Annals of Biomedical Engineering最新文献

The hemodynamic performance of different prosthetic heart valves is difficult to compare among studies due to a variety of test conditions and experimental techniques. Existing studies are typically limited to one family of valves (biological or mechanical) and testing conditions of 5l/min and often lack sufficient spatial resolution. To address these limitations, a pulse duplicator with a multi-view imaging system (Tomo-PIV) was employed to investigate the three-dimensional flow field in the aortic root of three different valves: a tri-leaflet mechanical heart valve (TRIFLO, Novostia), a bi-leaflet mechanical heart valve (On-X, Artivion), and a biological heart valve (Perimount, Edwards Lifesciences). The valves were tested at low (3 l/min), normal (5 l/min), and elevated (7 l/min) cardiac output ((CO)) under hypotensive (40/60mmHg), normotensive (80/120mmHg), and moderate hypertensive (105/170mmHg) pressure conditions, respectively. Compared to the Perimount, peak mean velocity was − 33%, − 24%, − 18% for the TRIFLO and − 32%, − 20%, − 11% for the On-X at low, moderate, and elevated (CO), respectively. Corresponding peak (TKE) values decreased by − 66%, − 57%, − 44% (TRIFLO) and − 60%, − 50%, − 36% (On-X). At low (CO), (EOA) was lower for Perimount (1.07cm²) than for TRIFLO (1.47cm²) and On-X (1.52cm²), while it increased for elevated (CO) to 2.75cm² (TRIFLO) and 2.16cm² (Perimount and On-X). For all valves, increasing (CO) led to increased flow velocities, higher (EOA,) and higher levels of turbulence, and the spatial influence of the valve on the flow field in the ascending aorta was extended. (TKE) peaked closer to the STJ than for TRIFLO and Perimount.

Purpose

The patchy anatomical distribution of atherosclerosis has been attributed to variation in haemodynamic wall shear stress (WSS). The consensus is that low WSS and a high Oscillatory Shear Index (OSI) trigger the disease. We found that atherosclerosis at aortic branch sites correlates threefold better with transverse WSS (transWSS), a metric which quantifies multidirectional near-wall flow. Coronary artery disease has greater clinical significance than aortic disease but computation of WSS metrics is complicated by the substantial vessel motion occurring during each cardiac cycle. Here we present the first comparison of the distribution of atherosclerosis with WSS metrics computed for moving coronary arteries.

Methods

Maps of WSS metrics were computed using dynamic geometries reconstructed from angiograms of ten non-stenosed human right coronary arteries (RCAs). They were compared with maps of fatty streak prevalence derived from a previous study of 1852 RCAs.

Results

Time average WSS (TAWSS), OSI, transWSS and the cross-flow index (CFI), a non-dimensional form of the transWSS, gave non-significant or significant but low spatial correlations with lesion prevalence. The highest correlation coefficient (0.71) was for the relative residence time (RRT), a metric that decreases with TAWSS and increases with OSI. The coefficient was not changed if RRT was calculated using CFI, which captures multidirectional WSS only, rather than OSI, which encompasses both multidirectional and oscillatory WSS.

Conclusion

Contrary to our earlier findings in the aorta, low WSS in combination with highly multidirectional flow correlates best with lesion location in the RCA, explaining approximately half of its anatomical variation.

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, protein expression, and cytokine secretion over time. MDMs exposed to shear stress exhibited a rounder morphology compared to statically-cultured controls. RT-qPCR results showed significant upregulation of TNF-α, and analysis of cytokine release revealed increased secretion of IL-8, IL-18, fractalkine, and other chemokines. The upregulation of pro-inflammatory factors was evident with both increasing magnitudes of shear and time. Taken together, these results indicate that prolonged shear exposure induced a pro-inflammatory phenotype in human MDMs. These findings have implications for medical technology development, such as in situ vascular graft design wherein macrophages are exposed to shear and have been shown to affect graft resorption, and in delineating disease pathophysiology, for example to further illuminate the role of macrophages in atherosclerosis where shear is directly related to disease outcome.

To elucidate the mechanisms of cellular mechanotransduction, it is necessary to employ biomaterials that effectively merge biofunctionality with appropriate mechanical characteristics. Agarose and collagen separately are common biopolymers used in cartilage mechanobiology and mechanotransduction studies but lack features that make them ideal for functional engineered cartilage. In this study, agarose is blended with collagen type I to create hydrogels with final concentrations of 4% w/v or 2% w/v agarose with 2 mg/mL collagen. We hypothesized that the addition of collagen into a high-concentration agarose hydrogel does not diminish mechanical properties. Acellular and cell-laden studies were completed to assess rheologic and compressive properties, contraction, and structural homogeneity in addition to cell proliferation and sulfated glycosaminoglycan production. Over 21 days in culture, cellular 4% agarose–2 mg/mL collagen I hydrogels seeded with primary murine chondrocytes displayed structural and bulk mechanical behaviors that did not significantly alter from 4% agarose-only hydrogels, cell proliferation, and continual glycosaminoglycan production, indicating promise toward the development of an effective hydrogel for chondrocyte mechanotransduction and mechanobiology studies.

Blast traumatic brain injury (bTBI) is a prominent military health concern. The pervasiveness and long-term impacts of this injury highlight the need for investigation of the physiological outcomes of bTBI. Preclinical models allow for the evaluation of behavioral and neuropathological sequelae associated with bTBI. Studies have implemented rodent models to investigate bTBI due to the relative small size and low cost; however, a large animal model with similar neuroanatomical structure to humans is essential for clinical translation. Small blast simulators are used to induce bTBI in rodents, but a large animal model demands a larger device. This study describes a large advanced blast simulator (ABS4) that is a gas-detonation-driven system consisting of 5 sections totaling 40 ft in length with a cross-section of 4 × 4 ft at the test section. It is highly suitable for large animals and human surrogate investigations. This work characterized the ABS4 in preparation of large-scale bTBI testing. An array of tests were conducted with target overpressures in the test section ranging from 10 to 50 psi, and the pressure-time profiles clearly illustrate the essential characteristics of a free-field blast wave, specifically a sharp peak pressure and a defined negative phase. Multiple blast tests conducted at the same target pressure produced very similar pressure profiles, exhibiting the reproducibility of the ABS4 system. With its extensive range of pressures and substantial size, the ABS4 will permit military-relevant translational blast testing.

The migration of healthcare professionals from the Philippines, known as the ‘brain drain,’ poses a significant challenge to the nation’s health system. The shortfall in healthcare workers, exacerbated by this exodus, threatens disease control and overall public health. However, the rise of public medical schools offers a strategic response to this crisis. With new programs approved by the Commission on Higher Education, state universities are expanding access to medical education, particularly in underserved regions. This initiative is crucial for addressing the immediate shortage of healthcare professionals and building a more resilient and self-sustaining healthcare workforce in the Philippines.

The need for safe and effective methods to manage deep vein thrombosis (DVT), given the risks associated with anticoagulants and thrombolytic agents, motivated research into innovative approaches to resolve blood clots. In response to this challenge, sonothrombolysis is being explored as a technique that combines microbubbles, ultrasound, and thrombolytic agents to facilitate the aggressive dissolution of thrombi. Prior studies have indicated that relatively large microbubbles accelerate the dissolution process, either in an in vitro or an arterial model. However, sonothrombolysis using large microbubbles must be evaluated in venous thromboembolism diseases, where blood flow velocity is not comparable. In this study, the efficacy of sonothrombolysis was validated in a murine model of pre-existing DVT. During therapy, microfluidically produced microbubbles of 18 μm diameter and recombinant tissue plasminogen activator (rt-PA) were administered through a tail vein catheter for 30 min, while ultrasound was applied to the abdominal region of the mice. Three-dimensional ultrasound scans were performed before and after therapy for quantification. The residual volume of the thrombi was 20% in animals post sonothrombolysis versus 52% without therapy ((p = 0.012 < 0.05)), indicating a significant reduction in DVT volume. Histological analysis of tissue sections confirmed a reduction in DVT volume post-therapy. Therefore, large microbubbles generated from a microfluidic device show promise in ultrasound-assisted therapy to address concerns related to venous thromboembolism.

Purpose

Individuals with walking impairment, such as those with cerebral palsy, often face challenges in leading physically active lives due to the high energy cost of movement. Assistive devices like powered exoskeletons aim to alleviate this burden and improve mobility. Traditionally, optimizing the effectiveness of such devices has relied on time-consuming laboratory-based measurements of energy expenditure, which may not be feasible for some patient populations. To address this, our study aimed to enhance the state-of-the-art predictive model for estimating steady-state metabolic rate from 2-min walking trials to include individuals with and without walking disabilities and for a variety of terrains and wearable device conditions.

Methods

Using over 200 walking trials collected from eight prior exoskeleton-related studies, we trained a simple linear machine learning model to predict metabolic power at steady state based on condition-specific factors, such as whether the trial was conducted on a treadmill (level or incline) or outdoors, as well as demographic information, such as the participant’s weight or presence of walking impairment, and 2 minutes of metabolic data.

Results

We demonstrated the ability to predict steady-state metabolic rate to within an accuracy of 4.71 ± 2.7% on average across all walking conditions and patient populations, including with assistive devices and on different terrains.

Conclusion

This work seeks to unlock the use of in-the-loop optimization of wearable assistive devices in individuals with limited walking capacity. A freely available MATLAB application allows other researchers to easily apply our model.

An estimated 6.8 million people in the United States have an unruptured intracranial aneurysms, with approximately 30,000 people suffering from intracranial aneurysms rupture each year. Despite the development of population-based scores to evaluate the risk of rupture, retrospective analyses have suggested the limited usage of these scores in guiding clinical decision-making. With recent advancements in imaging technologies, artery wall motion has emerged as a promising biomarker for the general study of neurovascular mechanics and in assessing the risk of intracranial aneurysms. However, measuring arterial wall deformations in vivo itself poses several challenges, including how to image local wall motion and deriving the anisotropic wall strains over the cardiac cycle. To overcome these difficulties, we first developed a novel in vivo MRI-based imaging method to acquire cardiac gated images of the human basilar artery (BA) over the cardiac cycle. Next, complete BA endoluminal surfaces from each frame were segmented, producing high-resolution point clouds of the endoluminal surfaces. From these point clouds we developed a novel B-spline-based surface representation, then exploited the local support nature of B-splines to determine the local endoluminal surface strains. Results indicated distinct regional and temporal variations in BA wall deformation, highlighting the heterogeneous nature BA function. These included large circumferential strains (up to (sim) 20 (%)), and small longitudinal strains, which were often contractile and out of phase with the circumferential strains patterns. Of particular interest was the temporal phase lag in the maximum circumferential perimeter length, which indicated that the BA deforms asynchronously over the cardiac cycle. In summary, the proposed method enabled local deformation analysis, allowing for the successful reproduction of local features of the BA, such as regional principal stretches, areal changes, and pulsatile motion. Integrating the proposed method into existing population-based scores has the potential to improve our understanding of mechanical properties of human BA and enhance clinical decision-making.