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OBJECTIVE Currently available ventricular assist devices provide continuous flow and do not adapt to the changing needs of patients. Physiological control algorithms have been proposed that adapt the pump speed based on the left ventricular pressure. However, so far, no clinically used pump can acquire this pressure. Therefore, for the validation of physiological control concepts in vivo, a system that can continuously and accurately provide the left ventricular pressure signal is needed. METHODS We demonstrate the integration of two pressure sensors into a tapered inflow cannula compatible with the HeartMate 3 (HM3) ventricular assist device. Selective laser melting was used to incorporate functional elements with a small footprint and therefore retain the geometry, function and implantability of the original cannula. The system was tested on a hybrid mock circulation system. Static and simulated physiological flow and pressure profiles were used to evaluate the combined pressure and flow sensing capabilities of the modified cannula. CONCLUSION The cannula prototypes enabled continuous pressure measurements at two points of their inner wall in the range of 100 and 200 mmHg. The developed, Bernoulli-based, two sensor model improved the accuracy of the measured simulated left ventricular pressure by eliminating the influence of flow inside the cannula. This method reduced the flow induced pressure uncertainty from up to 7.6 mmHg in single sensor measurements to 0.3 mmHg. Additionally, the two-sensor system and model enable the measurement of the blood flow through the pump with an accuracy of 0.140.04 L/min, without dedicated flow sensors.

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.

Left ventricular end-diastolic volume (EDV) is an important parameter for monitoring patients with left ventricular assist devices (LVADs) and might be useful for automatic LVAD work adaptation. However, continuous information on the EDV is unavailable to date. The depolarization amplitude (DA) of the noncontact intracardiac electromyogram (iEMG) is physically related to the EDV. Here, we show how a left ventricular (LV) volume sensor based on the iEMG might provide beat-wise EDV estimates. The study was performed in six pigs while undergoing a series of controlled changes in hemodynamic states. The LV volume sensor consisted of four conventional pacemaker electrodes measuring the far-field iEMG inside the LV blood pool, using a novel unipolar amplifier. Simultaneously, noninvasive measurements of EDV and hematocrit were recorded. The proposed EDV predictor was tested for statistical significance using a mixed-effect model and associated confidence intervals. A statistically significant (p = 3e–07) negative correlation was confirmed between the DA of the iEMG and the EDV as measured by electric impedance at a slope of –0.069 (–0.089, –0.049) mV/mL. The DA was slightly decreased by increased hematocrit (p = 0.039) and moderately decreased with the opening of the thorax (p = 0.003). The DA of the iEMG proved to be a significant, independent predictor of EDV. The proposed LV volume sensor is simple to integrate into the inflow cannula of an LVAD and thus has the potential to inform the clinician about the state of LV volume in real time and to automatically control the LVAD., ASAIO Journal, 67 (12), ISSN:1058-2916, ISSN:1538-943X

Additive manufacturing (AM) is an effective tool for accelerating knowledge gain in development processes, as it enables the production of complex prototypes at low cost and with short lead times. In the development of mechanical circulatory support, the use of cheap polymer-based AM techniques for prototype manufacturing allows more design variations to be tested, promoting a better understanding of the respective system and its optimization parameters. Here, we compare four commonly used AM processes for polymers with respect to manufacturing accuracy, surface roughness, and shape fidelity in an aqueous environment. Impeller replicas of the CentriMag blood pump were manufactured with each process and integrated into original pump housings. The assemblies were tested for hydraulic properties and hemolysis in reference to the commercially available pump. Computational fluid dynamic simulations were carried out to support the transfer of the results to other applications. In hydraulic testing, the deviation in pressure head and motor current of all additively manufactured replicas from the reference pump remained below 2% over the entire operating range of the pump. In contrast, significant deviations of up to 620% were observed in hemolysis testing. Only the replicas produced by stereolithography showed a nonsignificant deviation from the reference pump, which we attribute to the low surface roughness of parts manufactured thereby. The results suggest that there is a flow-dependent threshold of roughness above which a surface strongly contributes to cell lysis by promoting a hydraulically rough boundary flow.

OBJECTIVE Ventricular assist devices (VADs) are implanted in patients suffering from end-stage heart failure to sustain the blood circulation. Real-time volume measurement could be a valuable tool to monitor patients and enable physiological control strategies to provide individualized therapy. However, volume measurement using one sensor modality requires re-calibration in the critical time post VAD implantation. METHODS To overcome this limitation, we have integrated ultrasound and impedance volume measurement techniques into a cannula of an apical VAD. We tested both modalities across a volume range from 140-420 mL using two differently sized and shaped biventricular silicon heart phantoms, which were subjected to physiological pressures in an in-vitro test bench. We compared results from standard calibrated measurements with calculations found by a quadratic optimization for the single modality and their combination (dual-modality) and validated the results using twofold cross-validation. RESULTS The dual-modality approach resulted in most favorable limits of agreement (LOA) of -0.83 ± 1.54% compared to -13.88 ± 5.90% for ultrasound and -43.45 ± 10.28% for electric impedance, separately. CONCLUSION The results of the dual-modality approach were as accurate as the standard calibrated measurement and valid over a large range of volumes (140-420 mL). In this in-vitro study, we show how a dual-modality ventricular volume measurement of ultrasound and electric impedance increases the robustness and renders calibration obsolete. SIGNIFICANCE Ventricular volumes could be measured accurately in the critical period post VAD implantation despite ventricular remodeling.

Introduction Intrafractional motion can cause substantial uncertainty in precision radiotherapy. Traditionally, the target volume is defined to be sufficiently large to cover the tumor in every position. With the robotic treatment couch, a real‐time motion compensation can improve tumor coverage and organ at risk sparing. However, this approach poses additional requirements, which are systematically developed and which allow the ideal robotic couch to be specified. Methods and materials Data of intrafractional tumor motion were collected and analyzed regarding motion range, frequency, speed, and acceleration. Using this data, ideal couch requirements were formulated. The four robotic couches Protura, Perfect Pitch, RoboCouch, and RPSbase were tested with respect to these requirements. Results The data collected resulted in maximum speed requirements of 60 mm/s in all directions and maximum accelerations of 80 mm/s2 in the longitudinal, 60 mm/s2 in the lateral, and 30 mm/s2 in the vertical direction. While the two robotic couches RoboCouch and RPSbase completely met the requirements, even these two showed a substantial residual motion (40% of input amplitude), arguably due to their time delays. Conclusion The requirements for the motion compensation by an ideal couch are formulated and found to be feasible for currently available robotic couches. However, the performance these couches can be improved further regarding the position control if the demanded speed and acceleration are taken into account as well.

Ventricular assist devices (VADs) are an established treatment option for heart failure (HF). However, the devices are often plagued by material-related hemocompatibility issues. In contrast to continuous flow VADs with high shear stresses, pulsatile VADs (pVADs) offer the potential for an endothelial cell coating that promises to prevent many adverse events caused by an insufficient hemocompatibility. However, their size and weight often precludes their intracorporeal implantation. A reduction of the pump body size and weight of the pump could be achieved by an increase in the stroke frequency while maintaining a similar cardiac output. We present a new pVAD system consisting of a pump and an actuator specifically designed for actuation frequencies of up to 240 bpm. In vitro and in vivo results of the short-term reaction of the cardiovascular system show no significant changes in left ventricular and aortic pressure between actuation frequencies from 60 to 240 bpm. The aortic pulsatility increases when the actuation frequency is raised while the heart rate remains unaffected in vivo. These results lead us to the conclusion that the cardiovascular system tolerates short-term increases of the pVAD stroke frequencies.

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.

The handling of left ventricular assist devices (LVADs) can be challenging for patients and requires appropriate training. The devices’ usability impacts patients’ safety and quality of life. In this study, an eye tracking supported human factors testing was performed to reveal problems during use and test the trainings’ effectiveness. In total 32 HeartWare HVAD patients (including 6 pre-VAD patients) and 3 technical experts as control group performed a battery change (BC) and a controller change (CC) as an everyday and emergency scenario on a training device. By tracking the patients’ gaze point, task duration and pump-off time were evaluated. Patients with LVAD support ≥1 year showed significantly shorter BC task duration than patients with LVAD support., Journal of Medical Systems, 45, ISSN:0148-5598, ISSN:1573-689X

Normal pressure hydrocephalus (NPH) is a chronic and progressive disease that affects predominantly elderly subjects. The most prevalent symptoms are gait disorders, generally determined by visual observation or measurements taken in complex laboratory environments. However, controlled testing environments can have a significant influence on the way subjects walk and hinder the identification of natural walking characteristics. The study aimed to investigate the differences in walking patterns between a controlled environment (10 m walking test) and real-world environment (72 h recording) based on measurements taken via a wearable gait assessment device. We tested whether real-world environment measurements can be beneficial for the identification of gait disorders by performing a comparison of patients’ gait parameters with an aged-matched control group in both environments. Subsequently, we implemented four machine learning classifiers to inspect the individual strides’ profiles. Our results on twenty young subjects, twenty elderly subjects and twelve NPH patients indicate that patients exhibited a considerable difference between the two environments, in particular gait speed (p-value p=0.0073), stride length (p-value p=0.0073), foot clearance (p-value p=0.0117) and swing/stance ratio (p-value p=0.0098). Importantly, measurements taken in real-world environments yield a better discrimination of NPH patients compared to the controlled setting. Finally, the use of stride classifiers provides promise in the identification of strides affected by motion disorders., Sensors, 21 (19), ISSN:1424-8220

BACKGROUND Training in transcatheter cardiovascular skills today represents a significant challenge because of the complexity of the interventions and an extensive use of multiple live imaging technologies. OBJECTIVES We describe the design, the face validation, and content validation of a newly developed physical transseptal puncture (TSP) simulator using additive manufacturing techniques and novel imaging simulation solutions. METHODS The TSP simulator contains a femoral vein catheterization pad, silicon phantoms of the venous system, a replaceable interatrial septum, and cameras to mimic live fluoroscopic and echocardiographic imaging. A validation study was conducted at the University Hospital of Zurich. A total of 14 interventional cardiologists and cardiac surgeons assessed the TSP simulator. Participants performed a TSP on the simulator using standard interventional tools. Face and content validity was demonstrated using a 5-point Likert scale. RESULTS The TSP simulator is a new training tool for transcatheter cardiovascular interventions. All interventional cardiologists and cardiac surgeons completed the training exercise and scoring. Overall impression was rated (out of 5) 4.04 ± 1.03, haptic feedback scored 4.13 ± 0.82, and the realism of fluoroscopy simulation 4.39 ± 0.79. Usability was rated 4.50 ± 0.63 by the participants, indicating that the simulator could be suitable for training. CONCLUSION We demonstrated face and content validity of a new simulator for transcatheter cardiovascular interventions. The TSP simulator's usability, haptic feedback, imaging solutions, and the overall impression of its usage were reported as very realistic. The TSP simulator represents a promising tool for simulation-based training using real interventional toolkits in a mimicked radiological environment.

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.

Flow fields in rotary blood pumps (RBPs) have a significant influence on hemocompatibility. Because flow characteristics vary with flow rate, different operating conditions play a role. Furthermore, turbulence is crucial in the evaluation of blood damage potential, but the level of turbulence in implantable RBPs is still unknown. In this study, we addressed both research aspects and for the first time measured turbulent flow fields in the HeartMate 3 (HM3) at different operating flows. The averaged, three-dimensional velocity field including fluctuating velocity components in a HM3 with a transparent lower housing was measured using three-dimensional particle tracking velocimetry (3D-PTV). In vitro results were compared with computational fluid dynamic (CFD) simulations for two flow cases, representing the lower and upper physiologic flow range (2.7 and 5.7 L/min), using two different turbulence models that account for fluctuating velocity fields: the k-ω shear stress transport and the Reynolds stress model (RSM). The measurements revealed higher mean and turbulent kinetic energies (TKEs) for the low-flow condition especially within the gap beneath the impeller. Computed mean fields agree well with 3D-PTV for both models, but the RSM predicts the TKE levels better than the k-ω model. Computational fluid dynamic results further show wall shear stresses higher than 150 Pa, a commonly used damage threshold, in the bottom gap for the lower flow condition. In conclusion, the low-flow condition was found to be more prone to blood damage. Furthermore, CFD predictions for turbulence must be carefully experimentally validated.

Future left ventricular assist devices (LVADs) are expected to respond to the physiologic need of patients; however, they still lack reliable pressure or volume sensors for feedback control. In the clinic, echocardiography systems are routinely used to measure left ventricular (LV) volume. Until now, echocardiography in this form was never integrated in LVADs due to its computational complexity. The aim of this study was to demonstrate the applicability of a simplified ultrasonic sensor to fit an LVAD cannula and to show the achievable accuracy in vitro. Our approach requires only two ultrasonic transducers because we estimated the LV volume with the LV end-diastolic diameter commonly used in clinical assessments. In order to optimize the accuracy, we assessed the optimal design parameters considering over 50 orientations of the two ultrasonic transducers. A test bench was equipped with five talcum-infused silicone heart phantoms, in which the intra-ventricular surface replicated papillary muscles and trabeculae carnae. The end-diastolic LV filling volumes of the five heart phantoms ranged from 180 to 480 mL. This reference volume was altered by ±40 mL with a syringe pump. Based on the calibrated measurements acquired by the two ultrasonic transducers, the LV volume was estimated well. However, the accuracies obtained are strongly dependent on the choice of the design parameters. Orientations toward the septum perform better, as they interfere less with the papillary muscles. The optimized design is valid for all hearts. Considering this, the Bland-Altman analysis reports the LV volume accuracy as a bias of ±10% and limits of agreement of 0%-40% in all but the smallest heart. The simplicity of traditional echocardiography systems was reduced by two orders of magnitude in technical complexity, while achieving a comparable accuracy to 2D echocardiography requiring a calibration of absolute volume only. Hence, our approach exploits the established benefits of echocardiography and makes them applicable as an LV volume sensor for LVADs.

Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end-stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3's characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high-resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility.

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., Biomedical Engineering / Biomedizinische Technik, 62 (6), ISSN:0013-5585, ISSN:1862-278X

Background:Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed. Methods:Complete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then gen-erated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed. Results:Comparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of vari-ability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal. Conclusion:While our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about the hydro-dynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states., Fluids and Barriers of the CNS, 17 (1), ISSN:2045-8118

Pulsatile ventricular assist devices (pVADs) yield a blood flow that imitates the pulsatile flow of the heart and, therefore, could diminish the adverse events related to the continuous flow provided by the ventricular assist devices that are commonly used. However, their intrinsic characteristics of larger size and higher weight set a burden to their implantation, that along with the frequent mechanical failures and thrombosis events, reduce the usage of pVADs in the clinical environment. In this study, we investigated the possibility to reduce the pump size by using high pump stroke ratios while maintaining the ability to control the hemodynamics of the cardiovascular system (CVS). In vitro and in vivo experiments were conducted with a custom pVAD implemented on a hybrid mock circulation system and in five sheep, respectively. The actuation of the pVAD was synchronized with the heartbeat. Variations of the pump stroke ratio, time delay between the pump stroke and the heart stroke, as well as duration of the pump systole in respect to the total cardiac cycle duration were used to evaluate the effects of various pump settings on the hemodynamics of the CVS. The results suggest that by varying the operating settings of the pVAD, a pulsatile flow that provides physiological hemodynamic parameters, as well as a control over the hemodynamic parameters, can be achieved. Additionally, by employing high pump stroke ratios, the size of the pVAD can be significantly reduced; however, at those high pump stroke ratios, the effect of the other pump parameters diminishes.

During the development process of active or passive cardio-vascular implants, such as ventricular assist devices or vascular grafts, extensive in-vitro testing is required. The aim of the study was to develop a versatile hybrid mock circulation (HMC) which can support the development of such implants that have a complex interaction with the circulation. The HMC operates based on the hardware-in-the-loop concept with a hydraulic interface of four pressure-controlled reservoirs allowing the in-teraction of the implant with a numerical model of the cardi-ovascular system. Three different conditions were investigated to highlight the versatility and the efficacy of the HMC during the development of such implants: 1) biventricular assist device (BiVAD) support with progressive aortic valve insufficiency, 2) total artificial heart (TAH) support with increasing pulmonary vascular resistance, and 3) flow distribution in a total cavo-pulmonary connection (TCPC) in a Fontan circulation during exercise. Realistic pathophysiologic waveforms were generated with the HMC and all hemodynamic conditions were simulated just by adapting the software. The results of the experiments indicated the potential of physiologic control during BiVAD or TAH support to prevent suction or congestion events, which may occur during constant-speed operation. The TCPC geom-etry influenced the flow distribution between the right and the left pulmonary artery, which was 10% higher in the latter and led to higher pressures. Together with rapid prototyping meth-ods, the HMC may enhance the design of implants to achieve better hemodynamics. Validation of the models with clinical recordings is suggested for increasing the reliability of the HMC., ASAIO Journal, 65 (5), ISSN:1058-2916, ISSN:1538-943X

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.

Purpose In precision radiotherapy, the intrafractional motion causes substantial uncertainty. Traditionally, the target volume is expanded to cover the tumor in all positions. Alternative approaches are gating and adaptive tracking, which require a time delay as small as possible between the actual tumor motion and the reaction to effectively compensate the motion. Current treatment machines often exhibit large time delays. Prediction filters offer a promising means to mitigate these time delays by predicting the future respiratory motion. Methods A total of 18 prediction filters were implemented and their hyperparameters optimized for various time delays and noise levels. A set of 93 traces were standardized to a sampling frequency of 25 Hz and smoothed using the Fourier transform with a 3 Hz cutoff frequency. The hyperparameter optimization was carried out with ten traces, and the optimal hyperparameters were evaluated on the remaining 83 traces. Results For smooth traces, the wavelet least mean squares prediction filter and the linear filter reached normalized root mean square errors of below 0.05 for time delays of 160 and 480 ms, respectively. For noisy signals, the performance of the prediction filters deteriorated and led to similar results. Conclusions Linear methods for prediction filters are sufficient for respiratory motion signals. Reducing the measurement noise generally improves the performance of the prediction filters investigated in this study, even during breathing irregularities.

In precision radiotherapy, the intrafractional motion can cause a considerable uncertainty of the location of the tumor to be treated. An established approach is the expansion of the target volume to account for the motion. An alternative approach is couch-tracking, in which the patient is continually moved to compensate the intrafractional motion. However, couch-tracking itself might induce uncertainty of the patient's body position, because the body is non-rigid. One hundred healthy volunteers were positioned supine on a robotic couch. Optical markers were placed on the torso of the volunteers as well as on the couch, and their positions were tracked with an optical surface measurement system. Using these markers, the uncertainty of the body position relative to the couch position was estimated while the couch was static or moving. Over the included 83 healthy volunteers, the median of the uncertainty increased by 0.8 mm (SI), 0.4 mm (LR) and 0.4 mm (AP) when the couch moved. Couch motion was found to increase the uncertainty of the body position relative to the couch. However, this uncertainty is one order of magnitude smaller than the intrafractional tumor motion amplitudes to be compensated. Therefore, even with body motion present, the couch-tracking approach is a viable option. The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal (SNCTP000001878).

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.

Various approaches for estimating the flow rate of a rotary blood pump have been proposed for monitoring and control purposes. They have been evaluated under different test conditions and, therefore, a direct comparison among them is difficult. Furthermore, a limited performance has been reported for the areas where the pump flow and motor current present a non-monotonic relationship. In this regard, we selected most approaches that have been presented in literature and added a modified one, resulting in four estimators, which are either non-invasive or invasive, i.e., inlet and outlet pump pressure sensors are used. Data from in vitro and in vivo studies with the Deltastream pump DP2 were used to compare the estimators under the same test conditions. These data included both constant and varying pre- and afterload, contractility, viscosity, as well as pump speed settings. Bland–Altman plots were used to evaluate the performance of the estimators. The mean error of the overall estimated flow in vitro ranged from 0.002 to 0.38 L/min and the limits of agreement (LoA) between ± 2 L/min. During negative flows the mean error decreased by about 25% when the pump inlet pressure was added as an input. In vivo, the mean errors increased, while the LoA remained in the same range. An estimator based on pump pressure difference improves the reliability in areas where flow and current relationship is not monotonic. A trade-off between estimation accuracy and number of sensors was identified. The estimation objective and the potential errors should be considered when selecting an estimation approach and designing the pump systems.

Purpose: Rotary blood pumps are a promising treatment approach for patients with a total cavopulmonary connection and a failing cardiovascular system. The aim of this study was to investigate the hemodynamic effects of cavopulmonary support using a numerical model with closed-loop baroreflex and exercise mechanisms. Methods: A numerical model of the univentricular cardiovascular system was developed, mimicking the hemodynamics during rest and exercise. Rotary blood pumps with different hydraulic pump characteristics (flat vs steep pressure-flow relationships) were investigated in the cavopulmonary position. Furthermore, two support modes—a constant speed setting and a physiologically controlled speed—were examined. Results: Hemodynamics without rotary blood pumps were achieved with less than 10% deviation from reported values during rest and exercise. Rotary blood pumps at constant speed improve the hemodynamics at rest, however, they constitute a hydraulic resistance during light (steep characteristics) or moderate (flat characteristics) exercise. In contrast, physiologic control increases cardiac output (moderate exercise: 8.2 vs 7.4 L/min) and reduces sympathetic activation (heart rate at moderate exercise: 111 vs 123 bpm). Conclusion: In this simulation study, the necessity of an automatically controlled rotary blood pump in the cavopulmonary position was shown. A pump at constant speed might constitute an additional resistance to venous return during physical activity. Therefore, a physiologic control algorithm based on the pressure difference between the caval veins and the atrial pressure is proposed to improve hemodynamics, especially during physical activity.

Regulation of intracranial pressure (ICP) is vital to proper brain function. Pathologic conditions such as traumatic brain injury and hydrocephalus can cause lethal changes in ICP through an imbalance of fluid passage into and out of the craniospinal space. The relationship between craniospinal volume and pressure determines to a large extent whether such imbalance can be compensated or if it will lead to neuronal damage. Phantom models are predisposed for the evaluation of medical procedures and devices that alter volume in the spinal or cranial space. However, current phantoms have substantial limitations in the reproduction of craniospinal pressure-volume relationships, which need to be overcome prior to their deployment outside the basic research setting. We present herein a novel feedback controlled phantom for the reproduction of any physiologic or pathologic pressure-volume relation. We compare its performance to those of existing passive methods, showing that it follows reference curves more precisely during both infusion of large volumes and fast oscillatory volume changes.

Background Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient’s stress and respiration behavior decreasing the couch-tracking effectiveness. Methods In total, 100 volunteers were positioned supine on a robotic couch, which moved dynamically and respiration synchronized. During the measurement, the skin conductivity, the heartrate, and the gaze location were measured indicating the volunteer’s stress. Volunteers rated the subjective motion sickness using a questionnaire. The measurement alternated between static and tracking segments (three cycles), each 1 min long. Results The respiration amplitude showed no significant difference between tracking and static segments, but decreased significantly from the first to the last tracking segment (p

The HeartWare HVAD is a radial rotary blood pump with a combination of passive magnetic and hydrodynamic bearings to levitate the impeller. The axial gap size between impeller and housing in this bearing and its sensitivity to speed, flow, and pressure difference is difficult to assess. Shear stresses are exceptionally high in this tiny gap making it important for blood damage and related adverse events. Therefore, the aim of this study was to measure the axial gap clearance in the HVAD at different operating conditions employing radiography. To quantify the gap size in the HVAD, the pump was positioned 30 mm in front of the X-ray source employing a microfocus X-ray tube with an acceleration voltage up to 300 kV. Beams were detected on a flat panel detector (Perkin Elmer XRD 1611-CP3). The pump was connected to a tubing circuit with a throttle to adjust flow (0, 5, 10 L/min) and a water glycerol mixture to set the desired viscosity (1, 4, 8 mPas). Rotational speed was varied between 1800 and 3600 rpm. In this study, for clinically relevant conditions at 5 L/min and 2700 rpm, the axial gap was 22 µm. The gap size increased with rotational speeds dependent on the viscosity (2.8, 6.9, and 9.4 µm/1000 rpm for 1, 4, and 8 mPas, respectively), but was independent from the volume flow and the pressure head at constant speeds. In summary, using X-ray radiographic imaging small gaps in a rotary blood pump during operation can be measured in a nondestructive contact-free way. The axial hydrodynamic bearing gap in the HVAD pump was determined to be in the range of about three times the diameter of a red blood cell. Its dependence on operating volume flow and generated pressure head across the pump is not pronounced.

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 (P loss ), 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 P loss 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 P loss . 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 P loss , based on refinement of commercially available options for image segmentation, computer-aided design, and flow simulations.

Various control and monitoring algorithms have been proposed to improve the left-ventricular assist device (LVAD) therapy by reducing the still-occurring adverse events. We developed a novel multi-objective physiological control system that relies on the pump inlet pressure (PIP). Signal-processing algorithms have been implemented to extract the required features from the PIP. These features then serve for meeting various objectives: pump flow adaptation to the perfusion requirements, aortic valve opening for a predefined time, augmentation of the aortic pulse pressure, and monitoring of the LV pre- and afterload conditions as well as the cardiac rhythm. Controllers were also implemented to ensure a safe operation and prevent LV suction, overload, and pump backflow. The performance of the control system was evaluated in vitro, under preload, afterload and contractility variations. The pump flow adapted in a physiological manner, following the preload changes, while the aortic pulse pressure yielded a threefold increase compared to a constant-speed operation. The status of the aortic valve was detected with an overall accuracy of 86% and was controlled as desired. The proposed system showed its potential for a safe physiological response to varying perfusion requirements that reduces the risk of myocardial atrophy and offers important hemodynamic indices for patient monitoring during LVAD therapy.

Various physiological controllers for left ventricular assist devices (LVADs) have been developed to prevent flow conditions that may lead to left ventricular (LV) suction and overload. In the current study, we selected and implemented six of the most promising physiological controllers presented in literature. We tuned the controllers for the same objectives by using the loop-shaping method from control theory. The in vitro experiments were derived from literature and included different preload, afterload, and contractility variations. All experiments were repeated with an increased or decreased contractility from the baseline pathological circulation and with simulated sensor drift. The controller performances were compared with an LVAD operated at constant speed (CS) and a physiological circulation. During preload variations, all controllers resulted in a pump flow change that resembled the cardiac output response of the physiological circulation. For afterload variations, the response varied among the controllers, whereas some of them presented a high sensitivity to contractility or sensor drift, leading to LV suction and overload. In such cases, the need for recalibration of the controllers or the sensor is indicated. Preload-based physiological controllers showed their clinical significance by outperforming the CS operation and promise many benefits for the LVAD therapy. However, their clinical implementation in the near future for long-term use is highly dependent on the sensor technology and its reliability.

Background: Postural changes are related to changes in cerebrospinal fluid (CSF) dynamics. While sitting up leads to a decrease in cranial CSF pressure, it also causes shifts in the craniospinal CSF volume and compliance distribution. We hypothesized that jugular vein collapse in upright posture is a major contributor to these shifts in CSF volume and compliance. Methods: To test this hypothesis, we implemented a mathematical lumped-parameter model of the CSF system and the relevant parts of the cardiovascular system. In this model, the CSF and the venous system are each divided into a cranial and a spinal part. The pressures in these cranial and spinal portions differ by the posture-dependent hydrostatic pressure columns in the connecting vessels. Jugular collapse is represented by a reduction of the hydrostatic pressure difference between cranial and spinal veins. The CSF pressure–volume relationship is implemented as a function of the local CSF to venous pressure gradient. This implies that an increase in CSF volume leads to a simultaneous displacement of blood from adjacent veins. CSF pulsations driven by the cardiovascular system are introduced through a pulsating cranial arterial volume. Results: In upright posture, the implemented CSF pressure–volume relationship shifts to lower cranial CSF pressures compared to the horizontal position, leading to a decrease in cranial CSF pressure when sitting up. Concurrently, the compliance of the spinal compartment decreases while the one of the cranial compartment increases. With this, in upright posture only 10% of the CSF system’s compliance is provided by the spinal compartment compared to 35% in horizontal posture. This reduction in spinal compliance is accompanied by a caudal shift of CSF volume. Also, the ability of the spinal CSF compartment to compensate for cerebral arterial volume pulsations reduces in upright posture, which in turn reduces the calculated craniospinal CSF flow pulsations. Conclusion: The mathematical model enabled us to isolate the effect of jugular collapse and quantify the induced shifts of compliance and CSF volume. The good concordance of the modelled changes with clinically observed values indicates that jugular collapse can be considered a major contributor to CSF dynamics in upright posture., Fluids and Barriers of the CNS, 14 (1), ISSN:2045-8118

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Over the last few decades, the left ventricular assist device (LVAD) technology has been tremendously improved transitioning from large and noisy paracorporeal volume displacement pumps to small implantable turbodynamic devices with only a single transcutaneous element, the driveline. Nevertheless, there remains a great demand for further improvements to meet the challenge of having a robust and safe device for long-term therapy. Here, we review the state of the art and highlight four key areas of needed improvement targeting long-term, sustainable LVAD function: (1) LVADs available today still have a high risk of thromboembolic and bleeding events that could be addressed by the rational fabrication of novel surface structures and endothelialization approaches aiming at improving the device hemocompatibility. (2) Novel, fluid dynamically optimized pump designs will further reduce blood damage. (3) Infection due to the paracorporeal driveline can be avoided with a transcutaneous energy transmission system that additionally allows for increased freedom of movement. (4) Finally, the lack of pump flow adaptation needs to be encountered with physiological control systems, working collaboratively with biocompatible sensor devices, targeting the adaptation of the LVAD flow to the perfusion requirements of the patient. The interdisciplinary Zurich Heart project investigates these technology gaps paving the way toward LVADs for long-term, sustainable therapy.

A mock circulation allows the in vitro investigation, development, and testing of ventricular assist devices. An aqueous-glycerol solution is commonly used to mimic the viscosity of blood. Due to evaporation and temperature changes, the viscosity of the solution drifts from its initial value and therefore, deviates substantially from the targeted viscosity of blood. Additionally, the solution needs to be exchanged to account for changing viscosities when mimicking different hematocrits. This article presents a method to control the viscosity in a mock circulation. This method makes use of the relationship between temperature and viscosity of aqueous-glycerol solutions and employs the automatic control of the viscosity of the fluid. To that end, an existing mock circulation was extended with an industrial viscometer, temperature probes, and a heating nozzle band. The results obtained with different fluid viscosities show that a viscosity controller is vital for repeatable experimental conditions on mock circulations. With a mixture ratio of 49 mass percent of aqueous-glycerol solution, the controller can mimic a viscosity range corresponding to a hematocrit between 29 and 42% in a temperature range of 30-42°C. The control response has no overshoot and the settling time is 8.4 min for a viscosity step of 0.3 cP, equivalent to a hematocrit step of 3.6%. Two rotary blood pumps that are in clinical use are tested at different viscosities. At a flow rate of 5 L/min, both show a deviation of roughly 15 and 10% in motor current for high rotor speeds. The influence of different viscosities on the measured head pressure is negligible. Viscosity control for a mock circulation thus plays an important role for assessing the required motor current of ventricular assist devices. For the investigation of the power consumption of rotary blood pumps and the development of flow estimators where the motor current is a model input, an integrated viscosity controller is a valuable contribution to an accurate testing environment.

Ventricular assist devices (VADs) are mechanical blood pumps that are clinically used to treat severe heart failure. Pulsatile VADs (pVADs) were initially used, but are today in most cases replaced by turbodynamic VADs (tVADs). The major concern with the pVADs is their size, which prohibits full pump body implantation for a majority of patients. A reduction of the necessary stroke volume can be achieved by increasing the stroke frequency, while maintaining the same level of support capability. This reduction in stroke volume in turn offers the possibility to reduce the pump’s overall dimensions. We simulated a human cardiovascular system (CVS) supported by a pVAD with three different stroke rates that were equal, two- or threefold the heart rate (HR). The pVAD was additionally synchronized to the HR for better control over the hemodynamics and the ventricular unloading. The simulation results with a HR of 90 bpm showed that a pVAD stroke volume can be reduced by 71%, while maintaining an aortic pulse pressure (PP) of 30 mm Hg, avoiding suction events, reducing the ventricular stroke work (SW) and allowing the aortic valve to open. A reduction by 67% offers the additional possibility to tune the interaction between the pVAD and the CVS. These findings allow a major reduction of the pVAD’s body size, while allowing the physician to tune the pVAD according to the patient’s needs., Biomedical Engineering / Biomedizinische Technik, 62 (2), ISSN:0013-5585, ISSN:1862-278X

The technology of 3D-printing has allowed the production of entirely soft pumps with complex chamber geometries. We used this technique to develop a completely soft pneumatically driven total artificial heart from silicone elastomers and evaluated its performance on a hybrid mock circulation. The goal of this study is to present an innovative concept of a soft total artificial heart (sTAH). Using the form of a human heart, we designed a sTAH, which consists of only two ventricles and produced it using a 3D-printing, lost-wax casting technique. The diastolic properties of the sTAH were defined and the performance of the sTAH was evaluated on a hybrid mock circulation under various physiological conditions. The sTAH achieved a blood flow of 2.2 L/min against a systemic vascular resistance of 1.11 mm Hg s/mL (afterload), when operated at 80 bpm. At the same time, the mean pulmonary venous pressure (preload) was fixed at 10 mm Hg. Furthermore, an aortic pulse pressure of 35 mm Hg was measured, with a mean aortic pressure of 48 mm Hg. The sTAH generated physiologically shaped signals of blood flow and pressures by mimicking the movement of a real heart. The preliminary results of this study show a promising potential of the soft pumps in heart replacements. Further work, focused on increasing blood flow and in turn aortic pressure is required.

The current article presents a novel physiological feedback controller for turbodynamic ventricular assist devices (tVADs). This controller is based on the recording of the left ventricular (LV) pressure measured at the inlet cannula of a tVAD thus requiring only one pressure sensor. The LV systolic pressure (SP) is proposed as an indicator to determine the varying perfusion requirements. The algorithm to extract the SP from the pump inlet pressure signal used for the controller to adjust the speed of the tVAD shows robust behavior. Its performance was evaluated on a hybrid mock circulation. The experiments with changing perfusion requirements were compared with a physiological circulation and a pathological one assisted with a tVAD operated at constant speed. A sensitivity analysis of the controller parameters was conducted to identify their limits and their influence on a circulation. The performance of the proposed SP controller was evaluated for various values of LV contractility, as well as for a simulated pressure sensor drift. The response of a pathological circulation assisted by a tVAD controlled by the introduced SP controller matched the physiological circulation well, while over- and underpumping events were eliminated. The controller presented a robust performance during experiments with simulated pressure sensor drift.

Tumor motion during radiation therapy increases the irradiation of healthy tissue. However, this problem may be mitigated by moving the patient via the treatment couch such that the tumor motion relative to the beam is minimized. The treatment couch poses limitations to the potential mitigation, thus the performance of the Protura (CIVCO) treatment couch was characterized and numerically modeled. The unknown parameters were identified using chirp signals and verified with one-dimensional tumor tracking. The Protura tracked chirp signals well up to 0.2 Hz in both longitudinal and vertical directions. If only the vertical or only the longitudinal direction was tracked, the Protura tracked well up to 0.3 Hz. However, there was unintentional yet substantial lateral motion in the former case. And during vertical motion, the extension caused rotation of the Protura around the lateral axis. The numerical model matched the Protura up to 0.3 Hz. Even though the Protura was designed for static positioning, it was able to reduce the tumor motion by 69% (median). The correlation coefficient between the tumor motion reductions of the Protura and the model was 0.99. Therefore, the model allows tumor-tracking results of the Protura to be predicted.

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.

Tumor motion increases safety margins around the clinical target volume and leads to an increased dose to the surrounding healthy tissue. The authors have developed and evaluated a one-dimensional treatment couch tracking system to counter steer respiratory tumor motion. Three different motion detection sensors with different lag times were evaluated.The couch tracking system consists of a motion detection sensor, which can be the topometrical system Topos (Cyber Technologies, Germany), the respiratory gating system RPM (Varian Medical Systems) or a laser triangulation system (Micro Epsilon), and the Protura treatment couch (Civco Medical Systems). The control of the treatment couch was implemented in the block diagram environment Simulink (MathWorks). To achieve real time performance, the Simulink models were executed on a real time engine, provided by Real-Time Windows Target (MathWorks). A proportional-integral control system was implemented. The lag time of the couch tracking system using the three different motion detection sensors was measured. The geometrical accuracy of the system was evaluated by measuring the mean absolute deviation from the reference (static position) during motion tracking. This deviation was compared to the mean absolute deviation without tracking and a reduction factor was defined. A hexapod system was moving according to seven respiration patterns previously acquired with the RPM system as well as according to a sin(6) function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion.A prototype system for treatment couch tracking of respiratory motion was developed. The laser based tracking system with a small lag time of 57 ms reduced the residual motion by a factor of 11.9 ± 5.5 (mean value ± standard deviation). An increase in delay time from 57 to 130 ms (RPM based system) resulted in a reduction by a factor of 4.7 ± 2.6. The Topos based tracking system with the largest lag time of 300 ms achieved a mean reduction by a factor of 3.4 ± 2.3. The increase in the penumbra of a profile (1 × 1 cm(2)) for a motion of 6 mm was 1.4 mm. With tracking applied there was no increase in the penumbra.Couch tracking with the Protura treatment couch is achievable. To reliably track all possible respiration patterns without prediction filters a short lag time below 100 ms is needed. More scientific work is necessary to extend our prototype to tracking of internal motion.

Turbodynamic blood pumps are used clinically as ventricular assist devices (VADs). They are mostly operated at a constant rotational speed, which results in a reduced pulsatility. Previous research has analyzed pulsing pump speeds (speed modulation) to alter the interaction between the cardiovascular system and the blood pump. In those studies, sine- or square-wave speed profiles that were synchronized to the natural cardiac cycle were analyzed in silico, in vitro and in vivo. The definitions of these profiles with respect to both timing and speed levels vary among different research groups. The current paper provides a definition of the timing of these speed profiles such that the resulting hemodynamic effects become comparable. The results published in the literature are summarized and compared using this definition. Further, applied to a turbodynamic VAD, a series of measurements is conducted on a hybrid mock circulation using a constant speed as well as different types of square-wave speed profiles and a sine-wave speed profile. When a consistent definition of the timing of the speed profiles is used, the hemodynamic effects observed in previous work are in agreement with the measurement data obtained for the current paper. These findings allow the conclusion that the speed modulation of turbodynamic VADs represents a consistent tool to systematically change the ventricular load and the pulsatility in the arterial tree. The timing that yields the minimal left ventricular load also yields the minimal arterial pulse pressure.

The current article presents a novel physiological control algorithm for ventricular assist devices (VADs), which is inspired by the preload recruitable stroke work. This controller adapts the hydraulic power output of the VAD to the end-diastolic volume of the left ventricle. We tested this controller on a hybrid mock circulation where the left ventricular volume (LVV) is known, i.e., the problem of measuring the LVV is not addressed in the current article. Experiments were conducted to compare the response of the controller with the physiological and with the pathological circulation, with and without VAD support. A sensitivity analysis was performed to analyze the influence of the controller parameters and the influence of the quality of the LVV signal on the performance of the control algorithm. The results show that the controller induces a response similar to the physiological circulation and effectively prevents over- and underpumping, i.e., ventricular suction and backflow from the aorta to the left ventricle, respectively. The same results are obtained in the case of a disturbed LVV signal. The results presented in the current article motivate the development of a robust, long-term stable sensor to measure the LVV.

The treatment of hydrocephalus requires insight into the intracranial dynamics in the patient. Resistance to CSF outflow (R0) is a clinically obtainable parameter of intracranial fluid dynamics that quantifies the apparent resistance to CSF absorption. It is used as a criterion for the selection of shunt candidates and serves as an indicator of shunt performance. The R0 is obtained clinically by performing 1 of 3 infusion tests: constant flow, constant pressure, or bolus infusion. Among these, the bolus infusion method has the shortest examination times and provides the shortest time of exposure of patients to artificially increased intracranial pressure (ICP) levels. However, for unknown reasons, the bolus infusion method systematically underestimates the R0. Here, the authors have tested and verified the hypothesis that this underestimation is due to lack of accounting for viscoelasticity of the craniospinal space in the calculation of the R0.The authors developed a phantom model of the human craniospinal space in order to reproduce in vivo pressure-volume (PV) relationships during infusion testing. The phantom model followed the Marmarou exponential PV equation and also included a viscoelastic response to volume changes. Parameters of intracranial fluid dynamics, such as the R0, could be controlled and set independently. In addition to the phantom model, the authors designed a computational framework for virtual infusion testing in which viscoelasticity can be turned on or off in a controlled manner. Constant flow, constant pressure, and bolus infusion tests were performed on the phantom model, as well as on the virtual computational platform, using standard clinical protocols. Values for the R0 were derived from each infusion test by using both a standard method based on the Marmarou PV equation and a novel method based on a system identification approach that takes into account viscoelastic behavior.Experiments with the phantom model confirmed clinical observations that both the constant flow and constant pressure infusion tests, but not the bolus infusion test, yield correct R0 values when they are determined with the standard method according to Marmarou. Equivalent results were obtained using the computational framework. When the novel system identification approach was used to determine the R0, all of the 3 infusion tests yielded correct values for the R0. CONCLUSIONS" The authors' investigations demonstrate that intracranial dynamics have a substantial viscoelastic component. When this viscoelastic component is taken into account in calculations, the R0, is no longer underestimated in the bolus infusion test.

While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.