Pub Date : 2025-10-01DOI: 10.1016/j.bbe.2025.11.003
Laureen Wegert , Luca Di Rienzo , Lorenzo Codecasa , Sicheng An , Marek Ziolkowski , Alexander Hunold , Irene Lange , Tim Kalla , Jens Haueisen
Non-invasive phrenic nerve stimulation can be used to overcome diaphragm insufficiency caused by mechanical ventilation. Detailed models and electromagnetic simulations are used to suggest appropriate stimulation parameters, but require accurate tissue properties. However, a wide range of electrical conductivity values is known from the literature. Here, we aim to perform an uncertainty analysis of the nerve activation threshold and the potential distribution along the phrenic nerve due to uncertain tissue conductivites.
We built a generalized polynomial chaos (gPC) model to calculate the phrenic nerve activation threshold. It was based on a reduced order model of a detailed anatomical finite element model of the neck including 13 tissue types to calculate the potential distribution, followed by a biophysiological nerve model. The tissue conductivity values investigated here were for the compartments of fat, muscle, nerve, and soft tissue. Their influence on the nerve activation threshold was investigated by changing conductivity values of the single tissues and all tissues at a time within a Monte Carlo analysis using the gPC model.
The phrenic nerve activation threshold varied between 33.8 mA and 46.9 mA for the combined variation of the conductivity values. Sobol indices and global sensitivity coefficients indicated the highest influence for muscle conductivity value, followed by soft tissue, fat, and nerve tissue.
Our results may have implications for understanding the experimentally observed variation in individual phrenic nerve activation thresholds affected by physiological and pathological conductivity changes. Accurate electric properties of muscle and soft tissue and detailed geometric representations should be considered in electromagnetic simulations.
{"title":"The influence of tissue conductivity uncertainty on the nerve activation thresholds in non-invasive electrical phrenic nerve stimulation","authors":"Laureen Wegert , Luca Di Rienzo , Lorenzo Codecasa , Sicheng An , Marek Ziolkowski , Alexander Hunold , Irene Lange , Tim Kalla , Jens Haueisen","doi":"10.1016/j.bbe.2025.11.003","DOIUrl":"10.1016/j.bbe.2025.11.003","url":null,"abstract":"<div><div>Non-invasive phrenic nerve stimulation can be used to overcome diaphragm insufficiency caused by mechanical ventilation. Detailed models and electromagnetic simulations are used to suggest appropriate stimulation parameters, but require accurate tissue properties. However, a wide range of electrical conductivity values is known from the literature. Here, we aim to perform an uncertainty analysis of the nerve activation threshold and the potential distribution along the phrenic nerve due to uncertain tissue conductivites.</div><div>We built a generalized polynomial chaos (gPC) model to calculate the phrenic nerve activation threshold. It was based on a reduced order model of a detailed anatomical finite element model of the neck including 13 tissue types to calculate the potential distribution, followed by a biophysiological nerve model. The tissue conductivity values investigated here were for the compartments of fat, muscle, nerve, and soft tissue. Their influence on the nerve activation threshold was investigated by changing conductivity values of the single tissues and all tissues at a time within a Monte Carlo analysis using the gPC model.</div><div>The phrenic nerve activation threshold varied between 33.8 mA and 46.9 mA for the combined variation of the conductivity values. Sobol indices and global sensitivity coefficients indicated the highest influence for muscle conductivity value, followed by soft tissue, fat, and nerve tissue.</div><div>Our results may have implications for understanding the experimentally observed variation in individual phrenic nerve activation thresholds affected by physiological and pathological conductivity changes. Accurate electric properties of muscle and soft tissue and detailed geometric representations should be considered in electromagnetic simulations.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 697-706"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617673","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}
Pub Date : 2025-10-01DOI: 10.1016/j.bbe.2025.10.001
Yuanzhe Zhao , Jeroen H.M. Bergmann
Accurate, real-time estimation of core body temperature is critical for preventing heat-related illness. While existing Kalman filter-based methods offer interpretable, single-input (heart rate) solutions, they are limited by fixed observation models that fail to capture the complex, non-linear, state-dependent dynamics of physiological signals.
To address this, we propose the Residual-Compensated Adaptive Kalman Filter (RCAKF), a novel hybrid framework. The RCAKF integrates a long short-term memory (LSTM) network to learn and correct structured, state-dependent errors in the observation model, alongside an adaptive noise estimator that dynamically adjusts for measurement uncertainty. This architecture enhances the classic Kalman filter with data-driven flexibility while maintaining its recursive structure and interpretability.
Evaluation was conducted on a controlled experimental dataset with 22 participants performing exercise and recovery under varied thermal conditions. Compared to five baseline models: extended Kalman filter (EKF: RMSE = 0.39 °C), the improved ECTemp model with a sigmoid observation function (ECTemp-S: RMSE = 0.40 °C), biphasic Kalman filter-based model (BKFB: RMSE = 0.48 °C), moving-average Kalman filter (MAKF: RMSE = 0.38 °C), and a standalone LSTM network (RMSE = 0.46 °C), RCAKF achieved the best accuracy with an RMSE of 0.31 °C.
By augmenting the Kalman filter with a learned residual correction and adaptive uncertainty, the RCAKF framework significantly enhances core temperature tracking from a single heart rate signal. Its accuracy and reliance on a single, common sensor make it a practical and promising solution for real-time deployment on wearable devices for safety monitoring.
{"title":"Estimating core body temperature from heart rate using a residual-compensated adaptive Kalman filter","authors":"Yuanzhe Zhao , Jeroen H.M. Bergmann","doi":"10.1016/j.bbe.2025.10.001","DOIUrl":"10.1016/j.bbe.2025.10.001","url":null,"abstract":"<div><div>Accurate, real-time estimation of core body temperature is critical for preventing heat-related illness. While existing Kalman filter-based methods offer interpretable, single-input (heart rate) solutions, they are limited by fixed observation models that fail to capture the complex, non-linear, state-dependent dynamics of physiological signals.</div><div>To address this, we propose the Residual-Compensated Adaptive Kalman Filter (RCAKF), a novel hybrid framework. The RCAKF integrates a long short-term memory (LSTM) network to learn and correct structured, state-dependent errors in the observation model, alongside an adaptive noise estimator that dynamically adjusts for measurement uncertainty. This architecture enhances the classic Kalman filter with data-driven flexibility while maintaining its recursive structure and interpretability.</div><div>Evaluation was conducted on a controlled experimental dataset with 22 participants performing exercise and recovery under varied thermal conditions. Compared to five baseline models: extended Kalman filter (EKF: RMSE = 0.39 °C), the improved ECTemp model with a sigmoid observation function (ECTemp-S: RMSE = 0.40 °C), biphasic Kalman filter-based model (BKFB: RMSE = 0.48 °C), moving-average Kalman filter (MAKF: RMSE = 0.38 °C), and a standalone LSTM network (RMSE = 0.46 °C), RCAKF achieved the best accuracy with an RMSE of 0.31 °C.</div><div>By augmenting the Kalman filter with a learned residual correction and adaptive uncertainty, the RCAKF framework significantly enhances core temperature tracking from a single heart rate signal. Its accuracy and reliance on a single, common sensor make it a practical and promising solution for real-time deployment on wearable devices for safety monitoring.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 617-629"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323893","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}
Code-modulated visual evoked potentials (c-VEP) have demonstrated high performance in non-invasive brain-computer interfaces (BCIs). Recently, research has begun to consider practical aspects such as visual comfort, where non-binary sequences and variations in the spatial frequency of stimuli play significant roles. However, calibration requirements remain underexplored in performance comparisons. This study aims to analyze a multi-variable tradeoff crucial to the practical application of c-VEP-based BCIs: decoding accuracy, decoding speed, and calibration time. Visual comfort is retrospectively evaluated using two pre-recorded datasets. Models were trained with increasing calibration cycles and tested across varying decoding times, depicting learning and decoding curves. The datasets comprised 32 healthy subjects, and featured different stimulus paradigms: plain non-binary stimuli and checkerboard-like binary stimuli with spatial frequency variations. Results showed that all conditions achieved over 97 % grand-averaged accuracy with sufficient calibration. However, a clear tradeoff emerged between calibration duration and performance. Achieving 95 % average accuracy within a 2 s decoding window required mean calibration durations of 28.7 ± 19.0 s for binary stimuli, or 148.7 ± 72.3 s for non-binary stimuli. The binary checkerboard-based condition with a spatial frequency of 1.2 c/º (C016) proved to be particularly effective, achieving over 95 % accuracy within 2 s decoding window using only 7.3 s of calibration, and reporting a significant improvement in visual comfort. A minimum calibration time of 1 min was considered essential to adequately estimate the brain response, critical in template-matching paradigms. In conclusion, achieving optimal c-VEP performance requires balancing calibration duration, decoding speed and accuracy, and visual comfort.
{"title":"Reevaluating performance in c-VEP BCIs: The impact of calibration time","authors":"Víctor Martínez-Cagigal , Eduardo Santamaría-Vázquez , Sergio Pérez-Velasco , Ana Martín-Fernández , Roberto Hornero","doi":"10.1016/j.bbe.2025.10.006","DOIUrl":"10.1016/j.bbe.2025.10.006","url":null,"abstract":"<div><div>Code-modulated visual evoked potentials (c-VEP) have demonstrated high performance in non-invasive brain-computer interfaces (BCIs). Recently, research has begun to consider practical aspects such as visual comfort, where non-binary sequences and variations in the spatial frequency of stimuli play significant roles. However, calibration requirements remain underexplored in performance comparisons. This study aims to analyze a multi-variable tradeoff crucial to the practical application of c-VEP-based BCIs: decoding accuracy, decoding speed, and calibration time. Visual comfort is retrospectively evaluated using two pre-recorded datasets. Models were trained with increasing calibration cycles and tested across varying decoding times, depicting learning and decoding curves. The datasets comprised 32 healthy subjects, and featured different stimulus paradigms: plain non-binary stimuli and checkerboard-like binary stimuli with spatial frequency variations. Results showed that all conditions achieved over 97 % grand-averaged accuracy with sufficient calibration. However, a clear tradeoff emerged between calibration duration and performance. Achieving 95 % average accuracy within a 2 s decoding window required mean calibration durations of 28.7 ± 19.0 s for binary stimuli, or 148.7 ± 72.3 s for non-binary stimuli. The binary checkerboard-based condition with a spatial frequency of 1.2 c/º (C016) proved to be particularly effective, achieving over 95 % accuracy within 2 s decoding window using only 7.3 s of calibration, and reporting a significant improvement in visual comfort. A minimum calibration time of 1 min was considered essential to adequately estimate the brain response, critical in template-matching paradigms. In conclusion, achieving optimal c-VEP performance requires balancing calibration duration, decoding speed and accuracy, and visual comfort.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 685-696"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519677","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}
Pub Date : 2025-10-01DOI: 10.1016/j.bbe.2025.10.005
Jan Kalina , Jaromir Kukal , Oldrich Vysata
Electroencephalography (EEG) signals are widely used in neuroscience research and biomedical applications, particularly for comparative analyses between two cohorts: patients and control subjects. In EEG research, multivariate two-sample tests remain underused, while multiple comparison procedures are often misapplied as a substitute, leading to inadequate error control. Moreover, existing rank-based tests rely solely on Euclidean distances and lack robustness to outliers. The objective of this work is to develop and evaluate a new class of rank-based tests for high-dimensional data that employ robust Mahalanobis interpoint distances, and to demonstrate their practical value in the analysis of EEG signals. This class includes a version based on the MRWCD (minimum regularized weighted covariance determinant) estimator, which enhances the robustness of the Mahalanobis distances by mitigating the influence of outliers.
To illustrate the effectiveness of these tests, EEG data consisting of 1216 variables from 28 patients with Alzheimer’s disease and 146 healthy control individuals were analyzed. The results of multivariate tests reveal significant findings, which are also explored in the context of individual EEG channels and frequencies. Among the approaches tested, rank-based tests using the newly proposed interpoint distances, particularly in combination with the Cucconi test statistic, yield the strongest results. For the comparison between patients and controls, a p-value of 0.004 was obtained, which is below the significance level , indicating a statistically significant difference.
{"title":"A novel class of rank tests for high-dimensional data with an application to Alzheimer’s disease","authors":"Jan Kalina , Jaromir Kukal , Oldrich Vysata","doi":"10.1016/j.bbe.2025.10.005","DOIUrl":"10.1016/j.bbe.2025.10.005","url":null,"abstract":"<div><div>Electroencephalography (EEG) signals are widely used in neuroscience research and biomedical applications, particularly for comparative analyses between two cohorts: patients and control subjects. In EEG research, multivariate two-sample tests remain underused, while multiple comparison procedures are often misapplied as a substitute, leading to inadequate error control. Moreover, existing rank-based tests rely solely on Euclidean distances and lack robustness to outliers. The objective of this work is to develop and evaluate a new class of rank-based tests for high-dimensional data that employ robust Mahalanobis interpoint distances, and to demonstrate their practical value in the analysis of EEG signals. This class includes a version based on the MRWCD (minimum regularized weighted covariance determinant) estimator, which enhances the robustness of the Mahalanobis distances by mitigating the influence of outliers.</div><div>To illustrate the effectiveness of these tests, EEG data consisting of 1216 variables from 28 patients with Alzheimer’s disease and 146 healthy control individuals were analyzed. The results of multivariate tests reveal significant findings, which are also explored in the context of individual EEG channels and frequencies. Among the approaches tested, rank-based tests using the newly proposed interpoint distances, particularly in combination with the Cucconi test statistic, yield the strongest results. For the comparison between patients and controls, a <em>p</em>-value of 0.004 was obtained, which is below the significance level <span><math><mrow><mi>α</mi><mo>=</mo><mn>0.05</mn></mrow></math></span>, indicating a statistically significant difference.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 707-717"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617670","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}
Pub Date : 2025-10-01DOI: 10.1016/j.bbe.2025.11.004
Chiara Veneroni , Enrico Conca , Davide Bizzotto , Kenneth Lutchen , Alberto Tosi , Raffaele L. Dellacà
Background
Lung aeration must rapidly develop at birth, but how to promote it without injuring the fragile lung is still unknown. Mathematical models simulating lung mechanics during this transition may help understand the underlying physiological mechanisms and design protective ventilation strategies. This study develops a morphologically-coherent computational lung model incorporating changing physical conditions during the transition from liquid-filled to gas-filled lungs.
Methods
We adapted a 3-D morphological model of the adult airway tree adjusting airway dimensions, lung volume, and lung tissue mechanical properties. Changes in resistance, inertia, and compliance during aeration were modeled by considering the differing properties of fetal fluid versus air. The capillary pressure at the liquid–air interface was computed using Laplace equation. Terminal airway diameters increased with lung volume due to airway-parenchymal interdependence. An integrated circuit simulator solved the entire network in the time domain.
Results
The air volume entering the model at different applied pressures increased exponentially with time. With 30 cmH2O applied, lung volume reached total capacity after 15 s, matching lung aeration dynamics observed in animal models and human infants. In contrast, after the same time, at 15 cmH2O, lung volume was slightly above functional residual capacity, and at 10 cmH2O, it remained below.
Conclusions
The proposed in-silico newborn lung model simulates lung aeration at birth, allowing observation of the airway emptying sequence and the heterogeneity of aeration at each time point. Integrating this model with comprehensive acinar models may aid in defining protective resuscitation ventilation strategies for recruiting the lung minimizing risk of injuries.
{"title":"A morphometric lung model for evaluating lung aeration at birth","authors":"Chiara Veneroni , Enrico Conca , Davide Bizzotto , Kenneth Lutchen , Alberto Tosi , Raffaele L. Dellacà","doi":"10.1016/j.bbe.2025.11.004","DOIUrl":"10.1016/j.bbe.2025.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Lung aeration must rapidly develop at birth, but how to promote it without injuring the fragile lung is still unknown. Mathematical models simulating lung mechanics during this transition may help understand the underlying physiological mechanisms and design protective ventilation strategies. This study develops a morphologically-coherent computational lung model incorporating changing physical conditions during the transition from liquid-filled to gas-filled lungs.</div></div><div><h3>Methods</h3><div>We adapted a 3-D morphological model of the adult airway tree adjusting airway dimensions, lung volume, and lung tissue mechanical properties. Changes in resistance, inertia, and compliance during aeration were modeled by considering the differing properties of fetal fluid versus air. The capillary pressure at the liquid–air interface was computed using Laplace equation. Terminal airway diameters increased with lung volume due to airway-parenchymal interdependence. An integrated circuit simulator solved the entire network in the time domain.</div></div><div><h3>Results</h3><div>The air volume entering the model at different applied pressures increased exponentially with time. With 30 cmH<sub>2</sub>O applied, lung volume reached total capacity after 15 s, matching lung aeration dynamics observed in animal models and human infants. In contrast, after the same time, at 15 cmH<sub>2</sub>O, lung volume was slightly above functional residual capacity, and at 10 cmH<sub>2</sub>O, it remained below.</div></div><div><h3>Conclusions</h3><div>The proposed in-silico newborn lung model simulates lung aeration at birth, allowing observation of the airway emptying sequence and the heterogeneity of aeration at each time point. Integrating this model with comprehensive acinar models may aid in defining protective resuscitation ventilation strategies for recruiting the lung minimizing risk of injuries.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 718-725"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617672","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}
Pub Date : 2025-10-01DOI: 10.1016/j.bbe.2025.10.004
Zhaokun Zhang , Wangrui Xu , Hanyu Gan , Chunlei K. Song , Albert J. Shih
Lower-limb prosthesis (LLP) is critical for the mobility and quality of life of amputees. Ensuring the reliability and durability of LLPs is essential to users’ safety, comfort, and mobility. While the current standard (ISO 10328) for the mechanical test of LLPs has served as a foundation, the sinusoidal cyclic loading method used for fatigue testing does not replicate the actual loading conditions on LLPs during a human walking gait. In normal walking, LLPs are subjected to a dual-peak loading condition with two distinct force peaks at the heel-strike and toe-off phases. Such a cyclic and dual-peak dynamic loading pattern on LLP is essential to test the durability of the LLP effectively and reliably. In this study, two simple and effective dual-peak cyclic loading test apparatuses are designed and built to evaluate the durability and functionality of LLPs. Two loading plates are used to contact the heel and toe of the prosthetic foot to simulate the dual-peak heel-strike and toe-off loadings between the foot and the ground. This dual-peak loading on the LLP is controlled and replicated by adjusting the positions of two loading plates and the actuator stroke to change the contact forces. Experimental results show that the proposed testing apparatuses and procedures can emulate the dual-peak axial loading of the LLP during normal walking gait, providing a more accurate testing method of the dynamic loading condition on LLPs than the current ISO standard.
{"title":"Dual-peak cyclic loading for evaluation of lower-limb prostheses","authors":"Zhaokun Zhang , Wangrui Xu , Hanyu Gan , Chunlei K. Song , Albert J. Shih","doi":"10.1016/j.bbe.2025.10.004","DOIUrl":"10.1016/j.bbe.2025.10.004","url":null,"abstract":"<div><div>Lower-limb prosthesis (LLP) is critical for the mobility and quality of life of amputees. Ensuring the reliability and durability of LLPs is essential to users’ safety, comfort, and mobility. While the current standard (ISO 10328) for the mechanical test of LLPs has served as a foundation, the sinusoidal cyclic loading method used for fatigue testing does not replicate the actual loading conditions on LLPs during a human walking gait. In normal walking, LLPs are subjected to a dual-peak loading condition with two distinct force peaks at the heel-strike and toe-off phases. Such a cyclic and dual-peak dynamic loading pattern on LLP is essential to test the durability of the LLP effectively and reliably. In this study, two simple and effective dual-peak cyclic loading test apparatuses are designed and built to evaluate the durability and functionality of LLPs. Two loading plates are used to contact the heel and toe of the prosthetic foot to simulate the dual-peak heel-strike and toe-off loadings between the foot and the ground. This dual-peak loading on the LLP is controlled and replicated by adjusting the positions of two loading plates and the actuator stroke to change the contact forces. Experimental results show that the proposed testing apparatuses and procedures can emulate the dual-peak axial loading of the LLP during normal walking gait, providing a more accurate testing method of the dynamic loading condition on LLPs than the current ISO standard.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 642-654"},"PeriodicalIF":6.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416927","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}
Pub Date : 2025-09-21DOI: 10.1016/j.bbe.2025.09.001
Alessio Luschi , Linda Tognetti , Alessandra Cartocci , Elisa Cinotti , Giovanni Rubegni , Laura Calabrese , Martina D’onghia , Martina Dragotto , Elvira Moscarella , Gabriella Brancaccio , Giulia Briatico , Camila Scharf , Dario Buononato , Vittorio Tancredi , Carmen Cantisani , Camilla Chello , Luca Ambrosio , Pietro Scribani Rossi , Marco Virone , Giovanni Pellacani , Ernesto Iadanza
Malignant melanoma is the deadliest form of skin cancer, and artificial intelligence could help address its diagnostic challenges. Generative Adversarial Networks (GANs) can generate synthetic dermoscopic images to augment limited real datasets, but the lack of standardised validation protocols holds back models’ reliability and clinicians’ trust. This study aims to design and develop a systematic validation protocol combining quantitative metrics and qualitative expert assessments to evaluate the realism, fidelity, diversity, and usefulness of synthetic dermoscopic melanoma images. A StyleGAN2 model, designed and trained in a previous study, was selected for its superior quantitative performance and exploited to generate 25 synthetic melanoma images, matched with 25 real images. A panel of 17 dermoscopists assessed the images using a 7-point Likert scale, across multiple qualitative attributes (real vs. synthetic, skin texture, visual realism, and confidence) and pattern analysis. Accuracy, sensitivity, specificity, Fleiss’ Kappa, and Krippendorff’s Alpha were calculated to analyse inter-rater agreement and evaluation outcomes. Accuracy in real vs synthetic images classification was moderate (64 %), with sensitivity at 73 % and specificity at 56 %, with poor inter-rater concordance over qualitative attributes. Synthetic images obtained superior scores in medium visual and overall realism, and confidence level, while the frequency of recognition of pigment network-patterns was comparable with real images. The proposed holistic validation protocol can effectively estimate the quality level of synthetic dermoscopic images, regardless of the architecture of the model used for generation, offering an objective and reliable evaluation tool, as qualitative evaluations remain crucial to ensure their safe deployment in clinical settings.
{"title":"Design and development of a systematic validation protocol for synthetic melanoma images for responsible use in medical artificial intelligence","authors":"Alessio Luschi , Linda Tognetti , Alessandra Cartocci , Elisa Cinotti , Giovanni Rubegni , Laura Calabrese , Martina D’onghia , Martina Dragotto , Elvira Moscarella , Gabriella Brancaccio , Giulia Briatico , Camila Scharf , Dario Buononato , Vittorio Tancredi , Carmen Cantisani , Camilla Chello , Luca Ambrosio , Pietro Scribani Rossi , Marco Virone , Giovanni Pellacani , Ernesto Iadanza","doi":"10.1016/j.bbe.2025.09.001","DOIUrl":"10.1016/j.bbe.2025.09.001","url":null,"abstract":"<div><div>Malignant melanoma is the deadliest form of skin cancer, and artificial intelligence could help address its diagnostic challenges. Generative Adversarial Networks (GANs) can generate synthetic dermoscopic images to augment limited real datasets, but the lack of standardised validation protocols holds back models’ reliability and clinicians’ trust. This study aims to design and develop a systematic validation protocol combining quantitative metrics and qualitative expert assessments to evaluate the realism, fidelity, diversity, and usefulness of synthetic dermoscopic melanoma images. A StyleGAN2 model, designed and trained in a previous study, was selected for its superior quantitative performance and exploited to generate 25 synthetic melanoma images, matched with 25 real images. A panel of 17 dermoscopists assessed the images using a 7-point Likert scale, across multiple qualitative attributes (real vs. synthetic, skin texture, visual realism, and confidence) and pattern analysis. Accuracy, sensitivity, specificity, Fleiss’ Kappa, and Krippendorff’s Alpha were calculated to analyse inter-rater agreement and evaluation outcomes. Accuracy in real vs synthetic images classification was moderate (64 %), with sensitivity at 73 % and specificity at 56 %, with poor inter-rater concordance over qualitative attributes. Synthetic images obtained superior scores in medium visual and overall realism, and confidence level, while the frequency of recognition of pigment network-patterns was comparable with real images. The proposed holistic validation protocol can effectively estimate the quality level of synthetic dermoscopic images, regardless of the architecture of the model used for generation, offering an objective and reliable evaluation tool, as qualitative evaluations remain crucial to ensure their safe deployment in clinical settings.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 608-616"},"PeriodicalIF":6.6,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099872","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}
Pub Date : 2025-08-30DOI: 10.1016/j.bbe.2025.08.007
Xiaoyu Gu , Wei Zhong , Yan Shi , Meng Xu , Zhaohui Tong , Yixuan Wang
Objectives
Implantable diaphragm pacing (DP) system can effectively restore patients’ breathing.
Conventional diaphragm pacemakers have some practical limitations, such as transmission stability and high price. This study proposes an innovative, wirelessly powered dual-channel and inexpensive DP system to overcome some of these constraints.
Methods
The system realizes wireless power supply based on electromagnetic resonance coupling to improve stability. It comprised an external controller, two off-body transmitters and two in-vivo rectifier-integrated receivers. PCB spiral coils are used for energy transmission in wireless systems to ensure system stability and convenient processing. Receiver encapsulated with biocompatible PDMS convert received power into electrical stimulation energy. Stimulation waveform, multi-media environment and animal experimental tests were conducted to validate system’s performance. Specific absorption rate (SAR) in human tissue was calculated to confirm safety of implantation.
Results
Electrical stimulation parameters of the proposed DP system can be precisely adjusted. The stimulation amplitude range is 3–12 V with 0.1 V step resolution. Pulse width and frequency are adjustable from 100-300 µs and 10–100 Hz respectively. The breathing cycle and inhalation time can also be set individually. Wireless energy transmission has wide transmission distance (>14 mm), good anti-offset capability (horizontal offset>8mm) and implantation safety (SAR<1.6 W/kg). Further time series of stimulation signals issued by the two channels are synchronized. The developed system effectively realizes respiratory response of animals to bilateral phrenic nerve stimulation with 17 mm wireless energy transmission distance and implantation of two receivers in vivo.
Conclusion
Our work provides a new optimization scheme for the design of implantable diaphragm pacemaker.
{"title":"A wireless, implantable, dual-channel phrenic nerve stimulator for diaphragm pacing using electromagnetic resonance coupling","authors":"Xiaoyu Gu , Wei Zhong , Yan Shi , Meng Xu , Zhaohui Tong , Yixuan Wang","doi":"10.1016/j.bbe.2025.08.007","DOIUrl":"10.1016/j.bbe.2025.08.007","url":null,"abstract":"<div><h3>Objectives</h3><div>Implantable diaphragm pacing (DP) system can effectively restore patients’ breathing.</div><div>Conventional diaphragm pacemakers have some practical limitations, such as transmission stability and high price. This study proposes an innovative, wirelessly powered dual-channel and inexpensive DP system to overcome some of these constraints.</div></div><div><h3>Methods</h3><div>The system realizes wireless power supply based on electromagnetic resonance coupling to improve stability. It comprised an external controller, two off-body transmitters and two in-vivo rectifier-integrated receivers. PCB spiral coils are used for energy transmission in wireless systems to ensure system stability and convenient processing. Receiver encapsulated with biocompatible PDMS convert received power into electrical stimulation energy. Stimulation waveform, multi-media environment and animal experimental tests were conducted to validate system’s performance. Specific absorption rate (SAR) in human tissue was calculated to confirm safety of implantation.</div></div><div><h3>Results</h3><div>Electrical stimulation parameters of the proposed DP system can be precisely adjusted. The stimulation amplitude range is 3–12 V with 0.1 V step resolution. Pulse width and frequency are adjustable from 100-300 µs and 10–100 Hz respectively. The breathing cycle and inhalation time can also be set individually. Wireless energy transmission has wide transmission distance (>14 mm), good anti-offset capability (horizontal offset>8mm) and implantation safety (SAR<1.6 W/kg). Further time series of stimulation signals issued by the two channels are synchronized. The developed system effectively realizes respiratory response of animals to bilateral phrenic nerve stimulation with 17 mm wireless energy transmission distance and implantation of two receivers in vivo.</div></div><div><h3>Conclusion</h3><div>Our work provides a new optimization scheme for the design of implantable diaphragm pacemaker.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 593-607"},"PeriodicalIF":6.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916952","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}
Pub Date : 2025-08-29DOI: 10.1016/j.bbe.2025.08.006
Shanglin Yang , Yuyang Lin , Xuwei Liao , Jianjung Chen , Hsientsai Wu
This cross-sectional observational study introduces the T-R interval (TRI), a novel electrocardiographic parameter designed to improve heart rate variability (HRV) assessment in ageing and diabetic populations. Defined as the R-R interval (RRI) minus the heart rate-corrected RT interval (RTc), TRI incorporates both depolarisation and repolarisation phases of the cardiac cycle, thereby offering deeper insights into autonomic function. A total of 126 participants, including 58 individuals with type 2 diabetes mellitus and 68 healthy controls, were assessed using conventional HRV indices. These included the low-to-high frequency power ratio (LHR), the short-to-long variability ratio (SSR), and the baroreflex entropy index (BEI), all of which were calculated from both RRI and TRI data. TRI-based indices demonstrated superior sensitivity in detecting autonomic dysfunction. Significant group differences were observed for TRI-derived MSELS (mean difference = 0.205, 95 % CI: 0.093–0.317, p = 0.036), SSR (mean difference = − 0.083, 95 % CI: −0.136–−0.029, p = 0.051), and BEI (mean difference = 0.205, 95 % CI: 0.093–0.318, p = 0.002), while their RRI-based equivalents did not reach statistical significance. ROC curve analysis showed improvements in the area under the curve (AUC) when TRI was used as the input parameter, with gains of 5.9 % for MSELS, 10.6 %for SSR, and 6.1 % for BEI. Logistic regression further identified TRI-based BEI as a protective factor against new-onset T2DM (OR = 0.058; 95 % CI: 0.009–0.378; p = 0.003). These findings suggest that TRI improves the diagnostic performance of HRV analysis and may support earlier detection of autonomic dysfunction, especially in clinical and wearable monitoring settings.
这项横断面观察性研究引入了T-R间隔(TRI),这是一种新的心电图参数,旨在改善老年人和糖尿病人群的心率变异性(HRV)评估。TRI被定义为R-R间期(RRI)减去心率校正后的RT间期(RTc),它结合了心脏周期的去极化和复极化阶段,从而对自主神经功能提供了更深入的了解。共有126名参与者,包括58名2型糖尿病患者和68名健康对照者,使用常规HRV指数进行评估。其中低高频功率比(LHR)、短长变异性比(SSR)和气压反射熵指数(BEI)均由RRI和TRI数据计算得到。基于tri的指数在检测自主神经功能障碍方面表现出更高的灵敏度。tri衍生的MSELS(平均差异= 0.205,95% CI: 0.093-0.317, p = 0.036)、SSR(平均差异= - 0.083,95% CI: - 0.136 - - 0.029, p = 0.051)和BEI(平均差异= 0.205,95% CI: 0.093-0.318, p = 0.002)组间差异显著,而基于rri的等效性差异无统计学意义。ROC曲线分析显示,以TRI作为输入参数时,MSELS、SSR和BEI的曲线下面积(AUC)分别增加了5.9%、10.6%和6.1%。Logistic回归进一步确定基于三因素的BEI是预防新发T2DM的保护因素(OR = 0.058; 95% CI: 0.009-0.378; p = 0.003)。这些发现表明,TRI提高了HRV分析的诊断性能,并可能支持自主神经功能障碍的早期检测,特别是在临床和可穿戴监测设置中。
{"title":"TRI-based heart rate variability parameterisation: advancing autonomic dysfunction assessment in diabetes and aging—A cross-sectional observational study","authors":"Shanglin Yang , Yuyang Lin , Xuwei Liao , Jianjung Chen , Hsientsai Wu","doi":"10.1016/j.bbe.2025.08.006","DOIUrl":"10.1016/j.bbe.2025.08.006","url":null,"abstract":"<div><div>This cross-sectional observational study introduces the T-R interval (TRI), a novel electrocardiographic parameter designed to improve heart rate variability (HRV) assessment in ageing and diabetic populations. Defined as the R-R interval (RRI) minus the heart rate-corrected RT interval (RTc), TRI incorporates both depolarisation and repolarisation phases of the cardiac cycle, thereby offering deeper insights into autonomic function. A total of 126 participants, including 58 individuals with type 2 diabetes mellitus and 68 healthy controls, were assessed using conventional HRV indices. These included the low-to-high frequency power ratio (LHR), the short-to-long variability ratio (SSR), and the baroreflex entropy index (BEI), all of which were calculated from both RRI and TRI data. TRI-based indices demonstrated superior sensitivity in detecting autonomic dysfunction. Significant group differences were observed for TRI-derived MSE<sub>LS</sub> (mean difference = 0.205, 95 % CI: 0.093–0.317, <em>p</em> = 0.036), SSR (mean difference = − 0.083, 95 % CI: −0.136–−0.029, <em>p</em> = 0.051), and BEI (mean difference = 0.205, 95 % CI: 0.093–0.318, <em>p</em> = 0.002), while their RRI-based equivalents did not reach statistical significance. ROC curve analysis showed improvements in the area under the curve (AUC) when TRI was used as the input parameter, with gains of 5.9 % for MSE<sub>LS</sub>, 10.6 %for SSR, and 6.1 % for BEI. Logistic regression further identified TRI-based BEI as a protective factor against new-onset T2DM (OR = 0.058; 95 % CI: 0.009–0.378; <em>p</em> = 0.003). These findings suggest that TRI improves the diagnostic performance of HRV analysis and may support earlier detection of autonomic dysfunction, especially in clinical and wearable monitoring settings.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 4","pages":"Pages 581-592"},"PeriodicalIF":6.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914029","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}
Pub Date : 2025-07-01DOI: 10.1016/j.bbe.2025.07.003
Zhongwei Sun , Jiabao Pan , Weishi Liang , Changwen Mi , Peng Yin
This study proposes a probabilistic biphasic-swelling parameterized finite element framework, with the aim of which is to systematically evaluate the impact of lumbar intervertebral disc (L-IVD) geometry and annulus fibrosus collagen fiber configuration on multi-axial biomechanical behavior. Thirty anatomical L-IVD geometric sets were sampled via Latin hypercube sampling of clinical anatomical variations. Three annulus fibrosus layer-wise fiber configurations were implemented: Constant , Circumferential variation (), and Circumferential-radial variation (). Consequently, the construction of three groups, comprising a total of ninety biphasic L-IVD finite element models, was undertaken. Five loading protocols were then simulated to reveal the critical dependencies of L-IVD biomechanical behavior. A statistical comparative analysis was performed to evaluate the influence of disc geometries and orientation strategies. The findings demonstrated that fiber orientation configuration exerts a substantial influence on swelling responses, compression stiffness, and flexion stiffness (). Disc height exhibited strong inverse correlations with intradiscal pressure (, ) and compression stiffness (, ). Anterior-posterior length emerged as the primary predictor of sagittal stiffness (flexion: ; extension: ) and torsional resistance (), linked to altered moment arm mechanics. The nucleus pulposus volume ratio moderately affected intradiscal pressure (, ) but showed negligible impact on segmental stiffness. This parametric modelling framework facilitates systematic investigation of L-IVD biomechanics across anatomical variations. Additionally, these findings advocate for microstructure-informed computational models to optimize personalized implant designs and biomechanical assessments.
{"title":"Lumbar intervertebral disc biomechanics: Geometry and collagen fiber orientation configurations effects","authors":"Zhongwei Sun , Jiabao Pan , Weishi Liang , Changwen Mi , Peng Yin","doi":"10.1016/j.bbe.2025.07.003","DOIUrl":"10.1016/j.bbe.2025.07.003","url":null,"abstract":"<div><div>This study proposes a probabilistic biphasic-swelling parameterized finite element framework, with the aim of which is to systematically evaluate the impact of lumbar intervertebral disc (L-IVD) geometry and annulus fibrosus collagen fiber configuration on multi-axial biomechanical behavior. Thirty anatomical L-IVD geometric sets were sampled via Latin hypercube sampling of clinical anatomical variations. Three annulus fibrosus layer-wise fiber configurations were implemented: Constant <span><math><msup><mn>30</mn><mo>∘</mo></msup></math></span>, Circumferential variation (<span><math><mrow><msup><mn>25</mn><mo>∘</mo></msup><mo>−</mo><mo>−</mo><msup><mn>45</mn><mo>∘</mo></msup></mrow></math></span>), and Circumferential-radial variation (<span><math><mrow><msup><mn>23</mn><mo>∘</mo></msup><mo>−</mo><mo>−</mo><msup><mn>50</mn><mo>∘</mo></msup></mrow></math></span>). Consequently, the construction of three groups, comprising a total of ninety biphasic L-IVD finite element models, was undertaken. Five loading protocols were then simulated to reveal the critical dependencies of L-IVD biomechanical behavior. A statistical comparative analysis was performed to evaluate the influence of disc geometries and orientation strategies. The findings demonstrated that fiber orientation configuration exerts a substantial influence on swelling responses, compression stiffness, and flexion stiffness (<span><math><mrow><mi>p</mi><mo><</mo><mo>.</mo><mn>050</mn></mrow></math></span>). Disc height exhibited strong inverse correlations with intradiscal pressure (<span><math><mrow><mi>r</mi><mo><</mo><mo>−</mo><mn>0.80</mn></mrow></math></span>, <span><math><mrow><mi>p</mi><mo><</mo><mo>.</mo><mn>001</mn></mrow></math></span>) and compression stiffness (<span><math><mrow><mi>r</mi><mo><</mo><mo>−</mo><mn>0.85</mn></mrow></math></span>, <span><math><mrow><mi>p</mi><mo><</mo><mo>.</mo><mn>001</mn></mrow></math></span>). Anterior-posterior length emerged as the primary predictor of sagittal stiffness (flexion: <span><math><mrow><mi>r</mi><mo>></mo><mn>0.70</mn></mrow></math></span>; extension: <span><math><mrow><mi>r</mi><mo>></mo><mn>0.75</mn></mrow></math></span>) and torsional resistance (<span><math><mrow><mi>r</mi><mo>></mo><mn>0.50</mn></mrow></math></span>), linked to altered moment arm mechanics. The nucleus pulposus volume ratio moderately affected intradiscal pressure (<span><math><mrow><mi>r</mi><mo>></mo><mn>0.30</mn></mrow></math></span>, <span><math><mrow><mi>p</mi><mo><</mo><mo>.</mo><mn>05</mn></mrow></math></span>) but showed negligible impact on segmental stiffness. This parametric modelling framework facilitates systematic investigation of L-IVD biomechanics across anatomical variations. Additionally, these findings advocate for microstructure-informed computational models to optimize personalized implant designs and biomechanical assessments.</div></div>","PeriodicalId":55381,"journal":{"name":"Biocybernetics and Biomedical Engineering","volume":"45 3","pages":"Pages 496-506"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654464","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}