Chenyu Wang

Lei Bai, Dongang Wang, Michael Barnett et al.

Accurately measuring the evolution of Multiple Sclerosis (MS) with magnetic resonance imaging (MRI) critically informs understanding of disease progression and helps to direct therapeutic strategy. Deep learning models have shown promise for automatically segmenting MS lesions, but the scarcity of accurately annotated data hinders progress in this area. Obtaining sufficient data from a single clinical site is challenging and does not address the heterogeneous need for model robustness. Conversely, the collection of data from multiple sites introduces data privacy concerns and potential label noise due to varying annotation standards. To address this dilemma, we explore the use of the federated learning framework while considering label noise. Our approach enables collaboration among multiple clinical sites without compromising data privacy under a federated learning paradigm that incorporates a noise-robust training strategy based on label correction. Specifically, we introduce a Decoupled Hard Label Correction (DHLC) strategy that considers the imbalanced distribution and fuzzy boundaries of MS lesions, enabling the correction of false annotations based on prediction confidence. We also introduce a Centrally Enhanced Label Correction (CELC) strategy, which leverages the aggregated central model as a correction teacher for all sites, enhancing the reliability of the correction process. Extensive experiments conducted on two multi-site datasets demonstrate the effectiveness and robustness of our proposed methods, indicating their potential for clinical applications in multi-site collaborations.

Dongnan Liu, Mariano Cabezas, Dongang Wang et al.

Federated learning (FL) has been widely employed for medical image analysis to facilitate multi-client collaborative learning without sharing raw data. Despite great success, FL's performance is limited for multiple sclerosis (MS) lesion segmentation tasks, due to variance in lesion characteristics imparted by different scanners and acquisition parameters. In this work, we propose the first FL MS lesion segmentation framework via two effective re-weighting mechanisms. Specifically, a learnable weight is assigned to each local node during the aggregation process, based on its segmentation performance. In addition, the segmentation loss function in each client is also re-weighted according to the lesion volume for the data during training. Comparison experiments on two FL MS segmentation scenarios using public and clinical datasets have demonstrated the effectiveness of the proposed method by outperforming other FL methods significantly. Furthermore, the segmentation performance of FL incorporating our proposed aggregation mechanism can exceed centralised training with all the raw data. The extensive evaluation also indicated the superiority of our method when estimating brain volume differences estimation after lesion inpainting.

Yang Ma, Dongang Wang, Peilin Liu et al.

The heterogeneity of neurological conditions, ranging from structural anomalies to functional impairments, presents a significant challenge in medical imaging analysis tasks. Moreover, the limited availability of well-annotated datasets constrains the development of robust analysis models. Against this backdrop, this study introduces a novel approach leveraging the inherent anatomical symmetrical features of the human brain to enhance the subsequent detection and segmentation analysis for brain diseases. A novel Symmetry-Aware Cross-Attention (SACA) module is proposed to encode symmetrical features of left and right hemispheres, and a proxy task to detect symmetrical features as the Symmetry-Aware Head (SAH) is proposed, which guides the pretraining of the whole network on a vast 3D brain imaging dataset comprising both healthy and diseased brain images across various MRI and CT. Through meticulous experimentation on downstream tasks, including both classification and segmentation for brain diseases, our model demonstrates superior performance over state-of-the-art methodologies, particularly highlighting the significance of symmetry-aware learning. Our findings advocate for the effectiveness of incorporating symmetry awareness into pretraining and set a new benchmark for medical imaging analysis, promising significant strides toward accurate and efficient diagnostic processes. Code is available at https://github.com/bitMyron/sa-swin.

Chenyu Wang, Zhou Yang, Yunbo Lyu et al.

Artificial Intelligence (AI) is now used across nearly every industry, making AI model quality essential for building reliable and trustworthy systems. Historically, correctness has been the main focus, but industry AI models must also satisfy many other important quality attributes. To understand how these attributes are perceived, the challenges they create, and the solutions used in practice, we identify nine key quality attributes and interview 15 AI practitioners from diverse backgrounds. The interviews show that practitioners prioritize attributes differently depending on context. For example, efficiency can matter more than correctness in real-time applications, while scalability and deployability are no longer seen as primary concerns. Data imbalance emerges as a major obstacle to maintaining model correctness and robustness, and practitioners commonly use mitigation strategies such as active learning. We validate our main findings with a survey of 50 practitioners, which shows that most of the findings are widely recognized. These results can help researchers focus on the attributes practitioners value most and avoid improving one attribute at the expense of others that are considered more critical.

Sheng Chen, Zihao Tang, Dongnan Liu et al.

Precise thigh muscle volumes are crucial to monitor the motor functionality of patients with diseases that may result in various degrees of thigh muscle loss. T1-weighted MRI is the default surrogate to obtain thigh muscle masks due to its contrast between muscle and fat signals. Deep learning approaches have recently been widely used to obtain these masks through segmentation. However, due to the insufficient amount of precise annotations, thigh muscle masks generated by deep learning approaches tend to misclassify intra-muscular fat (IMF) as muscle impacting the analysis of muscle volumetrics. As IMF is infiltrated inside the muscle, human annotations require expertise and time. Thus, precise muscle masks where IMF is excluded are limited in practice. To alleviate this, we propose a few-shot segmentation framework to generate thigh muscle masks excluding IMF. In our framework, we design a novel pseudo-label correction and evaluation scheme, together with a new noise robust loss for exploiting high certainty areas. The proposed framework only takes $1\%$ of the fine-annotated training dataset, and achieves comparable performance with fully supervised methods according to the experimental results.

Masatoshi Uehara, Yulai Zhao, Chenyu Wang et al. · princeton

This tutorial provides an in-depth guide on inference-time guidance and alignment methods for optimizing downstream reward functions in diffusion models. While diffusion models are renowned for their generative modeling capabilities, practical applications in fields such as biology often require sample generation that maximizes specific metrics (e.g., stability, affinity in proteins, closeness to target structures). In these scenarios, diffusion models can be adapted not only to generate realistic samples but also to explicitly maximize desired measures at inference time without fine-tuning. This tutorial explores the foundational aspects of such inference-time algorithms. We review these methods from a unified perspective, demonstrating that current techniques -- such as Sequential Monte Carlo (SMC)-based guidance, value-based sampling, and classifier guidance -- aim to approximate soft optimal denoising processes (a.k.a. policies in RL) that combine pre-trained denoising processes with value functions serving as look-ahead functions that predict from intermediate states to terminal rewards. Within this framework, we present several novel algorithms not yet covered in the literature. Furthermore, we discuss (1) fine-tuning methods combined with inference-time techniques, (2) inference-time algorithms based on search algorithms such as Monte Carlo tree search, which have received limited attention in current research, and (3) connections between inference-time algorithms in language models and diffusion models. The code of this tutorial on protein design is available at https://github.com/masa-ue/AlignInversePro

Sheng Chen, Zihao Tang, Mariano Cabezas et al.

Diffusion-weighted imaging (DWI) is a type of Magnetic Resonance Imaging (MRI) technique sensitised to the diffusivity of water molecules, offering the capability to inspect tissue microstructures and is the only in-vivo method to reconstruct white matter fiber tracts non-invasively. The DWI signal can be analysed with the diffusion tensor imaging (DTI) model to estimate the directionality of water diffusion within voxels. Several scalar metrics, including axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA), can be further derived from DTI to quantitatively summarise the microstructural integrity of brain tissue. These scalar metrics have played an important role in understanding the organisation and health of brain tissue at a microscopic level in clinical studies. However, reliable DTI metrics rely on DWI acquisitions with high gradient directions, which often go beyond the commonly used clinical protocols. To enhance the utility of clinically acquired DWI and save scanning time for robust DTI analysis, this work proposes DirGeo-DTI, a deep learning-based method to estimate reliable DTI metrics even from a set of DWIs acquired with the minimum theoretical number (6) of gradient directions. DirGeo-DTI leverages directional encoding and geometric constraints to facilitate the training process. Two public DWI datasets were used for evaluation, demonstrating the effectiveness of the proposed method. Extensive experimental results show that the proposed method achieves the best performance compared to existing DTI enhancement methods and potentially reveals further clinical insights with routine clinical DWI scans.

Yifei Sun, Mariano Cabezas, Jiah Lee et al.

The human brain is a complex and highly dynamic system, and our current knowledge of its functional mechanism is still very limited. Fortunately, with functional magnetic resonance imaging (fMRI), we can observe blood oxygen level-dependent (BOLD) changes, reflecting neural activity, to infer brain states and dynamics. In this paper, we ask the question of whether the brain states rep-resented by the regional brain fMRI can be predicted. Due to the success of self-attention and the transformer architecture in sequential auto-regression problems (e.g., language modelling or music generation), we explore the possi-bility of the use of transformers to predict human brain resting states based on the large-scale high-quality fMRI data from the human connectome project (HCP). Current results have shown that our model can accurately predict the brain states up to 5.04s with the previous 21.6s. Furthermore, even though the prediction error accumulates for the prediction of a longer time period, the gen-erated fMRI brain states reflect the architecture of functional connectome. These promising initial results demonstrate the possibility of developing gen-erative models for fMRI data using self-attention that learns the functional or-ganization of the human brain. Our code is available at: https://github.com/syf0122/brain_state_pred.

Chenyu Wang, Masatoshi Uehara, Yichun He et al.

Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences across domains from natural language to biological sequence generation. For example, in the protein inverse folding task, conditional diffusion models have achieved impressive results in generating natural-like sequences that fold back into the original structure. However, practical design tasks often require not only modeling a conditional distribution but also optimizing specific task objectives. For instance, we may prefer protein sequences with high stability. To address this, we consider the scenario where we have pre-trained discrete diffusion models that can generate natural-like sequences, as well as reward models that map sequences to task objectives. We then formulate the reward maximization problem within discrete diffusion models, analogous to reinforcement learning (RL), while minimizing the KL divergence against pretrained diffusion models to preserve naturalness. To solve this RL problem, we propose a novel algorithm, DRAKES, that enables direct backpropagation of rewards through entire trajectories generated by diffusion models, by making the originally non-differentiable trajectories differentiable using the Gumbel-Softmax trick. Our theoretical analysis indicates that our approach can generate sequences that are both natural-like and yield high rewards. While similar tasks have been recently explored in diffusion models for continuous domains, our work addresses unique algorithmic and theoretical challenges specific to discrete diffusion models, which arise from their foundation in continuous-time Markov chains rather than Brownian motion. Finally, we demonstrate the effectiveness of DRAKES in generating DNA and protein sequences that optimize enhancer activity and protein stability, respectively, important tasks for gene therapies and protein-based therapeutics.

Cai Zhou, Chenxiao Yang, Yi Hu et al.

Diffusion language models, especially masked discrete diffusion models, have achieved great success recently. While there are some theoretical and primary empirical results showing the advantages of latent reasoning with looped transformers or continuous chain-of-thoughts, continuous diffusion models typically underperform their discrete counterparts. In this paper, we argue that diffusion language models do not necessarily need to be in the discrete space. In particular, we prove that continuous diffusion models have stronger expressivity than discrete diffusions and looped transformers. We attribute the contradiction between the theoretical expressiveness and empirical performance to their practical trainability: while continuous diffusion provides intermediate supervision that looped transformers lack, they introduce additional difficulty decoding tokens into the discrete token space from the continuous representation space. We therefore propose Coevolutionary Continuous Discrete Diffusion (CCDD), which defines a joint multimodal diffusion process on the union of a continuous representation space and a discrete token space, leveraging a single model to simultaneously denoise in the joint space. By combining two modalities, CCDD is expressive with rich semantics in the latent space, as well as good trainability and sample quality with the help of explicit discrete tokens. We also propose effective architectures and advanced training/sampling techniques for CCDD, which reveals strong empirical performance in extensive language modeling experiments on real-world tasks.

Dongang Wang, Peilin Liu, Hengrui Wang et al.

Training deep neural networks reliably requires access to large-scale datasets. However, obtaining such datasets can be challenging, especially in the context of neuroimaging analysis tasks, where the cost associated with image acquisition and annotation can be prohibitive. To mitigate both the time and financial costs associated with model development, a clear understanding of the amount of data required to train a satisfactory model is crucial. This paper focuses on an early stage phase of deep learning research, prior to model development, and proposes a strategic framework for estimating the amount of annotated data required to train patch-based segmentation networks. This framework includes the establishment of performance expectations using a novel Minor Boundary Adjustment for Threshold (MinBAT) method, and standardizing patch selection through the ROI-based Expanded Patch Selection (REPS) method. Our experiments demonstrate that tasks involving regions of interest (ROIs) with different sizes or shapes may yield variably acceptable Dice Similarity Coefficient (DSC) scores. By setting an acceptable DSC as the target, the required amount of training data can be estimated and even predicted as data accumulates. This approach could assist researchers and engineers in estimating the cost associated with data collection and annotation when defining a new segmentation task based on deep neural networks, ultimately contributing to their efficient translation to real-world applications.

Chuyang Zhou, Ziao Ji, Daochang Liu et al.

Understanding how spontaneous brain activity relates to stimulus-driven neural responses is a fundamental challenge in cognitive neuroscience. While task-based functional magnetic resonance imaging (fMRI) captures localized stimulus-evoked brain activation, its acquisition is costly, time-consuming, and difficult to scale across populations. In contrast, resting-state fMRI (rs-fMRI) is task-free and abundant, but lacks direct interpretability. We introduce Rest2Visual, a conditional generative model that predicts visually evoked fMRI (ve-fMRI) from resting-state input and 2D visual stimuli. It follows a volumetric encoder--decoder design, where multiscale 3D features from rs-fMRI are modulated by image embeddings via adaptive normalization, enabling spatially accurate, stimulus-specific activation synthesis. To enable model training, we construct a large-scale triplet dataset from the Natural Scenes Dataset (NSD), aligning each rs-fMRI volume with stimulus images and their corresponding ve-fMRI activation maps. Quantitative evaluation shows that the predicted activations closely match ground truth across standard similarity and representational metrics, and support successful image reconstruction in downstream decoding. Notably, the predicted maps preserve subject-specific structure, demonstrating the model's capacity to generate individualized functional surrogates. Our results provide compelling evidence that individualized spontaneous neural activity can be transformed into stimulus-aligned representations, opening new avenues for scalable, task-free functional brain modeling.

Dongnan Liu, Chaoyi Zhang, Yang Song et al.

Recent advances in unsupervised domain adaptation (UDA) techniques have witnessed great success in cross-domain computer vision tasks, enhancing the generalization ability of data-driven deep learning architectures by bridging the domain distribution gaps. For the UDA-based cross-domain object detection methods, the majority of them alleviate the domain bias by inducing the domain-invariant feature generation via adversarial learning strategy. However, their domain discriminators have limited classification ability due to the unstable adversarial training process. Therefore, the extracted features induced by them cannot be perfectly domain-invariant and still contain domain-private factors, bringing obstacles to further alleviate the cross-domain discrepancy. To tackle this issue, we design a Domain Disentanglement Faster-RCNN (DDF) to eliminate the source-specific information in the features for detection task learning. Our DDF method facilitates the feature disentanglement at the global and local stages, with a Global Triplet Disentanglement (GTD) module and an Instance Similarity Disentanglement (ISD) module, respectively. By outperforming state-of-the-art methods on four benchmark UDA object detection tasks, our DDF method is demonstrated to be effective with wide applicability.

Yang Ma, Chaoyi Zhang, Mariano Cabezas et al.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system, characterized by the appearance of focal lesions in the white and gray matter that topographically correlate with an individual patient's neurological symptoms and signs. Magnetic resonance imaging (MRI) provides detailed in-vivo structural information, permitting the quantification and categorization of MS lesions that critically inform disease management. Traditionally, MS lesions have been manually annotated on 2D MRI slices, a process that is inefficient and prone to inter-/intra-observer errors. Recently, automated statistical imaging analysis techniques have been proposed to detect and segment MS lesions based on MRI voxel intensity. However, their effectiveness is limited by the heterogeneity of both MRI data acquisition techniques and the appearance of MS lesions. By learning complex lesion representations directly from images, deep learning techniques have achieved remarkable breakthroughs in the MS lesion segmentation task. Here, we provide a comprehensive review of state-of-the-art automatic statistical and deep-learning MS segmentation methods and discuss current and future clinical applications. Further, we review technical strategies, such as domain adaptation, to enhance MS lesion segmentation in real-world clinical settings.

Hao Xiong, Chaoyue Wang, Dacheng Tao et al.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in focal injury to the grey and white matter. The presence of white matter lesions biases morphometric analyses such as registration, individual longitudinal measurements and tissue segmentation for brain volume measurements. Lesion-inpainting with intensities derived from surrounding healthy tissue represents one approach to alleviate such problems. However, existing methods inpaint lesions based on texture information derived from local surrounding tissue, often leading to inconsistent inpainting and the generation of artifacts such as intensity discrepancy and blurriness. Based on these observations, we propose non-local partial convolutions (NLPC) that integrates a Unet-like network with the non-local module. The non-local module is exploited to capture long range dependencies between the lesion area and remaining normal-appearing brain regions. Then, the lesion area is filled by referring to normal-appearing regions with more similar features. This method generates inpainted regions that appear more realistic and natural. Our quantitative experimental results also demonstrate superiority of this technique of existing state-of-the-art inpainting methods.

Prasoon Goyal, Zhiting Hu, Xiaodan Liang et al.

The recently developed variational autoencoders (VAEs) have proved to be an effective confluence of the rich representational power of neural networks with Bayesian methods. However, most work on VAEs use a rather simple prior over the latent variables such as standard normal distribution, thereby restricting its applications to relatively simple phenomena. In this work, we propose hierarchical nonparametric variational autoencoders, which combines tree-structured Bayesian nonparametric priors with VAEs, to enable infinite flexibility of the latent representation space. Both the neural parameters and Bayesian priors are learned jointly using tailored variational inference. The resulting model induces a hierarchical structure of latent semantic concepts underlying the data corpus, and infers accurate representations of data instances. We apply our model in video representation learning. Our method is able to discover highly interpretable activity hierarchies, and obtain improved clustering accuracy and generalization capacity based on the learned rich representations.