Yidong Zhao

Yadi Cao, Sicheng Lai, Jiahe Huang et al.

Evaluating LLM agents for scientific tasks has focused on token costs while ignoring tool-use costs like simulation time and experimental resources. As a result, metrics like pass@k become impractical under realistic budget constraints. To address this gap, we introduce SimulCost, the first benchmark targeting cost-sensitive parameter tuning in physics simulations. SimulCost compares LLM tuning cost-sensitive parameters against traditional scanning approach in both accuracy and computational cost, spanning 2,916 single-round (initial guess) and 1,900 multi-round (adjustment by trial-and-error) tasks across 12 simulators from fluid dynamics, solid mechanics, and plasma physics. Each simulator's cost is analytically defined and platform-independent. Frontier LLMs achieve 46--64% success rates in single-round mode, dropping to 35--54% under high accuracy requirements, rendering their initial guesses unreliable especially for high accuracy tasks. Multi-round mode improves rates to 71--80%, but LLMs are 1.5--2.5x slower than traditional scanning, making them uneconomical choices. We also investigate parameter group correlations for knowledge transfer potential, and the impact of in-context examples and reasoning effort, providing practical implications for deployment and fine-tuning. We open-source SimulCost as a static benchmark and extensible toolkit to facilitate research on improving cost-aware agentic designs for physics simulations, and for expanding new simulation environments. Code and data are available at https://github.com/Rose-STL-Lab/SimulCost-Bench.

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.

Yidong Zhao, Lars Blatny, Xiang Feng et al.

The material point method (MPM) is a hybrid particle-grid method widely used for simulating large deformation with history-dependent behavior. Standard MPM often relies on a dense background grid, which can be highly inefficient when material occupies a small fraction of the computational domain. Such sparsity is common in many large-scale problems, from geophysical mass flows over large terrain domains to visual-computing applications. Here, we introduce a unified sparse background-grid framework for large-scale MPM simulation. The framework treats sparse grid construction as a general active-node indexing problem. We develop two architecture-specific implementations to realize the same sparse framework: a scan-based strategy for CPUs and a hash-based strategy for GPUs. Through benchmark problems and a large-scale landslide simulation, we show that the framework provides the same results as standard dense MPM while reducing computational time and memory usage by one to two orders of magnitude in strongly sparse cases.

Xinqi Li, Yi Zhang, Yidong Zhao et al.

Quantitative cardiac magnetic resonance imaging (MRI) is an increasingly important diagnostic tool for cardiovascular diseases. Yet, co-registration of all baseline images within the quantitative MRI sequence is essential for the accuracy and precision of quantitative maps. However, co-registering all baseline images from a quantitative cardiac MRI sequence remains a nontrivial task because of the simultaneous changes in intensity and contrast, in combination with cardiac and respiratory motion. To address the challenge, we propose a novel motion correction framework based on robust principle component analysis (rPCA) that decomposes quantitative cardiac MRI into low-rank and sparse components, and we integrate the groupwise CNN-based registration backbone within the rPCA framework. The low-rank component of rPCA corresponds to the quantitative mapping (i.e. limited degree of freedom in variation), while the sparse component corresponds to the residual motion, making it easier to formulate and solve the groupwise registration problem. We evaluated our proposed method on cardiac T1 mapping by the modified Look-Locker inversion recovery (MOLLI) sequence, both before and after the Gadolinium contrast agent administration. Our experiments showed that our method effectively improved registration performance over baseline methods without introducing rPCA, and reduced quantitative mapping error in both in-domain (pre-contrast MOLLI) and out-of-domain (post-contrast MOLLI) inference. The proposed rPCA framework is generic and can be integrated with other registration backbones.

Yi Zhang, Yidong Zhao, Qian Tao

Deformable image registration remains a central challenge in medical image analysis, particularly under multi-modal scenarios where intensity distributions vary significantly across scans. While deep learning methods provide efficient feed-forward predictions, they often fail to generalize robustly under distribution shifts at test time. A straightforward remedy is full network fine-tuning, yet for modern architectures such as Transformers or deep U-Nets, this adaptation is prohibitively expensive in both memory and runtime when operating in 3D. Meanwhile, the naive fine-tuning struggles more with potential degradation in performance in the existence of drastic domain shifts. In this work, we propose a registration framework that integrates a frozen pretrained \textbf{mono-modal} registration model with a lightweight adaptation pipeline for \textbf{multi-modal} image registration. Specifically, we employ style transfer based on contrast-agnostic representation generation and refinement modules to bridge modality and domain gaps with instance optimization at test time. This design is orthogonal to the choice of backbone mono-modal model, thus avoids the computational burden of full fine-tuning while retaining the flexibility to adapt to unseen domains. We evaluate our approach on the Learn2Reg 2025 LUMIR validation set and observe consistent improvements over the pretrained state-of-the-art mono-modal backbone. In particular, the method ranks second on the multi-modal subset, third on the out-of-domain subset, and achieves fourth place overall in Dice score. These results demonstrate that combining frozen mono-modal models with modality adaptation and lightweight instance optimization offers an effective and practical pathway toward robust multi-modal registration.

Yi Zhang, Yidong Zhao, Tijmen Toxopeus et al.

Quantitative cardiac magnetic resonance imaging (MRI) enables non-invasive myocardial tissue characterization but relies on robust motion correction within these variable-length, variable-contrast image sequences. Groupwise registration, which simultaneously aligns all images, has shown greater robustness than pairwise registration for motion correction. However, current deep-learning-based groupwise registration methods cannot generalize across MRI sequences: the architecture typically encodes input data as a fixed-length channel stack, which rigidly couples network design to protocol-specific sequence length, input ordering, and contrast dynamics. At inference time, any change in imaging protocols will render the network unusable. In this work, we introduce \emph{\AnyTwoReg}, a new set-based groupwise registration framework that takes a quantitative MRI sequence as an unordered set. This set formulation fundamentally decouples network design from sequence length and input ordering. By utilizing a shared encoder and correlation-guided feature aggregation, \emph{\AnyTwoReg} constructs a permutation-invariant canonical reference for registration, and learns a permutation-equivariant mapping from images to deformation fields. Additionally, we extract contrast-insensitive image features from an existing foundation model to handle extreme contrast variations. Trained exclusively on a single public $T_1$ mapping dataset (STONE, sequence length $L=11$), \AnyTwoReg generalizes to two unseen quantitative MRI datasets (MOLLI, ASL) with variable lengths ($L \in [11, 60]$) and different contrast dynamics. It achieves strong cross-protocol generalization in a zero-shot manner, and consistently improves downstream quantitative mapping quality. Notably, while designed for quantitative MRI sequences, our framework is directly applicable to Cine MRI sequences for inter-cardiac-phase registration.

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.

Yidong Zhao, Peter Kellman, Hui Xue et al.

Pretrained segmentation models for cardiac magnetic resonance imaging (MRI) struggle to generalize across different imaging sequences due to significant variations in image contrast. These variations arise from changes in imaging protocols, yet the same fundamental spin properties, including proton density, T1, and T2 values, govern all acquired images. With this core principle, we introduce Reverse Imaging, a novel physics-driven method for cardiac MRI data augmentation and domain adaptation to fundamentally solve the generalization problem. Our method reversely infers the underlying spin properties from observed cardiac MRI images, by solving ill-posed nonlinear inverse problems regularized by the prior distribution of spin properties. We acquire this "spin prior" by learning a generative diffusion model from the multiparametric SAturation-recovery single-SHot acquisition sequence (mSASHA) dataset, which offers joint cardiac T1 and T2 maps. Our method enables approximate but meaningful spin-property estimates from MR images, which provide an interpretable "latent variable" that lead to highly flexible image synthesis of arbitrary novel sequences. We show that Reverse Imaging enables highly accurate segmentation across vastly different image contrasts and imaging protocols, realizing wide-spectrum generalization of cardiac MRI segmentation.

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.