Qian Tao

Yunjie Chen, Marius Staring, Olaf M. Neve et al.

Multi-sequence magnetic resonance imaging (MRI) has found wide applications in both modern clinical studies and deep learning research. However, in clinical practice, it frequently occurs that one or more of the MRI sequences are missing due to different image acquisition protocols or contrast agent contraindications of patients, limiting the utilization of deep learning models trained on multi-sequence data. One promising approach is to leverage generative models to synthesize the missing sequences, which can serve as a surrogate acquisition. State-of-the-art methods tackling this problem are based on convolutional neural networks (CNN) which usually suffer from spectral biases, resulting in poor reconstruction of high-frequency fine details. In this paper, we propose Conditional Neural fields with Shift modulation (CoNeS), a model that takes voxel coordinates as input and learns a representation of the target images for multi-sequence MRI translation. The proposed model uses a multi-layer perceptron (MLP) instead of a CNN as the decoder for pixel-to-pixel mapping. Hence, each target image is represented as a neural field that is conditioned on the source image via shift modulation with a learned latent code. Experiments on BraTS 2018 and an in-house clinical dataset of vestibular schwannoma patients showed that the proposed method outperformed state-of-the-art methods for multi-sequence MRI translation both visually and quantitatively. Moreover, we conducted spectral analysis, showing that CoNeS was able to overcome the spectral bias issue common in conventional CNN models. To further evaluate the usage of synthesized images in clinical downstream tasks, we tested a segmentation network using the synthesized images at inference.

Yidong Zhao, Changchun Yang, Artur Schweidtmann et al.

The self-configuring nnU-Net has achieved leading performance in a large range of medical image segmentation challenges. It is widely considered as the model of choice and a strong baseline for medical image segmentation. However, despite its extraordinary performance, nnU-Net does not supply a measure of uncertainty to indicate its possible failure. This can be problematic for large-scale image segmentation applications, where data are heterogeneous and nnU-Net may fail without notice. In this work, we introduce a novel method to estimate nnU-Net uncertainty for medical image segmentation. We propose a highly effective scheme for posterior sampling of weight space for Bayesian uncertainty estimation. Different from previous baseline methods such as Monte Carlo Dropout and mean-field Bayesian Neural Networks, our proposed method does not require a variational architecture and keeps the original nnU-Net architecture intact, thereby preserving its excellent performance and ease of use. Additionally, we boost the segmentation performance over the original nnU-Net via marginalizing multi-modal posterior models. We applied our method on the public ACDC and M&M datasets of cardiac MRI and demonstrated improved uncertainty estimation over a range of baseline methods. The proposed method further strengthens nnU-Net for medical image segmentation in terms of both segmentation accuracy and quality control.

Yunjie Chen, Jelmer M. Wolterink, Olaf M. Neve et al.

Vestibular schwannomas (VS) are benign tumors that are generally managed by active surveillance with MRI examination. To further assist clinical decision-making and avoid overtreatment, an accurate prediction of tumor growth based on longitudinal imaging is highly desirable. In this paper, we introduce DeepGrowth, a deep learning method that incorporates neural fields and recurrent neural networks for prospective tumor growth prediction. In the proposed method, each tumor is represented as a signed distance function (SDF) conditioned on a low-dimensional latent code. Unlike previous studies that perform tumor shape prediction directly in the image space, we predict the latent codes instead and then reconstruct future shapes from it. To deal with irregular time intervals, we introduce a time-conditioned recurrent module based on a ConvLSTM and a novel temporal encoding strategy, which enables the proposed model to output varying tumor shapes over time. The experiments on an in-house longitudinal VS dataset showed that the proposed model significantly improved the performance ($\ge 1.6\%$ Dice score and $\ge0.20$ mm 95\% Hausdorff distance), in particular for top 20\% tumors that grow or shrink the most ($\ge 4.6\%$ Dice score and $\ge 0.73$ mm 95\% Hausdorff distance). Our code is available at ~\burl{https://github.com/cyjdswx/DeepGrowth}

Yidong Zhao, Joao Tourais, Iain Pierce et al.

Deep learning (DL)-based methods have achieved state-of-the-art performance for many medical image segmentation tasks. Nevertheless, recent studies show that deep neural networks (DNNs) can be miscalibrated and overconfident, leading to "silent failures" that are risky for clinical applications. Bayesian DL provides an intuitive approach to DL failure detection, based on posterior probability estimation. However, the posterior is intractable for large medical image segmentation DNNs. To tackle this challenge, we propose a Bayesian learning framework using Hamiltonian Monte Carlo (HMC), tempered by cold posterior (CP) to accommodate medical data augmentation, named HMC-CP. For HMC computation, we further propose a cyclical annealing strategy, capturing both local and global geometries of the posterior distribution, enabling highly efficient Bayesian DNN training with the same computational budget as training a single DNN. The resulting Bayesian DNN outputs an ensemble segmentation along with the segmentation uncertainty. We evaluate the proposed HMC-CP extensively on cardiac magnetic resonance image (MRI) segmentation, using in-domain steady-state free precession (SSFP) cine images as well as out-of-domain datasets of quantitative T1 and T2 mapping. Our results show that the proposed method improves both segmentation accuracy and uncertainty estimation for in- and out-of-domain data, compared with well-established baseline methods such as Monte Carlo Dropout and Deep Ensembles. Additionally, we establish a conceptual link between HMC and the commonly known stochastic gradient descent (SGD) and provide general insight into the uncertainty of DL. This uncertainty is implicitly encoded in the training dynamics but often overlooked. With reliable uncertainty estimation, our method provides a promising direction toward trustworthy DL in clinical applications.

Yidong Zhao, Yi Zhang, Qian Tao

Deep learning-based methods have achieved prestigious performance for magnetic resonance imaging (MRI) reconstruction, enabling fast imaging for many clinical applications. Previous methods employ convolutional networks to learn the image prior as the regularization term. In quantitative MRI, the physical model of nuclear magnetic resonance relaxometry is known, providing additional prior knowledge for image reconstruction. However, traditional reconstruction networks are limited to learning the spatial domain prior knowledge, ignoring the relaxometry prior. Therefore, we propose a relaxometry-guided quantitative MRI reconstruction framework to learn the spatial prior from data and the relaxometry prior from MRI physics. Additionally, we also evaluated the performance of two popular reconstruction backbones, namely, recurrent variational networks (RVN) and variational networks (VN) with U- Net. Experiments demonstrate that the proposed method achieves highly promising results in quantitative MRI reconstruction.

Yi Zhang, Yidong Zhao, Qian Tao

Deformable image registration is inherently a multi-objective optimization (MOO) problem, requiring a delicate balance between image similarity and deformation regularity. These conflicting objectives often lead to poor optimization outcomes, such as being trapped in unsatisfactory local minima or experiencing slow convergence. Deep learning methods have recently gained popularity in this domain due to their efficiency in processing large datasets and achieving high accuracy. However, they often underperform during test time compared to traditional optimization techniques, which further explore iterative, instance-specific gradient-based optimization. This performance gap is more pronounced when a distribution shift between training and test data exists. To address this issue, we focus on the instance optimization (IO) paradigm, which involves additional optimization for test-time instances based on a pre-trained model. IO effectively combines the generalization capabilities of deep learning with the fine-tuning advantages of instance-specific optimization. Within this framework, we emphasize the use of gradient projection to mitigate conflicting updates in MOO. This technique projects conflicting gradients into a common space, better aligning the dual objectives and enhancing optimization stability. We validate our method using a state-of-the-art foundation model on the 3D Brain inter-subject registration task (LUMIR) from the Learn2Reg 2024 Challenge. Our results show significant improvements over standard gradient descent, leading to more accurate and reliable registration results.

Nuno Capitão, Yi Zhang, Yidong Zhao et al.

Spin-lattice relaxation time ($T_1$) is an important biomarker in cardiac parametric mapping for characterizing myocardial tissue and diagnosing cardiomyopathies. Conventional Modified Look-Locker Inversion Recovery (MOLLI) acquires 11 breath-hold baseline images with interleaved rest periods to ensure mapping accuracy. However, prolonged scanning can be challenging for patients with poor breathholds, often leading to motion artifacts that degrade image quality. In addition, $T_1$ mapping requires voxel-wise nonlinear fitting to a signal recovery model involving an iterative estimation process. Recent studies have proposed deep-learning approaches for rapid $T_1$ mapping using shortened sequences to reduce acquisition time for patient comfort. Nevertheless, existing methods overlook important physics constraints, limiting interpretability and generalization. In this work, we present an accelerated, end-to-end $T_1$ mapping framework leveraging Physics-Informed Neural Ordinary Differential Equations (ODEs) to model temporal dynamics and address these challenges. Our method achieves high-accuracy $T_1$ estimation from a sparse subset of baseline images and ensures efficient null index estimation at test time. Specifically, we develop a continuous-time LSTM-ODE model to enable selective Look-Locker (LL) data acquisition with arbitrary time lags. Experimental results show superior performance in $T_1$ estimation for both native and post-contrast sequences and demonstrate the strong benefit of our physics-based formulation over direct data-driven $T_1$ priors.

Yi Zhang, Yidong Zhao, Qian Tao

Deformable medical image registration is traditionally formulated as an optimization problem. While classical methods solve this problem iteratively, recent learning-based approaches use recurrent neural networks (RNNs) to mimic this process by unrolling the prediction of deformation fields in a fixed number of steps. However, classical methods typically converge after sufficient iterations, but learning-based unrolling methods lack a theoretical convergence guarantee and show instability empirically. In addition, unrolling methods have a practical bottleneck at training time: GPU memory usage grows linearly with the unrolling steps due to backpropagation through time (BPTT). To address both theoretical and practical challenges, we propose DEQReg, a novel registration framework based on Deep Equilibrium Models (DEQ), which formulates registration as an equilibrium-seeking problem, establishing a natural connection between classical optimization and learning-based unrolling methods. DEQReg maintains constant memory usage, enabling theoretically unlimited iteration steps. Through extensive evaluation on the public brain MRI and lung CT datasets, we show that DEQReg can achieve competitive registration performance, while substantially reducing memory consumption compared to state-of-the-art unrolling methods. We also reveal an intriguing phenomenon: the performance of existing unrolling methods first increases slightly then degrades irreversibly when the inference steps go beyond the training configuration. In contrast, DEQReg achieves stable convergence with its inbuilt equilibrium-seeking mechanism, bridging the gap between classical optimization-based and modern learning-based registration methods.

Yi Zhang, Yidong Zhao, Hui Xue et al.

Image registration is essential for medical image applications where alignment of voxels across multiple images is needed for qualitative or quantitative analysis. With recent advancements in deep neural networks and parallel computing, deep learning-based medical image registration methods become competitive with their flexible modelling and fast inference capabilities. However, compared to traditional optimization-based registration methods, the speed advantage may come at the cost of registration performance at inference time. Besides, deep neural networks ideally demand large training datasets while optimization-based methods are training-free. To improve registration accuracy and data efficiency, we propose a novel image registration method, termed Recurrent Inference Image Registration (RIIR) network. RIIR is formulated as a meta-learning solver to the registration problem in an iterative manner. RIIR addresses the accuracy and data efficiency issues, by learning the update rule of optimization, with implicit regularization combined with explicit gradient input. We evaluated RIIR extensively on brain MRI and quantitative cardiac MRI datasets, in terms of both registration accuracy and training data efficiency. Our experiments showed that RIIR outperformed a range of deep learning-based methods, even with only $5\%$ of the training data, demonstrating high data efficiency. Key findings from our ablation studies highlighted the important added value of the hidden states introduced in the recurrent inference framework for meta-learning. Our proposed RIIR offers a highly data-efficient framework for deep learning-based medical image registration.

Yi Zhang, Yidong Zhao, Lu Huang et al.

Quantitative $T_1$ mapping by MRI is an increasingly important tool for clinical assessment of cardiovascular diseases. The cardiac $T_1$ map is derived by fitting a known signal model to a series of baseline images, while the quality of this map can be deteriorated by involuntary respiratory and cardiac motion. To correct motion, a template image is often needed to register all baseline images, but the choice of template is nontrivial, leading to inconsistent performance sensitive to image contrast. In this work, we propose a novel deep-learning-based groupwise registration framework, which omits the need for a template, and registers all baseline images simultaneously. We design two groupwise losses for this registration framework: the first is a linear principal component analysis (PCA) loss that enforces alignment of baseline images irrespective of the intensity variation, and the second is an auxiliary relaxometry loss that enforces adherence of intensity profile to the signal model. We extensively evaluated our method, termed ``PCA-Relax'', and other baseline methods on an in-house cardiac MRI dataset including both pre- and post-contrast $T_1$ sequences. All methods were evaluated under three distinct training-and-evaluation strategies, namely, standard, one-shot, and test-time-adaptation. The proposed PCA-Relax showed further improved performance of registration and mapping over well-established baselines. The proposed groupwise framework is generic and can be adapted to applications involving multiple images.

Shuai Guo, Jiatong Shi, Tao Qian et al.

Deep learning based singing voice synthesis (SVS) systems have been demonstrated to flexibly generate singing with better qualities, compared to conventional statistical parametric based methods. However, neural systems are generally data-hungry and have difficulty to reach reasonable singing quality with limited public available training data. In this work, we explore different data augmentation methods to boost the training of SVS systems, including several strategies customized to SVS based on pitch augmentation and mix-up augmentation. To further stabilize the training, we introduce the cycle-consistent training strategy. Extensive experiments on two public singing databases demonstrate that our proposed augmentation methods and the stabilizing training strategy can significantly improve the performance on both objective and subjective evaluations.

Zixia Zhou, Yuanyuan Wang, Boudewijn P. F. Lelieveldt et al.

t-distributed stochastic neighbor embedding (t-SNE) is a well-established visualization method for complex high-dimensional data. However, the original t-SNE method is nonparametric, stochastic, and often cannot well prevserve the global structure of data as it emphasizes local neighborhood. With t-SNE as a reference, we propose to combine the deep neural network (DNN) with the mathematical-grounded embedding rules for high-dimensional data embedding. We first introduce a deep embedding network (DEN) framework, which can learn a parametric mapping from high-dimensional space to low-dimensional embedding. DEN has a flexible architecture that can accommodate different input data (vector, image, or tensor) and loss functions. To improve the embedding performance, a recursive training strategy is proposed to make use of the latent representations extracted by DEN. Finally, we propose a two-stage loss function combining the advantages of two popular embedding methods, namely, t-SNE and uniform manifold approximation and projection (UMAP), for optimal visualization effect. We name the proposed method Deep Recursive Embedding (DRE), which optimizes DEN with a recursive training strategy and two-stage losse. Our experiments demonstrated the excellent performance of the proposed DRE method on high-dimensional data embedding, across a variety of public databases. Remarkably, our comparative results suggested that our proposed DRE could lead to improved global structure preservation.

Zhaohan Xiong, Qing Xia, Zhiqiang Hu et al.

Segmentation of cardiac images, particularly late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) widely used for visualizing diseased cardiac structures, is a crucial first step for clinical diagnosis and treatment. However, direct segmentation of LGE-MRIs is challenging due to its attenuated contrast. Since most clinical studies have relied on manual and labor-intensive approaches, automatic methods are of high interest, particularly optimized machine learning approaches. To address this, we organized the "2018 Left Atrium Segmentation Challenge" using 154 3D LGE-MRIs, currently the world's largest cardiac LGE-MRI dataset, and associated labels of the left atrium segmented by three medical experts, ultimately attracting the participation of 27 international teams. In this paper, extensive analysis of the submitted algorithms using technical and biological metrics was performed by undergoing subgroup analysis and conducting hyper-parameter analysis, offering an overall picture of the major design choices of convolutional neural networks (CNNs) and practical considerations for achieving state-of-the-art left atrium segmentation. Results show the top method achieved a dice score of 93.2% and a mean surface to a surface distance of 0.7 mm, significantly outperforming prior state-of-the-art. Particularly, our analysis demonstrated that double, sequentially used CNNs, in which a first CNN is used for automatic region-of-interest localization and a subsequent CNN is used for refined regional segmentation, achieved far superior results than traditional methods and pipelines containing single CNNs. This large-scale benchmarking study makes a significant step towards much-improved segmentation methods for cardiac LGE-MRIs, and will serve as an important benchmark for evaluating and comparing the future works in the field.

Wenjun Yan, Yuanyuan Wang, Shengjia Gu et al.

Convolutional neural network (CNN), in particular the Unet, is a powerful method for medical image segmentation. To date Unet has demonstrated state-of-art performance in many complex medical image segmentation tasks, especially under the condition when the training and testing data share the same distribution (i.e. come from the same source domain). However, in clinical practice, medical images are acquired from different vendors and centers. The performance of a U-Net trained from a particular source domain, when transferred to a different target domain (e.g. different vendor, acquisition parameter), can drop unexpectedly. Collecting a large amount of annotation from each new domain to retrain the U-Net is expensive, tedious, and practically impossible. In this work, we proposed a generic framework to address this problem, consisting of (1) an unpaired generative adversarial network (GAN) for vendor-adaptation, and (2) a Unet for object segmentation. In the proposed Unet-GAN architecture, GAN learns from Unet at the feature level that is segmentation-specific. We used cardiac cine MRI as the example, with three major vendors (Philips, Siemens, and GE) as three domains, while the methodology can be extended to medical images segmentation in general. The proposed method showed significant improvement of the segmentation results across vendors. The proposed Unet-GAN provides an annotation-free solution to the cross-vendor medical image segmentation problem, potentially extending a trained deep learning model to multi-center and multi-vendor use in real clinical scenario.

Wenjun Yan, Yuanyuan Wang, Zeju Li et al.

Quantitative assessment of left ventricle (LV) function from cine MRI has significant diagnostic and prognostic value for cardiovascular disease patients. The temporal movement of LV provides essential information on the contracting/relaxing pattern of heart, which is keenly evaluated by clinical experts in clinical practice. Inspired by the expert way of viewing Cine MRI, we propose a new CNN module that is able to incorporate the temporal information into LV segmentation from cine MRI. In the proposed CNN, the optical flow (OF) between neighboring frames is integrated and aggregated at feature level, such that temporal coherence in cardiac motion can be taken into account during segmentation. The proposed module is integrated into the U-net architecture without need of additional training. Furthermore, dilated convolution is introduced to improve the spatial accuracy of segmentation. Trained and tested on the Cardiac Atlas database, the proposed network resulted in a Dice index of 95% and an average perpendicular distance of 0.9 pixels for the middle LV contour, significantly outperforming the original U-net that processes each frame individually. Notably, the proposed method improved the temporal coherence of LV segmentation results, especially at the LV apex and base where the cardiac motion is difficult to follow.