Nian Wu

Yaosen Min, Ye Wei, Peizhuo Wang et al.

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because they only take advantage of static crystal structures while the actual binding affinities are generally determined by the thermodynamic ensembles between proteins and ligands. One effective way to approximate such a thermodynamic ensemble is to use molecular dynamics (MD) simulation. Here, an MD dataset containing 3,218 different protein-ligand complexes is curated, and Dynaformer, a graph-based deep learning model is further developed to predict the binding affinities by learning the geometric characteristics of the protein-ligand interactions from the MD trajectories. In silico experiments demonstrated that the model exhibits state-of-the-art scoring and ranking power on the CASF-2016 benchmark dataset, outperforming the methods hitherto reported. Moreover, in a virtual screening on heat shock protein 90 (HSP90) using Dynaformer, 20 candidates are identified and their binding affinities are further experimentally validated. Dynaformer displayed promising results in virtual drug screening, revealing 12 hit compounds (two are in the submicromolar range), including several novel scaffolds. Overall, these results demonstrated that the approach offer a promising avenue for accelerating the early drug discovery process.

Nian Wu, Jiarui Xing, Miaomiao Zhang

This paper presents a novel approach, termed {\em Temporal Latent Residual Network (TLRN)}, to predict a sequence of deformation fields in time-series image registration. The challenge of registering time-series images often lies in the occurrence of large motions, especially when images differ significantly from a reference (e.g., the start of a cardiac cycle compared to the peak stretching phase). To achieve accurate and robust registration results, we leverage the nature of motion continuity and exploit the temporal smoothness in consecutive image frames. Our proposed TLRN highlights a temporal residual network with residual blocks carefully designed in latent deformation spaces, which are parameterized by time-sequential initial velocity fields. We treat a sequence of residual blocks over time as a dynamic training system, where each block is designed to learn the residual function between desired deformation features and current input accumulated from previous time frames. We validate the effectivenss of TLRN on both synthetic data and real-world cine cardiac magnetic resonance (CMR) image videos. Our experimental results shows that TLRN is able to achieve substantially improved registration accuracy compared to the state-of-the-art. Our code is publicly available at https://github.com/nellie689/TLRN.

Nian Wu, Miaomiao Zhang

This paper presents NeurEPDiff, a novel network to fast predict the geodesics in deformation spaces generated by a well known Euler-Poincaré differential equation (EPDiff). To achieve this, we develop a neural operator that for the first time learns the evolving trajectory of geodesic deformations parameterized in the tangent space of diffeomorphisms(a.k.a velocity fields). In contrast to previous methods that purely fit the training images, our proposed NeurEPDiff learns a nonlinear mapping function between the time-dependent velocity fields. A composition of integral operators and smooth activation functions is formulated in each layer of NeurEPDiff to effectively approximate such mappings. The fact that NeurEPDiff is able to rapidly provide the numerical solution of EPDiff (given any initial condition) results in a significantly reduced computational cost of geodesic shooting of diffeomorphisms in a high-dimensional image space. Additionally, the properties of discretiztion/resolution-invariant of NeurEPDiff make its performance generalizable to multiple image resolutions after being trained offline. We demonstrate the effectiveness of NeurEPDiff in registering two image datasets: 2D synthetic data and 3D brain resonance imaging (MRI). The registration accuracy and computational efficiency are compared with the state-of-the-art diffeomophic registration algorithms with geodesic shooting.

Jiarui Xing, Nivetha Jayakumar, Nian Wu et al.

Motion and deformation analysis of cardiac magnetic resonance (CMR) imaging videos is crucial for assessing myocardial strain of patients with abnormal heart functions. Recent advances in deep learning-based image registration algorithms have shown promising results in predicting motion fields from routinely acquired CMR sequences. However, their accuracy often diminishes in regions with subtle appearance changes, with errors propagating over time. Advanced imaging techniques, such as displacement encoding with stimulated echoes (DENSE) CMR, offer highly accurate and reproducible motion data but require additional image acquisition, which poses challenges in busy clinical flows. In this paper, we introduce a novel Latent Motion Diffusion model (LaMoD) to predict highly accurate DENSE motions from standard CMR videos. More specifically, our method first employs an encoder from a pre-trained registration network that learns latent motion features (also considered as deformation-based shape features) from image sequences. Supervised by the ground-truth motion provided by DENSE, LaMoD then leverages a probabilistic latent diffusion model to reconstruct accurate motion from these extracted features. Experimental results demonstrate that our proposed method, LaMoD, significantly improves the accuracy of motion analysis in standard CMR images; hence improving myocardial strain analysis in clinical settings for cardiac patients. Our code is publicly available at https://github.com/jr-xing/LaMoD.

Jiarui Xing, Nian Wu, Kenneth Bilchick et al.

This paper presents a multimodal deep learning framework that utilizes advanced image techniques to improve the performance of clinical analysis heavily dependent on routinely acquired standard images. More specifically, we develop a joint learning network that for the first time leverages the accuracy and reproducibility of myocardial strains obtained from Displacement Encoding with Stimulated Echo (DENSE) to guide the analysis of cine cardiac magnetic resonance (CMR) imaging in late mechanical activation (LMA) detection. An image registration network is utilized to acquire the knowledge of cardiac motions, an important feature estimator of strain values, from standard cine CMRs. Our framework consists of two major components: (i) a DENSE-supervised strain network leveraging latent motion features learned from a registration network to predict myocardial strains; and (ii) a LMA network taking advantage of the predicted strain for effective LMA detection. Experimental results show that our proposed work substantially improves the performance of strain analysis and LMA detection from cine CMR images, aligning more closely with the achievements of DENSE.

Nian Wu, Miaomiao Zhang

This paper presents a novel method, named geodesic deformable networks (GDN), that for the first time enables the learning of geodesic flows of deformation fields derived from images. In particular, the capability of our proposed GDN being able to predict geodesics is important for quantifying and comparing deformable shape presented in images. The geodesic deformations, also known as optimal transformations that align pairwise images, are often parameterized by a time sequence of smooth vector fields governed by nonlinear differential equations. A bountiful literature has been focusing on learning the initial conditions (e.g., initial velocity fields) based on registration networks. However, the definition of geodesics central to deformation-based shape analysis is blind to the networks. To address this problem, we carefully develop an efficient neural operator to treat the geodesics as unknown mapping functions learned from the latent deformation spaces. A composition of integral operators and smooth activation functions is then formulated to effectively approximate such mappings. In contrast to previous works, our GDN jointly optimizes a newly defined geodesic loss, which adds additional benefits to promote the network regularizability and generalizability. We demonstrate the effectiveness of GDN on both 2D synthetic data and 3D real brain magnetic resonance imaging (MRI).

Jingjing Liu, Nian Wu, Xianchao Xiu et al.

Non-negative matrix factorization (NMF) is a popular unsupervised learning approach widely used in image clustering. However, in real-world clustering scenarios, most existing NMF methods are highly sensitive to noise corruption and are unable to effectively leverage limited supervised information. To overcome these drawbacks, we propose a unified non-convex framework with label propagation called robust orthogonal nonnegative matrix factorization (RONMF). This method not only considers the graph Laplacian and label propagation as regularization terms but also introduces a more effective non-convex structure to measure the reconstruction error and imposes orthogonal constraints on the basis matrix to reduce the noise corruption, thereby achieving higher robustness. To solve RONMF, we develop an alternating direction method of multipliers (ADMM)-based optimization algorithm. In particular, all subproblems have closed-form solutions, which ensures its efficiency. Experimental evaluations on eight public image datasets demonstrate that the proposed RONMF outperforms state-of-the-art NMF methods across various standard metrics and shows excellent robustness. The code will be available at https://github.com/slinda-liu.

Nian Wu, Jian Wang, Miaomiao Zhang et al.

Registration-based atlas building often poses computational challenges in high-dimensional image spaces. In this paper, we introduce a novel hybrid atlas building algorithm that fast estimates atlas from large-scale image datasets with much reduced computational cost. In contrast to previous approaches that iteratively perform registration tasks between an estimated atlas and individual images, we propose to use learned priors of registration from pre-trained neural networks. This newly developed hybrid framework features several advantages of (i) providing an efficient way of atlas building without losing the quality of results, and (ii) offering flexibility in utilizing a wide variety of deep learning based registration methods. We demonstrate the effectiveness of this proposed model on 3D brain magnetic resonance imaging (MRI) scans.