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Abstract Introduction Most investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed. Methods Six awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal pressure (ICP, ITP, ABP, CVP, IAPcr, IAPcd, IAPds, IAPve, respectively). They were maneuvered upright by placing in a chair for two minutes; repeated 25 times over one month. Changes in mean and pulse pressure were calculated by comparing pre-chair, P0, with three phases during the maneuver: P1, chair entrance; P2, chair halftime; P3, prior to chair exit. Statistical significance (p ≤ .05) was assessed using repeated measures ANOVA. Results Significant mean pressure changes of (P1 − P0) and (P3 − P0) were measured at − 12.1 ± 3.1 and − 14.2 ± 3.0(p

Abstract Introduction Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. Methods An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between –13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3

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.

BackgroundThe 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.ObjectiveWe 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).MethodsFive 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.ResultsNine 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 ≥0.44 m and gait velocity of ≥0.39 m/s.ConclusionThere 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 Introduction The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. Methods An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer’s solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. Results All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively—showing deviations between the two estimation methods. Conclusions Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.

Abstract 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.

Current shunt treatments of hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid (CSF) and intracranial pressure (ICP) fluctuations, suffer malfunctions caused by changes in patient’s posture. Research toward a quantitative model describing posture dependent dynamics of CSF related pressures such as ICP and blood pressure (BP) shall provide relevant information that can lead to a better understanding of CSF dynamics and thus, improved treatment outcomes. In this pilot study, ICP and femoral blood pressure (FBP) were measured concurrently in anaesthetized as well as awake and freely moving rats using radio telemetry. It was shown that despite the inherent challenges of limited space for sensor implants and rapid movements leading to strong artefacts, influences on CSF related pressure fluctuations due to posture changes can be observed in individual rats

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

Aiming to address clinical requirements subsequent to SARS-CoV-2-related pulmonary disease, multiple research groups and industry groups carried out intensive studies to develop pandemic ventilators (PDVs). In vitro testing to critically evaluate the specific performance of the developed apparatuses is an essential requirement. This study presents a test protocol which promotes a test-oriented, iterative, and agile assessment and consecutive development of such PDVs. It allows for fast identification of specific characteristics of each PDV in the individual test features. The test protocol includes an evaluation of the accuracy of control systems and instruments at changing parameters, the oxygen dynamics, and the response to trigger signals. The test environment is a mechanical lung, which allows reproducing various lung mechanics and to simulate active breathing cycles. A total of three PDVs that are under development were iteratively tested, with a Hamilton T1 as a reference. Continuous testing of the PDVs under development enables quick identification of critical application aspects that deserve further improved. Based on the present test protocol, the ventilators demonstrate a promising performance justifying continued development.

Continuous flow ventricular assist devices (cfVADs) constitute a viable and increasingly used therapy for end-stage heart failure patients. However, they are still operating at a fixed-speed mode that precludes physiological cfVAD response and it is often related to adverse events of cfVAD therapy. To ameliorate this, various physiological controllers have been proposed, however, the majority of these controllers do not account for the lack of pulsatility in the cfVAD operation, which is supposed to be beneficial for the physiological function of the cardiovascular system. In this study, we present a physiological data-driven iterative learning controller (PDD-ILC) that accurately tracks predefined pump flow trajectories, aiming to achieve physiological, pulsatile, and treatment-driven response of cfVADs. The controller has been extensively tested in an in-silico environment under various physiological conditions, and compared with a physiologic pump flow proportional-integral-derivative controller (PF-PIDC) developed in this study as well as the constant speed (CS) control that is the current state of the art in clinical practice. Additionally, two treatment objectives were investigated to achieve pulsatility maximization and left ventricular stroke work (LVSW) minimization by implementing copulsation and counterpulsation pump modes, respectively. Under all experimental conditions, the PDD-ILC as well as the PF-PIDC demonstrated highly accurate tracking of the reference pump flow trajectories, outperforming existing model-based iterative learning control approaches. Additionally, the developed controllers achieved the predefined treatment objectives and resulted in improved hemodynamics and preload sensitivities compared to the CS support.

While earlier studies reported no relevant effect of the HeartMate 3 (HM3) artificial pulse (AP) on bulk pump washout, its effect on regions with prolonged residence times remains unexplored. Using numerical simulations, we compared pump washout in the HM3 with and without AP with a focus on the clearance of the last 5% of the pump volume. Results were examined in terms of flush-volume (Vf, number of times the pump was flushed with new blood) to probe the effect of the AP independent of changing flow rate. Irrespective of the flow condition, the HM3 washout scaled linearly with flush volume up to 70% washout and slowed down for the last 30%. Flush volumes needed to washout 95% of the pump were comparable with and without the AP (1.3–1.4 Vf), while 99% washout required 2.1–2.2 Vf with the AP vs. 2.5 Vf without the AP. The AP enhanced washout of the bend relief and near-wall regions. It also transiently shifted or eliminated stagnation regions and led to rapid wall shear stress fluctuations below the rotor and in the secondary flow path. Our results suggest potential benefits of the AP for clearance of fluid regions that might elicit in-pump thrombosis and provide possible mechanistic rationale behind clinical data showing very low rate of in-pump thrombosis with the HM3. Further optimization of the AP sequence is warranted to balance washout efficacy while limiting blood damage.

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.

A high-quality, low-cost ventilator, dubbed HEV, has been developed by the particle physics community working together with biomedical engineers and physicians around the world. The HEV design is suitable for use both in and out of hospital intensive care units, provides a variety of modes and is capable of supporting spontaneous breathing and supplying oxygen-enriched air. An external air supply can be combined with the unit for use in situations where compressed air is not readily available. HEV supports remote training and post market surveillance via a Web interface and data logging to complement standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the ventilation performance, especially the quality and accuracy of the pressure curves, reactivity of the trigger, measurement of delivered volume and control of oxygen mixing, delivering a global performance which will be applicable to ventilator needs beyond the COVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with a performance evaluation.

Abstract 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 generated 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 variability 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 hydrodynamic 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.