A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus.

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: in vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus.

The impact of right ventricular hemodynamics on the performance of a left ventricular assist device in a numerical simulation model.

OBJECTIVES: Left ventricular assist devices (LVADs) have been established as alternative to heart transplantation for patients with end-stage heart failure refractory to medical therapy. Right heart failure (RHF) after LVAD implantation is associated with inferior outcome. Its preoperative anticipation may influence the selection between a pure left ventricular and a biventricular device type and, thus, improve outcomes. Reliable algorithms to predict RHF are missing. METHODS: A numerical model was used for simulation of a cardiovascular circulation. The LVAD was placed as parallel circuit between left ventricle and aorta. In contrast to other studies, the dynamic hydraulic behavior of a pulsatile LVAD was replaced by that of a continuous LVAD. A variety of hemodynamic states was tested mimicking different right heart conditions. Adjustable parameters included heart rate (HR), pulmonary vascular resistance (PVR), tricuspid regurgitation (TR), right ventricular contractility (RVC) and pump speed. Outcome parameters comprised central venous pressure (CVP), mean pulmonary artery pressure (mPAP), cardiac output (CO) and occurrence of suction. RESULTS: Alteration of HR, PVR, TR, RVC and pump speed resulted in diverse effects on CO, CVP and mPAP, resulting in improvement, impairment or no change of the circulation, depending on the degree of alteration. CONCLUSIONS: The numerical simulation model allows prediction of circulatory changes and LVAD behaviour following variation of hemodynamic parameters. Such a prediction may be of particular advantage to anticipate RHF after LVAD implantation. It may help preoperatively to choose the appropriate strategy of only left ventricular or both left and right ventricular support.

Building an interdisciplinary program of cardiovascular research at the Swiss Federal Institute of Technology- the ETHeart story.

In this backstory, researchers from Swiss Federal Institute of Technology (ETH Zurich) who initiated an interdisciplinary program to generate innovative solutions for different cardiovascular diseases, such as myocardial infarction, valvular replacement, and movement-based rehabilitation therapy, discuss the benefits and challenges of interdisciplinary research.

Cardiac Output Estimation: Online Implementation for Left Ventricular Assist Device Support.

OBJECTIVE: We present a novel pipeline that consists of various algorithms for the estimation of the cardiac output (CO) during ventricular assist devices (VADs) support using a single pump inlet pressure (PIP) sensor as well as pump intrinsic signals. METHODS: A machine learning (ML) model was constructed for the prediction of the aortic valve opening status. When a closed aortic valve is detected, the estimated CO equals the estimated pump flow. Otherwise, the estimated CO equals the sum of the estimated pump flow and the aortic valve flow, estimated via a Kalman-filter approach. Both the pathophysiological conditions and the pump speed of an in-vitro test bench were adjusted in various combinations to evaluate the performance of the pipeline, as well as the individual estimators. RESULTS: The ML model yielded a Matthews correlation coefficient of 0.771, a sensitivity of 0.913 and a specificity of 0.871. An overall CO root mean square error (RMSE) of 0.69 L/min was achieved. Replacing the pump flow and aortic pressure estimators with sensors would decrease the RMSE below 0.5 L/min. CONCLUSION: The performance of the proposed pipeline is considered the state of the art for VADs with an integrated PIP sensor. The effect of the individual estimators on the overall performance of the pipeline was thoroughly investigated and their limitations were identified for future research. SIGNIFICANCE: The clinical application of the proposed solution could provide the clinicians with essential information about the interaction between the patient's heart and the VAD to further improve the VAD therapy.

Posture related in-vitro characterization of a flow regulated MEMS CSF valve.

Overdrainage in upright position is one of the most prevalent issues in treating hydrocephalus with a cerebrospinal fluid (CSF) shunt. Anti-siphon devices (ASDs) are employed to reduce this problem. A novel microelectromechanical system (MEMS)-based valve, termed Chronoflow device, aims to regulate CSF drainage indifferently of the body posture. With this study, the suitability of this MEMS-based valve is evaluated regarding its use for the treatment of hydrocephalus, particularly for the prevention of overdrainage and blockage. In total, four Chronoflow devices were tested. An established in-vitro hardware-in-the-loop (HIL) test bed was used to investigate the valves regarding their pressure-flow characteristics, their behaviors towards CSF dynamics, and their capabilities to prevent CSF overdrainage in upright position. Additionally, a contamination test was conducted to evaluate the susceptibility of the device to blockage due to particles. All valves tested regulated the drainage rate at similar nominal flows and independently of posture. The pressure-flow relation measured, however, was notably higher than numerically calculated. Regarding the CSF dynamics, the first three valves tested led to a decreased steady-state intracranial pressure in supine position and showed stable drainage rate in upright position. During the transitional phase from supine to upright and vice versa, the valves continuously adjusted the outflow resistance, which resulted in a stable transitional phase preventing overdrainage. Yet, the fourth valve showed continuous overdrainage in upright position due to an increased nominal flow. However, after several test iterations the nominal flow decreased and stabilized at a level similar to that of the first three valves tested. The contamination test showed that most particles initially adhere to the pillars and spread throughout the cavity of the valve as the concentration of particles increases, thereby affecting the displacement of the membrane. The devices generally provide a stable flow regulation and prevent overdrainage in upright position. Specifically, their drainage behaviors during the posture changes are very effective. However, they also showed high hysteresis and sensitivity towards particle contamination, which resulted in initial increased and altering nominal flows after many test iterations. This result suggests that the MEMS design presented lacks robustness. Yet, an upstream filter and specific coatings on the fluid pathway may increase significantly its reliability.

Performance of modern syringe infusion pump assemblies at low infusion rates in the perioperative setting.

BACKGROUND: Syringe infusion pumps are used for the precise continuous administration of intravenous drugs. Their compliance and mechanical deficiencies have been found to cause considerable start-up delays, flow irregularities during vertical displacement, as well extensive delays of occlusion alarms at low infusion rates. The aim of this study was to evaluate the performance of several modern syringe infusion pumps at low infusion rates and the impact on drug concentration. METHODS: Seven currently marketed syringe infusion pump assemblies were assessed in an in vitro study during start-up, vertical displacement manoeuvres, and infusion line occlusion at a set flow rate of 1 ml h-1. The measured data were used as input for a pharmacokinetic simulation modelling plasma concentration during a standard neonatal continuous epinephrine infusion. RESULTS: The mean time from starting the infusion pump to steady-state flow varied from 89 to 1622 s. The zero-drug delivery time after lowering the pump ranged from 145 to 335 s. In all assemblies tested, occlusion alarm delays and measured flow irregularities during vertical displacement manoeuvres resulted in relevant deviations in plasma epinephrine concentration (>25%) as calculated by the pharmacokinetic simulation model. CONCLUSION: Problems with the performance of syringe infusion pump assemblies can have considerable impact on plasma drug concentration when highly concentrated short-acting cardiovascular drugs are administered at low flow rates. The problems, which affected all assemblies tested, are mainly related to the functional principle of syringe infusion pumps and will only partially be solved by incremental improvements of existing equipment.

Hydraulic Characterization of Implantable Rotary Blood Pumps.

OBJECTIVE: The hydraulic properties of implantable rotary blood pumps (RBPs) determine their interaction with the cardiovascular system. A systematic comparison in this regard has not yet been performed for different clinically used RBPs. The aim of this study is to describe the hydraulic characteristics of four RBPs with a universal mathematical model and to compare their behavior under clinical operating conditions. METHODS: First, static and dynamic pump properties of four RBPs (HVAD, Heartmate II, Heartmate 3, and Incor) including their peripheral components were identified in an in vitro setup; results were translated into mathematical models based on principles of turbomachinery including the low and backflow regions. Second, the four hydraulic models were compared in a numerical simulation of the cardiovascular system for full- and partial-support conditions. RESULTS: A model structure applicable to each of the investigated RBPs was developed. Deviations between simulated and measured signals for static and dynamic properties were small (2.6 ± 0.5 mmHg, 0.38 ± 0.14 L/min, respectively). For a simulated partial support condition, flow pulsatility ranged from 4.1 (Incor) to 9.1 L/min (HVAD). Negative flow rates during diastole were observed in three out of four pumps. CONCLUSION: Hydraulic properties differ greatly between the investigated RBPs, with flat characteristics for the HVAD and Heartmate II and steeper curves for the Heartmate 3 and especially the Incor. SIGNIFICANCE: Hydraulic characteristics of implantable RBPs are particularly important at lower pump flow rates if backflow is to be avoided. For further research, we provide dynamic hydraulic models of the four RBPs including their periphery.

Viscosity Prediction in a Physiologically Controlled Ventricular Assist Device.

OBJECTIVE: We present a novel machine learning model to accurately predict the blood-analog viscosity during support of a pathological circulation with a rotary ventricular assist device (VAD). The aim is the continuous monitoring of the hematocrit (HCT) of VAD patients with the benefit of a more reliable pump flow estimation and a possible early detection of adverse events, such as bleeding or pump thrombosis. METHODS: A large dataset was generated with a blood pump connected to a hybrid mock circulation by varying the pump speed, the physiological requirements of the modeled circulation, and the viscosity of the blood-analog. The inlet pressure and the intrinsic signals of the pump were considered as inputs for the model. Gaussian process yielded models with the best performance, which were then combined using a variant of stacked generalization to derive the final model. The final model was evaluated with unseen testing data from the dataset created. RESULTS: For these data, the model yielded a mean absolute deviation of 1.81% from the true HCT, while it proved to correctly predict the direction of the HCT change. It showed to be independent of the set speed and of the condition of the simulated cardiovascular circulation. CONCLUSION: The accuracy of the prediction model allows an improvement of the quality of flow estimators and the detection of adverse events at an early stage. The evaluation of this approach with blood is suggested for further validation. SIGNIFICANCE: Its clinical application could provide the clinicians with reliable and important hemodynamic information of the patient and, thus, enhance patient monitoring and supervision.

Virtual surgical planning, flow simulation, and 3-dimensional electrospinning of patient-specific grafts to optimize Fontan hemodynamics.

BACKGROUND: Despite advances in the Fontan procedure, there is an unmet clinical need for patient-specific graft designs that are optimized for variations in patient anatomy. The objective of this study is to design and produce patient-specific Fontan geometries, with the goal of improving hepatic flow distribution (HFD) and reducing power loss (Ploss), and manufacturing these designs by electrospinning. METHODS: Cardiac magnetic resonance imaging data from patients who previously underwent a Fontan procedure (n = 2) was used to create 3-dimensional models of their native Fontan geometry using standard image segmentation and geometry reconstruction software. For each patient, alternative designs were explored in silico, including tube-shaped and bifurcated conduits, and their performance in terms of Ploss and HFD probed by computational fluid dynamic (CFD) simulations. The best-performing options were then fabricated using electrospinning. RESULTS: CFD simulations showed that the bifurcated conduit improved HFD between the left and right pulmonary arteries, whereas both types of conduits reduced Ploss. In vitro testing with a flow-loop chamber supported the CFD results. The proposed designs were then successfully electrospun into tissue-engineered vascular grafts. CONCLUSIONS: Our unique virtual cardiac surgery approach has the potential to improve the quality of surgery by manufacturing patient-specific designs before surgery, that are also optimized with balanced HFD and minimal Ploss, based on refinement of commercially available options for image segmentation, computer-aided design, and flow simulations.

Response of a physiological controller for ventricular assist devices during acute patho-physiological events: an in vitro study.

The current paper analyzes the performance of a physiological controller for turbodynamic ventricular assist devices (tVADs) during acute patho-physiological events. The numerical model of the human blood circulation implemented on our hybrid mock circulation was extended in order to simulate the Valsalva maneuver (VM) and premature ventricular contractions (PVCs). The performance of an end-diastolic volume (EDV)-based physiological controller for VADs, named preload responsive speed (PRS) controller was evaluated under VM and PVCs. A slow and a fast response of the PRS controller were implemented by using a 3 s moving window, and a beat-to-beat method, respectively, to extract the EDV index. The hemodynamics of a pathological circulation, assisted by a tVAD controlled by the PRS controller were analyzed and compared with a constant speed support case. The results show that the PRS controller prevented suction during the VM with both methods, while with constant speed, this was not the case. On the other hand, the pump flow reduction with the PRS controller led to low aortic pressure, while it remained physiological with the constant speed control. Pump backflow was increased when the moving window was used but it avoided sudden undesirable speed changes, which occurred during PVCs with the beat-to-beat method. In a possible clinical implementation of any physiological controller, the desired performance during frequent clinical acute scenarios should be considered.

Patient Specific Hardware-in-the-Loop Testing of Cerebrospinal Fluid Shunt Systems.

GOAL: The development of increasingly sophisticated cerebrospinal fluid (CSF) shunts calls for test beds that can reproduce an ever larger range of physiologic and pathophysiologic behaviors. In particular, upcoming smart and active devices will require extensive testing under complex dynamic conditions. Herein, we describe a test bed that allows for fast, cost effective, and realistic in vitro testing of active and passive, gravitational and nongravitational CSF shunts based on the hardware-in-the-loop principle. METHODS: The shunt to be tested is placed in a dynamic in vitro setup that interfaces with a mathematical model of the patient's relevant physiology, which is evaluated numerically in real time. The model parameters can be identified using standard clinical tests. The test bed accounts for posture-dependent behavior and viscoelastic effects. RESULTS: Simulations of infusion tests, of intracranial pressure modulation by cardiovascular action, and of the effects of postural changes show good agreement with published results. Evaluation of valves without and with gravitational units show in modeled sitting patients the expected behavior of overdrainage and avoidance thereof, respectively. Finally, a 24-h test cycle based on recorded patient data elucidates the interaction between patient and shunt system expressed by drainage rate and intracranial pressure during typical daily activities. CONCLUSION: We envision this test bed as a tool to quantify a shunt's performance within a realistic yet reproducible testing environment. SIGNIFICANCE: The test bed can improve our understanding of the complex interaction between patient and shunt system and may catalyze the development of active shunts, while reducing the number of necessary in vivo experiments.