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Zaiyi Liu

Publications and source records attributed to Zaiyi Liu.

34 records · Page 2Linked to original sources

Rethinking Mitosis Detection: Towards Diverse Data and Feature Representation

Mitosis detection is one of the fundamental tasks in computational pathology, which is extremely challenging due to the heterogeneity of mitotic cell. Most of the current studies solve the heterogeneity in the technical aspect by increasing the model complexity. However, lacking consideration of the biological knowledge and the complex model design may lead to the overfitting problem while limited the generalizability of the detection model. In this paper, we systematically study the morphological appearances in different mitotic phases as well as the ambiguous non-mitotic cells and identify that balancing the data and feature diversity can achieve better generalizability. Based on this observation, we propose a novel generalizable framework (MitDet) for mitosis detection. The data diversity is considered by the proposed diversity-guided sample balancing (DGSB). And the feature diversity is preserved by inter- and intra- class feature diversity-preserved module (InCDP). Stain enhancement (SE) module is introduced to enhance the domain-relevant diversity of both data and features simultaneously. Extensive experiments have demonstrated that our proposed model outperforms all the SOTA approaches in several popular mitosis detection datasets in both internal and external test sets using minimal annotation efforts with point annotations only. Comprehensive ablation studies have also proven the effectiveness of the rethinking of data and feature diversity balancing. By analyzing the results quantitatively and qualitatively, we believe that our proposed model not only achieves SOTA performance but also might inspire the future studies in new perspectives. Source code is at https://github.com/Onehour0108/MitDet.

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Devil is in the Queries: Advancing Mask Transformers for Real-world Medical Image Segmentation and Out-of-Distribution Localization

Real-world medical image segmentation has tremendous long-tailed complexity of objects, among which tail conditions correlate with relatively rare diseases and are clinically significant. A trustworthy medical AI algorithm should demonstrate its effectiveness on tail conditions to avoid clinically dangerous damage in these out-of-distribution (OOD) cases. In this paper, we adopt the concept of object queries in Mask Transformers to formulate semantic segmentation as a soft cluster assignment. The queries fit the feature-level cluster centers of inliers during training. Therefore, when performing inference on a medical image in real-world scenarios, the similarity between pixels and the queries detects and localizes OOD regions. We term this OOD localization as MaxQuery. Furthermore, the foregrounds of real-world medical images, whether OOD objects or inliers, are lesions. The difference between them is less than that between the foreground and background, possibly misleading the object queries to focus redundantly on the background. Thus, we propose a query-distribution (QD) loss to enforce clear boundaries between segmentation targets and other regions at the query level, improving the inlier segmentation and OOD indication. Our proposed framework is tested on two real-world segmentation tasks, i.e., segmentation of pancreatic and liver tumors, outperforming previous state-of-the-art algorithms by an average of 7.39% on AUROC, 14.69% on AUPR, and 13.79% on FPR95 for OOD localization. On the other hand, our framework improves the performance of inlier segmentation by an average of 5.27% DSC when compared with the leading baseline nnUNet.

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CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

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Rethinking Annotation Granularity for Overcoming Shortcuts in Deep Learning-based Radiograph Diagnosis: A Multicenter Study

Two DL models were developed using radiograph-level annotations (yes or no disease) and fine-grained lesion-level annotations (lesion bounding boxes), respectively named CheXNet and CheXDet. The models' internal classification performance and lesion localization performance were compared on a testing set (n=2,922), external classification performance was compared on NIH-Google (n=4,376) and PadChest (n=24,536) datasets, and external lesion localization performance was compared on NIH-ChestX-ray14 dataset (n=880). The models were also compared to radiologists on a subset of the internal testing set (n=496). Given sufficient training data, both models performed comparably to radiologists. CheXDet achieved significant improvement for external classification, such as in classifying fracture on NIH-Google (CheXDet area under the ROC curve [AUC]: 0.67, CheXNet AUC: 0.51; p<.001) and PadChest (CheXDet AUC: 0.78, CheXNet AUC: 0.55; p<.001). CheXDet achieved higher lesion detection performance than CheXNet for most abnormalities on all datasets, such as in detecting pneumothorax on the internal set (CheXDet jacknife alternative free-response ROC-figure of merit [JAFROC-FOM]: 0.87, CheXNet JAFROC-FOM: 0.13; p<.001) and NIH-ChestX-ray14 (CheXDet JAFROC-FOM: 0.55, CheXNet JAFROC-FOM: 0.04; p<.001). To summarize, fine-grained annotations overcame shortcut learning and enabled DL models to identify correct lesion patterns, improving the models' generalizability.

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2D and 3D CT Radiomic Features Performance Comparison in Characterization of Gastric Cancer: A Multi-center Study

Objective: Radiomics, an emerging tool for medical image analysis, is potential towards precisely characterizing gastric cancer (GC). Whether using one-slice 2D annotation or whole-volume 3D annotation remains a long-time debate, especially for heterogeneous GC. We comprehensively compared 2D and 3D radiomic features' representation and discrimination capacity regarding GC, via three tasks. Methods: Four-center 539 GC patients were retrospectively enrolled and divided into the training and validation cohorts. From 2D or 3D regions of interest (ROIs) annotated by radiologists, radiomic features were extracted respectively. Feature selection and model construction procedures were customed for each combination of two modalities (2D or 3D) and three tasks. Subsequently, six machine learning models (Model_2D^LNM, Model_3D^LNM; Model_2D^LVI, Model_3D^LVI; Model_2D^pT, Model_3D^pT) were derived and evaluated to reflect modalities' performances in characterizing GC. Furthermore, we performed an auxiliary experiment to assess modalities' performances when resampling spacing is different. Results: Regarding three tasks, the yielded areas under the curve (AUCs) were: Model_2D^LNM's 0.712 (95% confidence interval, 0.613-0.811), Model_3D^LNM's 0.680 (0.584-0.775); Model_2D^LVI's 0.677 (0.595-0.761), Model_3D^LVI's 0.615 (0.528-0.703); Model_2D^pT's 0.840 (0.779-0.901), Model_3D^pT's 0.813 (0.747-0.879). Moreover, the auxiliary experiment indicated that Models_2D are statistically more advantageous than Models3D with different resampling spacings. Conclusion: Models constructed with 2D radiomic features revealed comparable performances with those constructed with 3D features in characterizing GC. Significance: Our work indicated that time-saving 2D annotation would be the better choice in GC, and provided a related reference to further radiomics-based researches.

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HoVer-Trans: Anatomy-aware HoVer-Transformer for ROI-free Breast Cancer Diagnosis in Ultrasound Images

Ultrasonography is an important routine examination for breast cancer diagnosis, due to its non-invasive, radiation-free and low-cost properties. However, the diagnostic accuracy of breast cancer is still limited due to its inherent limitations. It would be a tremendous success if we can precisely diagnose breast cancer by breast ultrasound images (BUS). Many learning-based computer-aided diagnostic methods have been proposed to achieve breast cancer diagnosis/lesion classification. However, most of them require a pre-define ROI and then classify the lesion inside the ROI. Conventional classification backbones, such as VGG16 and ResNet50, can achieve promising classification results with no ROI requirement. But these models lack interpretability, thus restricting their use in clinical practice. In this study, we propose a novel ROI-free model for breast cancer diagnosis in ultrasound images with interpretable feature representations. We leverage the anatomical prior knowledge that malignant and benign tumors have different spatial relationships between different tissue layers, and propose a HoVer-Transformer to formulate this prior knowledge. The proposed HoVer-Trans block extracts the inter- and intra-layer spatial information horizontally and vertically. We conduct and release an open dataset GDPH&SYSUCC for breast cancer diagnosis in BUS. The proposed model is evaluated in three datasets by comparing with four CNN-based models and two vision transformer models via five-fold cross validation. It achieves state-of-the-art classification performance with the best model interpretability. In the meanwhile, our proposed model outperforms two senior sonographers on the breast cancer diagnosis when only one BUS image is given.

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CKD-TransBTS: Clinical Knowledge-Driven Hybrid Transformer with Modality-Correlated Cross-Attention for Brain Tumor Segmentation

Brain tumor segmentation (BTS) in magnetic resonance image (MRI) is crucial for brain tumor diagnosis, cancer management and research purposes. With the great success of the ten-year BraTS challenges as well as the advances of CNN and Transformer algorithms, a lot of outstanding BTS models have been proposed to tackle the difficulties of BTS in different technical aspects. However, existing studies hardly consider how to fuse the multi-modality images in a reasonable manner. In this paper, we leverage the clinical knowledge of how radiologists diagnose brain tumors from multiple MRI modalities and propose a clinical knowledge-driven brain tumor segmentation model, called CKD-TransBTS. Instead of directly concatenating all the modalities, we re-organize the input modalities by separating them into two groups according to the imaging principle of MRI. A dual-branch hybrid encoder with the proposed modality-correlated cross-attention block (MCCA) is designed to extract the multi-modality image features. The proposed model inherits the strengths from both Transformer and CNN with the local feature representation ability for precise lesion boundaries and long-range feature extraction for 3D volumetric images. To bridge the gap between Transformer and CNN features, we propose a Trans&CNN Feature Calibration block (TCFC) in the decoder. We compare the proposed model with five CNN-based models and six transformer-based models on the BraTS 2021 challenge dataset. Extensive experiments demonstrate that the proposed model achieves state-of-the-art brain tumor segmentation performance compared with all the competitors.

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WSSS4LUAD: Grand Challenge on Weakly-supervised Tissue Semantic Segmentation for Lung Adenocarcinoma

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma (LUAD) is the most common subtype. Exploiting the potential value of the histopathology images can promote precision medicine in oncology. Tissue segmentation is the basic upstream task of histopathology image analysis. Existing deep learning models have achieved superior segmentation performance but require sufficient pixel-level annotations, which is time-consuming and expensive. To enrich the label resources of LUAD and to alleviate the annotation efforts, we organize this challenge WSSS4LUAD to call for the outstanding weakly-supervised semantic segmentation (WSSS) techniques for histopathology images of LUAD. Participants have to design the algorithm to segment tumor epithelial, tumor-associated stroma and normal tissue with only patch-level labels. This challenge includes 10,091 patch-level annotations (the training set) and over 130 million labeled pixels (the validation and test sets), from 87 WSIs (67 from GDPH, 20 from TCGA). All the labels were generated by a pathologist-in-the-loop pipeline with the help of AI models and checked by the label review board. Among 532 registrations, 28 teams submitted the results in the test phase with over 1,000 submissions. Finally, the first place team achieved mIoU of 0.8413 (tumor: 0.8389, stroma: 0.7931, normal: 0.8919). According to the technical reports of the top-tier teams, CAM is still the most popular approach in WSSS. Cutmix data augmentation has been widely adopted to generate more reliable samples. With the success of this challenge, we believe that WSSS approaches with patch-level annotations can be a complement to the traditional pixel annotations while reducing the annotation efforts. The entire dataset has been released to encourage more researches on computational pathology in LUAD and more novel WSSS techniques.

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A Standardized Pipeline for Colon Nuclei Identification and Counting Challenge

Nuclear segmentation and classification is an essential step for computational pathology. TIA lab from Warwick University organized a nuclear segmentation and classification challenge (CoNIC) for H&E stained histopathology images in colorectal cancer with two highly correlated tasks, nuclei segmentation and classification task and cellular composition task. There are a few obstacles we have to address in this challenge, 1) limited training samples, 2) color variation, 3) imbalanced annotations, 4) similar morphological appearance among classes. To deal with these challenges, we proposed a standardized pipeline for nuclear segmentation and classification by integrating several pluggable components. First, we built a GAN-based model to automatically generate pseudo images for data augmentation. Then we trained a self-supervised stain normalization model to solve the color variation problem. Next we constructed a baseline model HoVer-Net with cost-sensitive loss to encourage the model pay more attention on the minority classes. According to the results of the leaderboard, our proposed pipeline achieves 0.40665 mPQ+ (Rank 49th) and 0.62199 r2 (Rank 10th) in the preliminary test phase.

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RestainNet: a self-supervised digital re-stainer for stain normalization

Color inconsistency is an inevitable challenge in computational pathology, which generally happens because of stain intensity variations or sections scanned by different scanners. It harms the pathological image analysis methods, especially the learning-based models. A series of approaches have been proposed for stain normalization. However, most of them are lack flexibility in practice. In this paper, we formulated stain normalization as a digital re-staining process and proposed a self-supervised learning model, which is called RestainNet. Our network is regarded as a digital restainer which learns how to re-stain an unstained (grayscale) image. Two digital stains, Hematoxylin (H) and Eosin (E) were extracted from the original image by Beer-Lambert's Law. We proposed a staining loss to maintain the correctness of stain intensity during the restaining process. Thanks to the self-supervised nature, paired training samples are no longer necessary, which demonstrates great flexibility in practical usage. Our RestainNet outperforms existing approaches and achieves state-of-the-art performance with regard to color correctness and structure preservation. We further conducted experiments on the segmentation and classification tasks and the proposed RestainNet achieved outstanding performance compared with SOTA methods. The self-supervised design allows the network to learn any staining style with no extra effort.

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Radiomic biomarker extracted from PI-RADS 3 patients support more eìcient and robust prostate cancer diagnosis: a multi-center study

Prostate Imaging Reporting and Data System (PI-RADS) based on multi-parametric MRI classiêes patients into 5 categories (PI-RADS 1-5) for routine clinical diagnosis guidance. However, there is no consensus on whether PI-RADS 3 patients should go through biopsies. Mining features from these hard samples (HS) is meaningful for physicians to achieve accurate diagnoses. Currently, the mining of HS biomarkers is insuìcient, and the eéectiveness and robustness of HS biomarkers for prostate cancer diagnosis have not been explored. In this study, biomarkers from diéerent data distributions are constructed. Results show that HS biomarkers can achieve better performances in diéerent data distributions.

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PDBL: Improving Histopathological Tissue Classification with Plug-and-Play Pyramidal Deep-Broad Learning

Histopathological tissue classification is a fundamental task in pathomics cancer research. Precisely differentiating different tissue types is a benefit for the downstream researches, like cancer diagnosis, prognosis and etc. Existing works mostly leverage the popular classification backbones in computer vision to achieve histopathological tissue classification. In this paper, we proposed a super lightweight plug-and-play module, named Pyramidal Deep-Broad Learning (PDBL), for any well-trained classification backbone to further improve the classification performance without a re-training burden. We mimic how pathologists observe pathology slides in different magnifications and construct an image pyramid for the input image in order to obtain the pyramidal contextual information. For each level in the pyramid, we extract the multi-scale deep-broad features by our proposed Deep-Broad block (DB-block). We equipped PDBL in three popular classification backbones, ShuffLeNetV2, EfficientNetb0, and ResNet50 to evaluate the effectiveness and efficiency of our proposed module on two datasets (Kather Multiclass Dataset and the LC25000 Dataset). Experimental results demonstrate the proposed PDBL can steadily improve the tissue-level classification performance for any CNN backbones, especially for the lightweight models when given a small among of training samples (less than 10%), which greatly saves the computational time and annotation efforts.

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Multi-Layer Pseudo-Supervision for Histopathology Tissue Semantic Segmentation using Patch-level Classification Labels

Tissue-level semantic segmentation is a vital step in computational pathology. Fully-supervised models have already achieved outstanding performance with dense pixel-level annotations. However, drawing such labels on the giga-pixel whole slide images is extremely expensive and time-consuming. In this paper, we use only patch-level classification labels to achieve tissue semantic segmentation on histopathology images, finally reducing the annotation efforts. We proposed a two-step model including a classification and a segmentation phases. In the classification phase, we proposed a CAM-based model to generate pseudo masks by patch-level labels. In the segmentation phase, we achieved tissue semantic segmentation by our proposed Multi-Layer Pseudo-Supervision. Several technical novelties have been proposed to reduce the information gap between pixel-level and patch-level annotations. As a part of this paper, we introduced a new weakly-supervised semantic segmentation (WSSS) dataset for lung adenocarcinoma (LUAD-HistoSeg). We conducted several experiments to evaluate our proposed model on two datasets. Our proposed model outperforms two state-of-the-art WSSS approaches. Note that we can achieve comparable quantitative and qualitative results with the fully-supervised model, with only around a 2\% gap for MIoU and FwIoU. By comparing with manual labeling, our model can greatly save the annotation time from hours to minutes. The source code is available at: \url{https://github.com/ChuHan89/WSSS-Tissue}.

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Annotation-efficient deep learning for automatic medical image segmentation

Automatic medical image segmentation plays a critical role in scientific research and medical care. Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, we introduce Annotation-effIcient Deep lEarning (AIDE), an open-source framework to handle imperfect training datasets. Methodological analyses and empirical evaluations are conducted, and we demonstrate that AIDE surpasses conventional fully-supervised models by presenting better performance on open datasets possessing scarce or noisy annotations. We further test AIDE in a real-life case study for breast tumor segmentation. Three datasets containing 11,852 breast images from three medical centers are employed, and AIDE, utilizing 10% training annotations, consistently produces segmentation maps comparable to those generated by fully-supervised counterparts or provided by independent radiologists. The 10-fold enhanced efficiency in utilizing expert labels has the potential to promote a wide range of biomedical applications.

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X-Net: Brain Stroke Lesion Segmentation Based on Depthwise Separable Convolution and Long-range Dependencies

The morbidity of brain stroke increased rapidly in the past few years. To help specialists in lesion measurements and treatment planning, automatic segmentation methods are critically required for clinical practices. Recently, approaches based on deep learning and methods for contextual information extraction have served in many image segmentation tasks. However, their performances are limited due to the insufficient training of a large number of parameters, which sometimes fail in capturing long-range dependencies. To address these issues, we propose a depthwise separable convolution based X-Net that designs a nonlocal operation namely Feature Similarity Module (FSM) to capture long-range dependencies. The adopted depthwise convolution allows to reduce the network size, while the developed FSM provides a more effective, dense contextual information extraction and thus facilitates better segmentation. The effectiveness of X-Net was evaluated on an open dataset Anatomical Tracings of Lesions After Stroke (ATLAS) with superior performance achieved compared to other six state-of-the-art approaches. We make our code and models available at https://github.com/Andrewsher/X-Net.

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Learning Cross-Modal Deep Representations for Multi-Modal MR Image Segmentation

Multi-modal magnetic resonance imaging (MRI) is essential in clinics for comprehensive diagnosis and surgical planning. Nevertheless, the segmentation of multi-modal MR images tends to be time-consuming and challenging. Convolutional neural network (CNN)-based multi-modal MR image analysis commonly proceeds with multiple down-sampling streams fused at one or several layers. Although inspiring performance has been achieved, the feature fusion is usually conducted through simple summation or concatenation without optimization. In this work, we propose a supervised image fusion method to selectively fuse the useful information from different modalities and suppress the respective noise signals. Specifically, an attention block is introduced as guidance for the information selection. From the different modalities, one modality that contributes most to the results is selected as the master modality, which supervises the information selection of the other assistant modalities. The effectiveness of the proposed method is confirmed through breast mass segmentation in MR images of two modalities and better segmentation results are achieved compared to the state-of-the-art methods.

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