Computer methods and programs in biomedicine最新文献

Background and Objective

Histologic assessment of the immune infiltrate in H&E slides is vital in diagnosing and managing inflammatory bowel diseases, but these assessments are subjective and time-consuming even for those with expertise. The development of deep learning models to aid in these assessments has been limited by the paucity of image data with reliably annotated immune cells available for training.

Methods

To address these challenges, we developed a pipeline that automates the neutrophil and lymphocyte labeling in ROIs from digital H&E slides. The data included ROIs extracted from 19 digitized H&E slides and the same slides restained with immunohistochemistry. Our pipeline first delineates each nucleus in H&E ROIs. Using the colorimetric features of the immunohistochemical stains (red: neutrophils, green: lymphocytes) in the immunohistochemistry ROIs, each cell was labeled as a neutrophil, a lymphocyte, or another cell. The labels were then transferred to the corresponding H&E ROIs by image registration, and the ROI registration accuracy was assessed by the median target registration error resulting in a labeled dataset. The newly formed dataset (NeuLy-IHC) comprising 519 ROIs with 235,256 labeled cells (74,339 lymphocytes, 16,326 neutrophils and 144,591 other cells) was used to train the HoVer-Net^(NeuLy) model. The performance of HoVer-Net^(NeuLy) measured by DICE coefficient (segmentation accuracy) and F1-scores (classification accuracy), was compared to those achieved by HoVer-Net^(MoNuSAC) and SMILE^(MoNuSAC) publicly available models trained on cancer-containing ROIs from the MoNuSAC dataset with manual cell labeling and pathologists’ annotations.

Results

The 1.0 μm median target registration error of ROIs observed was low demonstrating robust transferring of cellular labels from immunohistochemistry ROIs to H&E ROIs. In the test set comprising 76 NeuLy-IHC and 78 MoNuSAC ROIs, the HoVer-Net^(NeuLy) achieved a DICE coefficient of 0.861 and F1-sores of 0.827, 0.838, and 0.828, for neutrophils, lymphocytes, and other cells, respectively, outperforming the HoVer-Net^(MoNuSAC)'s and SMILE^(MoNuSAC)’s DICE coefficient and F1 scores for each cell category.

Conclusions

We attribute the improved performance of HoVer-Net^(NeuLy) to the larger number of immune cells in the NeuLy-IHC dataset (in total 5x more, including 21x more neutrophils) than in the MoNuSAC dataset. Despite being trained on data from inflammatory bowel disease specimens, our model maintained robust performance when tested on previously unseen data derived from cancer specimens. The NeuLy-IHC set provides opportunities for training accurate models to quantify the inflammatory infiltrate in digital histologic slides.

Background and Objective:

The accurate diagnosis of schizophrenia spectrum disorder plays an important role in improving patient outcomes, enabling timely interventions, and optimizing treatment plans. Functional connectivity analysis, utilizing functional magnetic resonance imaging data, has been demonstrated to offer invaluable biomarkers conducive to clinical diagnosis. However, previous studies mainly focus on traditional machine learning methods or hand-crafted neural networks, which may not fully capture the spatial topological relationship between brain regions.

Methods:

This paper proposes an evolutionary algorithm (EA) based graph neural architecture search (GNAS) method. EA-GNAS has the ability to search for high-performance graph neural networks for schizophrenia spectrum disorder prediction. Moreover, we adopt GNNExplainer to investigate the explainability of the acquired architectures, ensuring that the model’s predictions are both accurate and comprehensible.

Results:

The results suggest that the graph neural network model, derived using genetic algorithm search, outperforms under five-fold cross-validation, achieving a fitness of 0.1850. Relative to conventional machine learning and other deep learning approaches, the proposed method yields superior accuracy, F1 score, and AUC values of 0.8246, 0.8438, and 0.8258, respectively.

Conclusion:

Based on a multi-site dataset from schizophrenia spectrum disorder patients, the findings reveal an enhancement over prior methods, advancing our comprehension of brain function and potentially offering a biomarker for diagnosing schizophrenia spectrum disorder.

Background and objective

Understanding the intricate interactions among leucocyte subpopulations following radiotherapy is crucial for advancing cancer research and immunology. Recently, interest in recent radiotherapy modalities, such as protons, has increased. Herein, we present a framework utilizing Bayesian networks to uncover these complex relationships via an illustrative example of brain irradiation in rodents.

Methods

We utilized data from 96 healthy C57BL/6 adult mice subjected to either X-ray or proton brain irradiation. Leucocyte subpopulations in the blood collected 12 h after the final irradiated fraction were quantified. We employed Bayesian networks to detect causal interplay between physiological parameters, radiation variables and circulating leucocytes. The causal structure was learned via the use of the Bayesian information criterion as a scored criterion. Parameter estimation was performed to quantify the strength of the identified causal relationships. Cross-validation was used to validate our Bayesian network model's performance.

Results

In the X-ray model, we discovered previously undisclosed interactions between NK-cells and neutrophils, and between monocytes and T-CD4⁺ cells. The proton model revealed an interplay involving T-CD4⁺ cells and neutrophils. Both X-rays and protons led to heightened interactions between T-CD8+ cells and B cells, indicating their significant role in orchestrating immune responses. Additionally, the proton model displayed strengthened interactions between T-CD4⁺ and T-CD8⁺ cells, emphasizing a dynamic and coordinated immune response post-irradiation. Cross-validation results demonstrated the robustness of the Bayesian network model in explaining data uncertainty.

Conclusion

The use of Bayesian networks as tools for causal structure discovery has revealed novel insights into the dynamics of immune responses to radiation exposure.

Background and Objective

Materials and Methods

Results

Conclusions

Background and Objective:

Only about 14% of eligible EU citizens finally participate in colorectal cancer (CRC) screening programs despite it being the third most common type of cancer worldwide. The development of CRC risk models can enable predictions to be embedded in decision-support tools facilitating CRC screening and treatment recommendations. This paper develops a predictive model that aids in characterizing CRC risk groups and assessing the influence of a variety of risk factors on the population.

Methods:

A CRC Bayesian Network is learnt by aggregating extensive expert knowledge and data from an observational study and making use of structure learning algorithms to model the relations between variables. The network is then parametrised to characterize these relations in terms of local probability distributions at each of the nodes. It is finally used to predict the risks of developing CRC together with the uncertainty around such predictions.

Results:

A graphical CRC risk mapping tool is developed from the model and used to segment the population into risk subgroups according to variables of interest. Furthermore, the network provides insights on the predictive influence of modifiable risk factors such as alcohol consumption and smoking, and medical conditions such as diabetes or hypertension linked to lifestyles that potentially have an impact on an increased risk of developing CRC.

Conclusion:

CRC is most commonly developed in older individuals. However, some modifiable behavioral factors seem to have a strong predictive influence on its potential risk of development. Modeling these effects facilitates identifying risk groups and targeting influential variables which are subsequently helpful in the design of screening and treatment programs.

Background and objective

Accurate prognosis prediction for cancer patients plays a significant role in the formulation of treatment strategies, considerably impacting personalized medicine. Recent advancements in this field indicate that integrating information from various modalities, such as genetic and clinical data, and developing multi-modal deep learning models can enhance prediction accuracy. However, most existing multi-modal deep learning methods either overlook patient similarities that benefit prognosis prediction or fail to effectively capture diverse information due to measuring patient similarities from a single perspective. To address these issues, a novel framework called multi-modal multi-view graph convolutional networks (MMGCN) is proposed for cancer prognosis prediction.

Methods

Initially, we utilize the similarity network fusion (SNF) algorithm to merge patient similarity networks (PSNs), individually constructed using gene expression, copy number alteration, and clinical data, into a fused PSN for integrating multi-modal information. To capture diverse perspectives of patient similarities, we treat the fused PSN as a multi-view graph by considering each single-edge-type subgraph as a view graph, and propose multi-view graph convolutional networks (GCNs) with a view-level attention mechanism. Moreover, an edge homophily prediction module is designed to alleviate the adverse effects of heterophilic edges on the representation power of GCNs. Finally, comprehensive representations of patient nodes are obtained to predict cancer prognosis.

Results

Experimental results demonstrate that MMGCN outperforms state-of-the-art baselines on four public datasets, including METABRIC, TCGA-BRCA, TCGA-LGG, and TCGA-LUSC, with the area under the receiver operating characteristic curve achieving 0.827 ± 0.005, 0.805 ± 0.014, 0.925 ± 0.007, and 0.746 ± 0.013, respectively.

Conclusions

Our study reveals the effectiveness of the proposed MMGCN, which deeply explores patient similarities related to different modalities from a broad perspective, in enhancing the performance of multi-modal cancer prognosis prediction. The source code is publicly available at https://github.com/ping-y/MMGCN.

Background and objective

Invasive fractional flow reserve (FFR) measurement is the gold standard method for coronary artery disease (CAD) diagnosis. FFR-CT exploits computational fluid dynamics (CFD) for non-invasive evaluation of FFR, simulating coronary flow in virtual geometries reconstructed from computed tomography (CT), but suffers from cost-intensive computing process and uncertainties in the definition of patient specific boundary conditions (BCs). In this work, we investigated the use of time-averaged steady BCs, compared to pulsatile to reduce the computational time and deployed a self-adjusting method for the tuning of BCs to patient-specific clinical data.

Methods

133 coronary arteries were reconstructed form CT images of patients suffering from CAD. For each vessel, invasive FFR was measured. After segmentation, the geometries were prepared for CFD simulation by clipping the outlets and discretizing into tetrahedral mesh. Steady BCs were defined in two steps: (i) rest BCs were extrapolated from clinical and image-derived data; (ii) hyperemic BCs were computed from resting conditions. Flow rate was iteratively adjusted during the simulation, until patient's aortic pressure was matched. Pulsatile BCs were defined exploiting the convergence values of steady BCs. After CFD simulation, lesion-specific hemodynamic indexes were computed and compared between group of patients for which surgery was indicated and not. The whole pipeline was implemented as a straightforward process, in which each single step is performed automatically.

Results

Steady and pulsatile FFR-CT yielded a strong correlation (r = 0.988, p < 0.001) and correlated with invasive FFR (r = 0.797, p < 0.001). The per-point difference between the pressure and FFR-CT field predicted by the two methods was below 1 % and 2 %, respectively. Both approaches exhibited a good diagnostic performance: accuracy was 0.860 and 0.864, the AUC was 0.923 and 0.912, for steady and pulsatile case, respectively. The computational time required by steady BCs CFD was approximatively 30-folds lower than pulsatile case.

Conclusions

This work shows the feasibility of using steady BCs CFD for computing the FFR-CT in coronary arteries, as well as its computational and diagnostic performance within a fully automated pipeline.

Background and objective:

Electrocardiogram (ECG) analysis is crucial in diagnosing cardiovascular diseases (CVDs). It is important to consider both temporal and spatial features in ECG analysis to improve automated CVDs diagnosis. Significant progress has been made in automated CVDs diagnosis based on ECG with the continuous development of deep learning. Current most researches often treat 12-lead ECG signals as synchronous sequences in Euclidean space, focusing primarily on extracting temporal features while overlooking the spatial relationships among the 12-lead. However, the spatial distribution of 12-lead ECG electrodes can be more naturally represented using non-Euclidean data structures, which makes the relationships among leads more consistent with their intrinsic characteristics.

Methods:

This study proposes an innovative method, Convolutional Residual Graph Neural Network (Conv-RGNN), for ECG classification. The first step is to segment the 12-lead ECG into twelve single-lead ECG, which are then mapped to nodes in a graph that captures the relationships between the different leads through spatial connections, resulting in the 12-lead ECG graph. The graph is then used as input for Conv-RGNN. A convolutional neural network with a position attention mechanism is used to extract temporal sequence information and selectively integrate contextual information to enhance semantic features at different positions. The spatial features of the 12-lead ECG graph are extracted using the residual graph neural network.

Results:

The experimental results indicate that Conv-RGNN is highly competitive in two multi-label datasets and one single-label dataset, demonstrating exceptional parameter efficiency, inference speed, model performance, and robustness.

Conclusion:

The Conv-RGNN proposed in this paper offer a promising and feasible approach for intelligent diagnosis in resource-constrained environments.

Background and Objective:

Automatic sleep staging is essential for assessing and diagnosing sleep disorders, serving millions of people who suffer from them. Numerous sleep staging models have been proposed recently, but most of them have not fully explored the sleep transition rules that are essential for sleep experts to identify sleep stages. Therefore, one objective of this paper is to develop an automatic sleep staging model to capture the transition rules between sleep stages.

Methods:

In this paper, we propose a novel sleep staging model named SleepGCN. It utilizes the deep features of electroencephalogram (EEG) and electrooculogram (EOG) signals extracted by the sleep representation learning (SRL) module, in conjunction with the transition rules learned by the sleep transition rule learning (STRL) module to identify sleep stages. Specifically, the SRL module utilizes the residual network (ResNet) and Long Short Term Memory (LSTM) structure to capture the deep time-invariant features and temporal information of each sleep stage from the two-channel EEG-EOG, and then applies a feature enhancement block to obtain the refined features. The STRL module employs a Graph Convolutional Network (GCN) and a transition rule matrix to capture transition rules between sleep stages based on the sequence labels of the input signals.

Results:

We evaluate SleepGCN on five public datasets: SleepEDF-20, SleepEDF-78, SHHS, DOD-H and DOD-O. Overall, SleepGCN achieves an accuracy of 89.70%, 87.70%, 86.16%, 82.07%, and 81.20%, alongside a macro-average F1-score of 85.20%, 82.70%, 77.69%, 72.44%, and 72.93% across these datasets, respectively.

Conclusions:

The results achieved by our proposed model are much better than those of all other compared models. The ablation study validates the contributions of the SRL and STRL modules proposed in SleepGCN to the sleep staging tasks. Additionally, it shows that the sleep staging model using two-channel EEG-EOG outperforms the model using single-channel EEG or EOG. Overall, SleepGCN is an effective solution for sleep staging using two-channel EEG-EOG.

Background and Objective

The increasing implementation and use of electronic health records over the last few decades has made a significant volume of clinical data being available. Over the past 20 years, hospitals have also adopted and implemented data warehouse technology to facilitate the reuse of administrative and clinical data for research. However, the implementation of clinical data warehouses encounters a set of barriers: ethical, legislative, technical, human and organizational. This paper proposes an overview of difficulties and barriers encountered during a clinical data warehouse (CDW) development and implementation project.

Methods

We conducted a focus group at the 2023 Medical Informatics Europe Conference and invited professionals involved in the implementation of CDW. These experts described their CDW and the difficulties and barriers they encountered at each phase: (i) launching of the data warehouse project, (ii) implementing the data warehouse and (iii) using a data warehouse in routine operations. They were also asked to propose solutions they were able to implement to address the barriers previously reported.

Results

After synthesis and consensus, a total of 26 barriers were identified, 10 pertained to tasks, 5 to tools and technologies, 4 to persons, 4 to organization, and 3 to the external environment. To address these challenges, a set of 15 practical recommendations was offered, covering essential aspects such as governance, stakeholder engagement, interdisciplinary collaboration, and external expertise utilization.

Conclusions

These recommendations serve as a valuable resource for healthcare institutions seeking to establish and optimize CDWs, offering a roadmap for leveraging clinical data for research, quality enhancement, and improved patient care.