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Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor. [ABSTRACT FROM AUTHOR]

Introduction: In radiotherapy, tumors may move due to the patient’s respiration, which decreases treatment accuracy. Some motion mitigation methods require measuring the tumor position during treatment. Current available sensors often suffer from time delays, which degrade the motion mitigation performance. However, the tumor motion is often periodic and continuous, which allows predicting the motion ahead. Method and Materials: A couch tracking system was simulated in MATLAB and five prediction filters selected from literature were implemented and tested on 51 respiration signals (median length: 103 s). The five filters were the linear filter (LF), the local regression (LOESS), the neural network (NN), the support vector regression (SVR), and the wavelet least mean squares (wLMS). The time delay to compensate was 320 ms. The normalized root mean square error (nRMSE) was calculated for all prediction filters and respiration signals. The correlation coefficients between the nRMSE of the prediction filters were computed. Results: The prediction filters were grouped into a low and a high nRMSE group. The low nRMSE group consisted of the LF, the NN, and the wLMS with a median nRMSE of 0.14, 0.15, and 0.14, respectively. The high nRMSE group consisted of the LOESS and the SVR with both a median nRMSE of 0.34. The correlations between the low nRMSE filters were above 0.87 and between the high nRMSE filters it was 0.64. Conclusion: The low nRMSE prediction filters not only have similar median nRMSEs but also similar nRMSEs for the same respiration signals as the high correlation shows. Therefore, good prediction filters perform similarly for identical respiration patterns, which might indicate a minimally achievable nRMSE for a given respiration pattern.

Background: The identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests. Objective: We aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC). Methods: Five wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement. Results: Nine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of =5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of =0.44m and gait velocity of =0.39 m/s. Conclusion: There was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern. [ABSTRACT FROM AUTHOR]

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 < 0.0001). The respiration frequency differed significantly between tracking and static segments (p < 0.0001), but not between the first and the last tracking segment. The physiological parameters and the questionnaire showed mild signals of stress and motion sickness.Conclusion: Generally, people tolerated the couch motions. The interaction between couch motion and the patient's breathing pattern should be considered for a clinical implementation.Trial Registration: The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal ( SNCTP000001878 ) on June 20, 2016. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper presents a novel mock circulation for the evaluation of ventricular assist devices (VADs), which is based on a hardware-in-the-loop concept. A numerical model of the human blood circulation runs in real time and computes instantaneous pressure, volume, and flow rate values. The VAD to be tested is connected to a numerical-hydraulic interface, which allows the interaction between the VAD and the numerical model of the circulation. The numerical-hydraulic interface consists of two pressure-controlled reservoirs, which apply the computed pressure values from the model to the VAD, and a flow probe to feed the resulting VAD flow rate back to the model. Experimental results are provided to show the proper interaction between a numerical model of the circulation and a mixed-flow blood pump. [ABSTRACT FROM PUBLISHER]

The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF) dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young (24±3 years) and eleven elderly subjects (70±5 years) with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross-correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and crosscorrelations between arterial blood and CSF flow reveal significant age-dependence of phase-shift between these, as do the waveforms of arterial blood, as well as cervical-spinal and aqueductal CSF flows. These findings accentuate the need for ageand sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus. [ABSTRACT FROM AUTHOR]

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

Objectives: Left ventricular assist devices (LVADs) have been established as alternative to heart transplantation for patients with end-stage heart failure refractory to medical therapy. Right heart failure (RHF) after LVAD implantation is associated with inferior outcome. Its preoperative anticipation may influence the selection between a pure left ventricular and a biventricular device type and, thus, improve outcomes. Reliable algorithms to predict RHF are missing., Methods: A numerical model was used for simulation of a cardiovascular circulation. The LVAD was placed as parallel circuit between left ventricle and aorta. In contrast to other studies, the dynamic hydraulic behavior of a pulsatile LVAD was replaced by that of a continuous LVAD. A variety of hemodynamic states was tested mimicking different right heart conditions. Adjustable parameters included heart rate (HR), pulmonary vascular resistance (PVR), tricuspid regurgitation (TR), right ventricular contractility (RVC) and pump speed. Outcome parameters comprised central venous pressure (CVP), mean pulmonary artery pressure (mPAP), cardiac output (CO) and occurrence of suction., Results: Alteration of HR, PVR, TR, RVC and pump speed resulted in diverse effects on CO, CVP and mPAP, resulting in improvement, impairment or no change of the circulation, depending on the degree of alteration., Conclusions: The numerical simulation model allows prediction of circulatory changes and LVAD behaviour following variation of hemodynamic parameters. Such a prediction may be of particular advantage to anticipate RHF after LVAD implantation. It may help preoperatively to choose the appropriate strategy of only left ventricular or both left and right ventricular support., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

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.