Intracranial aneurysm is a life-threatening cerebrovascular disease. Recent studies have shown that irregular pulsations are associated with an increased risk of rupture. Currently, there is an urgent need for an objective and real-time method for analyzing wall deformation associated with irregular pulsations. In this study, we developed a fast and robust analytical framework based on an improved Horn-Schunck optical flow method. Verification experiments demonstrated that the proposed method exhibited sufficient accuracy and robustness. Patient-specific deformation analysis showed that irregular pulsation sites exhibited higher displacement and strain values compared with other regions of the aneurysm surface. The maximum first principal strains were significantly higher in intracranial aneurysms with irregular pulsation than in those without irregular pulsation (0.26 [0.20-0.28] vs. 0.19 [0.18-0.20], p=0.032; Wilcoxon rank-sum test). Overall, this framework can objectively identify irregular pulsations during the cardiac cycle and offers straightforward, user-friendly applicability for clinical diagnosis.
During spaceflight, assessment of jugular vein (JV) alterations is critical as it reflects systemic responses to fluid redistribution and carries a risk of thrombosis, a potentially fatal condition if undetected. Imaging options during spaceflight are restricted, making ultrasound the only feasible modality. However, available data on JV alterations are from small astronaut cohorts (typically n <12), limiting statistical power and robust validation. As a result, ground-based microgravity simulation studies are required to characterise microgravity-induced physiological changes, including JV alterations. This systematic review synthesised ultrasound-based findings on JV alterations across simulated microgravity models, including the effects of countermeasure techniques intended to mitigate these simulated microgravity-induced changes. The findings were compared with reported spaceflight JV measurements to examine similarities in venous responses. This review further reports variability in ultrasound systems, probes, and imaging methods, highlighting their implications for measurement consistency and translational relevance to true microgravity. Of 102 records identified, 21 studies were included in the review and four simulated microgravity models were identified: head-down tilt (n = 9), head-down bed rest (n = 6), dry immersion (n = 3) and parabolic flight (n = 3). Nine studies tested countermeasures, including thigh cuffs (n = 4), lower body negative pressure (n = 3) and exercise (n = 2). Across models, JV cross-sectional area, volume and pressure increased with greater intensity or longer exposure to simulation, indicating progressive venous distension. Lower body negative pressure was most effective at mitigating JV changes, thigh cuffs provided transient benefit and exercise showed limited mitigation of venous enlargement. Comparisons with spaceflight data showed that simulated microgravity reproduces the direction but often exaggerates the magnitude of venous changes, particularly in short-term models. Methodological variability and male-dominant cohorts limit the translational validity of findings to spaceflight ultrasound assessment, highlighting the need for standardised protocols and larger, sex-balanced cohorts in future simulated microgravity studies. From the countermeasure evidence identified in this review, future studies should further optimise and validate approaches that mitigate JV distension, minimise venous stasis and reduce the risk of thrombosis in simulated microgravity and, by extension, spaceflight.
The effects of non-Newtonian rheology on the dynamics of three-dimensional collapsible tube systems are investigated numerically using an immersed boundary-lattice Boltzmann method coupled with a finite element structural solver. A power-law constitutive model is employed to characterize shear-dependent viscosity effects across a wide range of power-law indices (n = 0.7-2.0). The results reveal that fluid rheology significantly modifies the system's dynamic response and apparent stability: shear-thickening fluids (n > 1) stabilize the collapsible tube and suppress flow-induced oscillations, while shear-thinning fluids (n < 1) promote instability and trigger self-excited oscillations. Mechanistically, shear-thinning effects amplify local velocity gradients in collapsed regions, enhancing fluid-structure coupling and destabilizing the system. In contrast, shear-thickening effects increase effective viscosity in the high-shear areas, providing mechanical damping that suppresses oscillations. The rheological properties significantly affect both structural deformation patterns and the pressure drop-flow rate relationship, with these effects demonstrating the critical importance of accounting for non-Newtonian behavior in physiologically and technologically relevant applications.
Atrial fibrillation (AF) is a common arrhythmia that increases the risk of stroke, heart failure, and other cardiovascular complications due to blood clot formation. While catheter ablation is a key treatment, its effectiveness is often limited by patient-specific variations, leading to recurrence. Recent studies show increasing precision and adaptability in using digital twin technology for AF ablation. Digital twins create patient-specific virtual heart models based on anatomical and physiological data, offering a promising approach for personalized ablation simulations. This review examines the role of digital twin technology in AF ablation, focusing on its foundational principles, recent advancements, and potential future directions. We critically assessed key components of digital twin models, including biophysical modeling and personalized data acquisition, highlighting their contributions to more precise and tailored treatment strategies. However, challenges remain, such as improving model accuracy, overcoming limited data availability, and developing regulatory frameworks for safe and effective clinical implementation. Addressing these challenges could lead to a transformative shift in the personalized management of AF, with broader implications for cardiac care.
Abstract Intracranial aneurysm (IA) rupture is catastrophic, yet current models of rupture-risk inadequately capture underlying IA remodelling mechanisms. Endothelial-haemodynamic interactions are central to these processes, but in vitro flow platforms often lack vessel-relevant geometry or long-term perfusion. Here, temporal and spatial endothelial responses to haemodynamic stress were investigated across idealised and patient-specific vascular models. Polydimethylsiloxane models were endothelialised with human aortic endothelial cells then perfused at up to 1.6 Pa wall shear stress for five days. IA models were exposed to steady or cardiovascular flow waveforms, with endothelial phenotype assessed by immunofluorescence and cytokine profiling. Flow initiation induced a transient inflammatory response, with elevated MCP-1 and TNF-α at day two, followed by a resolution of cytokine levels by day five, including a ∼7.5-fold reduction in MCP-1, despite increased haemodynamic loading. Endothelial cells retained a cobblestone-like morphology with eNOS undetected, resembling a partially activated phenotype. Compared with steady flow, cardiovascular flow reduced TGF-β1 and IL-8 secretion and decreased FGF-b consumption (∼2.5 fold), suggesting enhanced phenotypic stability. This study presents the first in vitro IA model incorporating a cardiovascular flow waveform and identifies cytokine signatures with potential utility as biomarkers of IA remodelling, highlighting the importance of long-term perfusion for modelling chronic vascular disease. Table of Contents Figure An in vitro model of an intracranial aneurysm was developed to investigate how fluid flow dynamics impact endothelial remodelling and inflammation. Pulsatile cardiac flow promoted stabilisation of inflammatory signalling, which was sustained under a steady flow regime. Cytokine signatures emerged with potential utility as biomarkers of IA remodelling, highlighting the importance of long-term perfusion for modelling chronic vascular disease. The schematic of the cytokine release dynamics used in the graphical abstract below was generated with the assistance of AI-based tools including ChatGPT (v5.5) and M365 Copilot to align with key results from this manuscript.
Effective tissue regeneration is often hindered by inadequate oxygen and nutrient diffusion within porous scaffolds, which restricts cell survival in the scaffold core. To address this critical challenge, this study introduces a novel hierarchical scaffold design inspired by the layered architecture of nacre and the channel structures found in vascularized structures in plants, like lotus root and bamboo. The scaffolds are fabricated using an innovative combination of freeze casting and molds manufactured by 3D printing, composed of polyvinyl alcohol (PVA) reinforced with tannic acid-functionalized graphene. The nacre-like microscale architecture was achieved via unidirectional freeze casting, while the lotus root- and bamboo-inspired macrostructure was created using a 3D printed mold. The results showed that introducing bamboo- (single large channel) and lotus root-inspired (multiple small channels) channels did not significantly compromise compressive properties. In particular, the lotus root-inspired scaffold achieved a wicking velocity of 30.11 mm s-1, approximately threefold higher than the non-channeled and single-channel designs, enabling faster and more uniform fluid penetration.
Accurate wall pressure measurements quantify pressure gradients in internal flows, yet a flush wall tap is not passive: tap geometry can bias static pressure, and the tap, pressure tubing, and sensor pathway can attenuate pulsatile fluctuations. We quantify wall pressure measurement fidelity over Reynolds numbers up to 704 by separating steady tap effects, dynamic transmission, and sensitivity to as-built geometry in experiments and computational fluid dynamics (CFD). Steady tests evaluated tap diameter bias (0.4, 0.8, and 1.0 mm) and compared CFD on computer-aided design and micro-computed tomography reconstructed lumens. A symmetric phantom with mirrored taps was tested at 1 Hz to quantify attenuation for 0.5 and 1.0 mm taps and two tubing lengths (560 and 2240 mm). The workflow was applied to a patient-specific intracranial aneurysm (IA) phantom with ten taps, fabricated by three-dimensional printing. Steady cases and a sinusoidal case were compared with matched rigid-wall CFD driven by the measured inflow waveform. Tap diameter weakly affected steady differential pressure, but 0.5 mm taps attenuated pulsatile amplitude, while tubing length changed amplitude by <1% at 1 Hz. In the IA phantom, the main discrepancies were in pressure magnitude rather than spatial pattern: CFD captured normalized spatial pressure distributions but underpredicted gauge pressure by 22%-28% in steady flow, pulsatile amplitude by 42%, and peak differential pressure by 15%. These results show that agreement in waveform shape or spatial trends can coexist with large magnitude error unless pressure transmission, as-built geometry, and inlet definition are verified and uncertainties are considered.
BackgroundStent implantation in vessels with moderate/severe coronary tortuosity is associated with increased rates of target vessel failure due to higher rates of target vessel-related myocardial infarction or ischemia-driven target vessel revascularization. Local wall shear stress (WSS) changes might contribute to this phenomenon. This study investigates the impact of stenting on the hemodynamic environment of tortuous coronary arteries in a numerical simulation model.Materials and methodsA numerical simulation model was established to explore the characteristics of hemodynamic parameters before and after simulated stent implantation in tortuous coronary vessels. The numerical simulation model is composed of four tortuous arcs. By controlling the curvature of these arcs, three groups with different tortuosity were formed. Four different stenosis degrees (40%, 50%, 60%, and 70%) were formed by changing the diameter of the third arc in each group. Finally, 12 models with different degrees of stenosis and tortuosity were analyzed.ResultsThe velocity and WSS were reduced in proportion to increased stenosis after stent implantation in tortuous segments mimicking tortuous coronary vessels with low, medium, and high tortuosity.ConclusionOur results indicate that further reduced WSS in tortuous coronary vessels post stenting might lead to increased endothelial dysfunction, vascular inflammation, and neointimal hyperplasia, all of which facilitate the formation of in-stent restenosis, especially in tortuous coronary vessels with severe stenosis.
Translating patient-specific vascular geometries into functional microfluidic devices remains challenging due to fabrication limitations and lengthy processing times. Here, an ultrafast microfabrication platform is introduced using glass-substrate digital light processing 3D printing for creating patient-specific carotid artery-on-a-chip devices. The optimized protocol employs treated glass slides as printing substrates and custom-designed mechanical clamping, reducing manufacturing time from over 10 h to under 2 h with ≈100% success rate. The system accurately reproduces complex anatomical features from CT angiography data of stroke patients, including stenoses, bifurcations, and ulcerations that conventional reconstruction methods often miss. Computational fluid dynamics validation confirms preserved hemodynamic similarity between patient-scale and chip-scale geometries, with matched wall shear rates maintaining physiological relevance despite 30-fold size reduction. The platform supports endothelialization and blood perfusion, enabling real-time visualization of thrombotic processes. Integration with laser ablation technology allows controlled endothelial injury modeling at patient-specific vulnerable sites. Quantitative analysis reveals 7-10-fold higher platelet translocation in the high shear zone (>1000 s-1), demonstrating the platform's capability to capture shear-dependent thrombotic mechanisms. This rapid biomanufacturing approach represents a significant advance in patient-specific organ-on-a-chip technology, with applications in personalized medicine and vascular device development.
Digital volume correlation-based optical coherence elastography (DVC-based OCE) may easily suffer from multiplicative speckle noise of optical coherence tomography (OCT) imaging, which can introduce non-negligible calculation errors. In this study, Hamilton-Jacobi partial differential equations were adopted for multiplicative noise removal of OCT images and the impact of multiplicative noise removal on DVC-based OCE was investigated. Several deformation conditions, including static, sub-pixel translation, uniform compression and non-uniform deformation, were tested. Results showed that multiplicative noise removal can suppress the maximum noise-induced error to less than 0.15 pixels in static tests. A more precise sub-pixel translation with an accuracy of 0.6 pixels was obtained. For uniform compression, multiplicative noise removal can extend the strain upper limit to 0.116 with an error less than 15% and a correlation value higher than 0.8. It also worked better in non-uniform deformation with more reliable calculation points. These findings provide a way to improve the measurement accuracy of the DVC-based OCE method by removing multiplicative noise on OCT images.
The meniscus plays an important role in the biomechanical function of the knee joint, but knee osteoarthritis (OA) deteriorates the mechanical properties of the meniscus. Thus understanding the mechanical behaviour of the OA meniscus is very important. This study aimed to assess the quasi-static nonlinear mechanical behaviours of the three zones of the OA meniscus by a proposed meso-indentation method, and further to investigate its nonlinear mechanical responses under the stance. Four pairs of menisci were harvested from OA patients during total knee arthroplasty. One pair of the menisci was first used for the histological analysis. Binocular fringe projection technology was then employed to reconstruct the morphology of the other three pairs of the menisci. Subsequently, a meso-indentation method was proposed to characterize the nonlinear behaviors of the meniscus zones, moreover, the hyperelastic model (HEM) together with the Hertz’s elastic model (EM) was used to fit the indentation force-depth curves of the meniscus zones. Furthermore, the fitted HEM and EM materials parameters were used to simulate the mechanical response of the meniscus in the stance by two simplified meniscus models. The results showed that the type III collagen widely existed in the OA menisci, and the red-white zone exhibited the best mechanical performance, and the 3-term Mooney-Rivlin model was the best descriptor for the nonlinear mechanical characterization of the three zones. Moreover, the stress or strain distributions of the simplified meniscus models differed significantly between the HEM and EM under the stance, and the EM underestimated the mechanical behaviours of the meniscus. The current work generally provides a novel testing method to study the nonlinear mechanical behaviour of soft biological materials, and is specifically helpful to understand the nonlinear mechanical behaviour of the OA meniscus for which the HEM should be used in the meniscus-related biomechanical studies.
Identifying haemodynamic factors associated with thin-walled regions (TWRs) of intracranial aneurysms is critical for improving pre-surgical rupture risk assessment. Intraoperatively, these regions are visually distinguished by a red, translucent appearance and are considered highly rupture prone. However, current imaging modalities lack the resolution to detect such vulnerable areas preoperatively. This study aimed to determine whether thin-walled regions exhibit distinct local haemodynamic profiles compared to adjacent normal-appearing wall regions. Sixteen patient-specific models of unruptured middle cerebral artery aneurysms were reconstructed from digital subtraction angiography images. Intraoperative TWRs were identified using a colour segmentation method based on Delta E metrics. Computational fluid dynamics (CFD) simulations were used to compute six haemodynamic parameters: wall shear stress (WSS), time-averaged WSS (TaWSS), oscillatory shear index (OSI), relative residence time (RRT), WSS divergence (WSSD), and pressure. Haemodynamic data were extracted from spatially localised surface patches within confirmed thin and normal regions. Linear mixed-effects models were applied to compare parameters while accounting for patient-level and intra-patient variability, using normalised values to improve model fit. Thin regions exhibited significantly higher WSS, TaWSS, WSSD, and pressure, and reduced RRT. WSS and TaWSS were approximately 3.3
Bone achieves exceptional performance by integrating strength, toughness and biological function. Replicating this synergy through synthetic scaffolds remains a major challenge in bone tissue engineering. Conventional biomaterials typically provide mechanical strength or toughness, but infrequently both. Nacre-inspired composite and nanocomposite scaffolds offer an attractive alternative due to their brick-and-mortar structure, which provides strength and toughness similar to cortical bone at the same time. However, almost all reported nacre-inspired scaffolds emphasized mechanical evaluations over important biological characteristics such as vascularization and osteoinductive potential. All currently proposed designs are dense and in bulk form, neglecting the inherent porosity of cortical bone and its pivotal functions in vascular integration, tissue remodelling and nutrient distribution. This review critically assesses recent progress, highlights unresolved issues and proposes future directions for evolving nacre-inspired scaffolds into multifunctional systems that can support clinical bone regeneration.
We consider learning surrogate models that directly predict cardiovascular flow fields by mapping geometry and/or fluid properties to hemodynamic parameters. Various machine learning approaches have been developed, but they generally do not extrapolate well to problems beyond the range covered by the training data. We propose a transductive physics informed neural network (T-PINN) approach to improve the extrapolation performance. Our approach builds on the standard PINN approach, which uses governing partial differential equations (PDEs) and labeled data for problems in the training regime to guide the training of neural network surrogate, but we additionally incorporate the governing PDEs for test problems from the extrapolation regimes. T-PINN demonstrates improved extrapolation performance on three synthetic cardiovascular flow problems as compared to purely data-driven neural network surrogates and standard PINNs. Additionally, we perform experiments to investigate how T-PINN's performance varies when the physical constraints are softened, with hard boundary constraints replaced by soft ones, or simplified PDEs by full PDEs. Our results indicate that these two variants result in similar equation residuals as the original T-PINN but lead to less accurate velocity and pressure predictions. T-PINN's enhanced extrapolation performance can be particularly significant for cardiovascular flow predictions in clinical settings, where patient morphologies and fluid properties often exhibit variations outside the collected data.
Biodegradable vascular stents (BVSs) face challenges related to inadequate mechanical strength, which can lead to adverse clinical outcomes. Improving the mechanical behavior of biodegradable vascular stents through structural design has been extensively explored. However, the corresponding effects of these mechanical enhancements on degradation characteristics remain under-investigated. The present work focuses on examining how different stent design strategies affect the mechanical behavior and degradation characteristics of poly (lactic acid) (PLA) stents. The commercial PLA stent DESolve was adopted, and nine modified stents were constructed based on the geometrical configuration of the DESolve stent. The mechanical properties of the modified stents during radial crimping and three-point bending simulations were thoroughly studied. The degradation dynamics of the stents were characterized by four indices (i.e., mean number average molecular weight, residual volume fraction, mean von Mises stress, and stent diameter). The results indicated that both the widening ratio and direction affected the mechanical performance of the stents by increasing the radial stiffness and radial strength, minimizing recoil%, and decreasing the bending flexibility. Although the widening direction had a relatively minor influence on stent degradation, the associated increase in material volume contributed to an improved volumetric integrity and enhanced lumen preservation. This study established a theoretical basis for evaluating both the mechanical and degradation behaviors of PLA stents, offering valuable insights for future structural design optimization.
Patients with atrial fibrillation (AF) are at risk for cardioembolic stroke. The recent studies suggest that reduced two-dimensional left atrial (LA) deformation, such as longitudinal strain, may be a potential indicator of stroke risk. We aim to evaluate three-dimensional (3-D) LA global and local strain derived from four-dimensional computed tomography angiography in patients with persistent atrial fibrillation, and compare those with and without cardioembolic stroke history.22 patients with persistent atrial fibrillation (11 with documented cardioembolic stroke) were included in this study. The LA strain was calculated by our novel mesh-regularised sub-volume tracking method. LA morphology, CHADS-VASC2, and 3-D global and local strain in 8 LA regions (anterior, lateral, appendage, roof, posterior, mitral isthmus, floor, and septum) were analysed. To explore the potential performance of the collected parameters for stroke risk evaluation, we used logistic regression to assess the outcomes of using these parameters to identify patients with cardioembolic stroke.Compared to those without previous stroke events, the patients with cardioembolic stroke presented lower global strain (0.090 vs 0.101; p = 0.006). Patients with cardioembolic stroke also had lower strain values in the roof (0.087 vs 0.106, p = 0.030), posterior (0.055 vs 0.072, p < 0.001) and floor (0.083 vs 0.097, p = 0.022). Results from logistic regression indicated that the accuracy of LA posterior strain as the indicator for previous stroke events was 0.8958.Therefore, 3-D LA global and local strain (especially in the posterior wall) could be useful in identifying patients with persistent AF and at high risk for a cardioembolic stroke.
The gold standard scaffold requires a perfect mechanical match between the scaffold and bones to create a suitable local mechanical microenvironment for bone repair; otherwise, the bone repair probably fails due to postoperative complications. Differently from the extensive biological evaluations of various scaffolds in the field of bone tissue engineering, this study first investigated the mechanical anisotropy match of a parameterized body-centered-cuboid (pBCC) scaffold to the trabecular bone. By varying two independent angle variables (B and rp) of the scaffold, the mechanical anisotropy of the scaffold was fully characterized by the theory, experiment and finite element method, and its deformation patterns and failure features related to the two variables were clarified. In particular, the elastic modulus anisotropy ratios of the scaffold and the femoral-head trabecular bone were calculated to examine their match. The results demonstrated that the normalized elastic moduli and yield strengths of the scaffolds could be reliably predicted by the theory which was validated by the experiments and finite element analysis. Moreover, the deformation patterns and failure features of the scaffold were strongly influenced by the two angle variables which actually determined the scaffold height. Importantly, the scaffold could be designed to achieve a high anisotropy ratio to allow various elastic modulus anisotropy ratio match with trabecular bones from the femoral head, proximal tibia, lumbar spine, and mandibular condyle. In addition, the developed theory could be generalized to design suitable scaffolds made of common biomaterials for bone repair for other anatomical sites by the modulus-strength chart. This study novelly presented that the mechanical anisotropy match between the scaffold and the trabecular bone could be achieved through a flexible parameterization design of the scaffold via the current methodology, which might offer promising applications in the fields of the bone tissue engineering and the regenerative medicine.