Design and Analysis of a Polymeric Left Ventricular Simulator via Computational Modelling.

Preclinical testing of medical devices is an essential step in the product life cycle, whereas testing of cardiovascular implants requires specialised testbeds or numerical simulations using computer software Ansys 2016. Existing test setups used to evaluate physiological scenarios and test cardiac implants such as mock circulatory systems or isolated beating heart platforms are driven by sophisticated hardware which comes at a high cost or raises ethical concerns. On the other hand, computational methods used to simulate blood flow in the cardiovascular system may be simplified or computationally expensive. Therefore, there is a need for low-cost, relatively simple and efficient test beds that can provide realistic conditions to simulate physiological scenarios and evaluate cardiovascular devices. In this study, the concept design of a novel left ventricular simulator made of latex rubber and actuated by pneumatic artificial muscles is presented. The designed left ventricular simulator is geometrically similar to a native left ventricle, whereas the basal diameter and long axis length are within an anatomical range. Finite element simulations evaluating left ventricular twisting and shortening predicted that the designed left ventricular simulator rotates approximately 17 degrees at the apex and the long axis shortens around 11 mm. Experimental results showed that the twist angle is 18 degrees and the left ventricular simulator shortens 5 mm. Twist angles and long axis shortening as in a native left ventricle show it is capable of functioning like a native left ventricle and simulating a variety of scenarios, and therefore has the potential to be used as a test platform.

Unconventional Breathing Currents Far beyond the Quantum Tunneling Distances in Large-Gapped Nanoplasmonic Systems.

Localized surface plasmon resonance (LSPR) in plasmonic nanoparticles propels the field of plasmo-electronics, holding promise for transformative optoelectronic devices through efficient light-to-current conversion. Plasmonic excitations strongly influence the charge distribution within nanoparticles, giving rise to electromagnetic fields that can significantly impact the macroscopic charge flows within the nanoparticle housing material. In this study, we present evidence of ultralow, unconventional breathing currents resulting from dynamic irradiance interactions between widely separated nanoparticles, extending far beyond conventional electron (quantum) tunneling distances. We develop an electric analogue model and derive an empirical expression to elucidate the generation of these unconventional breathing currents in cascaded nanoplasmonic systems under irradiance modulation. This technique and theoretical model have significant potential for applications requiring a deeper understanding of current dynamics, particularly on large nanostructured surfaces relevant to photocatalysis, energy harvesting, sensing, imaging, and the development of future photonic devices.

Computational evaluation of heart failure and continuous flow left ventricular assist device support in anaemia.

Anaemia is common in end-stage heart failure patients supported with continuous flow left ventricular assist device (CF-LVAD) and is associated with adverse outcomes such as heart failure readmission. This study evaluates the haemodynamic effects of anaemia on cardiac function and cerebral blood flow in heart failure patients supported with CF-LVAD using computational simulations. A dynamic model simulating cardiac function, systemic, pulmonary and cerebral circulations, cerebral flow autoregulatory mechanisms and gas contents in blood was used to evaluate the effects of anaemia and iron deficiency in heart failure and during CF-LVAD support. CF-LVAD therapy was simulated by a model describing HeartMate 3. Anaemia and iron deficiency were simulated by reducing the haemoglobin level from 15 to 9 g/dL and modifying scaling coefficients in the models simulating heart chamber volumes. Reduced haemoglobin levels decreased the arterial O2 content, which increased cerebral blood flow rate by more than 50% in heart failure and during CF-LVAD assistance. Reduced haemoglobin levels simulating anaemia had minimal effect on the arterial and atrial blood pressures and ventricular volumes. In contrast, iron deficiency increased end-diastolic left and right ventricular diameters in heart failure from 6.6 cm to 7 cm and 2.9 cm to 3.1 cm and during CF-LVAD support from 6.1 to 6.4 cm and 3.1 to 3.3 cm. The developed numerical model simulates the effects of anaemia in failing heart and during CF-LVAD therapy. It is in good agreement with clinical data and can be utilised to assess CF-LVAD therapy.

Automated surgical planning in spring-assisted sagittal craniosynostosis correction using finite element analysis and machine learning.

Sagittal synostosis is a condition caused by the fused sagittal suture and results in a narrowed skull in infants. Spring-assisted cranioplasty is a correction technique used to expand skulls with sagittal craniosynostosis by placing compressed springs on the skull before six months of age. Proposed methods for surgical planning in spring-assisted sagittal craniosynostosis correction provide information only about the skull anatomy or require iterative finite element simulations. Therefore, the selection of surgical parameters such as spring dimensions and osteotomy sizes may remain unclear and spring-assisted cranioplasty may yield sub-optimal surgical results. The aim of this study is to develop the architectural structure of an automated tool to predict post-operative surgical outcomes in sagittal craniosynostosis correction with spring-assisted cranioplasty using machine learning and finite element analyses. Six different machine learning algorithms were tested using a finite element model which simulated a combination of various mechanical and geometric properties of the calvarium, osteotomy sizes, spring characteristics, and spring implantation positions. Also, a statistical shape model representing an average sagittal craniosynostosis calvarium in 5-month-old patients was used to assess the machine learning algorithms. XGBoost algorithm predicted post-operative cephalic index in spring-assisted sagittal craniosynostosis correction with high accuracy. Finite element simulations confirmed the prediction of the XGBoost algorithm. The presented architectural structure can be used to develop a tool to predict the post-operative cephalic index in spring-assisted cranioplasty in patients with sagittal craniosynostosis can be used to automate surgical planning and improve post-operative surgical outcomes in spring-assisted cranioplasty.

Evaluation of Potential Effects of Increased Outdoor Temperatures Due to Global Warming on Cerebral Blood Flow Rate and Respiratory Function in Chronic Obstructive Disease and Anemia.

Global warming due to increased outdoor carbon dioxide (CO2) levels may cause several health problems such as headaches, cognitive impairment, or kidney dysfunction. It is predicted that further increases in CO2 levels will increase the morbidity and mortality of patients affected by a variety of diseases. For instance, patients with Chronic Obstructive Pulmonary Disease (COPD) may suffer cognitive impairments or intracranial bleeding due to an increased cerebral blood flow rate. Predicting the harmful effects of global warming on human health will help to take measures for potential problems. Therefore, the quantification of physiological parameters is an essential step to investigate the effects of global warming on human health. In this study, the effects of increased outdoor temperatures due to climate change on cerebral blood flow rate and respiratory function in healthy subjects and COPD patients with anemia and respiratory acidosis are evaluated utilizing numerical simulations. The numerical model simulates cardiac function and blood circulation in systemic, pulmonary and cerebral circulations, cerebral autoregulatory functions, respiratory function, alveolar gas exchange, oxygen (O2) and CO2 contents, and hemoglobin levels in the blood. The simulation results show that although the cardiovascular function is not significantly altered, the respiratory function and cerebral blood flow rates are altered remarkably.

Parametric Design and Prototyping of a Low-Power Planar Biped Robot.

This study proposes a design approach and the development of a low-power planar biped robot named YU-Bibot. The kinematic structure of the robot consists of six independently driven axes, and it weighs approximately 20 kg. Based on biomimetics, the robot dimensions were selected as the average anthropomorphic dimensions of the human lower extremities. The optimization of the mechanical design and actuator selection of the robot was based on the results of parametric simulations. The natural human walking gait was mimicked as a walking pattern in these simulations. As a result of the optimization, a low power-to-weight ratio of 30 W/kg was obtained. The drive system of the robot joints consists of servo-controlled brushless DC motors with reduction gears and additional bevel gears at the knee and ankle joints. The robot features spring-supported knee and ankle joints that counteract the robot's weight and compensate for the backlash present in these joints. The robot is constrained to move only in the sagittal plane by using a lateral support structure. The robot's feet are equipped with low-cost, force-sensitive resistor (FSR)-type sensors for monitoring ground contact and zero-moment point (ZMP) criterion. The experimental results indicate that the proposed robot mechanism can follow the posture commands accurately and demonstrate locomotion at moderate stability. The proposed parametric natural gait simulation-based design approach and the resulting biped robot design with a low power/weight ratio are the main contributions of this study.

IABP versus Impella Support in Cardiogenic Shock: "In Silico" Study.

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most commonly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the comparison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronised mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different rotational speeds. The percentage variation with respect to baseline conditions was calculated for haemodynamic and energetic variables during IABP and Impella assistance. The Impella pump driven with a rotational speed of 50,000 rpm increased the total flow by 4.36% with a reduction in left ventricular end-diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) assistance. The simulation outcome suggests that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support.

Computational Modelling of Cerebral Blood Flow Rate at Different Stages of Moyamoya Disease in Adults and Children.

Moyamoya disease is a cerebrovascular disorder which causes a decrease in the cerebral blood flow rate. In this study, a lumped parameter model describing the pressures and flow rates in the heart chambers, circulatory system, and cerebral circulation with the main arteries in the circle of Willis, pial circulation, cerebral capillaries, and veins was used to simulate Moyamoya disease with and without coarctation of the aorta in adults and children. Cerebral blood flow rates were 724 mL/min and 1072 mL/min in the healthy adult and child cardiovascular system models. The cerebral blood flow rates in the adult and child cardiovascular system models simulating Moyamoya disease were 676 mL/min and 1007 mL/min in stage 1, 627 mL/min and 892 mL/min in stage 2, 571 mL/min and 831 in stage 3, and 444 and 537 mL/min in stage 4. The cerebral blood flow rates were 926 mL/min and 1421 mL/min in the adult and child cardiovascular system models simulating coarctation of the aorta. Furthermore, the cerebral blood flow rates in the adult and child cardiovascular system model simulating Moyamoya disease with coarctation of the aorta were 867 mL/min and 1341 mL/min in stage 1, 806 mL/min and 1197 mL/min in stage 2, 735 mL/min and 1121 in stage 3, and 576 and 741 mL/min in stage 4. The numerical model utilised in this study can simulate the advancing stages of Moyamoya disease and evaluate the associated risks with Moyamoya disease.

Assessment of cardiac dimensions in children diagnosed with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant heart disease, characterized by increased left ventricular wall thickness and abnormal loading conditions. Imaging modalities are the first choice for diagnosis and risk stratification. Although heart dimensions have been characterized widely in HCM adults from cardiac imaging, there is limited information about children affected by HCM. The aim of this study is to evaluate left ventricular function and left heart dimensions in a small population of children diagnosed with HCM. METHODS: A total of 16 (seven male, nine female) pediatric patients with an average age of 14.0 ± 2.5 years diagnosed with HCM at Great Ormond Street Hospital for Children were included in this study. Cardiac magnetic resonance (CMR) images were used to measure left and right ventricular dimensions, and septal and left ventricular free wall thicknesses in Simpleware ScanIP. The gender groups were compared using student t-test or non-parametric Mann-Whitney U-test depending on the sample distribution. RESULTS: Differences in heart rate, left ventricular end-diastolic volume and end-diastolic volume index, left ventricular stroke volume and stroke volume index, left ventricular end-systolic long axis length, left ventricular end-systolic long axis length index, left ventricular end-diastolic mid-cavity diameter, left ventricular end-diastolic free wall thickness, left ventricular end-diastolic free wall thickness index, right ventricular end-diastolic long axis length were statistically significant in males and females. CONCLUSION: Left ventricular wall and intraventricular septal thickness increase affecting left ventricle cavity dimensions and there may be differences in anatomical and physiological parameters in males and females affected by HCM.

Patient-Specific Modelling and Parameter Optimisation to Simulate Dilated Cardiomyopathy in Children.

PURPOSE: Lumped parameter modelling has been widely used to simulate cardiac function and physiological scenarios in cardiovascular research. Whereas several patient-specific lumped parameter models have been reported for adults, there is a limited number of studies aiming to simulate cardiac function in children. The aim of this study is to simulate patient-specific cardiovascular dynamics in children diagnosed with dilated cardiomyopathy, using a lumped parameter model. METHODS: Patient data including age, gender, heart rate, left and right ventricular end-systolic and end-diastolic volumes, cardiac output, systolic and diastolic aortic pressures were collected from 3 patients at Great Ormond Street Hospital for Children, London, UK. Ventricular geometrical data were additionally retrieved from cardiovascular magnetic resonance images. 23 parameters in the lumped parameter model were optimised to simulate systolic and diastolic pressures, end-systolic and end-diastolic volumes, cardiac output and left and right ventricular diameters in the patients using a direct search optimisation method. RESULTS: Difference between the haemodynamic parameters in the optimised cardiovascular system models and clinical data was less than 10%. CONCLUSION: The simulation results show the potential of patient-specific lumped parameter modelling to simulate clinical cases. Modelling patient specific cardiac function and blood flow in the paediatric patients would allow us to evaluate a variety of physiological scenarios and treatment options.

Mechanical and morphological properties of parietal bone in patients with sagittal craniosynostosis.

Limited information is available on the effect of sagittal craniosynostosis (CS) on morphological and material properties of the parietal bone. Understanding these properties would not only provide an insight into bone response to surgical procedures but also improve the accuracy of computational models simulating these surgeries. The aim of the present study was to characterise the mechanical and microstructural properties of the cortical table and diploe in parietal bone of patients affected by sagittal CS. Twelve samples were collected from pediatric patients (11 males, and 1 female; age 5.2 ± 1.3 months) surgically treated for sagittal CS. Samples were imaged using micro-computed tomography (micro-CT); and mechanical properties were extracted by means of micro-CT based finite element modelling (micro-FE) of three-point bending test, calibrated using sample-specific experimental data. Reference point indentation (RPI) was used to validate the micro-FE output. Bone samples were classified based on their macrostructure as unilaminar or trilaminar (sandwich) structure. The elastic moduli obtained using RPI and micro-FE approaches for cortical tables (ERPI 3973.33 ± 268.45 MPa and Emicro-FE 3438.11 ± 387.38 MPa) in the sandwich structure and diploe (ERPI1958.17 ± 563.79 MPa and Emicro-FE 1960.66 ± 492.44 MPa) in unilaminar samples were in strong agreement (r = 0.86, p < .01). We found that the elastic modulus of cortical tables and diploe were correlated with bone mineral density. Changes in the microstructure and mechanical properties of bone specimens were found to be irrespective of patients' age. Although younger patients are reported to benefit more from surgical intervention as skull is more malleable, understanding the material properties is critical to better predict the surgical outcome in patients <1 year old since age-related changes were minimal.

Complications in children with ventricular assist devices: systematic review and meta-analyses.

Heart failure is a significant cause of mortality in children with cardiovascular diseases. Treatment of heart failure depends on patients' symptoms, age, and severity of their condition, with heart transplantation required when other treatments are unsuccessful. However, due to lack of fitting donor organs, many patients are left untreated, or their transplant is delayed. In these patients, ventricular assist devices (VADs) are used to bridge to heart transplant. However, VAD support presents various complications in patients. The aim of this study was to compile, review, and analyse the studies reporting risk factors and aetiologies of complications of VAD support in children. Random effect risk ratios (RR) with 95% confidence intervals were calculated to analyse relative risk of thrombosis (RR = 3.53 [1.04, 12.06] I2 = 0% P = 0.04), neurological problems (RR = 0.95 [0.29, 3.15] I2 = 53% P = 0.93), infection (RR = 0.31 [0.05, 2.03] I2 = 86% P = 0.22), bleeding (RR = 2.57 [0.76, 8.66] I2 = 0% P = 0.13), and mortality (RR = 2.20 [1.36, 3.55] I2 = 0% P = 0.001) under pulsatile-flow and continuous-flow VAD support, relative risk of mortality (RR = 0.45 [0.15, 1.37] I2 = 36% P = 0.16) under left VAD and biVAD support, relative risk of thrombosis (RR = 1.72 [0.46, 6.44] I2 = 0% P = 0.42), infection (RR = 1.77 [0.10, 32.24] I2 = 46% P = 0.70) and mortality (RR = 0.92 [0.14, 6.28] I2 = 45% P = 0.93) in children with body surface area < 1.2 m2 and > 1.2 m2 under VAD support, relative risk of mortality in children supported with VAD and diagnosed with cardiomyopathy and congenital heart diseases (RR = 1.31 [0.10, 16.61] I2 = 73% P = 0.84), and cardiomyopathy and myocarditis (RR = 0.91 [0.13, 6.24] I2 = 58% P = 0.92). Meta-analyses results show that further research is necessary to reduce complications under VAD support.

Validation of an in-silico modelling platform for outcome prediction in spring assisted posterior vault expansion.

BACKGROUND: Spring-Assisted Posterior Vault Expansion has been adopted at Great Ormond Street Hospital for Children, London, UK to treat raised intracranial pressure in patients affected by syndromic craniosynostosis, a congenital calvarial anomaly which causes premature fusion of skull sutures. This procedure aims at normalising head shape and augmenting intracranial volume by means of metallic springs which expand the back portion of the skull. The aim of this study is to create and validate a 3D numerical model able to predict the outcome of spring cranioplasty in patients affected by syndromic craniosynostosis, suitable for clinical adoption for preoperative surgical planning. METHODS: Retrospective spring expansion measurements retrieved from x-ray images of 50 patients were used to tune the skull viscoelastic properties for syndromic cases. Pre-operative computed tomography (CT) data relative to 14 patients were processed to extract patient-specific skull shape, replicate surgical cuts and simulate spring insertion. For each patient, the predicted finite element post-operative skull shape model was compared with the respective post-operative 3D CT data. FINDINGS: The comparison of the sagittal and transverse cross-sections of the simulated end-of-expansion calvaria and the post-operative skull shapes extracted from CT images showed a good shape matching for the whole population. The finite element model compared well in terms of post-operative intracranial volume prediction (R2 = 0.92, p < 0.0001). INTERPRETATION: These preliminary results show that Finite Element Modelling has great potential for outcome prediction of spring assisted posterior vault expansion. Further optimisation will make it suitable for clinical deployment.

The Science Behind the Springs: Using Biomechanics and Finite Element Modeling to Predict Outcomes in Spring-Assisted Sagittal Synostosis Surgery.

Spring-assisted surgery for the correction of scaphocephaly has gained popularity over the past 2 decades. Our unit utilizes standardized torsional springs with a central helix for spring-assisted surgery. This design allows a high degree of accuracy and reproducibility of the force vectors and force distance curves. In this manuscript, we expand on the biomechanical testing and properties of these springs. Standardization of design has enabled us to study the springs on bench and in vivo and a comprehensive repository of calvarial remodeling and spring dynamics has been acquired and analyzed.Finite element modeling is a technique utilized to predict the outcomes of spring-assisted surgery. We have found this to be a useful tool, in planning our surgical strategy and improving outcomes. This technique has also contributed significantly to the process of informed consent preoperatively. In this article, we expand on our spring design and dynamics as well as the finite element modeling used to predict and improve outcomes.In our unit, this practice has led to a significant improvement in patient outcomes and parental satisfaction and we hope to make our techniques available to a wider audience.

Computational modelling of patient specific spring assisted lambdoid craniosynostosis correction.

Lambdoid craniosynostosis (LC) is a rare non-syndromic craniosynostosis characterised by fusion of the lambdoid sutures at the back of the head. Surgical correction including the spring assisted cranioplasty is the only option to correct the asymmetry at the skull in LC. However, the aesthetic outcome from spring assisted cranioplasty may remain suboptimal. The aim of this study is to develop a parametric finite element (FE) model of the LC skulls that could be used in the future to optimise spring surgery. The skull geometries from three different LC patients who underwent spring correction were reconstructed from the pre-operative computed tomography (CT) in Simpleware ScanIP. Initially, the skull growth between the pre-operative CT imaging and surgical intervention was simulated using MSC Marc. The osteotomies and spring implantation were performed to simulate the skull expansion due to the spring forces and skull growth between surgery and post-operative CT imaging in MSC Marc. Surface deviation between the FE models and post-operative skull models reconstructed from CT images changed between ± 5 mm over the skull geometries. Replicating spring assisted cranioplasty in LC patients allow to tune the parameters for surgical planning, which may help to improve outcomes in LC surgeries in the future.

Computational analyses of aortic blood flow under varying speed CF-LVAD support.

Continuous Flow Left Ventricular Assist Devices (CF-LVADs) generally operate at a constant speed whilst supporting a failing heart. However, constant speed CF-LVAD support may cause complications and increase the morbidity rates in the patients. Therefore, different varying speed operating modes for CF-LVADs have been proposed to generate more physiological blood flow, which may reduce complication rates under constant speed CF-LVAD support. The proposed varying speed CF-LVAD algorithms simulate time-dependant dynamics and three dimensional blood flow patterns in aorta under varying speed CF-LVAD support remain unclear. The aim of this study is to evaluate three dimensional blood flow patterns in a patient-specific aorta model under co-pulsating and counter-pulsating CF-LVAD support modes driven by speed and flow rate control algorithms using numerical simulations. Aortic blood flow was evaluated for 10,000 rpm constant speed CF-LVAD support generating 4.71 L/min mean flow rate over a cardiac cycle. Co-pulsating and counter-pulsating CF-LVAD speed control operated the pump at the same average speed over a cardiac cycle and co-pulsating and counter-pulsating CF-LVAD flow rate control generated the same average flow rate over cardiac cycle as in the constant speed pump support. Simulation results show that the utilised counter-pulsating pump flow rate control may decrease the haemolysis to a third compared to the most commonly employed constant speed pump operating mode. Moreover, CF-LVAD support utilising counter-pulsating pump flow rate control generated the most favourable hemodynamic characteristics, i.e. low Dean number, least wall shear stress and least haemolysis values among the investigated cases.

Computational Evaluation of Potential Correction Methods for Unicoronal Craniosynostosis.

Unicoronal craniosynostosis is the second most common type of nonsyndromic craniosynostosis: it is characterized by ipsilateral forehead and fronto-parietal region flattening with contralateral compensatory bossing. It is a complex condition; therefore, which is difficult to treat because of the asymmetry in the orbits, cranium, and face. The aim of this study is to understand optimal osteotomy locations, dimensions, and force requirements for surgical operations of unicoronal craniosynostosis using a patient-specific finite element model and - at the same time - to evaluate the potential application of a new device made from Nitinol which was developed to expand the affected side of a unicoronal craniosynostosis skull without performing osteotomies. The model geometry was reconstructed using Simpleware ScanIP. The bone and sutures were modeled using elastic properties to perform the finite element analyses in MSc Marc software. The simulation results showed that expanding the cranium without osteotomy requires a significant amount of force. Therefore, expansion of the cranium achieved by Nitinol devices may not be sufficient to correct the deformity. Moreover, the size and locations of the osteotomies are crucial for an optimal outcome from surgical operations in unicoronal craniosynostosis.

Mathematical modeling of cardiac function to evaluate clinical cases in adults and children.

Time-varying elastance models can simulate only the pressure and volume signals in the heart chambers while the diagnosis of clinical cases and evaluation of different treatment techniques require more information. In this study, an extended model utilizing the geometric dimensions of the heart chambers was developed to describe the cardiac function. The new cardiac model was evaluated by simulating a healthy and dilated cardiomyopathy (DCM) condition for adults and children. The left ventricular ejection fraction, end-diastolic volume, end-diastolic diameter and diastolic sphericity index were 53.60%, 125 mL, 5.08 cm and 1.82 in the healthy adult cardiovascular system model and 23.70%, 173 mL, 6.60 cm and 1.40 in the DCM adult cardiovascular system model. In the healthy child cardiovascular system model, the left ventricular ejection fraction, end-diastolic volume, end-diastolic diameter and diastolic sphericity index were 59.70%, 92 mL, 4.10 cm and 2.26 respectively and 30.70%, 125 mL, 4.94 cm and 1.87 in the DCM child cardiovascular system model. The developed cardiovascular system model simulates the hemodynamic variables and clinical diagnostic indicators within the physiological range for healthy and DCM conditions proving the feasibility of this new model to evaluate clinical cases in adults and children.