Annals of Biomedical Engineering最新文献

Purpose: Simulation studies, such as finite element (FE) modeling, offer insights into knee joint biomechanics, which may not be achieved through experimental methods without direct involvement of patients. While generic FE models have been used to predict tissue biomechanics, they overlook variations in population-specific geometry, loading, and material properties. In contrast, subject-specific models account for these factors, delivering enhanced predictive precision but requiring significant effort and time for development.

Methods: This study aimed to facilitate subject-specific knee joint FE modeling by integrating an automated cartilage segmentation algorithm using a 3D Swin UNETR. This algorithm provided initial segmentation of knee cartilage, followed by automated geometry filtering to refine surface roughness and continuity. In addition to the standard metrics of image segmentation performance, such as Dice similarity coefficient (DSC) and Hausdorff distance, the method's effectiveness was also assessed in FE simulation. Nine pairs of knee cartilage FE models, using manual and automated segmentation methods, were developed to compare the predicted stress and strain responses during gait.

Results: The automated segmentation achieved high Dice similarity coefficients of 89.4% for femoral and 85.1% for tibial cartilage, with a Hausdorff distance of 2.3 mm between the automated and manual segmentation. Mechanical results including maximum principal stress and strain, fluid pressure, fibril strain, and contact area showed no significant differences between the manual and automated FE models.

Conclusion: These findings demonstrate the effectiveness of the proposed automated segmentation method in creating accurate knee joint FE models. The automated models developed in this study have been made publicly accessible to support biomechanical modeling and medical image segmentation studies ( https://data.mendeley.com/datasets/dc832g7j5m/1 ).

While studies indicate that females experience a higher concussion risk and more severe outcomes in soccer heading compared to males, comprehensive data on the underlying factors contributing to these sex-based differences are lacking. This study investigates the sex differences in the head-to-ball impact kinematics among college-aged soccer headers in a laboratory-controlled setting. Forty subjects (20 females, 20 males) performed ten headers, and impact kinematics, including peak angular acceleration and velocity (PAA, PAV) and peak linear acceleration (PLA), were measured using mouthguards. Video recordings verified impacts and impact locations. Participants' head mass was estimated from their weights. The relationship between head mass and kinematic parameters was analyzed using Pearson correlation. The effects of head mass, sex, and impact location on kinematic parameters were assessed using MANOVA with and without head mass as a covariate. Results showed that head mass, larger in males than females, significantly affects PAA and PLA, the greater the head mass, the lower PAA and PLA. However, head mass has no effect on PAV. Females showed significantly higher PAA and PLA components but no significant differences in PAV. Impact location significantly influenced PAV, showing higher magnitudes for frontal impacts compared to top-front impacts, with no significant effects on PAA and PLA. Our results agree with epidemiological evidence that female soccer players face greater concussion risks than males, which can be attributed to their higher header-induced PAA. Future research could consider interventions like changing ball pressure, using protective headgear, and improving heading techniques to reduce high-magnitude accelerations in females.

Metastasis remains the leading cause (90%) of cancer-related mortality, especially in metastatic triple-negative breast cancer (TNBC). Improved understanding of molecular drivers in the metastatic cascade is crucial, to find accurate prognostic markers for invasiveness after chemotherapy treatment. Current breast cancer chemotherapy treatments include doxorubicin and paclitaxel, inducing various effects, such as the unfolded protein response (UPR). The key regulator of the UPR is the 78-kDa glucose-regulated protein (GRP78), which is associated with metastatic disease, although, its expression level in the context of invasiveness is still controversial. We evaluate doxorubicin effects on TNBC cells, identifying GRP78 subpopulations linked to invasiveness. Specifically, we evaluate the motility and invasiveness of GRP78 positive vs. negative cell subpopulations by two different assays: the in vitro Boyden chamber migration assay and our innovative, rapid (2-3 h) clinically relevant, mechanobiology-based invasiveness assay. We validate chemotherapy-induced increase in the subpopulation of cell-surface GRP78(+) in two human, metastatic TNBC cell lines: MDA-MB-231 and MDA-MB-468. The GRP78(+) cell subpopulation exhibits reduced invasiveness and metastatic potential, as compared to whole-population control and to the GRP78(-) cell subpopulation, which are both highly invasive. Thus, using our innovative, clinically relevant assay, we rapidly (on clinical timescale) validate that GRP78(-) cells are likely linked with invasiveness, yet also demonstrate that combination of the GRP78(+) and GRP78(-) cells could increase the overall metastatic potential. Our results and approach could provide patient-personalized predictive marker for the expected benefits of chemotherapy in TNBC patients and potentially reveal non-responders to chemotherapy while also allowing evaluation of the clinical risk for metastasis.

Purpose: To determine how the biomechanical vulnerability of the human brain is affected by features of individual anatomy and loading.

Methods: To identify the features that contribute most to brain vulnerability, we imparted mild harmonic acceleration to the head and measured the resulting brain motion and deformation using magnetic resonance elastography (MRE). Oscillatory motion was imparted to the heads of adult participants using a lateral actuator (n = 24) or occipital actuator (n = 24) at 20 Hz, 30 Hz, and 50 Hz. Displacement vector fields and strain tensor fields in the brain were obtained from MRE measurements. Anatomical images, as well as displacement and strain fields from each participant were rigidly and deformably aligned to a common atlas (MNI-152). Vulnerability of the brain to deformation was quantified by the ratio of strain energy (SE) to kinetic energy (KE) for each participant. Similarity of deformation patterns between participants was quantified using strain field correlation (C_V). Linear regression models were used to identify the effect of similarity of brain size, shape, and age, as well as similarity of loading, on C_V.

Results: The SE/KE ratio decreased with frequency and was larger for participants undergoing lateral, rather than occipital, actuation. Head rotation about the inferior-superior axis was correlated with larger SE/KE ratio. Strain field correlations were primarily affected by the similarity of rigid-body motion.

Conclusion: The motion applied to the skull is the most important factor in determining both the vulnerability of the brain to deformation and the similarity between strain fields in different individuals.

Purpose: Current gait rehabilitation protocols for older adults typically attempt to effect changes in leg movements, while the role of arm movements is often ignored despite evidence of the neurological coupling of the upper and lower extremities. In the present work, we examine the effectiveness of a novel wearable haptic cueing system that targets arm swing to improve various gait parameters in older adults.

Methods: Twenty participants ( $M=73.4\pm 6.2$  years) were recruited to analyze their gait during normal and fast walking without haptic cueing. Vibrotactors attached to the arms were then used to give haptic cues that were designed to either increase or decrease arm swing cycle time. The effects of such cueing on gait symmetry and spatiotemporal parameters were then analyzed.

Results: The presentation of the haptic cues significantly altered arm swing cycle time resulting in an increase in gait speed of 18.2% when arm cycle time was decreased and a 12.3% decrease in gait speed when arm cycle time was lengthened. The response to haptic cues was immediate, emphasizing the tight coupling of the arm and legs in the production of gait. Spatiotemporal analysis revealed improvements in gait parameters and symmetry metrics, indicating enhanced coordination between limbs when using tactile cues. Subjective evaluations further supported the system's potential for gait training.

Conclusion: The results reveal the significant potential of the haptic cueing system to modulate gait through arm swing manipulation, leveraging interlimb neural coupling. This aligns with the growing need for home-based gait training solutions, particularly for the older population, and presents a novel approach that could be integrated into current gait rehabilitation practices.

Vacuum-assisted delivery (VAD) uses a vacuum cup on the fetal scalp to apply traction during uterine contractions, assisting complicated vaginal deliveries. Despite its widespread use, VAD presents a higher risk of neonatal morbidity compared to natural vaginal delivery and biomechanical evidence for safe VAD traction forces is still limited. The aim of this study is to develop and assess the feasibility of an experimental VAD testing setup, and investigate the impact of traction forces on fetal brain deformation. A patient-specific fetal head phantom was developed and subjected to experimental VAD in two testing setups: one with manual and one with automatic force application. The skull phantom was 3D printed using multi-material Polyjet technology. The brain phantom was cast in a 3D-printed mold using a composite hydrogel, and sonomicrometry crystals were used to estimate the brain deformation in three brain regions. The experimental VADs on the fetal head phantom allowed for quantifying brain strain with traction forces up to 112 N. Consistent brain crystal movements aligned with the traction force demonstrated the feasibility of the setup. The estimated brain deformations reached up to 4% and correlated significantly with traction force (p < 0.05) in regions close to the suction cup. Despite limitations such as the absence of scalp modeling and a simplified strain computation, this study provides a baseline for numerical studies and supports further research to optimize the safety of VAD procedures and develop VAD training platforms.

Shins are one of the most vulnerable bones in human body. Shin guards are evaluated by their effectiveness in reducing the force applied to the bone. In this study, a structural modified mechanical lumped model of the shin guard was developed to provide maximum force distribution using physical parameter change modification technique and genetic algorithm. Modal analysis and finite element methods were used to determine the dynamic behavior of the system in the frequency range of 0-3000 Hz. In this research, FE results had an encouraging agreement with those in experimental test with a Mean Absolute Error (MAE) found as 34.94. The results proposed two design zones to select the stiffness of the shin guard. The stiffnesses K₁ and K₂ were selected between the values in the design zones. For situation, K₁ = 7.9 × 10⁵ N/m and K₂ = 6.3 × 10⁵ N/m, the distribution parameter was equal to 76% and f₁ = 1.87F, f₂ = 0.71F f₃ = 1.81F, meaning the force was effectively distributed.

Cerebral edema is associated with poor prognosis because brain swelling within the rigid skull raises intracranial pressure, exacerbating secondary injuries following traumatic brain injury. Brain swelling can be characterized by triphasic biomechanics, which models brain tissue as a mixture of a deformable porous solid matrix with a negative fixed-charged density (FCD), water, and monovalent counterions. When brain cells die, the intracellular FCD is exposed, attracting cations into the cells. The increase in intracellular solute concentration generates osmotic pressure via the Gibbs-Donnan effect, driving water into cells and causing swelling. This study quantifies the FCD of rat and pig brain tissue by measuring the pressure generated by tissue within a confined volume as cells died. Rat brain tissue generated an averaged swelling pressure of 52.92 ± 20.40 mmHg (mean ± one standard deviation). Variations were observed between pig cortical white matter (7.14 ± 4.79 mmHg) and cortical gray matter (33.86 ± 11.89 mmHg). The corresponding FCD values were 42.54 ± 8.14 mEq/L for rat brain tissue, and 15.18 ± 5.38 mEq/L and 34.22 ± 6.31 mEq/L for pig cortical white and gray matter, respectively. Treating the rat brain tissue with DNAse, heparinase I, heparinase III, and chondroitinase ABC to degrade FCD significantly reduced swelling pressure. Good agreement between the experimental and numerically simulated responses supported the role of the FCD in cerebral edema formation. The reported FCD values can improve the biofidelity of computational models to predict post-traumatic cerebral edema, aiding the improvement of safety systems.

The mechanism by which chondrocytes respond to reduced mechanical loading environments and the subsequent risk of developing osteoarthritis remains unclear. This is of particular concern for astronauts. In space the reduced joint loading forces during prolonged microgravity (10^-6 g) exposure could lead to osteoarthritis (OA), compromising quality of life post-spaceflight. In this study, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to mimic the cartilage microenvironment. We then exposed agarose-chondrocyte constructs to simulated microgravity (SM) for four days using a rotating wall vessel (RWV) bioreactor to better assess the cartilage health risks associated with spaceflight. Metabolites extracted from media and agarose gel constructs were analyzed on liquid chromatography-mass spectrometry. Global metabolomic profiling detected a total of 1205 metabolite features, with 497 significant metabolite features identified by ANOVA (FDR-corrected p-value < 0.05). Specific metabolic shifts detected in response to SM exposure resulted in clusters of co-regulated metabolites, with glutathione, nitrogen, histidine, vitamin B₃, and aminosugars metabolism identified by variable importance in projection scores. Microgravity-induced metabolic shifts in gel constructs and media were indicative of protein synthesis, energy and nucleotide metabolism, and oxidative catabolism. Microgravity associated-metabolic shifts were consistent with our previously published early osteoarthritic metabolomic profiles in human synovial fluid, suggesting that even short-term exposure to microgravity (or other reduced mechanical loading environments) may lead to the development of OA. This work further suggests the potential to detect these metabolic perturbations in synovial fluid in vivo to ascertain osteoarthritis risk in astronauts.