{"title":"Thrombogenic Risk Assessment of Transcatheter Prosthetic Heart Valves Using a Fluid-Structure Interaction Approach","authors":"","doi":"10.1016/j.cmpb.2024.108469","DOIUrl":"10.1016/j.cmpb.2024.108469","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Prosthetic heart valve interventions such as TAVR have surged over the past decade, but the associated complication of long-term, life-threatening thrombotic events continues to undermine patient outcomes. Thus, improving thrombogenic risk analysis of TAVR devices is crucial. In vitro studies for thrombogenicity are typically difficult to perform. However, revised ISO testing standards include computational testing for thrombogenic risk assessment of cardiovascular implants. We present a fluid-structure interaction (FSI) approach for assessing thrombogenic risk of transcatheter aortic valves.</div></div><div><h3>Methods</h3><div>An FSI framework was implemented via the incompressible computational fluid dynamics multi-physics solver of the ANSYS LS-DYNA software. The numerical modeling approach for flow analysis was validated by comparing the derived flow rate of the 29 mm CoreValve device from benchtop testing and orifice areas of commercial TAVR valves in the literature to in silico results. Thrombogenic risk was analyzed by computing stress accumulation (SA) on virtual platelets seeded in the flow fields via ANSYS EnSight. The integrated FSI-thrombogenicity methodology was subsequently employed to examine hemodynamics and thrombogenic risk of TAVR devices with two approaches: 1) engineering optimization and 2) clinical assessment.</div></div><div><h3>Results</h3><div>Simulated effective orifice areas for commercial valves were in reported ranges. In silico cardiac output and flow rate during the positive pressure differential period matched experimental results by approximately 93 %. The approach was used to analyze the effect of various TAVR leaflet designs on hemodynamics, where platelets experienced instantaneous stresses reaching around 10 Pa. Post-TAVR deployment hemodynamics in patient-specific bicuspid aortic valve anatomies revealed varying degrees of thrombogenic risk with the highest median SA around 70 dyn·s/cm<sup>2</sup> - nearly double the activation threshold - despite those being clinically classified as “mild” paravalvular leaks.</div></div><div><h3>Conclusions</h3><div>Our methodology can be used to improve the thromboresistance of prosthetic valves from the initial design stage to the clinic. It allows for unparalleled optimization of devices, uncovering key TAVR leaflet design parameters that can be used to mitigate thrombogenic risk, in addition to patient-specific modeling to evaluate device performance. This work demonstrates the utility of advanced in silico analysis of TAVR devices that can be utilized for thrombogenic risk assessment of other blood recirculating devices.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel López-Pérez, Alba Morquecho, Arne Schmidt, Fernando Pérez-Bueno, Aurelio Martín-Castro, Javier Mateos, Rafael Molina
{"title":"The CrowdGleason dataset: Learning the Gleason grade from crowds and experts.","authors":"Miguel López-Pérez, Alba Morquecho, Arne Schmidt, Fernando Pérez-Bueno, Aurelio Martín-Castro, Javier Mateos, Rafael Molina","doi":"10.1016/j.cmpb.2024.108472","DOIUrl":"https://doi.org/10.1016/j.cmpb.2024.108472","url":null,"abstract":"<p><strong>Background: </strong>Currently, prostate cancer (PCa) diagnosis relies on the human analysis of prostate biopsy Whole Slide Images (WSIs) using the Gleason score. Since this process is error-prone and time-consuming, recent advances in machine learning have promoted the use of automated systems to assist pathologists. Unfortunately, labeled datasets for training and validation are scarce due to the need for expert pathologists to provide ground-truth labels.</p><p><strong>Methods: </strong>This work introduces a new prostate histopathological dataset named CrowdGleason, which consists of 19,077 patches from 1045 WSIs with various Gleason grades. The dataset was annotated using a crowdsourcing protocol involving seven pathologists-in-training to distribute the labeling effort. To provide a baseline analysis, two crowdsourcing methods based on Gaussian Processes (GPs) were evaluated for Gleason grade prediction: SVGPCR, which learns a model from the CrowdGleason dataset, and SVGPMIX, which combines data from the public dataset SICAPv2 and the CrowdGleason dataset. The performance of these methods was compared with other crowdsourcing and expert label-based methods through comprehensive experiments.</p><p><strong>Results: </strong>The results demonstrate that our GP-based crowdsourcing approach outperforms other methods for aggregating crowdsourced labels (κ=0.7048±0.0207) for SVGPCR vs.(κ=0.6576±0.0086) for SVGP with majority voting). SVGPCR trained with crowdsourced labels performs better than GP trained with expert labels from SICAPv2 (κ=0.6583±0.0220) and outperforms most individual pathologists-in-training (mean κ=0.5432). Additionally, SVGPMIX trained with a combination of SICAPv2 and CrowdGleason achieves the highest performance on both datasets (κ=0.7814±0.0083 and κ=0.7276±0.0260).</p><p><strong>Conclusion: </strong>The experiments show that the CrowdGleason dataset can be successfully used for training and validating supervised and crowdsourcing methods. Furthermore, the crowdsourcing methods trained on this dataset obtain competitive results against those using expert labels. Interestingly, the combination of expert and non-expert labels opens the door to a future of massive labeling by incorporating both expert and non-expert pathologist annotators.</p>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovering explainable biomarkers for breast cancer anti-PD1 response via network Shapley value analysis.","authors":"Chenxi Sun, Zhi-Ping Liu","doi":"10.1016/j.cmpb.2024.108481","DOIUrl":"https://doi.org/10.1016/j.cmpb.2024.108481","url":null,"abstract":"<p><strong>Background and objective: </strong>Immunotherapy holds promise in enhancing pathological complete response rates in breast cancer, albeit confined to a select cohort of patients. Consequently, pinpointing factors predictive of treatment responsiveness is of paramount importance. Gene expression and regulation, inherently operating within intricate networks, constitute fundamental molecular machinery for cellular processes and often serve as robust biomarkers. Nevertheless, contemporary feature selection approaches grapple with two key challenges: opacity in modeling and scarcity in accounting for gene-gene interactions METHODS: To address these limitations, we devise a novel feature selection methodology grounded in cooperative game theory, harmoniously integrating with sophisticated machine learning models. This approach identifies interconnected gene regulatory network biomarker modules with priori genetic linkage architecture. Specifically, we leverage Shapley values on network to quantify feature importance, while strategically constraining their integration based on network expansion principles and nodal adjacency, thereby fostering enhanced interpretability in feature selection. We apply our methods to a publicly available single-cell RNA sequencing dataset of breast cancer immunotherapy responses, using the identified feature gene set as biomarkers. Functional enrichment analysis with independent validations further illustrates their effective predictive performance RESULTS: We demonstrate the sophistication and excellence of the proposed method in data with network structure. It unveiled a cohesive biomarker module encompassing 27 genes for immunotherapy response. Notably, this module proves adept at precisely predicting anti-PD1 therapeutic outcomes in breast cancer patients with classification accuracy of 0.905 and AUC value of 0.971, underscoring its unique capacity to illuminate gene functionalities CONCLUSION: The proposed method is effective for identifying network module biomarkers, and the detected anti-PD1 response biomarkers can enrich our understanding of the underlying physiological mechanisms of immunotherapy, which have a promising application for realizing precision medicine.</p>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianye Shi, Kiran Manjunatha, Felix Vogt, Stefanie Reese
{"title":"Data-driven reduced order surrogate modeling for coronary in-stent restenosis.","authors":"Jianye Shi, Kiran Manjunatha, Felix Vogt, Stefanie Reese","doi":"10.1016/j.cmpb.2024.108466","DOIUrl":"https://doi.org/10.1016/j.cmpb.2024.108466","url":null,"abstract":"<p><strong>Background: </strong>The intricate process of coronary in-stent restenosis (ISR) involves the interplay between different mediators, including platelet-derived growth factor, transforming growth factor-β, extracellular matrix, smooth muscle cells, endothelial cells, and drug elution from the stent. Modeling such complex multiphysics phenomena demands extensive computational resources and time.</p><p><strong>Methods: </strong>This paper proposes a novel non-intrusive data-driven reduced order modeling approach for the underlying multiphysics time-dependent parametrized problem. In the offline phase, a 3D convolutional autoencoder, comprising an encoder and decoder, is trained to achieve dimensionality reduction. The encoder condenses the full-order solution into a lower-dimensional latent space, while the decoder facilitates the reconstruction of the full solution from the latent space. To deal with the 5D input datasets (3D geometry + time series + multiple output channels), two ingredients are explored. The first approach incorporates time as an additional parameter and applies 3D convolution on individual time steps, encoding a distinct latent variable for each parameter instance within each time step. The second approach reshapes the 3D geometry into a 2D plane along a less interactive axis and stacks all time steps in the third direction for each parameter instance. This rearrangement generates a larger and complete dataset for one parameter instance, resulting in a singular latent variable across the entire discrete time-series. In both approaches, the multiple outputs are considered automatically in the convolutions. Moreover, Gaussian process regression is applied to establish correlations between the latent variable and the input parameter.</p><p><strong>Results: </strong>The constitutive model reveals a significant acceleration in neointimal growth between 30-60 days post percutaneous coronary intervention (PCI). The surrogate models applying both approaches exhibit high accuracy in pointwise error, with the first approach showcasing smaller errors across the entire evaluation period for all outputs. The parameter study on drug dosage against ISR rates provides noteworthy insights of neointimal growth, where the nonlinear dependence of ISR rates on the peak drug flux exhibits intriguing periodic patterns. Applying the trained model, the rate of ISR is effectively evaluated, and the optimal parameter range for drug dosage is identified.</p><p><strong>Conclusion: </strong>The demonstrated non-intrusive reduced order surrogate model proves to be a powerful tool for predicting ISR outcomes. Moreover, the proposed method lays the foundation for real-time simulations and optimization of PCI parameters.</p>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fast interactive simulations of cardiac electrical activity in anatomically accurate heart structures by compressing sparse uniform cartesian grids","authors":"","doi":"10.1016/j.cmpb.2024.108456","DOIUrl":"10.1016/j.cmpb.2024.108456","url":null,"abstract":"<div><h3>Background and Objective:</h3><div>Numerical simulations are valuable tools for studying cardiac arrhythmias. Not only do they complement experimental studies, but there is also an increasing expectation for their use in clinical applications to guide patient-specific procedures. However, numerical studies that solve the reaction–diffusion equations describing cardiac electrical activity remain challenging to set up, are time-consuming, and in many cases, are prohibitively computationally expensive for long studies. The computational cost of cardiac simulations of complex models on anatomically accurate structures necessitates parallel computing. Graphics processing units (GPUs), which have thousands of cores, have been introduced as a viable technology for carrying out fast cardiac simulations, sometimes including real-time interactivity. Our main objective is to increase the performance and accuracy of such GPU implementations while conserving computational resources.</div></div><div><h3>Methods:</h3><div>In this work, we present a compression algorithm that can be used to conserve GPU memory and improve efficiency by managing the sparsity that is inherent in using Cartesian grids to represent cardiac structures directly obtained from high-resolution MRI and mCT scans. Furthermore, we present a discretization scheme that includes the cross-diagonal terms in the computational cell to increase numerical accuracy, which is especially important for simulating thin tissue sections without the need for costly mesh refinement.</div></div><div><h3>Results:</h3><div>Interactive WebGL simulations of atrial/ventricular structures (on PCs, laptops, tablets, and phones) demonstrate the algorithm’s ability to reduce memory demand by an order of magnitude and achieve calculations up to 20x faster. We further showcase its superiority in slender tissues and validate results against experiments performed in live explanted human hearts.</div></div><div><h3>Conclusions:</h3><div>In this work, we present a compression algorithm that accelerates electrical activity simulations on realistic anatomies by an order of magnitude (up to 20x), thereby allowing the use of finer grid resolutions while conserving GPU memory. Additionally, improved accuracy is achieved through cross-diagonal terms, which are essential for thin tissues, often found in heart structures such as pectinate muscles and trabeculae, as well as Purkinje fibers. Our method enables interactive simulations with even interactive domain boundary manipulation (unlike finite element/volume methods). Finally, agreement with experiments and ease of mesh import into WebGL paves the way for virtual cohorts and digital twins, aiding arrhythmia analysis and personalized therapies.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lung nodule classification using radiomics model trained on degraded SDCT images","authors":"","doi":"10.1016/j.cmpb.2024.108474","DOIUrl":"10.1016/j.cmpb.2024.108474","url":null,"abstract":"<div><h3>Background and objective</h3><div>Low-dose computed tomography (LDCT) screening has shown promise in reducing lung cancer mortality; however, it suffers from high false positive rates and a scarcity of available annotated datasets. To overcome these challenges, we propose a novel approach using synthetic LDCT images generated from standard-dose CT (SDCT) scans from the LIDC-IDRI dataset. Our objective is to develop and validate an interpretable radiomics-based model for distinguishing likely benign from likely malignant pulmonary nodules.</div></div><div><h3>Methods</h3><div>From a total of 1010 CT images (695 SDCTs and 315 LDCTs), we degraded SDCTs in the sinogram domain and obtained 1950 nodules as the training set. The 675 nodules from the LDCTs were stratified into 50%-50% partitions for validation and testing. Radiomic features were extracted from nodules, and three feature sets were assessed using: a) only shape and size (SS) features, b) all features but SS features, and c) all features. A systematic pipeline was developed to optimize the feature set and evaluate multiple machine learning models. Models were trained using degraded SDCT, validated and tested on the LDCT nodules.</div></div><div><h3>Results</h3><div>Training a logistic regression model using three SS features yielded the most promising results, achieving on the test set mean balanced accuracy, sensitivity, specificity, and AUC-ROC scores of 0.81, 0.76, 0.85, and 0.87, respectively.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates the feasibility and effectiveness of using synthetic LDCT images for developing a relatively accurate radiomics-based model in lung nodule classification. This approach addresses challenges associated with LDCT screening, offering potential implications for improving lung cancer detection and reducing false positives.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of a reduced arterial axial pre-stretch ratio during aging on the cardiac output and cerebral blood flow in the healthy elders","authors":"","doi":"10.1016/j.cmpb.2024.108468","DOIUrl":"10.1016/j.cmpb.2024.108468","url":null,"abstract":"<div><h3>Background and objective</h3><div>It is an indisputable physiological phenomenon that the arterial axial pre-stretch ratio (AAPSR) decreases with age, but little attention has been paid to the effect of this reduction on chronic diseases during aging.</div></div><div><h3>Methods</h3><div>Here we reported an experimental method to simulate arteries aging, developed a fluid-structure interaction model with the effect of AAPSR changes, and compared it with the anatomy data and structural parameters of the human thoracic aorta.</div></div><div><h3>Results</h3><div>We showed that with the process of aging, the decrease of AAPSR leads to a decline of arterial elasticity, a decrease of arterial elastic strain energy, which weakens the ability to promote blood circulation, the corresponding decrease in cardiac output (CO) and cerebral blood flow (CBF) causes distal organ and body tissue ischemia, which is one of the main causes of increased blood pressure and decreased cerebral perfusion in the elderly.</div></div><div><h3>Conclusions</h3><div>Thus, reduced AAPSR is the one of main manifestation of arteries aging and has an important impact on hypertension and hypoperfusion of the brain in the process of human aging. The research contributes to a better understanding of the physiological and pathological mechanisms of aging-related diseases.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multi-scale dual-channel feature embedding decoder for biomedical image segmentation","authors":"","doi":"10.1016/j.cmpb.2024.108464","DOIUrl":"10.1016/j.cmpb.2024.108464","url":null,"abstract":"<div><h3>Background and Objective:</h3><div>Attaining global context along with local dependencies is of paramount importance for achieving highly accurate segmentation of objects from image frames and is challenging while developing deep learning-based biomedical image segmentation. Several transformer-based models have been proposed to handle this issue in biomedical image segmentation. Despite this, segmentation accuracy remains an ongoing challenge, as these models often fall short of the target range due to their limited capacity to capture critical local and global contexts. However, the quadratic computational complexity is the main limitation of these models. Moreover, a large dataset is required to train those models.</div></div><div><h3>Methods:</h3><div>In this paper, we propose a novel multi-scale dual-channel decoder to mitigate this issue. The complete segmentation model uses two parallel encoders and a dual-channel decoder. The encoders are based on convolutional networks, which capture the features of the input images at multiple levels and scales. The decoder comprises a hierarchy of Attention-gated Swin Transformers with a fine-tuning strategy. The hierarchical Attention-gated Swin Transformers implements a multi-scale, multi-level feature embedding strategy that captures short and long-range dependencies and leverages the necessary features without increasing computational load. At the final stage of the decoder, a fine-tuning strategy is implemented that refines the features to keep the rich features and reduce the possibility of over-segmentation.</div></div><div><h3>Results:</h3><div>The proposed model is evaluated on publicly available LiTS, 3DIRCADb, and spleen datasets obtained from Medical Segmentation Decathlon. The model is also evaluated on a private dataset from Medical College Kolkata, India. We observe that the proposed model outperforms the state-of-the-art models in liver tumor and spleen segmentation in terms of evaluation metrics at a comparative computational cost.</div></div><div><h3>Conclusion:</h3><div>The novel dual-channel decoder embeds multi-scale features and creates a representation of both short and long-range contexts efficiently. It also refines the features at the final stage to select only necessary features. As a result, we achieve better segmentation performance than the state-of-the-art models.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AI explainability and bias propagation in medical decision support","authors":"","doi":"10.1016/j.cmpb.2024.108465","DOIUrl":"10.1016/j.cmpb.2024.108465","url":null,"abstract":"","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}