotypical variations. Our conditional latent diffusion model incorporates shape guidance to better preserve vessel continuity and demonstrates superior performance when compared to alternative generative models, including conditional variants of 3D GAN and 3D VAE. We observed that our model generated CoW variants that are more realistic and demonstrate higher visual fidelity than competing approaches with an FID score 53\% better than the best-performing GAN-based model.

Haoran Dou, Nishant Ravikumar, Alejandro F. Frangi

The generation of virtual populations (VPs) of anatomy is essential for conducting in silico trials of medical devices. Typically, the generated VP should capture sufficient variability while remaining plausible and should reflect the specific characteristics and demographics of the patients observed in real populations. In several applications, it is desirable to synthesise virtual populations in a \textit{controlled} manner, where relevant covariates are used to conditionally synthesise virtual populations that fit a specific target population/characteristics. We propose to equip a conditional variational autoencoder (cVAE) with normalising flows to boost the flexibility and complexity of the approximate posterior learnt, leading to enhanced flexibility for controllable synthesis of VPs of anatomical structures. We demonstrate the performance of our conditional flow VAE using a data set of cardiac left ventricles acquired from 2360 patients, with associated demographic information and clinical measurements (used as covariates/conditional information). The results obtained indicate the superiority of the proposed method for conditional synthesis of virtual populations of cardiac left ventricles relative to a cVAE. Conditional synthesis performance was evaluated in terms of generalisation and specificity errors and in terms of the ability to preserve clinically relevant biomarkers in synthesised VPs, that is, the left ventricular blood pool and myocardial volume, relative to the real observed population.

Haoran Dou, Luyi Han, Yushuang He et al.

Tumor infiltration of the recurrent laryngeal nerve (RLN) is a contraindication for robotic thyroidectomy and can be difficult to detect via standard laryngoscopy. Ultrasound (US) is a viable alternative for RLN detection due to its safety and ability to provide real-time feedback. However, the tininess of the RLN, with a diameter typically less than 3mm, poses significant challenges to the accurate localization of the RLN. In this work, we propose a knowledge-driven framework for RLN localization, mimicking the standard approach surgeons take to identify the RLN according to its surrounding organs. We construct a prior anatomical model based on the inherent relative spatial relationships between organs. Through Bayesian shape alignment (BSA), we obtain the candidate coordinates of the center of a region of interest (ROI) that encloses the RLN. The ROI allows a decreased field of view for determining the refined centroid of the RLN using a dual-path identification network, based on multi-scale semantic information. Experimental results indicate that the proposed method achieves superior hit rates and substantially smaller distance errors compared with state-of-the-art methods.

Yuhao Huang, Xin Yang, Xiaoqiong Huang et al.

Deep segmentation models often face the failure risks when the testing image presents unseen distributions. Improving model robustness against these risks is crucial for the large-scale clinical application of deep models. In this study, inspired by human learning cycle, we propose a novel online reflective learning framework (RefSeg) to improve segmentation robustness. Based on the reflection-on-action conception, our RefSeg firstly drives the deep model to take action to obtain semantic segmentation. Then, RefSeg triggers the model to reflect itself. Because making deep models realize their segmentation failures during testing is challenging, RefSeg synthesizes a realistic proxy image from the semantic mask to help deep models build intuitive and effective reflections. This proxy translates and emphasizes the segmentation flaws. By maximizing the structural similarity between the raw input and the proxy, the reflection-on-action loop is closed with segmentation robustness improved. RefSeg runs in the testing phase and is general for segmentation models. Extensive validation on three medical image segmentation tasks with a public cardiac MR dataset and two in-house large ultrasound datasets show that our RefSeg remarkably improves model robustness and reports state-of-the-art performance over strong competitors.

Yuhao Huang, Xin Yang, Xiaoqiong Huang et al.

Deep classifiers may encounter significant performance degradation when processing unseen testing data from varying centers, vendors, and protocols. Ensuring the robustness of deep models against these domain shifts is crucial for their widespread clinical application. In this study, we propose a novel approach called Fourier Test-time Adaptation (FTTA), which employs a dual-adaptation design to integrate input and model tuning, thereby jointly improving the model robustness. The main idea of FTTA is to build a reliable multi-level consistency measurement of paired inputs for achieving self-correction of prediction. Our contribution is two-fold. First, we encourage consistency in global features and local attention maps between the two transformed images of the same input. Here, the transformation refers to Fourier-based input adaptation, which can transfer one unseen image into source style to reduce the domain gap. Furthermore, we leverage style-interpolated images to enhance the global and local features with learnable parameters, which can smooth the consistency measurement and accelerate convergence. Second, we introduce a regularization technique that utilizes style interpolation consistency in the frequency space to encourage self-consistency in the logit space of the model output. This regularization provides strong self-supervised signals for robustness enhancement. FTTA was extensively validated on three large classification datasets with different modalities and organs. Experimental results show that FTTA is general and outperforms other strong state-of-the-art methods.

Yash Deo, Rodrigo Bonazzola, Haoran Dou et al.

Magnetic resonance angiography (MRA) is an imaging modality for visualising blood vessels. It is useful for several diagnostic applications and for assessing the risk of adverse events such as haemorrhagic stroke (resulting from the rupture of aneurysms in blood vessels). However, MRAs are not acquired routinely, hence, an approach to synthesise blood vessel segmentations from more routinely acquired MR contrasts such as T1 and T2, would be useful. We present an encoder-decoder model for synthesising segmentations of the main cerebral arteries in the circle of Willis (CoW) from only T2 MRI. We propose a two-phase multi-objective learning approach, which captures both global and local features. It uses learned local attention maps generated by dilating the segmentation labels, which forces the network to only extract information from the T2 MRI relevant to synthesising the CoW. Our synthetic vessel segmentations generated from only T2 MRI achieved a mean Dice score of $0.79 \pm 0.03$ in testing, compared to state-of-the-art segmentation networks such as transformer U-Net ($0.71 \pm 0.04$) and nnU-net($0.68 \pm 0.05$), while using only a fraction of the parameters. The main qualitative difference between our synthetic vessel segmentations and the comparative models was in the sharper resolution of the CoW vessel segments, especially in the posterior circulation.

Haoran Dou, Seppo Virtanen, Nishant Ravikumar et al.

Generating virtual populations of anatomy that capture sufficient variability while remaining plausible is essential for conducting in-silico trials of medical devices. However, not all anatomical shapes of interest are always available for each individual in a population. Hence, missing/partially-overlapping anatomical information is often available across individuals in a population. We introduce a generative shape model for complex anatomical structures, learnable from datasets of unpaired datasets. The proposed generative model can synthesise complete whole complex shape assemblies coined virtual chimaeras, as opposed to natural human chimaeras. We applied this framework to build virtual chimaeras from databases of whole-heart shape assemblies that each contribute samples for heart substructures. Specifically, we propose a generative shape compositional framework which comprises two components - a part-aware generative shape model which captures the variability in shape observed for each structure of interest in the training population; and a spatial composition network which assembles/composes the structures synthesised by the former into multi-part shape assemblies (viz. virtual chimaeras). We also propose a novel self supervised learning scheme that enables the spatial composition network to be trained with partially overlapping data and weak labels. We trained and validated our approach using shapes of cardiac structures derived from cardiac magnetic resonance images available in the UK Biobank. Our approach significantly outperforms a PCA-based shape model (trained with complete data) in terms of generalisability and specificity. This demonstrates the superiority of the proposed approach as the synthesised cardiac virtual populations are more plausible and capture a greater degree of variability in shape than those generated by the PCA-based shape model.

Yuhao Huang, Xin Yang, Han Zhou et al.

The Segment Anything Model (SAM) can achieve satisfactory segmentation performance under high-quality box prompts. However, SAM's robustness is compromised by the decline in box quality, limiting its practicality in clinical reality. In this study, we propose a novel Robust Box prompt based SAM (\textbf{RoBox-SAM}) to ensure SAM's segmentation performance under prompts with different qualities. Our contribution is three-fold. First, we propose a prompt refinement module to implicitly perceive the potential targets, and output the offsets to directly transform the low-quality box prompt into a high-quality one. We then provide an online iterative strategy for further prompt refinement. Second, we introduce a prompt enhancement module to automatically generate point prompts to assist the box-promptable segmentation effectively. Last, we build a self-information extractor to encode the prior information from the input image. These features can optimize the image embeddings and attention calculation, thus, the robustness of SAM can be further enhanced. Extensive experiments on the large medical segmentation dataset including 99,299 images, 5 modalities, and 25 organs/targets validated the efficacy of our proposed RoBox-SAM.

Luyi Han, Tao Tan, Tianyu Zhang et al.

Adversarial learning helps generative models translate MRI from source to target sequence when lacking paired samples. However, implementing MRI synthesis with adversarial learning in clinical settings is challenging due to training instability and mode collapse. To address this issue, we leverage intermediate sequences to estimate the common latent space among multi-sequence MRI, enabling the reconstruction of distinct sequences from the common latent space. We propose a generative model that compresses discrete representations of each sequence to estimate the Gaussian distribution of vector-quantized common (VQC) latent space between multiple sequences. Moreover, we improve the latent space consistency with contrastive learning and increase model stability by domain augmentation. Experiments using BraTS2021 dataset show that our non-adversarial model outperforms other GAN-based methods, and VQC latent space aids our model to achieve (1) anti-interference ability, which can eliminate the effects of noise, bias fields, and artifacts, and (2) solid semantic representation ability, with the potential of one-shot segmentation. Our code is publicly available.

Xinrui Zhou, Yuhao Huang, Haoran Dou et al.

In the medical field, the limited availability of large-scale datasets and labor-intensive annotation processes hinder the performance of deep models. Diffusion-based generative augmentation approaches present a promising solution to this issue, having been proven effective in advancing downstream medical recognition tasks. Nevertheless, existing works lack sufficient semantic and sequential steerability for challenging video/3D sequence generation, and neglect quality control of noisy synthesized samples, resulting in unreliable synthetic databases and severely limiting the performance of downstream tasks. In this work, we present Ctrl-GenAug, a novel and general generative augmentation framework that enables highly semantic- and sequential-customized sequence synthesis and suppresses incorrectly synthesized samples, to aid medical sequence classification. Specifically, we first design a multimodal conditions-guided sequence generator for controllably synthesizing diagnosis-promotive samples. A sequential augmentation module is integrated to enhance the temporal/stereoscopic coherence of generated samples. Then, we propose a noisy synthetic data filter to suppress unreliable cases at semantic and sequential levels. Extensive experiments on 3 medical datasets, using 11 networks trained on 3 paradigms, comprehensively analyze the effectiveness and generality of Ctrl-GenAug, particularly in underrepresented high-risk populations and out-domain conditions.

Rusi Chen, Yuanting Yang, Jiezhi Yao et al.

Mitral regurgitation is one of the most prevalent cardiac disorders. Four-dimensional (4D) ultrasound has emerged as the primary imaging modality for assessing dynamic valvular morphology. However, 4D mitral valve (MV) analysis remains challenging due to limited phase annotations, severe motion artifacts, and poor imaging quality. Yet, the absence of inter-phase dependency in existing methods hinders 4D MV analysis. To bridge this gap, we propose a Motion-Topology guided consistency network (MTCNet) for accurate 4D MV ultrasound segmentation in semi-supervised learning (SSL). MTCNet requires only sparse end-diastolic and end-systolic annotations. First, we design a cross-phase motion-guided consistency learning strategy, utilizing a bi-directional attention memory bank to propagate spatio-temporal features. This enables MTCNet to achieve excellent performance both per- and inter-phase. Second, we devise a novel topology-guided correlation regularization that explores physical prior knowledge to maintain anatomically plausible. Therefore, MTCNet can effectively leverage structural correspondence between labeled and unlabeled phases. Extensive evaluations on the first largest 4D MV dataset, with 1408 phases from 160 patients, show that MTCNet performs superior cross-phase consistency compared to other advanced methods (Dice: 87.30%, HD: 1.75mm). Both the code and the dataset are available at https://github.com/crs524/MTCNet.

Yuhao Huang, Yueyue Xu, Haoran Dou et al.

Congenital uterine anomalies (CUAs) can lead to infertility, miscarriage, preterm birth, and an increased risk of pregnancy complications. Compared to traditional 2D ultrasound (US), 3D US can reconstruct the coronal plane, providing a clear visualization of the uterine morphology for assessing CUAs accurately. In this paper, we propose an intelligent system for simultaneous automated plane localization and CUA diagnosis. Our highlights are: 1) we develop a denoising diffusion model with local (plane) and global (volume/text) guidance, using an adaptive weighting strategy to optimize attention allocation to different conditions; 2) we introduce a reinforcement learning-based framework with unsupervised rewards to extract the key slice summary from redundant sequences, fully integrating information across multiple planes to reduce learning difficulty; 3) we provide text-driven uncertainty modeling for coarse prediction, and leverage it to adjust the classification probability for overall performance improvement. Extensive experiments on a large 3D uterine US dataset show the efficacy of our method, in terms of plane localization and CUA diagnosis. Code is available at https://github.com/yuhoo0302/CUA-US.

Yi Wang, Haoran Dou, Xiaowei Hu et al.

Automatic prostate segmentation in transrectal ultrasound (TRUS) images is of essential importance for image-guided prostate interventions and treatment planning. However, developing such automatic solutions remains very challenging due to the missing/ambiguous boundary and inhomogeneous intensity distribution of the prostate in TRUS, as well as the large variability in prostate shapes. This paper develops a novel 3D deep neural network equipped with attention modules for better prostate segmentation in TRUS by fully exploiting the complementary information encoded in different layers of the convolutional neural network (CNN). Our attention module utilizes the attention mechanism to selectively leverage the multilevel features integrated from different layers to refine the features at each individual layer, suppressing the non-prostate noise at shallow layers of the CNN and increasing more prostate details into features at deep layers. Experimental results on challenging 3D TRUS volumes show that our method attains satisfactory segmentation performance. The proposed attention mechanism is a general strategy to aggregate multi-level deep features and has the potential to be used for other medical image segmentation tasks. The code is publicly available at https://github.com/wulalago/DAF3D.

Yuhao Huang, Ao Chang, Haoran Dou et al.

Accurate segmentation of nodules in both 2D breast ultrasound (BUS) and 3D automated breast ultrasound (ABUS) is crucial for clinical diagnosis and treatment planning. Therefore, developing an automated system for nodule segmentation can enhance user independence and expedite clinical analysis. Unlike fully-supervised learning, weakly-supervised segmentation (WSS) can streamline the laborious and intricate annotation process. However, current WSS methods face challenges in achieving precise nodule segmentation, as many of them depend on inaccurate activation maps or inefficient pseudo-mask generation algorithms. In this study, we introduce a novel multi-agent reinforcement learning-based WSS framework called Flip Learning, which relies solely on 2D/3D boxes for accurate segmentation. Specifically, multiple agents are employed to erase the target from the box to facilitate classification tag flipping, with the erased region serving as the predicted segmentation mask. The key contributions of this research are as follows: (1) Adoption of a superpixel/supervoxel-based approach to encode the standardized environment, capturing boundary priors and expediting the learning process. (2) Introduction of three meticulously designed rewards, comprising a classification score reward and two intensity distribution rewards, to steer the agents' erasing process precisely, thereby avoiding both under- and over-segmentation. (3) Implementation of a progressive curriculum learning strategy to enable agents to interact with the environment in a progressively challenging manner, thereby enhancing learning efficiency. Extensively validated on the large in-house BUS and ABUS datasets, our Flip Learning method outperforms state-of-the-art WSS methods and foundation models, and achieves comparable performance as fully-supervised learning algorithms.

Fengming Lin, Arezoo Zakeri, Yidan Xue et al.

Deep learning-based medical image-to-mesh reconstruction has rapidly evolved, enabling the transformation of medical imaging data into three-dimensional mesh models that are critical in computational medicine and in silico trials for advancing our understanding of disease mechanisms, and diagnostic and therapeutic techniques in modern medicine. This survey systematically categorizes existing approaches into four main categories: template models, statistical models, generative models, and implicit models. Each category is analysed in detail, examining their methodological foundations, strengths, limitations, and applicability to different anatomical structures and imaging modalities. We provide an extensive evaluation of these methods across various anatomical applications, from cardiac imaging to neurological studies, supported by quantitative comparisons using standard metrics. Additionally, we compile and analyze major public datasets available for medical mesh reconstruction tasks and discuss commonly used evaluation metrics and loss functions. The survey identifies current challenges in the field, including requirements for topological correctness, geometric accuracy, and multi-modality integration. Finally, we present promising future research directions in this domain. This systematic review aims to serve as a comprehensive reference for researchers and practitioners in medical image analysis and computational medicine.

Fengming Lin, Yan Xia, Michael MacRaild et al.

Unsupervised domain adaptation (UDA) aims to align the labelled source distribution with the unlabelled target distribution to obtain domain-invariant predictive models. Since cross-modality medical data exhibit significant intra and inter-domain shifts and most are unlabelled, UDA is more important while challenging in medical image analysis. This paper proposes a simple yet potent contrastive learning framework for UDA to narrow the inter-domain gap between labelled source and unlabelled target distribution. Our method is validated on cerebral vessel datasets. Experimental results show that our approach can learn latent features from labelled 3DRA modality data and improve vessel segmentation performance in unlabelled MRA modality data.

Yuanji Zhang, Yuhao Huang, Haoran Dou et al.

Orofacial clefts are among the most common congenital craniofacial abnormalities, yet accurate prenatal detection remains challenging due to the scarcity of experienced specialists and the relative rarity of the condition. Early and reliable diagnosis is essential to enable timely clinical intervention and reduce associated morbidity. Here we show that an artificial intelligence system, trained on over 45,139 ultrasound images from 9,215 fetuses across 22 hospitals, can diagnose fetal orofacial clefts with sensitivity and specificity exceeding 93% and 95% respectively, matching the performance of senior radiologists and substantially outperforming junior radiologists. When used as a medical copilot, the system raises junior radiologists' sensitivity by more than 6%. Beyond direct diagnostic assistance, the system also accelerates the development of clinical expertise. A pilot study involving 24 radiologists and trainees demonstrated that the model can improve the expertise development for rare conditions. This dual-purpose approach offers a scalable solution for improving both diagnostic accuracy and specialist training in settings where experienced radiologists are scarce.

Ziwei Zou, Bei Zou, Xiaoyan Kui et al.

Atlas construction is fundamental to medical image analysis, offering a standardized spatial reference for tasks such as population-level anatomical modeling. While data-driven registration methods have recently shown promise in pairwise settings, their reliance on large training datasets, limited generalizability, and lack of true inference phases in groupwise contexts hinder their practical use. In contrast, model-driven methods offer training-free, theoretically grounded, and data-efficient alternatives, though they often face scalability and optimization challenges when applied to large 3D datasets. In this work, we introduce DARC (Diffeomorphic Atlas Registration via Coordinate descent), a novel model-driven groupwise registration framework for atlas construction. DARC supports a broad range of image dissimilarity metrics and efficiently handles arbitrary numbers of 3D images without incurring GPU memory issues. Through a coordinate descent strategy and a centrality-enforcing activation function, DARC produces unbiased, diffeomorphic atlases with high anatomical fidelity. Beyond atlas construction, we demonstrate two key applications: (1) One-shot segmentation, where labels annotated only on the atlas are propagated to subjects via inverse deformations, outperforming state-of-the-art few-shot methods; and (2) shape synthesis, where new anatomical variants are generated by warping the atlas mesh using synthesized diffeomorphic deformation fields. Overall, DARC offers a flexible, generalizable, and resource-efficient framework for atlas construction and applications.

Junxuan Yu, Yaofei Duan, Yuhao Huang et al.

Echocardiography is routine for cardiac examination. However, 2D ultrasound (US) struggles with accurate metric calculation and direct observation of 3D cardiac structures. Moreover, 3D US is limited by low resolution, small field of view and scarce availability in practice. Constructing the cardiac anatomical twin from 2D images is promising to provide precise treatment planning and clinical quantification. However, it remains challenging due to the rare paired data, complex structures, and US noises. In this study, we introduce a novel generative framework UltraTwin, to obtain cardiac anatomical twin from sparse multi-view 2D US. Our contribution is three-fold. First, pioneered the construction of a real-world and high-quality dataset containing strictly paired multi-view 2D US and CT, and pseudo-paired data. Second, we propose a coarse-to-fine scheme to achieve hierarchical reconstruction optimization. Last, we introduce an implicit autoencoder for topology-aware constraints. Extensive experiments show that UltraTwin reconstructs high-quality anatomical twins versus strong competitors. We believe it advances anatomical twin modeling for potential applications in personalized cardiac care.

Xinrui Zhou, Yuhao Huang, Wufeng Xue et al.

Echocardiography (ECHO) video is widely used for cardiac examination. In clinical, this procedure heavily relies on operator experience, which needs years of training and maybe the assistance of deep learning-based systems for enhanced accuracy and efficiency. However, it is challenging since acquiring sufficient customized data (e.g., abnormal cases) for novice training and deep model development is clinically unrealistic. Hence, controllable ECHO video synthesis is highly desirable. In this paper, we propose a novel diffusion-based framework named HeartBeat towards controllable and high-fidelity ECHO video synthesis. Our highlight is three-fold. First, HeartBeat serves as a unified framework that enables perceiving multimodal conditions simultaneously to guide controllable generation. Second, we factorize the multimodal conditions into local and global ones, with two insertion strategies separately provided fine- and coarse-grained controls in a composable and flexible manner. In this way, users can synthesize ECHO videos that conform to their mental imagery by combining multimodal control signals. Third, we propose to decouple the visual concepts and temporal dynamics learning using a two-stage training scheme for simplifying the model training. One more interesting thing is that HeartBeat can easily generalize to mask-guided cardiac MRI synthesis in a few shots, showcasing its scalability to broader applications. Extensive experiments on two public datasets show the efficacy of the proposed HeartBeat.

Fengming Lin, Yan Xia, Michael MacRaild et al.

The automated segmentation of cerebral aneurysms is pivotal for accurate diagnosis and treatment planning. Confronted with significant domain shifts and class imbalance in 3D Rotational Angiography (3DRA) data from various medical institutions, the task becomes challenging. These shifts include differences in image appearance, intensity distribution, resolution, and aneurysm size, all of which complicate the segmentation process. To tackle these issues, we propose a novel domain generalization strategy that employs gradient surgery exponential moving average (GS-EMA) optimization technique coupled with boundary-aware contrastive learning (BACL). Our approach is distinct in its ability to adapt to new, unseen domains by learning domain-invariant features, thereby improving the robustness and accuracy of aneurysm segmentation across diverse clinical datasets. The results demonstrate that our proposed approach can extract more domain-invariant features, minimizing over-segmentation and capturing more complete aneurysm structures.

Luyi Han, Haoran Dou, Yunzhi Huang et al.

Unsupervised learning strategy is widely adopted by the deformable registration models due to the lack of ground truth of deformation fields. These models typically depend on the intensity-based similarity loss to obtain the learning convergence. Despite the success, such dependence is insufficient. For the deformable registration of mono-modality image, well-aligned two images not only have indistinguishable intensity differences, but also are close in the statistical distribution and the boundary areas. Considering that well-designed loss functions can facilitate a learning model into a desirable convergence, we learn a deformable registration model for T1-weighted MR images by integrating multiple image characteristics via a hybrid loss. Our method registers the OASIS dataset with high accuracy while preserving deformation smoothness.

Yuhao Huang, Xin Yang, Yuxin Zou et al.

Nodule segmentation from breast ultrasound images is challenging yet essential for the diagnosis. Weakly-supervised segmentation (WSS) can help reduce time-consuming and cumbersome manual annotation. Unlike existing weakly-supervised approaches, in this study, we propose a novel and general WSS framework called Flip Learning, which only needs the box annotation. Specifically, the target in the label box will be erased gradually to flip the classification tag, and the erased region will be considered as the segmentation result finally. Our contribution is three-fold. First, our proposed approach erases on superpixel level using a Multi-agent Reinforcement Learning framework to exploit the prior boundary knowledge and accelerate the learning process. Second, we design two rewards: classification score and intensity distribution reward, to avoid under- and over-segmentation, respectively. Third, we adopt a coarse-to-fine learning strategy to reduce the residual errors and improve the segmentation performance. Extensively validated on a large dataset, our proposed approach achieves competitive performance and shows great potential to narrow the gap between fully-supervised and weakly-supervised learning.

Xin Yang, Yuhao Huang, Ruobing Huang et al.

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.

Xin Yang, Haoran Dou, Ruobing Huang et al.

Accurate standard plane (SP) localization is the fundamental step for prenatal ultrasound (US) diagnosis. Typically, dozens of US SPs are collected to determine the clinical diagnosis. 2D US has to perform scanning for each SP, which is time-consuming and operator-dependent. While 3D US containing multiple SPs in one shot has the inherent advantages of less user-dependency and more efficiency. Automatically locating SP in 3D US is very challenging due to the huge search space and large fetal posture variations. Our previous study proposed a deep reinforcement learning (RL) framework with an alignment module and active termination to localize SPs in 3D US automatically. However, termination of agent search in RL is important and affects the practical deployment. In this study, we enhance our previous RL framework with a newly designed adaptive dynamic termination to enable an early stop for the agent searching, saving at most 67% inference time, thus boosting the accuracy and efficiency of the RL framework at the same time. Besides, we validate the effectiveness and generalizability of our algorithm extensively on our in-house multi-organ datasets containing 433 fetal brain volumes, 519 fetal abdomen volumes, and 683 uterus volumes. Our approach achieves localization error of 2.52mm/10.26 degrees, 2.48mm/10.39 degrees, 2.02mm/10.48 degrees, 2.00mm/14.57 degrees, 2.61mm/9.71 degrees, 3.09mm/9.58 degrees, 1.49mm/7.54 degrees for the transcerebellar, transventricular, transthalamic planes in fetal brain, abdominal plane in fetal abdomen, and mid-sagittal, transverse and coronal planes in uterus, respectively. Experimental results show that our method is general and has the potential to improve the efficiency and standardization of US scanning.

Haoming Li, Xin Yang, Jiamin Liang et al.

Ultrasound (US) image segmentation embraced its significant improvement in deep learning era. However, the lack of sharp boundaries in US images still remains an inherent challenge for segmentation. Previous methods often resort to global context, multi-scale cues or auxiliary guidance to estimate the boundaries. It is hard for these methods to approach pixel-level learning for fine-grained boundary generating. In this paper, we propose a novel and effective framework to improve boundary estimation in US images. Our work has three highlights. First, we propose to formulate the boundary estimation as a rendering task, which can recognize ambiguous points (pixels/voxels) and calibrate the boundary prediction via enriched feature representation learning. Second, we introduce point-wise contrastive learning to enhance the similarity of points from the same class and contrastively decrease the similarity of points from different classes. Boundary ambiguities are therefore further addressed. Third, both rendering and contrastive learning tasks contribute to consistent improvement while reducing network parameters. As a proof-of-concept, we performed validation experiments on a challenging dataset of 86 ovarian US volumes. Results show that our proposed method outperforms state-of-the-art methods and has the potential to be used in clinical practice.

Yuhao Huang, Xin Yang, Rui Li et al.

3D ultrasound (US) is widely used due to its rich diagnostic information, portability and low cost. Automated standard plane (SP) localization in US volume not only improves efficiency and reduces user-dependence, but also boosts 3D US interpretation. In this study, we propose a novel Multi-Agent Reinforcement Learning (MARL) framework to localize multiple uterine SPs in 3D US simultaneously. Our contribution is two-fold. First, we equip the MARL with a one-shot neural architecture search (NAS) module to obtain the optimal agent for each plane. Specifically, Gradient-based search using Differentiable Architecture Sampler (GDAS) is employed to accelerate and stabilize the training process. Second, we propose a novel collaborative strategy to strengthen agents' communication. Our strategy uses recurrent neural network (RNN) to learn the spatial relationship among SPs effectively. Extensively validated on a large dataset, our approach achieves the accuracy of 7.05 degree/2.21mm, 8.62 degree/2.36mm and 5.93 degree/0.89mm for the mid-sagittal, transverse and coronal plane localization, respectively. The proposed MARL framework can significantly increase the plane localization accuracy and reduce the computational cost and model size.

Xin Yang, Xu Wang, Yi Wang et al.

Background and Objective: Biometric measurements of fetal head are important indicators for maternal and fetal health monitoring during pregnancy. 3D ultrasound (US) has unique advantages over 2D scan in covering the whole fetal head and may promote the diagnoses. However, automatically segmenting the whole fetal head in US volumes still pends as an emerging and unsolved problem. The challenges that automated solutions need to tackle include the poor image quality, boundary ambiguity, long-span occlusion, and the appearance variability across different fetal poses and gestational ages. In this paper, we propose the first fully-automated solution to segment the whole fetal head in US volumes. Methods: The segmentation task is firstly formulated as an end-to-end volumetric mapping under an encoder-decoder deep architecture. We then combine the segmentor with a proposed hybrid attention scheme (HAS) to select discriminative features and suppress the non-informative volumetric features in a composite and hierarchical way. With little computation overhead, HAS proves to be effective in addressing boundary ambiguity and deficiency. To enhance the spatial consistency in segmentation, we further organize multiple segmentors in a cascaded fashion to refine the results by revisiting context in the prediction of predecessors. Results: Validated on a large dataset collected from 100 healthy volunteers, our method presents superior segmentation performance (DSC (Dice Similarity Coefficient), 96.05%), remarkable agreements with experts. With another 156 volumes collected from 52 volunteers, we ahieve high reproducibilities (mean standard deviation 11.524 mL) against scan variations. Conclusion: This is the first investigation about whole fetal head segmentation in 3D US. Our method is promising to be a feasible solution in assisting the volumetric US-based prenatal studies.

Haoran Dou, Davood Karimi, Caitlin K. Rollins et al.

Fetal cortical plate segmentation is essential in quantitative analysis of fetal brain maturation and cortical folding. Manual segmentation of the cortical plate, or manual refinement of automatic segmentations is tedious and time-consuming. Automatic segmentation of the cortical plate, on the other hand, is challenged by the relatively low resolution of the reconstructed fetal brain MRI scans compared to the thin structure of the cortical plate, partial voluming, and the wide range of variations in the morphology of the cortical plate as the brain matures during gestation. To reduce the burden of manual refinement of segmentations, we have developed a new and powerful deep learning segmentation method. Our method exploits new deep attentive modules with mixed kernel convolutions within a fully convolutional neural network architecture that utilizes deep supervision and residual connections. We evaluated our method quantitatively based on several performance measures and expert evaluations. Results show that our method outperforms several state-of-the-art deep models for segmentation, as well as a state-of-the-art multi-atlas segmentation technique. We achieved average Dice similarity coefficient of 0.87, average Hausdorff distance of 0.96 mm, and average symmetric surface difference of 0.28 mm on reconstructed fetal brain MRI scans of fetuses scanned in the gestational age range of 16 to 39 weeks. With a computation time of less than 1 minute per fetal brain, our method can facilitate and accelerate large-scale studies on normal and altered fetal brain cortical maturation and folding.

Jiamin Liang, Xin Yang, Haoming Li et al.

Ultrasound (US) is widely accepted in clinic for anatomical structure inspection. However, lacking in resources to practice US scan, novices often struggle to learn the operation skills. Also, in the deep learning era, automated US image analysis is limited by the lack of annotated samples. Efficiently synthesizing realistic, editable and high resolution US images can solve the problems. The task is challenging and previous methods can only partially complete it. In this paper, we devise a new framework for US image synthesis. Particularly, we firstly adopt a sketch generative adversarial networks (Sgan) to introduce background sketch upon object mask in a conditioned generative adversarial network. With enriched sketch cues, Sgan can generate realistic US images with editable and fine-grained structure details. Although effective, Sgan is hard to generate high resolution US images. To achieve this, we further implant the Sgan into a progressive growing scheme (PGSgan). By smoothly growing both generator and discriminator, PGSgan can gradually synthesize US images from low to high resolution. By synthesizing ovary and follicle US images, our extensive perceptual evaluation, user study and segmentation results prove the promising efficacy and efficiency of the proposed PGSgan.

Zhendong Liu, Xin Yang, Rui Gao et al.

Deep Neural Networks (DNNs) suffer from the performance degradation when image appearance shift occurs, especially in ultrasound (US) image segmentation. In this paper, we propose a novel and intuitive framework to remove the appearance shift, and hence improve the generalization ability of DNNs. Our work has three highlights. First, we follow the spirit of universal style transfer to remove appearance shifts, which was not explored before for US images. Without sacrificing image structure details, it enables the arbitrary style-content transfer. Second, accelerated with Adaptive Instance Normalization block, our framework achieved real-time speed required in the clinical US scanning. Third, an efficient and effective style image selection strategy is proposed to ensure the target-style US image and testing content US image properly match each other. Experiments on two large US datasets demonstrate that our methods are superior to state-of-the-art methods on making DNNs robust against various appearance shifts.

Davood Karimi, Haoran Dou, Simon K. Warfield et al.

Supervised training of deep learning models requires large labeled datasets. There is a growing interest in obtaining such datasets for medical image analysis applications. However, the impact of label noise has not received sufficient attention. Recent studies have shown that label noise can significantly impact the performance of deep learning models in many machine learning and computer vision applications. This is especially concerning for medical applications, where datasets are typically small, labeling requires domain expertise and suffers from high inter- and intra-observer variability, and erroneous predictions may influence decisions that directly impact human health. In this paper, we first review the state-of-the-art in handling label noise in deep learning. Then, we review studies that have dealt with label noise in deep learning for medical image analysis. Our review shows that recent progress on handling label noise in deep learning has gone largely unnoticed by the medical image analysis community. To help achieve a better understanding of the extent of the problem and its potential remedies, we conducted experiments with three medical imaging datasets with different types of label noise, where we investigated several existing strategies and developed new methods to combat the negative effect of label noise. Based on the results of these experiments and our review of the literature, we have made recommendations on methods that can be used to alleviate the effects of different types of label noise on deep models trained for medical image analysis. We hope that this article helps the medical image analysis researchers and developers in choosing and devising new techniques that effectively handle label noise in deep learning.

Xin Yang, Wenlong Shi, Haoran Dou et al.

The 3D ultrasound (US) entrance inspires a multitude of automated prenatal examinations. However, studies about the structuralized description of the whole fetus in 3D US are still rare. In this paper, we propose to estimate the 3D pose of fetus in US volumes to facilitate its quantitative analyses in global and local scales. Given the great challenges in 3D US, including the high volume dimension, poor image quality, symmetric ambiguity in anatomical structures and large variations of fetal pose, our contribution is three-fold. (i) This is the first work about 3D pose estimation of fetus in the literature. We aim to extract the skeleton of whole fetus and assign different segments/joints with correct torso/limb labels. (ii) We propose a self-supervised learning (SSL) framework to finetune the deep network to form visually plausible pose predictions. Specifically, we leverage the landmark-based registration to effectively encode case-adaptive anatomical priors and generate evolving label proxy for supervision. (iii) To enable our 3D network perceive better contextual cues with higher resolution input under limited computing resource, we further adopt the gradient check-pointing (GCP) strategy to save GPU memory and improve the prediction. Extensively validated on a large 3D US dataset, our method tackles varying fetal poses and achieves promising results. 3D pose estimation of fetus has potentials in serving as a map to provide navigation for many advanced studies.

Haoran Dou, Xin Yang, Jikuan Qian et al.

Standard plane localization is crucial for ultrasound (US) diagnosis. In prenatal US, dozens of standard planes are manually acquired with a 2D probe. It is time-consuming and operator-dependent. In comparison, 3D US containing multiple standard planes in one shot has the inherent advantages of less user-dependency and more efficiency. However, manual plane localization in US volume is challenging due to the huge search space and large fetal posture variation. In this study, we propose a novel reinforcement learning (RL) framework to automatically localize fetal brain standard planes in 3D US. Our contribution is two-fold. First, we equip the RL framework with a landmark-aware alignment module to provide warm start and strong spatial bounds for the agent actions, thus ensuring its effectiveness. Second, instead of passively and empirically terminating the agent inference, we propose a recurrent neural network based strategy for active termination of the agent's interaction procedure. This improves both the accuracy and efficiency of the localization system. Extensively validated on our in-house large dataset, our approach achieves the accuracy of 3.4mm/9.6° and 2.7mm/9.1° for the transcerebellar and transthalamic plane localization, respectively. Ourproposed RL framework is general and has the potential to improve the efficiency and standardization of US scanning.

Xu Wang, Xin Yang, Haoran Dou et al.

Volumetric ultrasound has great potentials in promoting prenatal examinations. Automated solutions are highly desired to efficiently and effectively analyze the massive volumes. Segmentation and landmark localization are two key techniques in making the quantitative evaluation of prenatal ultrasound volumes available in clinic. However, both tasks are non-trivial when considering the poor image quality, boundary ambiguity and anatomical variations in volumetric ultrasound. In this paper, we propose an effective framework for simultaneous segmentation and landmark localization in prenatal ultrasound volumes. The proposed framework has two branches where informative cues of segmentation and landmark localization can be propagated bidirectionally to benefit both tasks. As landmark localization tends to suffer from false positives, we propose a distance based loss to suppress the noise and thus enhance the localization map and in turn the segmentation. Finally, we further leverage an adversarial module to emphasize the correspondence between segmentation and landmark localization. Extensively validated on a volumetric ultrasound dataset of fetal femur, our proposed framework proves to be a promising solution to facilitate the interpretation of prenatal ultrasound volumes.