Cardiovascular Engineering and Technology最新文献

Purpose: A triple lumen iteration of the novel photo-angioplasty drug eluting balloon catheter (DEBc) Lumi-Solve may be compromised by guidewire shadow (GWS)-mediated attenuation of balloon surface drug activation. The current study aimed to design and evaluate a novel triple lumen prototype, designated Lumi-Solve-T, to circumvent these issues.

Methods: Effects of guidewire shadowing (GWS) on vascular smooth muscle cell (VSMC) proliferation was evaluated using the MTT assay. In-silico modelling of GWS in the novel triple lumen design was conducted. Computer-aided design (CAD) and finite element analysis (FEA) contributed to development of a novel triple lumen catheter. 3D printing of rudimentary and refined prototypes of the catheter together with assembly of a novel fibre-optic (FO) complex and ex-vivo evaluation of the triple lumen device, Lumi-Solve T, was also performed.

Results: GW insertion in a parallel triple lumen FO: GW port orientation demonstrated significantly reduced inhibition of VSMC proliferation after 7 days confirming the need for an alternative triple lumen design. In-silico analysis identified a multi-fibre FO sleeve design supported uniform, radial and uninterrupted UV365nm light transmission to the angioplasty balloon surface. FEA confirmed a multi-fibre FO ribbon design afforded a practical method of FO sleeve generation and facilitated a novel hub configuration able to afford a FO ribbon to sleeve transition. 3D printed prototypes demonstrated the utility of the novel design.

Conclusions: A dedicated third port and lumen for the Lumi-Solve FO is required for optimal balloon surface photo-activation. A novel triple lumen design, Lumi-Solve-T, incorporating a ribbon to sleeve FO transition and novel hub design offers a realistic solution to current device limitations.

Purpose: Pulmonary atresia with intact ventricular septum is a multifactorial disease requiring complex surgeries. The treatment route is determined based on the right ventricle (RV) size, tricuspid annulus size and coronary circulation dependency of RV. Since multiple parameters influence the post-operative success, a personalized decision-making based on computed hemodynamics is hypothesized to improve the treatment efficacy.

Methods: A lumped parameter cardiovascular model is developed to calculate the hemodynamics of virtual patients which are generated by statistical distribution of circulation parameters. Four cohorts each with 30 digital patients are grouped based on RV size. For each patient, biventricular and one-and-half ventricle (1.5 V) repair were applied in silico and assessed via pressure, flow and saturations computed for every organ bed.

Results: Biventricular and 1.5 V repair yield significant increase in the pulmonary flow and oxygen saturation for all patients compared to the pre-operative state (p-values < 0.001). Approximately 30% of generated patients failed to meet the sufficient saturation and flow following biventricular repair and were directed to 1.5 V repair. However, 14% of these 1.5 V repair patients failed post-operatively, requiring Fontan completion. Based on the pre-determined hemodynamics criteria, this study implies that patients having RV sizes larger than 22 ml/m² are likely to undergo successful biventricular repair.

Conclusion: Pending further clinical trials, computational pre-interventional planning has the potential to screen patients that would not optimally fit to the traditional pathway prior to in vivo execution by providing personalized hemodynamic outcome. Statistical approach allows in silico clinical trials, useful for diseases with low patient numbers.

Purpose: CoRISMA MCS Systems Inc (Hamden CT) is developing an innovative mechanical circulatory support system (CMCS) as a durable therapeutic option for heart failure (HF) patients. The CMCS system is comprised of an axial flow pump, non-contacting hydrodynamic bearings, and integrated DC motor designed to be fully implantable in a left atrial (LA) to aortic (Ao) configuration; this unloading strategy may be particularly beneficial for HF patients with preserved ejection fraction (HFpEF). The small (5.5 cm³), lightweight (20 g), and low power (5-7 W) device design should allow for a less invasive off-pump implant. We present early-stage engineering development and testing of the prototype CoRISMA pumps.

Methods: Computational fluid dynamics (CFD) modeling was performed to evaluate flow and shear in two impeller (3 blades, 0.5 mm thickness, 8.9 mm diameter, 0.15 mm gap, polished titanium) and diffusor (5 blades, polished titanium) candidate designs. Test apparatuses were custom built to expedite development of the impeller/diffuser designs and iteratively refine the CFD models. Two candidate impeller/diffusor designs were fabricated and tested in each of the two test apparatuses (n = 4 impeller/diffuser + test fixture configurations) in static mock flow loops (hydrodynamic H-Q curves, 3.5 cP glycerol solution at 37 °C), and in dynamic mock flow loops (hemodynamics, 3.5 cP glycerol solution at 37 °C) tuned to HF conditions (mean aortic pressure 50 mmHg, central venous pressure 15 mmHg, aortic flow 3.0 L/min, and heart rate 80 bpm).

Results: CFD predicted flows of 4.56 L/min and 4.82 L/min at 100 mmHg for impellers/diffusers 1 and 2, respectively. Impeller 2 required less torque to generate a 6% increase in fluidic flow, and the diffuser had a larger area of high pressure, indicative of lower friction, which likely contributed to the increased efficiency. Experimental testing for all four configurations in the static and dynamic mock loops met performance metrics as evidenced by generating 4.0-4.5 L/min flow against 70-76 mmHg pressure at 25,000 rpm and restoring hemodynamics in the dynamic mock flow loop (MAP = 80 mmHg, CVP = 0 mmHg, total flow = 5.5 L/min) from baseline simulated HF test conditions.

Conclusion: These results demonstrate proof-of-concept of the early engineering design and performance of the prototype CoRISMA pumps. Engineering specifications, challenges observed, and proposed solutions for the next design iteration were identified for the continued development of an effective, reliable, and safe LA-to-Ao CMCS system for HF patients. Current design plans are underway for incorporating a wireless energy transfer system for communication and power, eliminating the need for and complications associated with an external driveline, to achieve a fully-implantable system.

Purpose: The purpose is to demonstrate the difference in closing volume fraction between the single opening&closing valve tester (SOCVT) and continuous pulsatile flow valve tester (CPFVT).

Methods: A comparative study was conducted in four hemodynamic conditions selected from the ISO 5840 on the four mitral valve states: normal annulus, 40% annulus dilation, 60% annulus dilation, and repaired valve with a clip device in both the SOCVT and CPFVT. The closing volume fractions were compared and errors calculated in the 16 cases.

Results: In the CPFVT, the flowrate waveform depends more on hemodynamic conditions rather than the valve morphology. For closing volume fractions in the two testers, twelve cases had errors between 10% and 20% and 3 cases had errors between 2.2% and 5.5%. There was no statistic difference in the closing volume fraction between the CPFVT and SOCVT for the normal annulus, 40% valve annulus dilation, 60% valve annulus dilation and repaired valves (P values = 0.44, 0.44, 0.33, and 0.08, respectively, n = 4).

Conclusion: There is certain error in closing volume measurements, even if no statistic difference in closing volume measured by the SOCVT and CPFVT. The typical flow waveforms of the mitral valve may be available to standardize testing of the SOCVT to evaluate valve hemodynamics. The SOCVT may be an alternative to the valve testing.

Purpose: To introduce a computational tool for peri-interventional intracranial aneurysm treatment guidance that maps preoperative planning information from simulation onto real-time X-Ray imaging.

Methods: Preoperatively, multiple flow diverter (FD) devices are simulated based on the 3D mesh of the vessel to treat, to choose the optimal size and location. In the peri-operative stage, this 3D information is aligned and mapped to the continuous 2D-X-Ray scan feed from the operating room. The current flow diverter position in the 3D model is estimated by automatically detecting the distal FD marker locations and mapping them to the treated vessel. This allows to visually assess the possible outcome of releasing the device at the current position, and compare it with the one chosen pre-operatively.

Results: The full pipeline was validated using retrospectively collected biplane images from four different patients (5 3D-DSA datasets in total). The distal FD marker detector obtained an average F1-score of 0.67 ( $\pm 0.224$ ) in 412 2D-X-Ray scans. After aligning 3D-DSA + 2D-X-Ray datasets, the average difference between simulated and deployed positions was 0.832 mm ( $\pm 0.521$ mm). Finally, we qualitatively show that the proposed approach is able to display the current location of the FD compared to their pre-operatively planned position.

Conclusions: The proposed method allows to support the FD deployment procedure by merging and presenting preoperative simulation information to the interventionists, aiding them to make more accurate and less risky decisions.

Purpose: To address the clinical need for totally implantable mechanical circulatory support devices, Bionet Sonar is developing a novel Ultrasonic Transcutaneous Energy Transmission (UTET) system that is designed to eliminate external power and/or data communication drivelines.

Methods: UTET systems were designed, fabricated, and pre-clinically tested using a non-clinical HeartWare HVAD in static and dynamic mock flow loop and acute animal models over a range of pump speeds (1800, 2400, 3000 RPM) and tissue analogue thicknesses (5, 10, 15 mm).

Results: The prototypes demonstrated feasibility as evidenced by meeting/exceeding function, operation, and performance metrics with no system failures, including achieving receiver (harvested) power exceeding HVAD power requirements and data communication rates of 10kB/s and pump speed control (> 95% sensitivity and specificity) for all experimental test conditions, and within healthy tissue temperature range with no acute tissue damage.

Conclusion: During early-stage development and testing, engineering challenges for UTET size reduction and stable and safe operation were identified, with solutions and plans to address the limitations in future design iterations also presented.

Purpose: The Wall Shear Stress (WSS) is the component tangential to the boundary of the normal stress tensor in an incompressible fluid, and it has been recognized as a quantity of primary importance in predicting possible adverse events in cardiovascular diseases, in general, and in coronary diseases, in particular. The quantification of the WSS in patient-specific settings can be achieved by performing a Computational Fluid Dynamics (CFD) analysis based on patient geometry, or it can be retrieved by a numerical approximation based on blood flow velocity data, e.g., ultrasound (US) Doppler measurements. This paper presents a novel method for WSS quantification from 2D vector Doppler measurements.

Methods: Images were obtained through unfocused plane waves and transverse oscillation to acquire both in-plane velocity components. These velocity components were processed using pseudo-spectral differentiation techniques based on Fourier approximations of the derivatives to compute the WSS.

Results: Our Pseudo-Spectral Method (PSM) is tested in two vessel phantoms, straight and stenotic, where a steady flow of 15 mL/min is applied. The method is successfully validated against CFD simulations and compared against current techniques based on the assumption of a parabolic velocity profile. The PSM accurately detected Wall Shear Stress (WSS) variations in geometries differing from straight cylinders, and is less sensitive to measurement noise. In particular, when using synthetic data (noise free, e.g., generated by CFD) on cylindrical geometries, the Poiseuille-based methods and PSM have comparable accuracy; on the contrary, when using the data retrieved from US measures, the average error of the WSS obtained with the PSM turned out to be 3 to 9 times smaller than that obtained by state-of-the-art methods.

Conclusion: The pseudo-spectral approach allows controlling the approximation errors in the presence of noisy data. This gives a more accurate alternative to the present standard and a less computationally expensive choice compared to CFD, which also requires high-quality data to reconstruct the vessel geometry.

In this study, we propose a new method for bioprinting 3D Spheroids to study complex congenital heart disease known as discrete subaortic stenosis (DSS). The bioprinter allows us to manipulate the extrusion pressure to change the size of the spheroids, and the alginate porosity increases in size over time. The spheroids are composed of human umbilical vein endothelial cells (HUVECs), and we demonstrated that pressure and time during the bioprinting process can modulate the diameter of the spheroids. In addition, we used Pluronic acid to maintain the shape and position of the spheroids. Characterization of HUVECs in the spheroids confirmed their uniform distribution and we demonstrated cell viability as a function of time. Compared to traditional 2D cell cultures, the 3D spheroids model provides more relevant physiological environments, making it valuable for drug testing and therapeutic applications.

Purpose: Myocardial infarction (MI) is a leading cause of irreversible functional cardiac tissue loss, requiring novel regenerative strategies. This study assessed the potential therapeutic efficacy of recellularized cardiac patches, incorporating fetal myocardial scaffolds with rat fetal cardiomyocytes and acellular human amniotic membrane, in adult Wistar rat models of MI.

Methods: Decellularized myocardial tissue was obtained from 14 to 16 week-old human fetuses that had been aborted. Chemical detergents (0.1% EDTA and 0.2% sodium dodecyl sulfate) were used to prepare the fetal extracellular matrix (ECM), which was characterized for bio-scaffold microstructure and biocompatibility via scanning electron microscopy (SEM) and MTT assay, respectively. Neonatal cardiomyocytes were extracted from the ventricles of one-day-old Wistar rats' littermates and characterized through immunostaining against Connexin-43 and α-smooth muscle actin. The isolated cells were seeded onto decellularized tissues and covered with decellularized amniotic membrane. Sixteen healthy adult Wistar rats were systematically allocated to control and MI groups. MI was induced via arterial ligation. Fourteen days post-operation, the MI group was received the engineered patches. Following a two-week post-implantation period, the animals were euthanized, and the hearts were harvested for the graft evaluation.

Results: Histological analysis, DAPI staining, and ultra-structural examination corroborated the successful depletion of cellular elements, while maintaining the integrity of the fetal ECM and architecture. Subsequent histological and immunohistochemichal (IHC) evaluations confirmed effective cardiomyocyte seeding on the scaffolds. The application of these engineered patches in MI models resulted in increased angiogenesis, reduced fibrosis, and restricted scar tissue formation, with the implanted cardiomyocytes remaining viable at graft sites, indicating prospective in vivo cell viability.

Conclusions: This study suggests that multi-layered recellularized cardiac patches are a promising surgical intervention for myocardial infarction, showcasing significant potential by promoting angiogenesis, mitigating fibrosis, and minimizing scar tissue formation in MI models. These features are pivotal for enhancing the therapeutic outcomes in MI patients, focusing on the restoration of the myocardial structure and function post-infarction.