Closed-cycle noble gas recycling system for high-repetition rate high-harmonic generation.

We present a compact closed-loop recycling system for noble and inert gases. It has been developed for an extreme-ultraviolet (XUV) frequency comb based on high-harmonic generation at 100 MHz repetition rate. The system collects gas injected at several bars of backing pressure through a micrometer-sized nozzle into the laser-interaction region with a differential pumping system comprising turbomolecular pumps, and subsequently compresses the gas to a pressure of up to 200 bar. By drastically reducing the waste of expensive gases such as xenon and krypton, it enables the long operation times needed for spectroscopic measurements, as well as for continuous operation of the XUV frequency comb.

Photoelectron tomography with an intra-cavity velocity-map imaging spectrometer at 100 MHz repetition rate.

We present a compact velocity-map imaging (VMI) spectrometer for photoelectron imaging at 100 MHz repetition rate. Ultrashort pulses from a near-infrared frequency comb laser are amplified in a polarization-insensitive passive femtosecond enhancement cavity. In the focus, multi-photon ionization (MPI) of gas-phase atoms is studied tomographically by rotating the laser polarization. We demonstrate the functioning of the VMI spectrometer by reconstructing photoelectron angular momentum distributions from xenon MPI. Our intra-cavity VMI setup collects electron energy spectra at high rates, with the advantage of transferring the coherence of the cavity-stabilized femtosecond pulses to the electrons. In addition, the setup will allow studies of strong-field effects in nanometric tips.

Enhanced wall shear stress prevents obstruction by astrocytes in ventricular catheters.

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.

Signal quality quantification and waveform reconstruction of arterial blood pressure recordings.

Arterial blood pressure (ABP) is an important vital sign of the cardiovascular system. As with other physiological signals, its measurement can be corrupted by different sources of noise, interference, and artifact. Here, we present an algorithm for the quantification of signal quality and for the reconstruction of the ABP waveform in noise-corrupted segments of the measurement. The algorithm quantifies the quality of the ABP signal on a beat-by-beat basis by computing the normalized mean of successive differences of the ABP amplitude over each beat. In segments of poor signal quality, the ABP wavelets are then reconstructed on the basis of the expected cycle duration and envelope information derived from neighboring ABP wavelet segments. The algorithm was tested on two datasets of ABP waveform signals containing both invasive radial artery ABP and noninvasive ABP waveforms. Our results show that the approach is efficient in identifying the noisy segments (accuracy, sensitivity and specificity over 95%) and reliable in reconstructing beats that were artificially corrupted.

Extraction of fetal heart rate from maternal surface ECG with provisions for multiple pregnancies.

Twin pregnancies carry an inherently higher risk than singleton pregnancies due to the increased chances of uterine growth restriction. It is thus desirable to monitor the wellbeing of the fetuses during gestation to detect potentially harmful conditions. The detection of fetal heart rate from the maternal abdominal ECG represents one possible approach for noninvasive and continuous fetal monitoring. Here, we propose a new algorithm for the extraction of twin fetal heart rate signals from maternal abdominal ECG recordings. The algorithm detects the fetal QRS complexes and converts the QRS onset series into a binary signal that is then recursively scanned to separate the contributions from the two fetuses. The algorithm was tested on synthetic singleton and twin abdominal recordings. It achieved an average sensitivity and accuracy for QRS complex detection of 97.5% and 93.6%, respectively.

Cycle-averaged dynamics of a periodically driven, closed-loop circulation model.

Time-varying elastance models have been used extensively in the past to simulate the pulsatile nature of cardiovascular waveforms. Frequently, however, one is interested in dynamics that occur over longer time scales, in which case a detailed simulation of each cardiac contraction becomes computationally burdensome. In this paper, we apply circuit-averaging techniques to a periodically driven, closed-loop, three-compartment recirculation model. The resultant cycle-averaged model is linear and time invariant, and greatly reduces the computational burden. It is also amenable to systematic order reduction methods that lead to further efficiencies. Despite its simplicity, the averaged model captures the dynamics relevant to the representation of a range of cardiovascular reflex mechanisms.

Model-based parameter estimation using cardiovascular response to orthostatic stress.

This paper presents a cardiovascular model that is capable of simulating the short-term (< or approximately equal to 3 min) transient hemodynamic response to gravitational stress and a gradient-based optimization method that allows for the automated estimation of model parameters from simulated or experimental data. We perform a sensitivity analysis of the transient heart rate response to determine which parameters of the model impact the heart rate dynamics significantly. We subsequently include only those parameters in the estimation routine that impact the transient heart rate dynamics substantially. We apply the estimation algorithm to both simulated and real data and showed that restriction to the 20 most important parameters does not impair our ability to match the data.

Numerical analysis of blood flow through a stenosed artery using a coupled, multiscale simulation method.

A global system model of the systemic circulation is combined with a local finite element solution to simulate blood flow in a stenosed coronary artery. Local fluid dynamic issues arise in connection with the detailed flow patterns within the stenosed coronary artery while the global system model is used to simulate the response of the rest of the circulation to the local perturbation. A PISO type finite element technique is employed to compute the local blood flow. The Navier-Stokes equations are solved with the assumption of viscous incompressible flow across the stenosed coronary artery. A detailed lumped parameter model simulates the characteristics of the coronary circulation and is imbedded in a coarse-grained lumped parameter model of the entire cardiovascular system. These two methods are coupled in that the lumped parameter calculations provide the time-dependent boundary conditions for the local finite element calculation. In turn, the local fluid dynamical computation provides estimates for the pressure drop across the stenosis, which is subsequently used to refine the lumped parameter calculation. Results are obtained for an axisymmetric coronary artery model with a stenosis of 90% area reduction over one cardiac cycle. Numerical results show that the flow rate and resistance are strongly coupled. Compared with the flow rate distribution computed from the global simulation with constant resistance, the coupled solution predicts a flow rate with only slight changes. The high flow rate during diastole increases the stenosis pressure drop and resistance. In turn, this increased resistance of the stenosis slightly reduces the flow rate computed in the lumped parameter simulation.

Computational model of cardiovascular function during orthostatic stress.

Orthostatic intolerance following spaceflight remains a critical problem in the current life-science space program. The study presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of gravitational stresses on the cardiovascular system of normals and microgravity adapted individuals. We employ a twelve compartment lumped parameter representation of the hemodynamic system coupled to set-point models of the arterial baroreflex and the cardiopulmonary reflex to investigate the transient response of heart rate to orthostatic stress. We simulate current hypotheses concerning the mechanisms underlying post-spaceflight orthostatic intolerance over a range of physiologically reasonable values and compare the simulations to astronaut stand-test data pre- and post-flight. Furthermore, we explore the effects of a potential countermeasure.

Computational models of cardiovascular function for analysis of post-flight orthostatic intolerance.

The work presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of microgravity on the cardiovascular system. In particular, a thirteen compartment lumped parameter representation of the cardiovascular system is used to simulate some of the current hypotheses concerning the mechanism of post-flight orthostatic intolerance. Simulations are compared to astronaut stand test data pre - and post-flight in an effort to quantitatively evaluate alternative hypotheses.