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Wenhui Lei

Wenhui Lei contributes to research discovery and scholarly infrastructure.

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Published work

6 published item(s)

preprint2026arXiv

Linking spatial biology and clinical histology via Haiku

Integrating molecular, morphological, and clinical data is essential for basic and translational biomedical research, yet systematic frameworks for jointly modeling these modalities remain limited. Here we present Haiku, a tri-modal contrastive learning model trained on multiplexed immunofluorescence (mIF). It comprises 26.7 million spatial proteomics patches from 3,218 tissue sections across 1,606 patients spanning 11 organ types, with matched hematoxylin and eosin (H&E) histology and clinical metadata aligned in a shared embedding space. Haiku enables three-way cross-modal retrieval, improves downstream classification and clinical prediction tasks over unimodal baselines, and supports zero-shot biomarker inference through fusion retrieval conditioned on clinical metadata-only text descriptions. Across tasks, Haiku outperforms competing approaches, achieving cross-modal retrieval (Recall@50 up to 0.611 versus near-zero baseline), survival prediction (C-index 0.737, +7.91% relative improvement), and zero-shot biomarker inference (mean Pearson correlation 0.718 across 52 biomarkers). Furthermore, we introduce a counterfactual prediction framework in which modifying only clinical metadata while fixing tissue morphology surfaces niche-specific molecular shifts associated with breast cancer stage progression and lung cancer survival outcomes. In a lung adenocarcinoma case study, the counterfactual analysis recovers niche-specific shifts characterized by increased CD8 and granzyme B, reduced PD-L1, and decreased Ki67, broadly consistent with patterns reported for favorable outcomes. We present these counterfactual results as exploratory, hypothesis-generating signals rather than mechanistic claims. These capabilities demonstrate that tri-modal alignment via Haiku enables integrative analysis of spatial biology, bridging molecular measurements with clinical context for biological exploration.

preprint2022arXiv

Contrastive Domain Disentanglement for Generalizable Medical Image Segmentation

Efficiently utilizing discriminative features is crucial for convolutional neural networks to achieve remarkable performance in medical image segmentation and is also important for model generalization across multiple domains, where letting model recognize domain-specific and domain-invariant information among multi-site datasets is a reasonable strategy for domain generalization. Unfortunately, most of the recent disentangle networks are not directly adaptable to unseen-domain datasets because of the limitations of offered data distribution. To tackle this deficiency, we propose Contrastive Domain Disentangle (CDD) network for generalizable medical image segmentation. We first introduce a disentangle network to decompose medical images into an anatomical representation factor and a modality representation factor. Then, a style contrastive loss is proposed to encourage the modality representations from the same domain to distribute as close as possible while different domains are estranged from each other. Finally, we propose a domain augmentation strategy that can randomly generate new domains for model generalization training. Experimental results on multi-site fundus image datasets for optic cup and disc segmentation show that the CDD has good model generalization. Our proposed CDD outperforms several state-of-the-art methods in domain generalizable segmentation.

preprint2022arXiv

Contrastive Semi-supervised Learning for Domain Adaptive Segmentation Across Similar Anatomical Structures

Convolutional Neural Networks (CNNs) have achieved state-of-the-art performance for medical image segmentation, yet need plenty of manual annotations for training. Semi-Supervised Learning (SSL) methods are promising to reduce the requirement of annotations, but their performance is still limited when the dataset size and the number of annotated images are small. Leveraging existing annotated datasets with similar anatomical structures to assist training has a potential for improving the model's performance. However, it is further challenged by the cross-anatomy domain shift due to the different appearance and even imaging modalities from the target structure. To solve this problem, we propose Contrastive Semi-supervised learning for Cross Anatomy Domain Adaptation (CS-CADA) that adapts a model to segment similar structures in a target domain, which requires only limited annotations in the target domain by leveraging a set of existing annotated images of similar structures in a source domain. We use Domain-Specific Batch Normalization (DSBN) to individually normalize feature maps for the two anatomical domains, and propose a cross-domain contrastive learning strategy to encourage extracting domain invariant features. They are integrated into a Self-Ensembling Mean-Teacher (SE-MT) framework to exploit unlabeled target domain images with a prediction consistency constraint. Extensive experiments show that our CS-CADA is able to solve the challenging cross-anatomy domain shift problem, achieving accurate segmentation of coronary arteries in X-ray images with the help of retinal vessel images and cardiac MR images with the help of fundus images, respectively, given only a small number of annotations in the target domain.

preprint2022arXiv

HMRNet: High and Multi-Resolution Network with Bidirectional Feature Calibration for Brain Structure Segmentation in Radiotherapy

Accurate segmentation of Anatomical brain Barriers to Cancer spread (ABCs) plays an important role for automatic delineation of Clinical Target Volume (CTV) of brain tumors in radiotherapy. Despite that variants of U-Net are state-of-the-art segmentation models, they have limited performance when dealing with ABCs structures with various shapes and sizes, especially thin structures (e.g., the falx cerebri) that span only few slices. To deal with this problem, we propose a High and Multi-Resolution Network (HMRNet) that consists of a multi-scale feature learning branch and a high-resolution branch, which can maintain the high-resolution contextual information and extract more robust representations of anatomical structures with various scales. We further design a Bidirectional Feature Calibration (BFC) block to enable the two branches to generate spatial attention maps for mutual feature calibration. Considering the different sizes and positions of ABCs structures, our network was applied after a rough localization of each structure to obtain fine segmentation results. Experiments on the MICCAI 2020 ABCs challenge dataset showed that: 1) Our proposed two-stage segmentation strategy largely outperformed methods segmenting all the structures in just one stage; 2) The proposed HMRNet with two branches can maintain high-resolution representations and is effective to improve the performance on thin structures; 3) The proposed BFC block outperformed existing attention methods using monodirectional feature calibration. Our method won the second place of ABCs 2020 challenge and has a potential for more accurate and reasonable delineation of CTV of brain tumors.

preprint2021arXiv

Automatic Segmentation of Gross Target Volume of Nasopharynx Cancer using Ensemble of Multiscale Deep Neural Networks with Spatial Attention

Radiotherapy is the main treatment modality for nasopharynx cancer. Delineation of Gross Target Volume (GTV) from medical images such as CT and MRI images is a prerequisite for radiotherapy. As manual delineation is time-consuming and laborious, automatic segmentation of GTV has a potential to improve this process. Currently, most of the deep learning-based automatic delineation methods of GTV are mainly performed on medical images like CT images. However, it is challenged by the low contrast between the pathology regions and surrounding soft tissues, small target region, and anisotropic resolution of clinical CT images. To deal with these problems, we propose a 2.5D Convolutional Neural Network (CNN) to handle the difference of inplane and through-plane resolution. Furthermore, we propose a spatial attention module to enable the network to focus on small target, and use channel attention to further improve the segmentation performance. Moreover, we use multi-scale sampling method for training so that the networks can learn features at different scales, which are combined with a multi-model ensemble method to improve the robustness of segmentation results. We also estimate the uncertainty of segmentation results based on our model ensemble, which is of great importance for indicating the reliability of automatic segmentation results for radiotherapy planning.

preprint2021arXiv

Automatic Segmentation of Organs-at-Risk from Head-and-Neck CT using Separable Convolutional Neural Network with Hard-Region-Weighted Loss

Nasopharyngeal Carcinoma (NPC) is a leading form of Head-and-Neck (HAN) cancer in the Arctic, China, Southeast Asia, and the Middle East/North Africa. Accurate segmentation of Organs-at-Risk (OAR) from Computed Tomography (CT) images with uncertainty information is critical for effective planning of radiation therapy for NPC treatment. Despite the stateof-the-art performance achieved by Convolutional Neural Networks (CNNs) for automatic segmentation of OARs, existing methods do not provide uncertainty estimation of the segmentation results for treatment planning, and their accuracy is still limited by several factors, including the low contrast of soft tissues in CT, highly imbalanced sizes of OARs and large inter-slice spacing. To address these problems, we propose a novel framework for accurate OAR segmentation with reliable uncertainty estimation. First, we propose a Segmental Linear Function (SLF) to transform the intensity of CT images to make multiple organs more distinguishable than existing methods based on a simple window width/level that often gives a better visibility of one organ while hiding the others. Second, to deal with the large inter-slice spacing, we introduce a novel 2.5D network (named as 3D-SepNet) specially designed for dealing with clinic HAN CT scans with anisotropic spacing. Thirdly, existing hardness-aware loss function often deal with class-level hardness, but our proposed attention to hard voxels (ATH) uses a voxel-level hardness strategy, which is more suitable to dealing with some hard regions despite that its corresponding class may be easy. Our code is now available at https://github.com/HiLab-git/SepNet.