The similar textures, diverse shapes and blurred boundaries of thyroid lesions in ultrasound images pose a significant challenge to accurate segmentation. Although several methods have been proposed to alleviate the aforementioned issues, their generalization is hindered by limited annotation data and insufficient ability to distinguish lesion from its surrounding tissues, especially in the presence of noise and outlier. Additionally, most existing methods lack uncertainty estimation which is essential for providing trustworthy results and identifying potential mispredictions. To this end, we propose knowledge-prompted trustworthy disentangled learning (KPTD) for thyroid ultrasound segmentation with limited annotations. The proposed method consists of three key components: 1) knowledge-aware prompt learning (KAPL) encodes TI-RADS reports into text features and introduces learnable prompts to extract contextual embeddings, which assist in generating region activation maps (serving as pseudo-labels for unlabeled images); 2) foreground-background disentangled learning (FBDL) leverages region activation maps to disentangle foreground and background representations, refining their prototype distributions through a contrastive learning strategy to enhance the model's discrimination and robustness; and 3) foreground-background trustworthy fusion (FBTF) integrates the foreground and background representations and estimates their uncertainty based on evidence theory, providing trustworthy segmentation results. Experimental results show that KPTD achieves superior segmentation performance under limited annotations, significantly outperforming state-of-the-art methods.

Longitudinal data with incomplete entries pose a significant challenge for clinical score regression over multiple time points. Although many methods primarily estimate longitudinal scores with complete baseline features (i.e., features collected at the initial time point), such snapshot features may overlook beneficial latent longitudinal traits for generalization. Alternatively, certain completion approaches (e.g., tensor decomposition technology) have been proposed to impute incomplete longitudinal data before score estimation, most of which, however, are transductive and cannot utilize label semantics. This work presents a tensor coupled learning (TCL) paradigm of incomplete longitudinal features and labels for clinical score regression. The TCL enjoys three advantages: 1) It drives semantic-aware factor matrices and collaboratively deals with incomplete longitudinal entries (of features and labels), during which a dynamic regularizer is designed for adaptive attribute selection. 2) It establishes a closed loop connecting baseline features and the coupled factor matrices, which enables inductive inference of longitudinal scores relying on only baseline features. 3) It reinforces the information encoding of baseline data by preserving the local manifold of longitudinal feature space and detecting the temporal alteration across multiple time points. Extensive experiments demonstrate the remarkable performance improvement of our method on clinical score regression with incomplete longitudinal data.

Biomedical multi-modality data (also named multi-omics data) refer to data that span different types and derive from multiple sources in clinical practices (e.g. gene sequences, proteomics and histopathological images), which can provide comprehensive perspectives for cancers and generally improve the performance of survival models. However, the performance improvement of multi-modality survival models may be hindered by two key issues as follows: (1) how to learn and fuse modality-sharable and modality-individual representations from multi-modality data; (2) how to explore the potential risk-aware characteristics in each risk subgroup, which is beneficial to risk stratification and prognosis evaluation. Additionally, learning-based survival models generally refer to numerous hyper-parameters, which requires time-consuming parameter setting and might result in a suboptimal solution. In this paper, we propose an adaptive risk-aware sharable and individual subspace learning method for cancer survival analysis. The proposed method jointly learns sharable and individual subspaces from multi-modality data, whereas two auxiliary terms (i.e. intra-modality complementarity and inter-modality incoherence) are developed to preserve the complementary and distinctive properties of each modality. Moreover, it equips with a grouping co-expression constraint for obtaining risk-aware representation and preserving local consistency. Furthermore, an adaptive-weighted strategy is employed to efficiently estimate crucial parameters during the training stage. Experimental results on three public datasets demonstrate the superiority of our proposed model.

Current survival analysis of cancers confronts two key issues. While comprehensive perspectives provided by data from multiple modalities often promote the performance of survival models, data with inadequate modalities at the testing phase are more ubiquitous in clinical scenarios, which makes multi-modality approaches not applicable. Additionally, incomplete observations (i.e., censored instances) bring a unique challenge for survival analysis, to tackle which, some models have been proposed based on certain strict assumptions or attribute distributions that, however, may limit their applicability. In this paper, we present a mutual-assistance learning paradigm for standalone mono-modality survival analysis of cancers. The mutual assistance implies the cooperation of multiple components and embodies three aspects: 1) it leverages the knowledge of multi-modality data to guide the representation learning of an individual modality via mutual-assistance similarity and geometry constraints; 2) it formulates mutual-assistance regression and ranking functions independent of strong hypotheses to estimate the relative risk, in which a bias vector is introduced to efficiently cope with the censoring problem; 3) it integrates representation learning and survival modeling into a unified mutual-assistance framework for alleviating the requirement of attribute distributions. Extensive experiments on several datasets demonstrate our method can significantly improve the performance of mono-modality survival model.

The Cox proportional hazard model has been widely applied to cancer prognosis prediction. Nowadays, multi-modal data, such as histopathological images and gene data, have advanced this field by providing histologic phenotype and genotype information. However, how to efficiently fuse and select the complementary information of high-dimensional multi-modal data remains challenging for Cox model, as it generally does not equip with feature fusion/selection mechanism. Many previous studies typically perform feature fusion/selection in the original feature space before Cox modeling. Alternatively, learning a latent shared feature space that is tailored for Cox model and simultaneously keeps sparsity is desirable. In addition, existing Cox-based models commonly pay little attention to the actual length of the observed time that may help to boost the model's performance. In this article, we propose a novel Cox-driven multi-constraint latent representation learning framework for prognosis analysis with multi-modal data. Specifically, for efficient feature fusion, a multi-modal latent space is learned via a bi-mapping approach under ranking and regression constraints. The ranking constraint utilizes the log-partial likelihood of Cox model to induce learning discriminative representations in a task-oriented manner. Meanwhile, the representations also benefit from regression constraint, which imposes the supervision of specific survival time on representation learning. To improve generalization and alleviate overfitting, we further introduce similarity and sparsity constraints to encourage extra consistency and sparseness. Extensive experiments on three datasets acquired from The Cancer Genome Atlas (TCGA) demonstrate that the proposed method is superior to state-of-the-art Cox-based models.

The multi-instance learning (MIL) has advanced cancer prognosis analysis with whole slide images (WSIs). However, current MIL methods for WSI analysis still confront unique challenges. Previous methods typically generate instance representations via a pre-trained model or a model trained by the instances with bag-level annotations, which, however, may not generalize well to the downstream task due to the introduction of excessive label noises and the lack of fine-grained information across multi-magnification WSIs. Additionally, existing methods generally aggregate instance representations as bag ones for prognosis prediction and have no consideration of intra-bag redundancy and inter-bag discrimination. To address these issues, we propose a dual-curriculum contrastive MIL method for cancer prognosis analysis with WSIs. The proposed method consists of two curriculums, i.e., saliency-guided weakly-supervised instance encoding with cross-scale tiles and contrastive-enhanced soft-bag prognosis inference. Extensive experiments on three public datasets demonstrate that our method outperforms state-of-the-art methods in this field. The code is available at https://github.com/YuZhang-SMU/Cancer-Prognosis-Analysis/tree/main/DC_MIL%20Code.

The integrative analysis of complementary phenotype information contained in multi-modality data (e.g., histopathological images and genomic data) has advanced the prognostic evaluation of cancers. However, multi-modality based prognosis analysis confronts two challenges: (1) how to explore underlying relations inherent in different modalities data for learning compact and discriminative multi-modality representations; (2) how to take full consideration of incomplete multi-modality data for constructing accurate and robust prognostic model, since a host of complete multi-modality data are not always available. Additionally, many existing multi-modality based prognostic methods commonly ignore relevant clinical variables (e.g., grade and stage), which, however, may provide supplemental information to promote the performance of model. In this paper, we propose a relation-aware shared representation learning method for prognosis analysis of cancers, which makes full use of clinical information and incomplete multi-modality data. The proposed method learns multi-modal shared space tailored for prognostic model via a dual mapping. Within the shared space, it equips with relational regularizers to explore the potential relations (i.e., feature-label and feature-feature relations) among multi-modality data for inducing discriminatory representations and simultaneously obtaining extra sparsity for alleviating overfitting. Moreover, it regresses and incorporates multiple auxiliary clinical attributes with dynamic coefficients to meliorate performance. Furthermore, in training stage, a partial mapping strategy is employed to extend and train a more reliable model with incomplete multi-modality data. We have evaluated our method on three public datasets derived from The Cancer Genome Atlas (TCGA) project, and the experimental results demonstrate the superior performance of the proposed method.

Deep learning methods, especially convolutional neural networks, have been successfully applied to lesion segmentation in breast ultrasound (BUS) images. However, pattern complexity and intensity similarity between the surrounding tissues (i.e., background) and lesion regions (i.e., foreground) bring challenges for lesion segmentation. Considering that such rich texture information is contained in background, very few methods have tried to explore and exploit background-salient representations for assisting foreground segmentation. Additionally, other characteristics of BUS images, i.e., 1) low-contrast appearance and blurry boundary, and 2) significant shape and position variation of lesions, also increase the difficulty in accurate lesion segmentation. In this paper, we present a saliency-guided morphology-aware U-Net (SMU-Net) for lesion segmentation in BUS images. The SMU-Net is composed of a main network with an additional middle stream and an auxiliary network. Specifically, we first propose generation of saliency maps which incorporate both low-level and high-level image structures, for foreground and background. These saliency maps are then employed to guide the main network and auxiliary network for respectively learning foreground-salient and background-salient representations. Furthermore, we devise an additional middle stream which basically consists of background-assisted fusion, shape-aware, edge-aware and position-aware units. This stream receives the coarse-to-fine representations from the main network and auxiliary network for efficiently fusing the foreground-salient and background-salient features and enhancing the ability of learning morphological information for network. Extensive experiments on five datasets demonstrate higher performance and superior robustness to the scale of dataset than several state-of-the-art deep learning approaches in breast lesion segmentation in ultrasound image.

The fusion of multi-modal data (e.g., magnetic resonance imaging (MRI) and positron emission tomography (PET)) has been prevalent for accurate identification of Alzheimer's disease (AD) by providing complementary structural and functional information. However, most of the existing methods simply concatenate multi-modal features in the original space and ignore their underlying associations which may provide more discriminative characteristics for AD identification. Meanwhile, how to overcome the overfitting issue caused by high-dimensional multi-modal data remains appealing. To this end, we propose a relation-induced multi-modal shared representation learning method for AD diagnosis. The proposed method integrates representation learning, dimension reduction, and classifier modeling into a unified framework. Specifically, the framework first obtains multi-modal shared representations by learning a bi-directional mapping between original space and shared space. Within this shared space, we utilize several relational regularizers (including feature-feature, feature-label, and sample-sample regularizers) and auxiliary regularizers to encourage learning underlying associations inherent in multi-modal data and alleviate overfitting, respectively. Next, we project the shared representations into the target space for AD diagnosis. To validate the effectiveness of our proposed approach, we conduct extensive experiments on two independent datasets (i.e., ADNI-1 and ADNI-2), and the experimental results demonstrate that our proposed method outperforms several state-of-the-art methods.

MOTIVATION: As a highly heterogeneous disease, clear cell renal cell carcinoma (ccRCC) has quite variable clinical behaviors. The prognostic biomarkers play a crucial role in stratifying patients suffering from ccRCC to avoid over- and under-treatment. Researches based on hand-crafted features and single-modal data have been widely conducted to predict the prognosis of ccRCC. However, these experience-dependent methods, neglecting the synergy among multimodal data, have limited capacity to perform accurate prediction. Inspired by complementary information among multimodal data and the successful application of convolutional neural networks (CNNs) in medical image analysis, a novel framework was proposed to improve prediction performance. RESULTS: We proposed a cross-modal feature-based integrative framework, in which deep features extracted from computed tomography/histopathological images by using CNNs were combined with eigengenes generated from functional genomic data, to construct a prognostic model for ccRCC. Results showed that our proposed model can stratify high- and low-risk subgroups with significant difference (P-value < 0.05) and outperform the predictive performance of those models based on single-modality features in the independent testing cohort [C-index, 0.808 (0.728-0.888)]. In addition, we also explored the relationship between deep image features and eigengenes, and make an attempt to explain deep image features from the view of genomic data. Notably, the integrative framework is available to the task of prognosis prediction of other cancer with matched multimodal data. AVAILABILITY AND IMPLEMENTATION: https://github.com/zhang-de-lab/zhang-lab? from=singlemessage. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Predicting malignant potential is one of the most critical components of a computer-aided diagnosis system for gastrointestinal stromal tumors (GISTs). These tumors have been studied only on the basis of subjective computed tomography findings. Among various methodologies, radiomics, and deep learning algorithms, specifically convolutional neural networks (CNNs), have recently been confirmed to achieve significant success by outperforming the state-of-the-art performance in medical image pattern classification and have rapidly become leading methodologies in this field. However, the existing methods generally use radiomics or deep convolutional features independently for pattern classification, which tend to take into account only global or local features, respectively. In this paper, we introduce and evaluate a hybrid structure that includes different features selected with radiomics model and CNNs and integrates these features to deal with GISTs classification. The Radiomics model and CNNs are constructed for global radiomics and local convolutional feature selection, respectively. Subsequently, we utilize distinct radiomics and deep convolutional features to perform pattern classification for GISTs. Specifically, we propose a new pooling strategy to assemble the deep convolutional features of 54 three-dimensional patches from the same case and integrate these features with the radiomics features for independent case, followed by random forest classifier. Our method can be extensively evaluated using multiple clinical datasets. The classification performance (area under the curve (AUC): 0.882; 95% confidence interval (CI): 0.816-0.947) consistently outperforms those of independent radiomics (AUC: 0.807; 95% CI: 0.724-0.892) and CNNs (AUC: 0.826; 95% CI: 0.795-0.856) approaches.