Wen Yan

Alexander Bukharin, Tianyi Liu, Shengjie Wang et al. · stanford

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as $O(n^3)$ to $O(n^7)$, with $n$ proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

Shaheer U. Saeed, Tom Syer, Wen Yan et al.

We propose an image synthesis mechanism for multi-sequence prostate MR images conditioned on text, to control lesion presence and sequence, as well as to generate paired bi-parametric images conditioned on images e.g. for generating diffusion-weighted MR from T2-weighted MR for paired data, which are two challenging tasks in pathological image synthesis. Our proposed mechanism utilises and builds upon the recent stable diffusion model by proposing image-based conditioning for paired data generation. We validate our method using 2D image slices from real suspected prostate cancer patients. The realism of the synthesised images is validated by means of a blind expert evaluation for identifying real versus fake images, where a radiologist with 4 years experience reading urological MR only achieves 59.4% accuracy across all tested sequences (where chance is 50%). For the first time, we evaluate the realism of the generated pathology by blind expert identification of the presence of suspected lesions, where we find that the clinician performs similarly for both real and synthesised images, with a 2.9 percentage point difference in lesion identification accuracy between real and synthesised images, demonstrating the potentials in radiological training purposes. Furthermore, we also show that a machine learning model, trained for lesion identification, shows better performance (76.2% vs 70.4%, statistically significant improvement) when trained with real data augmented by synthesised data as opposed to training with only real images, demonstrating usefulness for model training.

Wen Yan, Bernard Chiu, Ziyi Shen et al.

One of the distinct characteristics in radiologists' reading of multiparametric prostate MR scans, using reporting systems such as PI-RADS v2.1, is to score individual types of MR modalities, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced, and then combine these image-modality-specific scores using standardised decision rules to predict the likelihood of clinically significant cancer. This work aims to demonstrate that it is feasible for low-dimensional parametric models to model such decision rules in the proposed Combiner networks, without compromising the accuracy of predicting radiologic labels: First, it is shown that either a linear mixture model or a nonlinear stacking model is sufficient to model PI-RADS decision rules for localising prostate cancer. Second, parameters of these (generalised) linear models are proposed as hyperparameters, to weigh multiple networks that independently represent individual image modalities in the Combiner network training, as opposed to end-to-end modality ensemble. A HyperCombiner network is developed to train a single image segmentation network that can be conditioned on these hyperparameters during inference, for much improved efficiency. Experimental results based on data from 850 patients, for the application of automating radiologist labelling multi-parametric MR, compare the proposed combiner networks with other commonly-adopted end-to-end networks. Using the added advantages of obtaining and interpreting the modality combining rules, in terms of the linear weights or odds-ratios on individual image modalities, three clinical applications are presented for prostate cancer segmentation, including modality availability assessment, importance quantification and rule discovery.

Wen Yan, Michael Shelley

It is well-known that by placing judiciously chosen image point forces and doublets to the Stokeslet above a flat wall, the no-slip boundary condition can be conveniently imposed on the wall [Blake, J. R. Math. Proc. Camb. Philos. Soc. 70(2), 1971: 303.]. However, to further impose periodic boundary conditions on directions parallel to the wall usually involves tedious derivations because single or double periodicity in Stokes flow may require the periodic unit to have no net force, which is not satisfied by the well-known image system. In this work we present a force-neutral image system. This neutrality allows us to represent the Stokes image system in a universal formulation for non-periodic, singly periodic and doubly periodic geometries. This formulation enables the black-box style usage of fast kernel summation methods. We demonstrate the efficiency and accuracy of this new image method with the periodic kernel independent fast multipole method in both non-periodic and doubly periodic geometries. We then extend this new image system to other widely used Stokes fundamental solutions, including the Laplacian of the Stokeslet and the Rotne-Prager-Yamakawa tensor.

Qianye Yang, David Atkinson, Yunguan Fu et al.

In this work, we consider the task of pairwise cross-modality image registration, which may benefit from exploiting additional images available only at training time from an additional modality that is different to those being registered. As an example, we focus on aligning intra-subject multiparametric Magnetic Resonance (mpMR) images, between T2-weighted (T2w) scans and diffusion-weighted scans with high b-value (DWI$_{high-b}$). For the application of localising tumours in mpMR images, diffusion scans with zero b-value (DWI$_{b=0}$) are considered easier to register to T2w due to the availability of corresponding features. We propose a learning from privileged modality algorithm, using a training-only imaging modality DWI$_{b=0}$, to support the challenging multi-modality registration problems. We present experimental results based on 369 sets of 3D multiparametric MRI images from 356 prostate cancer patients and report, with statistical significance, a lowered median target registration error of 4.34 mm, when registering the holdout DWI$_{high-b}$ and T2w image pairs, compared with that of 7.96 mm before registration. Results also show that the proposed learning-based registration networks enabled efficient registration with comparable or better accuracy, compared with a classical iterative algorithm and other tested learning-based methods with/without the additional modality. These compared algorithms also failed to produce any significantly improved alignment between DWI$_{high-b}$ and T2w in this challenging application.

John LaGrone, Ricardo Cortez, Wen Yan et al.

The macroscopic properties of polymeric fluids are inherited from the material properties of the fibers embedded in the solvent. The behavior of such passive fibers in flow has been of interest in a wide range of systems, including cellular mechanics, nutrient aquisition by diatom chains in the ocean, and industrial applications such as paper manufacturing. The rotational dynamics and shape evolution of fibers in shear depends upon the slenderness of the fiber and the non-dimensional "elasto-viscous" number that measures the ratio of the fluid's viscous forces to the fiber's elastic forces. For a small elasto-viscous number, the nearly-rigid fiber rotates in the shear, but when the elasto-viscous number reaches a threshhold, buckling occurs. For even larger elasto-viscous numbers, there is a transition to a "snaking behavior" where the fiber remains aligned with the shear axis, but its ends curl in, in opposite directions. These experimentally-observed behaviors have recently been characterized computationally using slender-body theory and immersed boundary computations. However, classical experiments with nylon fibers and recent experiments with actin filaments have demonstrated that for even larger elasto-viscous numbers, multiple buckling sites and coiling can occur. Using a regularized Stokeslet framework coupled with a kernel independent fast multipole method, we present simulations that capture these complex fiber dynamics.

Yiwen Li, Yunguan Fu, Iani Gayo et al.

The prowess that makes few-shot learning desirable in medical image analysis is the efficient use of the support image data, which are labelled to classify or segment new classes, a task that otherwise requires substantially more training images and expert annotations. This work describes a fully 3D prototypical few-shot segmentation algorithm, such that the trained networks can be effectively adapted to clinically interesting structures that are absent in training, using only a few labelled images from a different institute. First, to compensate for the widely recognised spatial variability between institutions in episodic adaptation of novel classes, a novel spatial registration mechanism is integrated into prototypical learning, consisting of a segmentation head and an spatial alignment module. Second, to assist the training with observed imperfect alignment, support mask conditioning module is proposed to further utilise the annotation available from the support images. Extensive experiments are presented in an application of segmenting eight anatomical structures important for interventional planning, using a data set of 589 pelvic T2-weighted MR images, acquired at seven institutes. The results demonstrate the efficacy in each of the 3D formulation, the spatial registration, and the support mask conditioning, all of which made positive contributions independently or collectively. Compared with the previously proposed 2D alternatives, the few-shot segmentation performance was improved with statistical significance, regardless whether the support data come from the same or different institutes.

Yunguan Fu, Wenjia Bai, Wen Yan et al.

Diffusion-based unsupervised image registration has been explored for cardiac cine MR, but expensive multi-step inference limits practical use. We propose FlowReg, a flow-matching framework in displacement field space that achieves strong registration in as few as two steps and supports further refinement with more steps. FlowReg uses warmup-reflow training: a single-step network first acts as a teacher, then a student learns to refine from arbitrary intermediate states, removing the need for a pre-trained model as in existing methods. An Initial Guess strategy feeds back the model prediction as the next starting point, improving refinement from step two onward. On ACDC and MM2 across six tasks (including cross-dataset generalization), FlowReg outperforms the state of the art on five tasks (+0.6% mean Dice score on average), with the largest gain in the left ventricle (+1.09%), and reduces LVEF estimation error on all six tasks (-2.58 percentage points), using only 0.7% extra parameters and no segmentation labels. Code is available at https://github.com/mathpluscode/FlowReg.

Wen Yan, Qianye Yang, Yipei Wang et al.

Many registration problems are ill-posed in homogeneous or noisy regions, and dense voxel-wise decoders can be unnecessarily high-dimensional. A sparse control-point parameterisation provides a compact, smooth deformation representation while reducing memory and improving stability. This work investigates the required control points for learning-based registration network development. We present GridReg, a learning-based registration framework that replaces dense voxel-wise decoding with displacement predictions at a sparse grid of control points. This design substantially cuts the parameter count and memory while retaining registration accuracy. Multiscale 3D encoder feature maps are flattened into a 1D token sequence with positional encoding to retain spatial context. The model then predicts a sparse gridded deformation field using a cross-attention module. We further introduce grid-adaptive training, enabling an adaptive model to operate at multiple grid sizes at inference without retraining. This work quantitatively demonstrates the benefits of using sparse grids. Using three data sets for registering prostate gland, pelvic organs and neurological structures, the results suggested a significant improvement with the usage of grid-controled displacement field. Alternatively, the superior registration performance was obtained using the proposed approach, with a similar or less computational cost, compared with existing algorithms that predict DDFs or displacements sampled on scattered key points.

Yipei Wang, Yinsong Xu, Weixi Yi et al.

Many diagnostic and therapeutic clinical tasks for prostate cancer increasingly rely on multi-parametric MRI. Automating these tasks is challenging because they necessitate expert interpretations, which are difficult to scale to capitalise on modern deep learning. Although modern automated systems achieve expert-level performance in isolated tasks, their general clinical utility remains limited by the requirement of large task-specific labelled datasets. In this paper, we present ProFound, a domain-specialised vision foundation model for volumetric prostate mpMRI. ProFound is pre-trained using several variants of self-supervised approaches on a diverse, multi-institutional collection of 5,000 patients, with a total of over 22,000 unique 3D MRI volumes (over 1,800,000 2D image slices). We conducted a systematic evaluation of ProFound across a broad spectrum of $11$ downstream clinical tasks on over 3,000 independent patients, including prostate cancer detection, Gleason grading, lesion localisation, gland volume estimation, zonal and surrounding structure segmentation. Experimental results demonstrate that finetuned ProFound consistently outperforms or remains competitive with state-of-the-art specialised models and existing medical vision foundation models trained/finetuned on the same data.

Wen Yan, Yipei Wang, Shiqi Huang et al.

Label variability is a major challenge for prostate lesion segmentation. In multi-site datasets, annotations often reflect centre-specific contouring protocols, causing segmentation networks to overfit to local styles and generalise poorly to unseen sites in inference. We treat each observed annotation as a noisy observation of an underlying latent 'clean' lesion mask, and propose a hierarchical expectation-maximisation (HierEM) framework that alternates between: (1) inferring a voxel-wise posterior distribution over the latent mask, and (2) training a CNN using this posterior as a soft target and estimate site-specific sensitivity and specificity under a hierarchical prior. This hierarchical prior decomposes label-quality into a global mean with site- and case-level deviations, reducing site-specific bias by penalising the likelihood term contributed only by site deviations. Experiments on three cohorts demonstrate that the proposed hierarchical EM framework enhances cross-site generalisation compared to state-of-the-art methods. For pooled-dataset evaluation, the per-site mean DSC ranges from 29.50% to 39.69%; for leave-one-site-out generalisation, it ranges from 27.91% to 32.67%, yielding statistically significant improvements over comparison methods (p<0.039). The method also produces interpretable per-site latent label-quality estimates (sensitivity alpha ranges from 31.5% to 47.3% at specificity beta approximates 0.99), supporting post-hoc analyses of cross-site annotation variability. These results indicate that explicitly modelling site-dependent annotation can improve cross-site generalisation.

Tianze Zheng, Ailun Wang, Xu Han et al.

A force field is a critical component in molecular dynamics simulations for computational drug discovery. It must achieve high accuracy within the constraints of molecular mechanics' (MM) limited functional forms, which offers high computational efficiency. With the rapid expansion of synthetically accessible chemical space, traditional look-up table approaches face significant challenges. In this study, we address this issue using a modern data-driven approach, developing ByteFF, an Amber-compatible force field for drug-like molecules. To create ByteFF, we generated an expansive and highly diverse molecular dataset at the B3LYP-D3(BJ)/DZVP level of theory. This dataset includes 2.4 million optimized molecular fragment geometries with analytical Hessian matrices, along with 3.2 million torsion profiles. We then trained an edge-augmented, symmetry-preserving molecular graph neural network (GNN) on this dataset, employing a carefully optimized training strategy. Our model predicts all bonded and non-bonded MM force field parameters for drug-like molecules simultaneously across a broad chemical space. ByteFF demonstrates state-of-the-art performance on various benchmark datasets, excelling in predicting relaxed geometries, torsional energy profiles, and conformational energies and forces. Its exceptional accuracy and expansive chemical space coverage make ByteFF a valuable tool for multiple stages of computational drug discovery.

Shiqi Huang, Tingfa Xu, Ziyi Shen et al.

This paper describes a new spatial correspondence representation based on paired regions-of-interest (ROIs), for medical image registration. The distinct properties of the proposed ROI-based correspondence are discussed, in the context of potential benefits in clinical applications following image registration, compared with alternative correspondence-representing approaches, such as those based on sampled displacements and spatial transformation functions. These benefits include a clear connection between learning-based image registration and segmentation, which in turn motivates two cases of image registration approaches using (pre-)trained segmentation networks. Based on the segment anything model (SAM), a vision foundation model for segmentation, we develop a new registration algorithm SAMReg, which does not require any training (or training data), gradient-based fine-tuning or prompt engineering. The proposed SAMReg models are evaluated across five real-world applications, including intra-subject registration tasks with cardiac MR and lung CT, challenging inter-subject registration scenarios with prostate MR and retinal imaging, and an additional evaluation with a non-clinical example with aerial image registration. The proposed methods outperform both intensity-based iterative algorithms and DDF-predicting learning-based networks across tested metrics including Dice and target registration errors on anatomical structures, and further demonstrates competitive performance compared to weakly-supervised registration approaches that rely on fully-segmented training data. Open source code and examples are available at: https://github.com/sqhuang0103/SAMReg.git.

Wen Yan, Qianye Yang, Shiqi Huang et al.

Spatial correspondence can be represented by pairs of segmented regions, such that the image registration networks aim to segment corresponding regions rather than predicting displacement fields or transformation parameters. In this work, we show that such a corresponding region pair can be predicted by the same language prompt on two different images using the pre-trained large multimodal models based on GroundingDINO and SAM. This enables a fully automated and training-free registration algorithm, potentially generalisable to a wide range of image registration tasks. In this paper, we present experimental results using one of the challenging tasks, registering inter-subject prostate MR images, which involves both highly variable intensity and morphology between patients. Tell2Reg is training-free, eliminating the need for costly and time-consuming data curation and labelling that was previously required for this registration task. This approach outperforms unsupervised learning-based registration methods tested, and has a performance comparable to weakly-supervised methods. Additional qualitative results are also presented to suggest that, for the first time, there is a potential correlation between language semantics and spatial correspondence, including the spatial invariance in language-prompted regions and the difference in language prompts between the obtained local and global correspondences. Code is available at https://github.com/yanwenCi/Tell2Reg.git.

Ziyang Yu, Yi He, Wenbing Huang et al.

Estimating free energy differences quantifies thermodynamic preferences in molecular interactions, which is central to chemistry and drug discovery. Despite fruitful progress, existing methods still face key limitations: classical computational approaches remain prohibitively expensive due to their reliance on extensive molecular dynamics simulations, while deep learning-based methods are constrained by either less-expressive generative models or input dimensions tied to a specific system, resulting in negligible generalization. To address these challenges, we propose CARD, a generative framework that employs a novel radix-based decomposition to bijectively convert 3D coordinates into mixed discrete-continuous sequences, enabling coarse-to-fine autoregressive modeling with enhanced expressiveness. Notably, the model corresponds to a distribution with zero free energy, serving as a proposal for absolute free energy computation of arbitrary systems without relying on alchemical pathways. Experiments across diverse tasks demonstrate that CARD matches the accuracy of classical computational methods on unseen systems with diverse topologies, while achieving an approximately 40-fold speedup in inference.

Sheng Gong, Yumin Zhang, Zhenliang Mu et al.

Despite the widespread applications of machine learning force fields (MLFF) in solids and small molecules, there is a notable gap in applying MLFF to simulate liquid electrolyte, a critical component of the current commercial lithium-ion battery. In this work, we introduce BAMBOO (\textbf{B}yteDance \textbf{A}I \textbf{M}olecular Simulation \textbf{Boo}ster), a predictive framework for molecular dynamics (MD) simulations, with a demonstration of its capability in the context of liquid electrolyte for lithium batteries. We design a physics-inspired graph equivariant transformer architecture as the backbone of BAMBOO to learn from quantum mechanical simulations. Additionally, we introduce an ensemble knowledge distillation approach and apply it to MLFFs to reduce the fluctuation of observations from MD simulations. Finally, we propose a density alignment algorithm to align BAMBOO with experimental measurements. BAMBOO demonstrates state-of-the-art accuracy in predicting key electrolyte properties such as density, viscosity, and ionic conductivity across various solvents and salt combinations. The current model, trained on more than 15 chemical species, achieves the average density error of 0.01 g/cm$^3$ on various compositions compared with experiment.

Shiqi Huang, Tingfa Xu, Ziyi Shen et al.

The goal of image registration is to establish spatial correspondence between two or more images, traditionally through dense displacement fields (DDFs) or parametric transformations (e.g., rigid, affine, and splines). Rethinking the existing paradigms of achieving alignment via spatial transformations, we uncover an alternative but more intuitive correspondence representation: a set of corresponding regions-of-interest (ROI) pairs, which we demonstrate to have sufficient representational capability as other correspondence representation methods.Further, it is neither necessary nor sufficient for these ROIs to hold specific anatomical or semantic significance. In turn, we formulate image registration as searching for the same set of corresponding ROIs from both moving and fixed images - in other words, two multi-class segmentation tasks on a pair of images. For a general-purpose and practical implementation, we integrate the segment anything model (SAM) into our proposed algorithms, resulting in a SAM-enabled registration (SAMReg) that does not require any training data, gradient-based fine-tuning or engineered prompts. We experimentally show that the proposed SAMReg is capable of segmenting and matching multiple ROI pairs, which establish sufficiently accurate correspondences, in three clinical applications of registering prostate MR, cardiac MR and abdominal CT images. Based on metrics including Dice and target registration errors on anatomical structures, the proposed registration outperforms both intensity-based iterative algorithms and DDF-predicting learning-based networks, even yielding competitive performance with weakly-supervised registration which requires fully-segmented training data.

Martynas Pocius, Wen Yan, Dean C. Barratt et al.

In this paper we propose a reinforcement learning based weakly supervised system for localisation. We train a controller function to localise regions of interest within an image by introducing a novel reward definition that utilises non-binarised classification probability, generated by a pre-trained binary classifier which classifies object presence in images or image crops. The object-presence classifier may then inform the controller of its localisation quality by quantifying the likelihood of the image containing an object. Such an approach allows us to minimize any potential labelling or human bias propagated via human labelling for fully supervised localisation. We evaluate our proposed approach for a task of cancerous lesion localisation on a large dataset of real clinical bi-parametric MR images of the prostate. Comparisons to the commonly used multiple-instance learning weakly supervised localisation and to a fully supervised baseline show that our proposed method outperforms the multi-instance learning and performs comparably to fully-supervised learning, using only image-level classification labels for training.

Yiwen Li, Yunguan Fu, Iani J. M. B. Gayo et al.

For training registration networks, weak supervision from segmented corresponding regions-of-interest (ROIs) have been proven effective for (a) supplementing unsupervised methods, and (b) being used independently in registration tasks in which unsupervised losses are unavailable or ineffective. This correspondence-informing supervision entails cost in annotation that requires significant specialised effort. This paper describes a semi-weakly-supervised registration pipeline that improves the model performance, when only a small corresponding-ROI-labelled dataset is available, by exploiting unlabelled image pairs. We examine two types of augmentation methods by perturbation on network weights and image resampling, such that consistency-based unsupervised losses can be applied on unlabelled data. The novel WarpDDF and RegCut approaches are proposed to allow commutative perturbation between an image pair and the predicted spatial transformation (i.e. respective input and output of registration networks), distinct from existing perturbation methods for classification or segmentation. Experiments using 589 male pelvic MR images, labelled with eight anatomical ROIs, show the improvement in registration performance and the ablated contributions from the individual strategies. Furthermore, this study attempts to construct one of the first computational atlases for pelvic structures, enabled by registering inter-subject MRs, and quantifies the significant differences due to the proposed semi-weak supervision with a discussion on the potential clinical use of example atlas-derived statistics.

Yi He, Ailun Wang, Zhi Wang et al.

Recent advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD) remains limited due to critical data constraints. To address the limitation of training data for models targeting SBDD tasks, we propose an evolutionary framework named MEVO, which bridges the gap between billion-scale small molecule dataset and the scarce protein-ligand complex dataset, and effectively increase the abundance of training data for generative SBDD models. MEVO is composed of three key components: a high-fidelity VQ-VAE for molecule representation in latent space, a diffusion model for pharmacophore-guided molecule generation, and a pocket-aware evolutionary strategy for molecule optimization with physics-based scoring function. This framework efficiently generate high-affinity binders for various protein targets, validated with predicted binding affinities using free energy perturbation (FEP) methods. In addition, we showcase the capability of MEVO in designing potent inhibitors to KRAS$^{\textrm{G12D}}$, a challenging target in cancer therapeutics, with similar affinity to the known highly active inhibitor evaluated by FEP calculations. With high versatility and generalizability, MEVO offers an effective and data-efficient model for various tasks in structure-based ligand design.

Weixi Yi, Yipei Wang, Wen Yan et al.

Multiparametric MRI is increasingly recommended as a first-line noninvasive approach to detect and localize prostate cancer, requiring at minimum diffusion-weighted (DWI) and T2-weighted (T2w) MR sequences. Early machine learning attempts using only T2w images have shown promising diagnostic performance in segmenting radiologist-annotated lesions. Such uni-modal T2-only approaches deliver substantial clinical benefits by reducing costs and expertise required to acquire other sequences. This work investigates an arguably more challenging application using only T2w at inference, but to localize individual cancers based on independent histopathology labels. We formulate DWI images as a latent modality (readily available during training) to classify cancer presence at local Barzell zones, given only T2w images as input. In the resulting expectation-maximization algorithm, a latent modality generator (implemented using a flow matching-based generative model) approximates the latent DWI image posterior distribution in the E-steps, while in M-steps a cancer localizer is simultaneously optimized with the generative model to maximize the expected likelihood of cancer presence. The proposed approach provides a novel theoretical framework for learning from a privileged DWI modality, yielding superior cancer localization performance compared to approaches that lack training DWI images or existing frameworks for privileged learning and incomplete modalities. The proposed T2-only methods perform competitively or better than baseline methods using multiple input sequences (e.g., improving the patient-level F1 score by 14.4\% and zone-level QWK by 5.3\% over the T2w+DWI baseline). We present quantitative evaluations using internal and external datasets from 4,133 prostate cancer patients with histopathology-verified labels.

Zhe Liu, Yuyan Ni, Zhichen Pu et al.

Recently, sophisticated deep learning-based approaches have been developed for generating efficient initial guesses to accelerate the convergence of density functional theory (DFT) calculations. While the actual initial guesses are often density matrices (DM), quantities that can convert into density matrices also qualify as alternative forms of initial guesses. Hence, existing works mostly rely on the prediction of the Hamiltonian matrix for obtaining high-quality initial guesses. However, the Hamiltonian matrix is both numerically difficult to predict and intrinsically non-transferable, hindering the application of such models in real scenarios. In light of this, we propose a method that constructs DFT initial guesses by predicting the electron density in a compact auxiliary basis representation using E(3)-equivariant neural networks. Trained on small molecules with up to 20 atoms, our model is able to achieve an average 33.3% self-consistent field (SCF) step reduction on systems up to 60 atoms, substantially outperforming Hamiltonian-centric and DM-centric models. Critically, this acceleration remains nearly constant with increasing system sizes and exhibits strong transferring behaviors across orbital basis sets and exchange-correlation (XC) functionals. To the best of our knowledge, this work represents the first and robust candidate for a universally transferable DFT acceleration method. We are also releasing the SCFbench dataset and its accompanying code to facilitate future research in this promising direction.

Yucheng Tang, Pawel Rajwa, Alexander Ng et al.

Foundation models in medical imaging have shown promising label efficiency, achieving high performance on downstream tasks using only a fraction of the annotated data otherwise required. In this study, we evaluate this potential in the context of prostate multiparametric MRI using ProFound, a recently developed domain-specific vision foundation model pretrained on large-scale prostate MRI datasets. We investigate the impact of variable image quality on the label-efficient finetuning, by quantifying the generalisability of the finetuned models. We conduct a comprehensive set of experiments by systematically varying the ratios of high- and low-quality images in the finetuning and evaluation sets. Our findings indicate that image quality distribution and its finetune-and-test mismatch significantly affect model performance. In particular: a) Varying the ratio of high- to low-quality images between finetuning and test sets leads to notable differences in downstream performance; and b) The presence of sufficient high-quality images in the finetuning set is critical for maintaining strong performance, whilst the importance of matched finetuning and testing distribution varies between different downstream tasks, such as automated radiology reporting and prostate cancer detection. Importantly, experimental results also show that, although finetuning requires significantly less labeled data compared to training from scratch when the quality ratio is consistent, this label efficiency is not independent of the image quality distribution. For example, we show cases that, without sufficient high-quality images in finetuning, finetuned models may fail to outperform those without pretraining.

Shiqi Huang, Tingfa Xu, Wen Yan et al.

Establishing pixel/voxel-level or region-level correspondences is the core challenge in image registration. The latter, also known as region-based correspondence representation, leverages paired regions of interest (ROIs) to enable regional matching while preserving fine-grained capability at pixel/voxel level. Traditionally, this representation is implemented via two steps: segmenting ROIs in each image then matching them between the two images. In this paper, we simplify this into one step by directly "searching for corresponding prompts", using extensively pre-trained segmentation models (e.g., SAM) for a training-free registration approach, PromptReg. Firstly, we introduce the "corresponding prompt problem", which aims to identify a corresponding Prompt Y in Image Y for any given visual Prompt X in Image X, such that the two respectively prompt-conditioned segmentations are a pair of corresponding ROIs from the two images. Secondly, we present an "inverse prompt" solution that generates primary and optionally auxiliary prompts, inverting Prompt X into the prompt space of Image Y. Thirdly, we propose a novel registration algorithm that identifies multiple paired corresponding ROIs by marginalizing the inverted Prompt X across both prompt and spatial dimensions. Comprehensive experiments are conducted on five applications of registering 3D prostate MR, 3D abdomen MR, 3D lung CT, 2D histopathology and, as a non-medical example, 2D aerial images. Based on metrics including Dice and target registration errors on anatomical structures, the proposed registration outperforms both intensity-based iterative algorithms and learning-based DDF-predicting networks, even yielding competitive performance with weakly-supervised approaches that require fully-segmented training data.

Wen Yan, Qianye Yang, Tom Syer et al.

Dice similarity coefficient (DSC) and Hausdorff distance (HD) are widely used for evaluating medical image segmentation. They have also been criticised, when reported alone, for their unclear or even misleading clinical interpretation. DSCs may also differ substantially from HDs, due to boundary smoothness or multiple regions of interest (ROIs) within a subject. More importantly, either metric can also have a nonlinear, non-monotonic relationship with outcomes based on Type 1 and 2 errors, designed for specific clinical decisions that use the resulting segmentation. Whilst cases causing disagreement between these metrics are not difficult to postulate. This work first proposes a new asymmetric detection metric, adapting those used in object detection, for planning prostate cancer procedures. The lesion-level metrics is then compared with the voxel-level DSC and HD, whereas a 3D UNet is used for segmenting lesions from multiparametric MR (mpMR) images. Based on experimental results we report pairwise agreement and correlation 1) between DSC and HD, and 2) between voxel-level DSC and recall-controlled precision at lesion-level, with Cohen's [0.49, 0.61] and Pearson's [0.66, 0.76] (p-values}<0.001) at varying cut-offs. However, the differences in false-positives and false-negatives, between the actual errors and the perceived counterparts if DSC is used, can be as high as 152 and 154, respectively, out of the 357 test set lesions. We therefore carefully conclude that, despite of the significant correlations, voxel-level metrics such as DSC can misrepresent lesion-level detection accuracy for evaluating localisation of multifocal prostate cancer and should be interpreted with caution.

Shaheer U. Saeed, Wen Yan, Yunguan Fu et al.

Image quality assessment (IQA) in medical imaging can be used to ensure that downstream clinical tasks can be reliably performed. Quantifying the impact of an image on the specific target tasks, also named as task amenability, is needed. A task-specific IQA has recently been proposed to learn an image-amenability-predicting controller simultaneously with a target task predictor. This allows for the trained IQA controller to measure the impact an image has on the target task performance, when this task is performed using the predictor, e.g. segmentation and classification neural networks in modern clinical applications. In this work, we propose an extension to this task-specific IQA approach, by adding a task-agnostic IQA based on auto-encoding as the target task. Analysing the intersection between low-quality images, deemed by both the task-specific and task-agnostic IQA, may help to differentiate the underpinning factors that caused the poor target task performance. For example, common imaging artefacts may not adversely affect the target task, which would lead to a low task-agnostic quality and a high task-specific quality, whilst individual cases considered clinically challenging, which can not be improved by better imaging equipment or protocols, is likely to result in a high task-agnostic quality but a low task-specific quality. We first describe a flexible reward shaping strategy which allows for the adjustment of weighting between task-agnostic and task-specific quality scoring. Furthermore, we evaluate the proposed algorithm using a clinically challenging target task of prostate tumour segmentation on multiparametric magnetic resonance (mpMR) images, from 850 patients. The proposed reward shaping strategy, with appropriately weighted task-specific and task-agnostic qualities, successfully identified samples that need re-acquisition due to defected imaging process.

Yiwen Li, Yunguan Fu, Qianye Yang et al.

The ability to adapt medical image segmentation networks for a novel class such as an unseen anatomical or pathological structure, when only a few labelled examples of this class are available from local healthcare providers, is sought-after. This potentially addresses two widely recognised limitations in deploying modern deep learning models to clinical practice, expertise-and-labour-intensive labelling and cross-institution generalisation. This work presents the first 3D few-shot interclass segmentation network for medical images, using a labelled multi-institution dataset from prostate cancer patients with eight regions of interest. We propose an image alignment module registering the predicted segmentation of both query and support data, in a standard prototypical learning algorithm, to a reference atlas space. The built-in registration mechanism can effectively utilise the prior knowledge of consistent anatomy between subjects, regardless whether they are from the same institution or not. Experimental results demonstrated that the proposed registration-assisted prototypical learning significantly improved segmentation accuracy (p-values<0.01) on query data from a holdout institution, with varying availability of support data from multiple institutions. We also report the additional benefits of the proposed 3D networks with 75% fewer parameters and an arguably simpler implementation, compared with existing 2D few-shot approaches that segment 2D slices of volumetric medical images.

Zhe Min, Fernando J. Bianco, Qianye Yang et al.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Multi-parametric magnetic resonance (mpMR) imaging has emerged as a non-invasive diagnostic tool for detecting and localising prostate tumours by specialised radiologists. These radiological examinations, for example, for differentiating malignant lesions from benign prostatic hyperplasia in transition zones and for defining the boundaries of clinically significant cancer, remain challenging and highly skill-and-experience-dependent. We first investigate experimental results in developing object detection neural networks that are trained to predict the radiological assessment, using these high-variance labels. We further argue that such a computer-assisted diagnosis (CAD) system needs to have the ability to control the false-positive rate (FPR) or false-negative rate (FNR), in order to be usefully deployed in a clinical workflow, informing clinical decisions without further human intervention. This work proposes a novel PCa detection network that incorporates a lesion-level cost-sensitive loss and an additional slice-level loss based on a lesion-to-slice mapping function, to manage the lesion- and slice-level costs, respectively. Our experiments based on 290 clinical patients concludes that 1) The lesion-level FNR was effectively reduced from 0.19 to 0.10 and the lesion-level FPR was reduced from 1.03 to 0.66 by changing the lesion-level cost; 2) The slice-level FNR was reduced from 0.19 to 0.00 by taking into account the slice-level cost; (3) Both lesion-level and slice-level FNRs were reduced with lower FP/FPR by changing the lesion-level or slice-level costs, compared with post-training threshold adjustment using networks without the proposed cost-aware training.

Wen Yan, Yicheng Liu

With the development of human space exploration, the space environment is gradually filled with abandoned satellite debris and unknown micrometeorites, which will seriously affect capture motion of space robot. Hence, a novel fast collision-avoidance trajectory planning strategy for a dual-arm free-floating space robot (FFSR) with predefined-time pose feedback will be mainly studied to achieve micron-level tracking accuracy of end-effector in this paper. However, similar to control, the exponential feedback results in larger initial joint angular velocity relative to proportional feedback. Firstly, a pose-error-based kinematic model of the FFSR will be derived from a control perspective. Then, a cumulative dangerous field (CDF) collision-avoidance algorithm is applied in predefined-time trajectory planning to achieve micron-level collision-avoidance trajectory tracking precision. In the end, a GA-based optimization algorithm is used to optimize the predefined-time parameter to obtain a motion trajectory of low joint angular velocity of robotic arms. The simulation results verify our conjecture and conclusion.

Wen Yan, Michael Shelley

An important but missing component in the application of the kernel independent fast multipole method (KIFMM) is the capability for flexibly and efficiently imposing singly, doubly, and triply periodic boundary conditions. In most popular packages such periodicities are imposed with the hierarchical repetition of periodic boxes, which may give an incorrect answer due to the conditional convergence of some kernel sums. Here we present an efficient method to properly impose periodic boundary conditions using a near-far splitting scheme. The near-field contribution is directly calculated with the KIFMM method, while the far-field contribution is calculated with a multipole-to-local (M2L) operator which is independent of the source and target point distribution. The M2L operator is constructed with the far-field portion of the kernel function to generate the far-field contribution with the downward equivalent source points in KIFMM. This method guarantees the sum of the near-field \& far-field converge pointwise to results satisfying periodicity and compatibility conditions. The computational cost of the far-field calculation observes the same $\mathcal{O}(N)$ complexity as FMM and is designed to be small by reusing the data computed by KIFMM for the near-field. The far-field calculations require no additional control parameters, and observes the same theoretical error bound as KIFMM. We present accuracy and timing test results for the Laplace kernel in singly periodic domains and the Stokes velocity kernel in doubly and triply periodic domains.

Siyuan Shan, Wen Yan, Xiaoqing Guo et al.

We propose a registration algorithm for 2D CT/MRI medical images with a new unsupervised end-to-end strategy using convolutional neural networks. The contributions of our algorithm are threefold: (1) We transplant traditional image registration algorithms to an end-to-end convolutional neural network framework, while maintaining the unsupervised nature of image registration problems. The image-to-image integrated framework can simultaneously learn both image features and transformation matrix for registration. (2) Training with additional data without any label can further improve the registration performance by approximately 10 %. (3) The registration speed is 100x faster than traditional methods. The proposed network is easy to implement and can be trained efficiently. Experiments demonstrate that our system achieves state-of-the-art results on 2D brain registration and achieves comparable results on 2D liver registration. It can be extended to register other organs beyond liver and brain such as kidney, lung, and heart.