Pub Date : 2026-03-03DOI: 10.1007/s10439-026-04002-2
Ernest W C Lo, Francesca Pugliese, Leon Menezes, Ryo Torii
Background and objective: Computed tomography-based fractional flow reserve computation (CT-FFR) is widely used in clinical practice, based on its efficacy demonstrated in many studies. However, major assumptions remain with the outflow boundary conditions (BCs) representing coronary microvasculature, especially in hyperaemia. We here propose a novel method to estimate patient-specific microvascular response to hyperaemia for CT-FFR calculations, based on patients' routinely available demographic data.
Methods: A statistical model to predict microvascular flow response (MFR) from routinely collected patient demographic parameters was derived using PET-based perfusion data of 101 patients with coronary artery disease. CT-FFR computations were then conducted with patient-specific anatomical models and outflow BCs derived from various MFR models including the proposed approach. The FFR values were calculated for an independent test cohort of 10 patients who had undergone CT coronary angiography, CT perfusion imaging and invasive FFR measurement. Computed FFR values were compared against invasive FFR and other CT-FFR algorithms.
Results: A multivariate regression model predicting patient-specific MFR was derived as a function of sex, diabetes and smoking status of the patient. FFR values computed using our model agreed well with the invasive FFR (0.76 ± 0.09 vs. 0.75 ± 0.10, P = 0.217). The FFRs predicted with our model were also comparable to those calculated using outflow BC tuned with patient-specific perfusion data (FFR: 0.74 ± 0.10, P = 0.233 vs. invasive FFR) and showed marked improvement over the conventional approach (FFR: 0.68 ± 0.11, P = 0.004 vs. invasive FFR). Diagnostic accuracy vs. invasive FFR were 100, 91 and 82% for CT-FFR with CTP-based MFR, demography-based MFR, and conventional approach, respectively.
Discussion: The proposed demography-based MFR model significantly improves FFR computation accuracy compared with a typical conventional model that assumes constant, healthy and population average MFR. Although its diagnostic accuracy is slightly lower than that of CT-FFR calibrated with patient-specific perfusion imaging data (91 vs. 100%), the demography-based model offers a substantial practical advantage by not requiring additional non-standard data acquisition, such as perfusion imaging. Consequently, it shows strong potential as a practical enhancement to conventional CT-FFR algorithms.
背景与目的:基于CT-FFR的分数血流储备计算(CT-FFR)被广泛应用于临床实践,许多研究证明了它的有效性。然而,主要的假设仍然与流出边界条件(bc)代表冠状动脉微血管,特别是在充血。我们在此提出了一种新的方法来估计患者对充血的特异性微血管反应,用于CT-FFR计算,基于患者常规可用的人口统计数据。方法:利用101例冠状动脉疾病患者的pet灌注数据,通过常规收集的患者人口学参数,建立预测微血管血流反应(MFR)的统计模型。然后使用患者特异性解剖模型和来自各种MFR模型(包括本文提出的方法)的流出体bc进行CT-FFR计算。对10例接受CT冠状动脉造影、CT灌注成像和有创FFR测量的患者进行独立测试队列,计算FFR值。将计算的FFR值与侵袭性FFR和其他CT-FFR算法进行比较。结果:建立了预测患者特异性MFR的多变量回归模型,该模型与患者的性别、糖尿病和吸烟状况有关。采用该模型计算的FFR值与有创FFR值吻合较好(0.76±0.09 vs. 0.75±0.10,P = 0.217)。我们的模型预测的FFR也与根据患者特异性灌注数据调整的流出BC计算的FFR相当(FFR: 0.74±0.10,P = 0.233,与有创性FFR相比),并且比传统方法(FFR: 0.68±0.11,P = 0.004,与有创性FFR相比)显着改善。CT-FFR合并基于ctp的MFR、基于人口统计学的MFR和传统方法的诊断准确率分别为100%、91%和82%。讨论:与假设恒定、健康和人口平均MFR的典型传统模型相比,所提出的基于人口统计学的MFR模型显着提高了FFR计算精度。尽管其诊断准确性略低于使用患者特异性灌注成像数据校准的CT-FFR (91% vs. 100%),但基于人口统计学的模型由于不需要额外的非标准数据采集(如灌注成像)而具有实质性的实用优势。因此,作为传统CT-FFR算法的实际增强,它显示出强大的潜力。
{"title":"A Novel Demography-Based Approach to Define Patient-Specific Outflow Boundary Conditions in CT-Based FFR Computations.","authors":"Ernest W C Lo, Francesca Pugliese, Leon Menezes, Ryo Torii","doi":"10.1007/s10439-026-04002-2","DOIUrl":"https://doi.org/10.1007/s10439-026-04002-2","url":null,"abstract":"<p><strong>Background and objective: </strong>Computed tomography-based fractional flow reserve computation (CT-FFR) is widely used in clinical practice, based on its efficacy demonstrated in many studies. However, major assumptions remain with the outflow boundary conditions (BCs) representing coronary microvasculature, especially in hyperaemia. We here propose a novel method to estimate patient-specific microvascular response to hyperaemia for CT-FFR calculations, based on patients' routinely available demographic data.</p><p><strong>Methods: </strong>A statistical model to predict microvascular flow response (MFR) from routinely collected patient demographic parameters was derived using PET-based perfusion data of 101 patients with coronary artery disease. CT-FFR computations were then conducted with patient-specific anatomical models and outflow BCs derived from various MFR models including the proposed approach. The FFR values were calculated for an independent test cohort of 10 patients who had undergone CT coronary angiography, CT perfusion imaging and invasive FFR measurement. Computed FFR values were compared against invasive FFR and other CT-FFR algorithms.</p><p><strong>Results: </strong>A multivariate regression model predicting patient-specific MFR was derived as a function of sex, diabetes and smoking status of the patient. FFR values computed using our model agreed well with the invasive FFR (0.76 ± 0.09 vs. 0.75 ± 0.10, P = 0.217). The FFRs predicted with our model were also comparable to those calculated using outflow BC tuned with patient-specific perfusion data (FFR: 0.74 ± 0.10, P = 0.233 vs. invasive FFR) and showed marked improvement over the conventional approach (FFR: 0.68 ± 0.11, P = 0.004 vs. invasive FFR). Diagnostic accuracy vs. invasive FFR were 100, 91 and 82% for CT-FFR with CTP-based MFR, demography-based MFR, and conventional approach, respectively.</p><p><strong>Discussion: </strong>The proposed demography-based MFR model significantly improves FFR computation accuracy compared with a typical conventional model that assumes constant, healthy and population average MFR. Although its diagnostic accuracy is slightly lower than that of CT-FFR calibrated with patient-specific perfusion imaging data (91 vs. 100%), the demography-based model offers a substantial practical advantage by not requiring additional non-standard data acquisition, such as perfusion imaging. Consequently, it shows strong potential as a practical enhancement to conventional CT-FFR algorithms.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343406","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 : 2026-03-03DOI: 10.1007/s10439-026-04028-6
Nurul Qashri Mahardika T, Ali Ikhsanul Qauli, Yunendah Nur Fuadah, Aulia Khamas Heikhmakhtiar, Muhammad Adnan Pramudito, Ariyadi, Aroli Marcellinus, Yoo Seok Kim, Ki Moo Lim
Purpose: Established in silico frameworks for assessing Torsade de Pointes (TdP) risk primarily rely on single-cell electrophysiological biomarkers, which have demonstrated strong predictive capabilities. However, ventricular transmural electrophysiological heterogeneity is known to influence repolarization dynamics and arrhythmogenic mechanisms. Explicitly incorporating endocardium, epicardium, and mid-myocardium representations may enhance physiological interpretability, but direct integration of multi-cell features can introduce severe multicollinearity and compromise model stability. To address this challenge, we propose an ordinal logistic regression (OLR) framework that integrates multi-cell qNet information through probability averaging, preserving physiological context while maintaining robust statistical behavior.
Methods: values and Hill coefficients for 28 CiPA drugs were implemented in two ventricular cell models, the CiPAORdV1.0 and the ORd in silico models. qNet was computed independently for endocardium, epicardium, and mid-myocardium cells. Cell-specific OLR models produced class probabilities that were then averaged to generate the final prediction. Performance was compared against single-cell and direct multi-cell implementations across Manual and ChanTest datasets.
Results: For CiPA-ORd v1.0 using the ChanTest dataset, qNet achieved substantial performance, with AUCs for ROC1 and ROC2 of 1.000 and 0.958, respectively, and also meeting seven "excellent" classification criteria. In the ORd model, probability averaging consistently improved performance for both the Manual and ChanTest datasets relative to single-cell and direct multi-cell approaches.
Conclusion: Probability-averaged integration of multi-cell qNet predictions mitigates multicollinearity while preserving physiological relevance, yielding more stable and accurate in silico TdP risk classification and supporting broader applicability to preclinical safety assessment.
目的:建立评估TdP风险的计算机框架,主要依赖于单细胞电生理生物标志物,这些生物标志物已证明具有很强的预测能力。然而,已知心室跨壁电生理异质性会影响复极化动力学和心律失常机制。明确合并心内膜、心外膜和中肌层表征可以增强生理上的可解释性,但直接整合多细胞特征会引入严重的多重共线性并损害模型的稳定性。为了解决这一挑战,我们提出了一个有序逻辑回归(OLR)框架,该框架通过概率平均集成多细胞qNet信息,在保持稳健统计行为的同时保留生理背景。方法:采用CiPAORdV1.0和ORd in silico两种心室细胞模型对28种CiPA药物的c50值和Hill系数进行测定。qNet是独立计算心内膜、心外膜和中间心肌细胞的。特定于细胞的OLR模型产生类别概率,然后将其平均以生成最终预测。将性能与Manual和ChanTest数据集上的单单元和直接多单元实现进行比较。结果:对于使用ChanTest数据集的CiPA-ORd v1.0, qNet取得了可观的性能,ROC1和ROC2的auc分别为1.000和0.958,并且还满足七个“优秀”分类标准。在ORd模型中,相对于单细胞和直接多细胞方法,概率平均持续提高了Manual和ChanTest数据集的性能。结论:多细胞qNet预测的概率平均整合在保持生理相关性的同时减轻了多重共线性,产生了更稳定和准确的硅TdP风险分类,并支持更广泛的临床前安全性评估适用性。
{"title":"Improving In Silico Cardiac Safety Prediction by Consensus Averaging of Transmural Ventricular Cell Models.","authors":"Nurul Qashri Mahardika T, Ali Ikhsanul Qauli, Yunendah Nur Fuadah, Aulia Khamas Heikhmakhtiar, Muhammad Adnan Pramudito, Ariyadi, Aroli Marcellinus, Yoo Seok Kim, Ki Moo Lim","doi":"10.1007/s10439-026-04028-6","DOIUrl":"https://doi.org/10.1007/s10439-026-04028-6","url":null,"abstract":"<p><strong>Purpose: </strong>Established in silico frameworks for assessing Torsade de Pointes (TdP) risk primarily rely on single-cell electrophysiological biomarkers, which have demonstrated strong predictive capabilities. However, ventricular transmural electrophysiological heterogeneity is known to influence repolarization dynamics and arrhythmogenic mechanisms. Explicitly incorporating endocardium, epicardium, and mid-myocardium representations may enhance physiological interpretability, but direct integration of multi-cell features can introduce severe multicollinearity and compromise model stability. To address this challenge, we propose an ordinal logistic regression (OLR) framework that integrates multi-cell qNet information through probability averaging, preserving physiological context while maintaining robust statistical behavior.</p><p><strong>Methods: </strong><math><mrow><mi>I</mi> <msub><mi>C</mi> <mn>50</mn></msub> </mrow> </math> values and Hill coefficients for 28 CiPA drugs were implemented in two ventricular cell models, the CiPAORdV1.0 and the ORd in silico models. qNet was computed independently for endocardium, epicardium, and mid-myocardium cells. Cell-specific OLR models produced class probabilities that were then averaged to generate the final prediction. Performance was compared against single-cell and direct multi-cell implementations across Manual and ChanTest datasets.</p><p><strong>Results: </strong>For CiPA-ORd v1.0 using the ChanTest dataset, qNet achieved substantial performance, with AUCs for ROC1 and ROC2 of 1.000 and 0.958, respectively, and also meeting seven \"excellent\" classification criteria. In the ORd model, probability averaging consistently improved performance for both the Manual and ChanTest datasets relative to single-cell and direct multi-cell approaches.</p><p><strong>Conclusion: </strong>Probability-averaged integration of multi-cell qNet predictions mitigates multicollinearity while preserving physiological relevance, yielding more stable and accurate in silico TdP risk classification and supporting broader applicability to preclinical safety assessment.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343534","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 : 2026-03-02DOI: 10.1007/s10439-026-04020-0
Farhad Ahmadi, Shuchun Sun, Jichao Zhao, Jian Chen, Marshall B Wilson, Brooke Damon, Yongren Wu, Konstantinia Almpani, Rachel Chung, Priyam Jani, Peng Chen, Elizabeth H Slate, Janice S Lee, Benedikt Sagl, Hai Yao
Purpose: Biomechanical parameters of the temporomandibular joint (TMJ), such as joint contact forces and intra-articular stresses, are suggested to contribute to the development of temporomandibular joint disorders, but are impractical to measure. In this study, we present a computational framework for evaluating these parameters by integrating a function assessment system and a patient-specific modeling approach.
Methods: The pipeline consists of acquiring patients' functional and morphological data and developing combined multibody dynamics and finite-element (MBD-FE) models for simulating their specific biting tasks. We demonstrate the approach in a pre-/post-orthognathic surgery scenario and present the measured and simulated outputs.
Results: In a three-patient cohort of one Class I control and two surgical patients (one Class II and one Class III patient), surgery was accompanied by functional changes such as increased bite force capacity and shifts in muscle-usage during unilateral first premolar clenching that brought the surgical cases closer to the control case. Also, morphological measurements showed postoperative adaptations in condylar size and joint space. Simulations demonstrated that contralateral joint forces exceeded ipsilateral forces during unilateral biting and predicted regions of concentrated disc stress that coincided with regions of reduced joint gap and poorer articular congruency, highlighting how morphology-function interactions shape local mechanics.
Conclusion: By unifying individualized functional inputs and subject-specific geometries, the framework provides a practical basis for patient-tailored assessment of biomechanical parameters and decision support in TMJ care.
{"title":"A Computational Framework for Simulating Patient-Specific TMJ Biomechanics Using a Combined Multibody Dynamics and Finite Element Approach.","authors":"Farhad Ahmadi, Shuchun Sun, Jichao Zhao, Jian Chen, Marshall B Wilson, Brooke Damon, Yongren Wu, Konstantinia Almpani, Rachel Chung, Priyam Jani, Peng Chen, Elizabeth H Slate, Janice S Lee, Benedikt Sagl, Hai Yao","doi":"10.1007/s10439-026-04020-0","DOIUrl":"10.1007/s10439-026-04020-0","url":null,"abstract":"<p><strong>Purpose: </strong>Biomechanical parameters of the temporomandibular joint (TMJ), such as joint contact forces and intra-articular stresses, are suggested to contribute to the development of temporomandibular joint disorders, but are impractical to measure. In this study, we present a computational framework for evaluating these parameters by integrating a function assessment system and a patient-specific modeling approach.</p><p><strong>Methods: </strong>The pipeline consists of acquiring patients' functional and morphological data and developing combined multibody dynamics and finite-element (MBD-FE) models for simulating their specific biting tasks. We demonstrate the approach in a pre-/post-orthognathic surgery scenario and present the measured and simulated outputs.</p><p><strong>Results: </strong>In a three-patient cohort of one Class I control and two surgical patients (one Class II and one Class III patient), surgery was accompanied by functional changes such as increased bite force capacity and shifts in muscle-usage during unilateral first premolar clenching that brought the surgical cases closer to the control case. Also, morphological measurements showed postoperative adaptations in condylar size and joint space. Simulations demonstrated that contralateral joint forces exceeded ipsilateral forces during unilateral biting and predicted regions of concentrated disc stress that coincided with regions of reduced joint gap and poorer articular congruency, highlighting how morphology-function interactions shape local mechanics.</p><p><strong>Conclusion: </strong>By unifying individualized functional inputs and subject-specific geometries, the framework provides a practical basis for patient-tailored assessment of biomechanical parameters and decision support in TMJ care.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324454","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 : 2026-03-02DOI: 10.1007/s10439-026-04066-0
Barbara Batista de Oliveira, Frazer Heinis, Anastasia Desyatova, Jason MacTaggart, Alexey Kamenskiy
Purpose: Peripheral artery disease (PAD) predominantly affects the lower extremities, where complex biomechanical deformations during limb flexion contribute to disease progression and treatment failure. While human and cadaver studies have characterized these deformations, preclinical device testing requires large-animal models that replicate human arterial anatomy and biomechanics. Swine are commonly used, yet their biomechanical comparability to humans remains poorly defined.
Methods: We performed a detailed morphometric and biomechanical analysis of the external iliac (EIA), superficial femoral (SFA), and popliteal (PA) arteries in 20 Yucatan and 16 domestic swine using computed tomography angiography. Arteries were evaluated in straight and flexed limb postures to assess diameters, lengths, axial compression, tortuosity, bending angles, and inscribed sphere radii. Breed-specific effects of age and weight were also analyzed.
Results: Porcine arterial dimensions closely matched human lower extremity vessels. EIA diameters (4.9-7.2 mm) corresponded to human SFA, porcine SFA (4.1-5.9 mm) approximated human PA, and porcine PA (3.0-4.7 mm) resembled human tibial arteries. Segment lengths supported use of multiple devices. Flexion induced 12-33% axial compression, mimicking worst-case human scenarios. Tortuosity increased distally, and bending characteristics in porcine PAs aligned with human data. In Yucatan swine, vessel diameters were stable with age and weight, while domestic swine exhibited greater variability. Flexion-induced compression and tortuosity were not influenced by age or weight.
Conclusion: Swine are well-suited for modeling the geometry and biomechanics of human lower extremity arteries. Their anatomical compatibility and ability to replicate physiologic deformations make them valuable models for preclinical testing of PAD therapies and vascular devices.
{"title":"Biomechanical Characterization of Porcine Lower Limb Arteries for Preclinical Evaluation of Peripheral Vascular Devices.","authors":"Barbara Batista de Oliveira, Frazer Heinis, Anastasia Desyatova, Jason MacTaggart, Alexey Kamenskiy","doi":"10.1007/s10439-026-04066-0","DOIUrl":"10.1007/s10439-026-04066-0","url":null,"abstract":"<p><strong>Purpose: </strong>Peripheral artery disease (PAD) predominantly affects the lower extremities, where complex biomechanical deformations during limb flexion contribute to disease progression and treatment failure. While human and cadaver studies have characterized these deformations, preclinical device testing requires large-animal models that replicate human arterial anatomy and biomechanics. Swine are commonly used, yet their biomechanical comparability to humans remains poorly defined.</p><p><strong>Methods: </strong>We performed a detailed morphometric and biomechanical analysis of the external iliac (EIA), superficial femoral (SFA), and popliteal (PA) arteries in 20 Yucatan and 16 domestic swine using computed tomography angiography. Arteries were evaluated in straight and flexed limb postures to assess diameters, lengths, axial compression, tortuosity, bending angles, and inscribed sphere radii. Breed-specific effects of age and weight were also analyzed.</p><p><strong>Results: </strong>Porcine arterial dimensions closely matched human lower extremity vessels. EIA diameters (4.9-7.2 mm) corresponded to human SFA, porcine SFA (4.1-5.9 mm) approximated human PA, and porcine PA (3.0-4.7 mm) resembled human tibial arteries. Segment lengths supported use of multiple devices. Flexion induced 12-33% axial compression, mimicking worst-case human scenarios. Tortuosity increased distally, and bending characteristics in porcine PAs aligned with human data. In Yucatan swine, vessel diameters were stable with age and weight, while domestic swine exhibited greater variability. Flexion-induced compression and tortuosity were not influenced by age or weight.</p><p><strong>Conclusion: </strong>Swine are well-suited for modeling the geometry and biomechanics of human lower extremity arteries. Their anatomical compatibility and ability to replicate physiologic deformations make them valuable models for preclinical testing of PAD therapies and vascular devices.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343425","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}
The complexities of bone architecture, with its hierarchical organization and varying spatiotemporal scales, necessitate advanced modeling techniques to capture its mechanical behavior precisely. This review aims to highlight recent trends in capturing the multiscale nature of bone using two primary computational approaches: classical and data-driven frameworks. Each class is assessed regarding its versatility in achieving scale dimensions, modeling complex behavior, integrating biological data, and balancing computational efficiency and interpretability. In addition, hybrid techniques have been shown to offer future avenues for promising robust and generalizable modeling. Therefore, particular attention has been given to the synergy between these techniques. A hierarchical decision matrix is proposed to translate this review into actionable guidance, shedding light on the selection or combination of appropriate techniques based on specific application contexts, such as data availability, modeling objectives, and computational constraints. This review aims to serve as both a state-of-the-art synthesis and a practical reference for future advancements in multiscale bone biomechanics.
{"title":"Capturing the Multiscale Nature of Bone Behavior: Classical, Data-Driven and Hybrid Techniques.","authors":"Melika Mohammadkhah, Ardeshir Savari, Sandra Klinge","doi":"10.1007/s10439-026-04043-7","DOIUrl":"https://doi.org/10.1007/s10439-026-04043-7","url":null,"abstract":"<p><p>The complexities of bone architecture, with its hierarchical organization and varying spatiotemporal scales, necessitate advanced modeling techniques to capture its mechanical behavior precisely. This review aims to highlight recent trends in capturing the multiscale nature of bone using two primary computational approaches: classical and data-driven frameworks. Each class is assessed regarding its versatility in achieving scale dimensions, modeling complex behavior, integrating biological data, and balancing computational efficiency and interpretability. In addition, hybrid techniques have been shown to offer future avenues for promising robust and generalizable modeling. Therefore, particular attention has been given to the synergy between these techniques. A hierarchical decision matrix is proposed to translate this review into actionable guidance, shedding light on the selection or combination of appropriate techniques based on specific application contexts, such as data availability, modeling objectives, and computational constraints. This review aims to serve as both a state-of-the-art synthesis and a practical reference for future advancements in multiscale bone biomechanics.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343455","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 : 2026-02-28DOI: 10.1007/s10439-026-04026-8
Xiaoguang Liu, Pengyuan Lin, Yutong Wang, Tie Liang, Xiaodong Wang, Jun Li, Peng Xiong, Xiuling Liu
Purpose: Understanding how the neuromuscular system adapts to increasing force demands is essential for characterizing compensatory motor control. This study investigated force-dependent reconfiguration of muscle and cortical functional networks during isometric upper-limb tasks.
Methods: Twelve healthy participants performed isometric elbow flexion at 30%, 50%, and 70% of maximal voluntary contraction (MVC). Surface electromyography (sEMG) from eight upper-limb muscles and electroencephalography (EEG) from 21 scalp electrodes were recorded concurrently. Directed functional connectivity was estimated using generalized partial directed coherence (GPDC), and graph-theoretical metrics-average global efficiency (AGE), average clustering coefficient (ACC), and average path length (APL)-were computed separately for muscle and cortical networks.
Results: In the muscle network, a significant main effect of force level was observed. Compared with 30% MVC, AGE increased by 12.24% ( ) and APL decreased by 17.14% ( ) at 70% MVC, while ACC increased by 44.64% ( ). In the EEG beta band, AGE increased by 8.12% ( ) and APL decreased by 12.34% ( ) at 70% MVC relative to 30% MVC. Gamma band changes were limited or non-significant across conditions.
Conclusion: These results demonstrate systematic, force-dependent reconfiguration of both muscle and cortical functional networks during isometric force production. Rather than indicating improved performance or neural plasticity, the observed network changes suggest shifts in coordination strategies as force demands increase. The present framework provides quantitative network metrics that can be extended to clinical and longitudinal studies in future work.
{"title":"Network Reconfiguration Underlies Compensatory Muscle Control Across Force Gradients: Parallel Functional Network Evidence from EEG and sEMG.","authors":"Xiaoguang Liu, Pengyuan Lin, Yutong Wang, Tie Liang, Xiaodong Wang, Jun Li, Peng Xiong, Xiuling Liu","doi":"10.1007/s10439-026-04026-8","DOIUrl":"https://doi.org/10.1007/s10439-026-04026-8","url":null,"abstract":"<p><strong>Purpose: </strong>Understanding how the neuromuscular system adapts to increasing force demands is essential for characterizing compensatory motor control. This study investigated force-dependent reconfiguration of muscle and cortical functional networks during isometric upper-limb tasks.</p><p><strong>Methods: </strong>Twelve healthy participants performed isometric elbow flexion at 30%, 50%, and 70% of maximal voluntary contraction (MVC). Surface electromyography (sEMG) from eight upper-limb muscles and electroencephalography (EEG) from 21 scalp electrodes were recorded concurrently. Directed functional connectivity was estimated using generalized partial directed coherence (GPDC), and graph-theoretical metrics-average global efficiency (AGE), average clustering coefficient (ACC), and average path length (APL)-were computed separately for muscle and cortical networks.</p><p><strong>Results: </strong>In the muscle network, a significant main effect of force level was observed. Compared with 30% MVC, AGE increased by 12.24% ( <math><mrow><mi>P</mi> <mo>=</mo> <mn>0.043</mn></mrow> </math> ) and APL decreased by 17.14% ( <math><mrow><mi>P</mi> <mo>=</mo> <mn>0.031</mn></mrow> </math> ) at 70% MVC, while ACC increased by 44.64% ( <math><mrow><mi>P</mi> <mo>=</mo> <mn>0.018</mn></mrow> </math> ). In the EEG beta band, AGE increased by 8.12% ( <math><mrow><mi>P</mi> <mo>=</mo> <mn>0.048</mn></mrow> </math> ) and APL decreased by 12.34% ( <math><mrow><mi>P</mi> <mo>=</mo> <mn>0.036</mn></mrow> </math> ) at 70% MVC relative to 30% MVC. Gamma band changes were limited or non-significant across conditions.</p><p><strong>Conclusion: </strong>These results demonstrate systematic, force-dependent reconfiguration of both muscle and cortical functional networks during isometric force production. Rather than indicating improved performance or neural plasticity, the observed network changes suggest shifts in coordination strategies as force demands increase. The present framework provides quantitative network metrics that can be extended to clinical and longitudinal studies in future work.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321338","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 : 2026-02-28DOI: 10.1007/s10439-026-04030-y
Reza Ahmadi, Shahram Rasoulian, Hamidreza Heidary, Saied Jalal Aboodarda, Thomas K Uchida, Walter Herzog, Amin Komeili
Purpose: Assessment of muscle coordination during cycling can provide insight into motor control strategies and movement efficiency. This study evaluated muscle synergy patterns as indicators of neuromuscular coordination in the lower limbs across three power levels of cycling (LPL = Lowest Power Level, MPL = Middle Power Level, HPL = Highest Power Level).
Methods: Twenty recreational cyclists performed a graded cycling test on a stationary bicycle ergometer. Electromyography (EMG) was recorded bilaterally from seven lower-limb muscles and muscle synergies were extracted using non-negative matrix factorization. The Synergy Index (SI) and Synergy Coordination Index (SCI) were calculated to assess muscle coordination patterns.
Results: Four muscle synergies were identified consistently across power levels, with changes in synergy composition and activation timing correlated with increasing muscular demands. At the dominant hip, SI remained consistent across power levels (0.50 ± 0.11 at LPL, 0.56 ± 0.15 at MPL, 0.54 ± 0.15 at HPL). At the dominant knee, SI decreased with increasing power (0.47 ± 0.07 at LPL to 0.34 ± 0.05 at HPL; p < 0.01, ηp2 = 0.51). At the dominant ankle, SI increased with increasing power (0.19 ± 0.09 at LPL to 0.27 ± 0.10 at HPL; p < 0.01, ηp2 = 0.41). The SCI increased with increasing power level (0.08 ± 0.04 at LPL, 0.13 ± 0.08 at MPL, 0.24 ± 0.11 at HPL; p < 0.01, Kendall's W = 0.59).
Conclusion: These findings provide insight into how the central nervous system modulates its response to increasing mechanical demands. Combining synergy indices offers a promising approach to assess motor control, inform rehabilitation, and optimize performance in cycling tasks.
{"title":"Quantifying Lower-Limb Muscle Coordination During Cycling Using Electromyography-Informed Muscle Synergies.","authors":"Reza Ahmadi, Shahram Rasoulian, Hamidreza Heidary, Saied Jalal Aboodarda, Thomas K Uchida, Walter Herzog, Amin Komeili","doi":"10.1007/s10439-026-04030-y","DOIUrl":"https://doi.org/10.1007/s10439-026-04030-y","url":null,"abstract":"<p><strong>Purpose: </strong>Assessment of muscle coordination during cycling can provide insight into motor control strategies and movement efficiency. This study evaluated muscle synergy patterns as indicators of neuromuscular coordination in the lower limbs across three power levels of cycling (LPL = Lowest Power Level, MPL = Middle Power Level, HPL = Highest Power Level).</p><p><strong>Methods: </strong>Twenty recreational cyclists performed a graded cycling test on a stationary bicycle ergometer. Electromyography (EMG) was recorded bilaterally from seven lower-limb muscles and muscle synergies were extracted using non-negative matrix factorization. The Synergy Index (SI) and Synergy Coordination Index (SCI) were calculated to assess muscle coordination patterns.</p><p><strong>Results: </strong>Four muscle synergies were identified consistently across power levels, with changes in synergy composition and activation timing correlated with increasing muscular demands. At the dominant hip, SI remained consistent across power levels (0.50 ± 0.11 at LPL, 0.56 ± 0.15 at MPL, 0.54 ± 0.15 at HPL). At the dominant knee, SI decreased with increasing power (0.47 ± 0.07 at LPL to 0.34 ± 0.05 at HPL; p < 0.01, η<sub>p</sub><sup>2</sup> = 0.51). At the dominant ankle, SI increased with increasing power (0.19 ± 0.09 at LPL to 0.27 ± 0.10 at HPL; p < 0.01, η<sub>p</sub><sup>2</sup> = 0.41). The SCI increased with increasing power level (0.08 ± 0.04 at LPL, 0.13 ± 0.08 at MPL, 0.24 ± 0.11 at HPL; p < 0.01, Kendall's W = 0.59).</p><p><strong>Conclusion: </strong>These findings provide insight into how the central nervous system modulates its response to increasing mechanical demands. Combining synergy indices offers a promising approach to assess motor control, inform rehabilitation, and optimize performance in cycling tasks.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321303","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 : 2026-02-28DOI: 10.1007/s10439-026-04044-6
Zaid S Salameh, Edward J Jacobs, Rafael V Davalos
Purpose: Atherosclerotic vascular disease remains a leading cause of morbidity and mortality worldwide. Current treatments such as angioplasty, stenting, and atherectomy are invasive and limited by restenosis, thrombosis, and incomplete long-term efficacy. Pulsed field ablation (PFA), a nonthermal electroporation-based modality, has demonstrated safety in other cardiovascular applications, but it has not been applied for the treatment of endoluminal vascular diseases. We investigated whether pulsed electric fields could be delivered within the coronary artery and if PFA could selectively ablate the cellular components of atherosclerotic plaques.
Methods: An endoluminal bipolar PFA probe was fabricated using a balloon catheter with flexible electrodes and evaluated in potato and ex vivo porcine hearts. The electrical conductivities of human atherosclerotic plaques were derived from previous impedance measurements for patient-specific multi-tissue and single-cell electroporation modeling. PFA was then evaluated for selective decellularization within an electrical conductivity-matched 3D fibrotic atherosclerosis tissue mimic using high concentrations of human macrophages and aggregated oxidized low-density lipoproteins, encapsulated within a collagen matrix.
Results: Endoluminal probe positioning and high-voltage pulsed electric field delivery feasibility was established within the porcine left coronary arteries, with susequent potato lesions experiments demonstrating maximum ablations (6.99 cm2) and current (13 A) with equal treatment parameters. The multi-tissue model then indicated that endoluminal PFA can effectively cover > 95% of severe and thick plaques with irreversible electroporation, with single-cell modeling supporting the electroporation of foam cells within the plaque. The 3D atherosclerosis mimic validated the ability of PFA to completely ablate the foam cells with fibrotic tissue at > 1000 V/cm.
Conclusions: This study provides practical demonstration of PFA for the treatment of atherosclerotic vascular disease. By combining experimental validation with computational modeling, we establish proof-of-concept that endoluminal PFA can selectively ablate diseased cells while preserving extracellular architecture, laying the groundwork for future translational development of this therapy.
{"title":"Endoluminal Catheter Pulsed Field Ablation for the Treatment of Atherosclerotic Vascular Disease.","authors":"Zaid S Salameh, Edward J Jacobs, Rafael V Davalos","doi":"10.1007/s10439-026-04044-6","DOIUrl":"https://doi.org/10.1007/s10439-026-04044-6","url":null,"abstract":"<p><strong>Purpose: </strong>Atherosclerotic vascular disease remains a leading cause of morbidity and mortality worldwide. Current treatments such as angioplasty, stenting, and atherectomy are invasive and limited by restenosis, thrombosis, and incomplete long-term efficacy. Pulsed field ablation (PFA), a nonthermal electroporation-based modality, has demonstrated safety in other cardiovascular applications, but it has not been applied for the treatment of endoluminal vascular diseases. We investigated whether pulsed electric fields could be delivered within the coronary artery and if PFA could selectively ablate the cellular components of atherosclerotic plaques.</p><p><strong>Methods: </strong>An endoluminal bipolar PFA probe was fabricated using a balloon catheter with flexible electrodes and evaluated in potato and ex vivo porcine hearts. The electrical conductivities of human atherosclerotic plaques were derived from previous impedance measurements for patient-specific multi-tissue and single-cell electroporation modeling. PFA was then evaluated for selective decellularization within an electrical conductivity-matched 3D fibrotic atherosclerosis tissue mimic using high concentrations of human macrophages and aggregated oxidized low-density lipoproteins, encapsulated within a collagen matrix.</p><p><strong>Results: </strong>Endoluminal probe positioning and high-voltage pulsed electric field delivery feasibility was established within the porcine left coronary arteries, with susequent potato lesions experiments demonstrating maximum ablations (6.99 cm<sup>2</sup>) and current (13 A) with equal treatment parameters. The multi-tissue model then indicated that endoluminal PFA can effectively cover > 95% of severe and thick plaques with irreversible electroporation, with single-cell modeling supporting the electroporation of foam cells within the plaque. The 3D atherosclerosis mimic validated the ability of PFA to completely ablate the foam cells with fibrotic tissue at > 1000 V/cm.</p><p><strong>Conclusions: </strong>This study provides practical demonstration of PFA for the treatment of atherosclerotic vascular disease. By combining experimental validation with computational modeling, we establish proof-of-concept that endoluminal PFA can selectively ablate diseased cells while preserving extracellular architecture, laying the groundwork for future translational development of this therapy.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321365","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 : 2026-02-27DOI: 10.1007/s10439-026-04048-2
Augusto Marques, João Folgado, Carlos Quental
{"title":"Correction: Reconstruction of Scapula Bone Shapes from Digitized Skin Landmarks Using Statistical Shape Modeling and Multiple Linear Regression.","authors":"Augusto Marques, João Folgado, Carlos Quental","doi":"10.1007/s10439-026-04048-2","DOIUrl":"https://doi.org/10.1007/s10439-026-04048-2","url":null,"abstract":"","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301264","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 : 2026-02-26DOI: 10.1007/s10439-026-03999-w
Taotao Wu, Jared A Rifkin, Adam C Rayfield, Keith A Kroma-Wiley, Dani S Bassett, David F Meaney
Current research in predicting traumatic brain injury risk focuses on the relationship between head impacts and the likelihood of white matter damage, often overlooking the role of neurovascular coupling in the injury response. To fill this gap, we combined biomechanical and neurodynamic principles to simulate alterations to large-scale resting-state brain activity following head impacts. We simulated cortical neural activity with a network of Kuramoto phase oscillators, using structural connectivity to define coupling and a vascular-informed local resource term to capture neurovascular coupling. By combining the neurodynamic model with a brain mechanics model, we investigated two mechanistic pathways of network dysfunction: (1) white matter damage, reflected in degrading network edges, and (2) local tissue oxygenation decline, reflected in adjusting the resource term at each network node. We simulated 53 real-world head impacts using a vasculature template to evaluate the changes in simulated functional connectivity (FC) and neural dynamics relative to injury outcomes (concussion vs. no concussion). To assess vascular variability, simulations were repeated across 41 individual vasculature maps. Our results show simulated FC changes (measured by Pearson's correlation) consistently correlated well with injury outcomes, regardless of injury mechanism (AUC = 0.89 and 0.90), However, the two injury models yielded distinct FC patterns as indicated by graph metrics. Vascular variability substantially influenced how injury affected FC, with some brains exhibiting resilience to synchrony disruption depending on their vascular structure. These findings offer testable insight into the neurovascular mechanism of brain dysfunction after TBI and have important implications for individualized protection and treatment.
{"title":"A Proposed Novel Neurovascular Mechanism for Brain Network Dysfunction After Traumatic Injury.","authors":"Taotao Wu, Jared A Rifkin, Adam C Rayfield, Keith A Kroma-Wiley, Dani S Bassett, David F Meaney","doi":"10.1007/s10439-026-03999-w","DOIUrl":"https://doi.org/10.1007/s10439-026-03999-w","url":null,"abstract":"<p><p>Current research in predicting traumatic brain injury risk focuses on the relationship between head impacts and the likelihood of white matter damage, often overlooking the role of neurovascular coupling in the injury response. To fill this gap, we combined biomechanical and neurodynamic principles to simulate alterations to large-scale resting-state brain activity following head impacts. We simulated cortical neural activity with a network of Kuramoto phase oscillators, using structural connectivity to define coupling and a vascular-informed local resource term to capture neurovascular coupling. By combining the neurodynamic model with a brain mechanics model, we investigated two mechanistic pathways of network dysfunction: (1) white matter damage, reflected in degrading network edges, and (2) local tissue oxygenation decline, reflected in adjusting the resource term at each network node. We simulated 53 real-world head impacts using a vasculature template to evaluate the changes in simulated functional connectivity (FC) and neural dynamics relative to injury outcomes (concussion vs. no concussion). To assess vascular variability, simulations were repeated across 41 individual vasculature maps. Our results show simulated FC changes (measured by Pearson's correlation) consistently correlated well with injury outcomes, regardless of injury mechanism (AUC = 0.89 and 0.90), However, the two injury models yielded distinct FC patterns as indicated by graph metrics. Vascular variability substantially influenced how injury affected FC, with some brains exhibiting resilience to synchrony disruption depending on their vascular structure. These findings offer testable insight into the neurovascular mechanism of brain dysfunction after TBI and have important implications for individualized protection and treatment.</p>","PeriodicalId":7986,"journal":{"name":"Annals of Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301219","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}