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Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross‐sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi‐phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head‐over‐body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture‐induced changes in intracranial pressure that are comparable with those in humans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The current study aimed to evaluate the extent of the slide‐stick phenomenon in differently designed infusion syringes at various infusion rates and filling positions. Methods: Fluid delivery from three 50‐mL infusion syringe brands (BD; Codan; Fresenius) was investigated using a flow sensor at flow rates of 0.5, 1.0, or 5.0 mL h−1, with the syringes filled with either 10, 30, or 50 mL of distilled water. Two identical models (A/B) of the same infusion pump model were used. The effect of flow rate variations on the plasma concentration of a continuous epinephrine infusion in a 3 kg neonate receiving a continuous infusion of 0.1 μg kg min−1 epinephrine was studied using a pharmacokinetic simulation model. Results: Considerable variations in calculated plasma epinephrine concentration were detected between flow rates of 5 and 0.5 or 1 mL h−1 for all syringe types and filling volumes. The median deviation of plasma concentration for the 5 mL h−1 flow rate varied depending on assembly from 1.3% (Codan) to 1.8% (Fresenius). This was more pronounced for lower flow rates, where at 1 mL h−1 the deviation varied from 3.3% (BD) to 4.8% (Fresenius) and at 0.5 mL h−1from 4.9% (BD) to 5.4% (Fresenius). Differences between filling volumes (within syringe type and flow rate) did not appear to have relevant influence on variations in calculated plasma epinephrine concentration. Conclusion: Infusion set rate rather than syringe brand or filling volume was a major predictor for syringe stiction‐related amount of variation in the calculated plasma epinephrine concentration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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 sin6 function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion. Results: 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 cm2) for a motion of 6 mm was 1.4 mm. With tracking applied there was no increase in the penumbra. Conclusions: 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. [ABSTRACT FROM AUTHOR]