Toward a better noninvasive assessment of preejection period: A novel automatic algorithm for B-point detection and correction on thoracic impedance cardiogram.

Impedance cardiography is the most common clinically validated, noninvasive method for determining the timing of the opening of the aortic valve, an important event used for measuring preejection period, which reflects sympathetic beta-adrenergic influences on the heart. Automatic detection of the exact time of the opening of the aortic valve (B point on the impedance cardiogram) has proven to be challenging as its appearance varies between and within individuals and may manifest as a reversal, inflection, or rapid slope change of the thoracic impedance derivative's (dZ/dt) rapid rise. Here, a novel automatic algorithm is proposed for the detection of the B point by finding the main rapid rise of the dZ/dt signal, which is due to blood ejection. Several conditions based on zero crossings, minima, and maxima of the dZ/dt signal and its derivatives are considered to reject any unwanted noise and artifacts and select the true B-point location. The detected B-point locations are then corrected by modeling the B-point time data using forward and reverse autoregressive models. The proposed algorithm is validated against expert-detected B points and is compared with different conventional methods; it significantly outperforms them by at least 54% in mean error, 30% in mean absolute error, and 27% in standard deviation of error. This algorithm can be adopted in ambulatory studies requiring beat-to-beat evaluation of cardiac hemodynamic parameters over extended time periods where expert scoring is not feasible.

Analysis of age as a factor in NASA astronaut selection and career landmarks.

NASA's periodic selection of astronauts is a highly selective process accepting applications from the general population, wherein the mechanics of selection are not made public. This research was an effort to determine if biases (specifically age) exist in the process and, if so, at which points they might manifest. Two sets of analyses were conducted. The first utilized data requested via the Freedom of Information Act (FOIA) on NASA astronaut applicants for the 2009 and 2013 selection years. Using a series of multinomial and logistic regressions, the data were analyzed to uncover whether age of the applicants linearly or nonlinearly affected their likelihood of receiving an invitation, as well as their likelihood of being selected into the astronaut program. The second used public data on age at selection and age at other career milestones for every astronaut selected from 1959 to 2013 to analyze trends in age over time using ordinary least-squares (OLS) regression and Pearson's correlation. The results for the FOIA data revealed a nonlinear relationship between age and receiving an interview, as well as age and selection into the astronaut program, but the most striking observation was the loss of age diversity at each stage of selection. Applicants younger or older than approximately 40 years were significantly less likely to receive invitations for interviews and were significantly less likely to be selected as an astronaut. Analysis of the public-source data for all selections since the beginning of the astronaut program revealed significant age trends over time including a gradual increase in selectee age and decreased tenure at NASA after last flight, with average age at retirement steady over the entire history of the astronaut program at approximately 48 years.

Noninvasive pulse transit time measurement for arterial stiffness monitoring in microgravity.

The use of a noninvasive hemodynamic monitor to estimate arterial stiffness, by measurement of pulse transit time (PTT), was demonstrated in microgravity. The monitor's utility for space applications was shown by establishing the correlation between ground-based and microgravity-based measurements. The system consists of a scale-based ballistocardiogram (BCG) and a toe-mounted photoplethysmogram (PPG). PTT was measured from the BCG I-wave to the intersecting tangents of the first trough and maximum first derivative of the PPG waveforms of each subject. The system was tested on a recent series of parabolic flights in which the PTT of nine subjects was measured on the ground and in microgravity. An average of 60.2 ms PTT increase from ground to microgravity environments was shown, and was consistent across all test subjects (standard deviation = 32.9 ms). This increase in PTT could be explained by a number of factors associated with microgravity and reported in previous research, including elimination of hydrostatic pressure, reduction of intrathoracic pressure, and reduction of mean arterial pressure induced by vasodilation.

Standing ballistocardiography measurements in microgravity.

The performance and practicality of a scale-based ballistocardiogram (BCG) system for hemodynamic monitoring of astronauts on extended space missions was demonstrated. The system consists of a modified electronic weighing scale fitted with foot bindings to mechanically couple the subject to the scale. This system was tested on a recent series of parabolic flights in which scale-based and accelerometry-based free-floating BCG of 10 subjects was measured in microgravity. The signal-to-noise ratio (SNR) of the scale-based BCG was, on average, a factor of 2.1 (6.3 dB) higher than the free-floating method, suggesting that the tethered scale approach might be more robust in terms of signal quality. Additionally, this approach enables practical BCG-based hemodynamic monitoring in fractional-g environments, and on small space vehicles such as NASA's upcoming Orion capsule. The scale-based results in microgravity were also compared to ground measurements (1 g), where there was an average 38.7 ms RJ interval reduction from ground to microgravity environments that is consistent across 9 of 10 subjects. This phenomenon is likely due to the transient increase in venous return, and consequent decrease in pre-ejection period, experienced during the microgravity time intervals.

A frequency domain analysis of respiratory variations in the seismocardiogram signal.

The seismocardiogram (SCG) signal traditionally measured using a chest-mounted accelerometer contains low-frequency (0-100 Hz) cardiac vibrations that can be used to derive diagnostically relevant information about cardiovascular and cardiopulmonary health. This work is aimed at investigating the effects of respiration on the frequency domain characteristics of SCG signals measured from 18 healthy subjects. Toward this end, the 0-100 Hz SCG signal bandwidth of interest was sub-divided into 5 Hz and 10 Hz frequency bins to compare the spectral energy in corresponding frequency bins of the SCG signal measured during three key conditions of respiration--inspiration, expiration, and apnea. Statistically significant differences were observed between the power in ensemble averaged inspiratory and expiratory SCG beats and between ensemble averaged inspiratory and apneaic beats across the 18 subjects for multiple frequency bins in the 10-40 Hz frequency range. Accordingly, the spectral analysis methods described in this paper could provide complementary and improved classification of respiratory modulations in the SCG signal over and above time-domain SCG analysis methods.

A preliminary study investigating the quantification of beat-to-beat in seismocardiogram signals.

Ballistocardiography and seismocardiography are both non-invasive mechanical measurements of the vibrations of the body in response to the heartbeat. The ballistocardiogram (BCG) signal represents the movements of the whole body in response to cardiac ejection of blood into the vasculature; the seismocardiogram (SCG) corresponds to local vibrations of the chest wall associated with sub-audible tissue and blood movement and audio frequency heart-valve closure dynamics. This paper focuses on methods for quantifying "signal consistency"--a quantitative measure of how morphologically similar each heartbeat in a patient's recording is compared to the ensemble average taken over the recording. Before comparing each beat to the average, known physiological sources of inconsistency--such as respiratory amplitude and timing variability--are removed, then the remaining inconsistency is quantified. Previously described methods for BCG signals are expanded to fit the high-frequency (> 20 Hz) components of the SCG. The use of this method in future work could help enable proactive management of heart disease in extra-clinical settings.

Preliminary results from standing ballistocardiography measurements in microgravity.

We report on the feasibility of standing ballistocardiogram (BCG) measurements recorded in a microgravity environment. A clinically-tested BCG monitoring scale was adapted for parabolic flight for the microgravity measurements. Upon completion of this flight campaign, the BCG scale was shown to make measurements in micro-g and one-g environments--which is a first demonstration for a standing BCG system. This screening experiment demonstrated proof-of-concept attributes of the hardware design necessary for future characterization studies with multiple subjects. This scale-based BCG system is proposed as a practical device for hemodynamic monitoring for astronauts in Earth, Lunar, Martian, orbital, and interplanetary environments.

Microfluidic impedance cytometer for platelet analysis.

We present the design and performance characteristics of a platelet analysis platform based on a microfluidic impedance cytometer. Dielectrophoretic focusing is used to centre cells in a fluid stream, which then forms the core of a two-phase flow (dielectric focusing). This flow then passes between electrodes for analysis by differential impedance spectroscopy at multiple frequencies from 280 kHz to 4 MHz. This approach increases the signal-to-noise ratio relative to a single-phase, unfocused stream, while minimising the shear forces to which the cells are subjected. The percentage of activated platelets before and after passage through the chip was measured using flow cytometry, and no significant change was measured. Measuring the in-phase amplitude at a single frequency is sufficient to distinguish platelets from erythrocytes. Using multi-frequency impedance measurements and discriminant analysis, resting platelets can be discriminated from activated platelets. This multifrequency impedance cytometer therefore allows ready determination of the degree of platelet activation in blood samples.

Characterisation of electrophysiological conduction in cardiomyocyte co-cultures using co-occurrence analysis.

Cardiac arrhythmias are disturbances of the electrical conduction pattern in the heart with severe clinical implications. The damage of existing cells or the transplantation of foreign cells may disturb functional conduction pathways and may increase the risk of arrhythmias. Although these conduction disturbances are easily accessible with the human eye, there is no algorithmic method to extract quantitative features that quickly portray the conduction pattern. Here, we show that co-occurrence analysis, a well-established method for feature recognition in texture analysis, provides insightful quantitative information about the uniformity and the homogeneity of an excitation wave. As a first proof-of-principle, we illustrate the potential of co-occurrence analysis by means of conduction patterns of cardiomyocyte-fibroblast co-cultures, generated both in vitro and in silico. To characterise signal propagation in vitro, we perform a conduction analysis of co-cultured murine HL-1 cardiomyocytes and murine 3T3 fibroblasts using microelectrode arrays. To characterise signal propagation in silico, we establish a conduction analysis of co-cultured electrically active, conductive cardiomyocytes and non-conductive fibroblasts using the finite element method. Our results demonstrate that co-occurrence analysis is a powerful tool to create purity-conduction relationships and to quickly quantify conduction patterns in terms of co-occurrence energy and contrast. We anticipate this first preliminary study to be a starting point for more sophisticated analyses of different co-culture systems. In particular, in view of stem cell therapies, we expect co-occurrence analysis to provide valuable quantitative insight into the integration of foreign cells into a functional host system.

Extracting respiratory information from seismocardiogram signals acquired on the chest using a miniature accelerometer.

Seismocardiography (SCG) is a non-invasive measurement of the vibrations of the chest caused by the heartbeat. SCG signals can be measured using a miniature accelerometer attached to the chest, and are thus well-suited for unobtrusive and long-term patient monitoring. Additionally, SCG contains information relating to both cardiovascular and respiratory systems. In this work, algorithms were developed for extracting three respiration-dependent features of the SCG signal: intensity modulation, timing interval changes within each heartbeat, and timing interval changes between successive heartbeats. Simultaneously with a reference respiration belt, SCG signals were measured from 20 healthy subjects and a respiration rate was estimated using each of the three SCG features and the reference signal. The agreement between each of the three accelerometer-derived respiration rate measurements was computed with respect to the respiration rate derived from the reference respiration belt. The respiration rate obtained from the intensity modulation in the SCG signal was found to be in closest agreement with the respiration rate obtained from the reference respiration belt: the bias was found to be 0.06 breaths per minute with a 95% confidence interval of -0.99 to 1.11 breaths per minute. The limits of agreement between the respiration rates estimated using SCG (intensity modulation) and the reference were within the clinically relevant ranges given in existing literature, demonstrating that SCG could be used for both cardiovascular and respiratory monitoring. Furthermore, phases of each of the three SCG parameters were investigated at four instances of a respiration cycle-start inspiration, peak inspiration, start expiration, and peak expiration-and during breath hold (apnea). The phases of the three SCG parameters observed during the respiration cycle were congruent with existing literature and physiologically expected trends.

Spatiotemporally controlled cardiac conduction block using high-frequency electrical stimulation.

BACKGROUND: Methods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment - irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) - is highly desirable. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s). CONCLUSION/SIGNIFICANCE: Inhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.

High-frequency electrical stimulation of cardiac cells and application to artifact reduction.

A novel modality for the electrical stimulation of cardiac cells is described. The technique is based on HF stimulation-burst of HF (1-25 kHz) biphasic square waves-to depolarize the cells and trigger action potentials (APs). HF stimulation was demonstrated in HL-1 cardiomyocyte cultures using microelectrode arrays, and the underlying mechanisms were investigated using single-cell model simulations. Current thresholds for HF stimulation increased at higher frequencies or shorter burst durations, and were typically higher than thresholds for single biphasic pulses. Nonetheless, owing to the decreasing impedance of metal electrodes with increasing frequencies, HF bursts resulted in reduced electrode voltages (up to four fold). Such lowered potentials might be beneficial in reducing the probability of irreversible electrochemical reactions and tissue damage, especially for long-term stimulation. More significantly, stimulation at frequencies higher than the upper limit of the AP power spectrum allows effective artifact reduction by low-pass filtering. Shaping of the burst envelope provides further reduction of the remaining artifact. This ability to decouple extracellular stimulation and recording in the frequency domain allowed detection of APs during stimulation-something previously not achievable to the best of our knowledge.

Preliminary results from BCG and ECG measurements in the heart failure clinic.

We report on the preliminary deployment of a bathroom scale-based ballistocardiogram (BCG) system for the in-hospital monitoring of patients with heart failure. These early trials provided valuable insights into the challenges and opportunities for such monitoring. In particular, the need for robust algorithms and adapted BCG metric is suggested. The system was designed to be robust and user-friendly, with dual ballistocardiogram (BCG) and electrocardiogram (ECG) capabilities. The BCG was measured from a modified bathroom scale, while the ECG (used as timing reference) was measured using dry handlebar electrodes. The signal conditioning and digitization circuits were USB-powered, and data acquisition performed using a netbook. Four patients with a NYHA class III at admission were measured daily for the duration of their treatment at Stanford hospital. A measure of BCG quality, in essence a quantitative implementation of the BCG classes originally defined in the 1950s, is proposed as a practical parameter.

Determination of low bacterial concentrations in hyperarid Atacama soils: comparison of biochemical and microscopy methods with real-time quantitative PCR.

Hyperarid Atacama soils are reported to contain significantly reduced numbers of microbes per gram of soil relative to soils from other environments. Molecular methods have been used to evaluate microbial populations in hyperarid Atacama soils; however, conflicting results across the various studies, possibly caused by this low number of microorganisms and consequent biomass, suggest that knowledge of expected DNA concentrations in these soils becomes important to interpreting data from any method regarding microbial concentrations and diversity. In this paper we compare the number of bacteria per gram of Atacama Desert soils determined by real-time quantitative polymerase chain reaction with the number of bacteria estimated by the standard methods of phospholipids fatty acid analysis, adenine composition (determined by liquid chromatography - time-of-flight mass spectrometry), and SYBR-green microscopy. The number determined by real-time quantitative polymerase chain reaction as implemented in this study was several orders of magnitude lower than that determined by the other three methods and probably underestimates the concentrations of soil bacteria, most likely because of soil binding during the DNA extraction methods. However, the other methods very possibly overestimate the bacteria concentrations owing to desiccated, intact organisms, which would stain positive in microscopy and preserve both adenine and phospholipid fatty acid for the other methods.

A portable system for monitoring the behavioral activity of Drosophila.

We describe a low-cost system for monitoring the behavioral activity of the fruit fly, Drosophila melanogaster. The system is readily adaptable to one or more cameras for simultaneous recordings of behavior from different angles and can be used for monitoring multiple individuals in a population at the same time. Signal processing allows discriminating between active and inactive periods during locomotion or flying, and quantification of subtler movements related to changes in position of the wings or legs. The recordings can be taken continuously over long periods of time and can thus provide information about the dynamics of a population. The system was used to monitor responses to caffeine, changes in temperature and g-force, and activity in a variable size population.

Rapid assessment of cardiac contractility on a home bathroom scale.

Analyzing systolic time intervals-specifically the preejection-period (PEP)-is widely accepted as one of the few methods for the noninvasive assessment of cardiac contractility. In this paper, we investigated the ballistocardiogram (BCG) as a way to noninvasively measure myocardial contractility when combined with the ECG. Specifically, we derived a parameter from the BCG and ECG that we hypothesized would be highly correlated to PEP. This is the time delay between the J-wave peak of the BCG and the R-wave of the ECG, which we refer to as the RJ interval. The RJ interval was correlated to PEP (r(2) = 0.86) for 2126 heartbeats across ten subjects, with a y-intercept of 138 ms and slope of 1.05. This suggests that the RJ interval can be reliably used as a noninvasive assessment of cardiac contractility.

Automatic detection of motion artifacts in the ballistocardiogram measured on a modified bathroom scale.

Ballistocardiography (BCG) is a non-invasive technique used to measure the ejection force of blood into the aorta which can be used to estimate cardiac output and contractility change. In this work, a noise sensor was embedded in a BCG measurement system to detect excessive motion from standing subjects. For nine healthy subjects, the cross-correlation of the motion signal to the BCG noise--estimated using a simultaneously acquired electrocardiogram and statistics of the BCG signal--was found to be 0.94 and 0.87, during periods of standing still and with induced motion artifacts, respectively. In a separate study, where 35 recordings were taken from seven subjects, a threshold-based algorithm was used to flag motion-corrupted segments of the BCG signal using only the auxiliary motion sensor. Removing these flagged segments enhanced the BCG signal-to-noise ratio (SNR) by an average of 14 dB (P < 0.001). This integrated motion-sensing technique addresses a gap in methods available to identify and remove noise in standing BCG recordings due to movement, in a practical manner that does not require user intervention or obtrusive sensing.

Multi-signal electromechanical cardiovascular monitoring on a modified home bathroom scale.

A commercially available bathroom scale was modified to enable unobtrusive and robust cardiovascular monitoring in the home. Handlebar electrodes were interfaced to an ultra-low power, two-electrode electrocardiogram (ECG) acquisition circuit providing consistent and clean heartbeat timing information. In addition, the footpad electrodes were used to detect lower-body electromyogram (EMG) and lower-body impedance plethysmogram (IPG) signals using two parallel circuits. The lower-body EMG signal was used as an indication of excessive motion of the subject on the scale. The lower-body IPG signal is related to blood flow through the legs, and will be investigated further in future studies. Finally, the component of bodyweight that varies with time--the ballistocardiogram (BCG) signal--was amplified from the existing strain gauges built into the scale. A preliminary validation was completed on five healthy subjects of varying sizes. The average signal-to-noise ratio (SNR) values computed over all five subjects for the ECG, IPG, and BCG signals were 17.2, 12.0, and 9.0 dB, respectively.

Ballistocardiography--a method worth revisiting.

The field of ballistocardiography seems to be enjoying a recent resurgence, most notably through the development of novel technologies and signal processing methods for measurement and analysis. After the method almost vanished in the late 80's and 90's, it is reasonable to wonder what is different this time, and if the technique has now more chances of becoming what its pioneer always wanted - a widespread clinical tool. This paper is an effort to compare and contrast this novel wave of research (notably in the context of the authors' own work). It also suggests that the new approaches have several key differences with past embodiments that place them in a good position to address some specific issues such as cardiac resynchronization therapy device optimization or congestive heart failure monitoring. This optimism is largely fed by the recent technological advances enabling the measurement of the BCG unobtrusively, frequently, at home or in a hospital, and by a re-focus on monitoring and trending applications.

Physical modeling of low-frequency sound propagation through human thoracic tissue.

This work aims at modeling, in the presence of simplifying physical and geometrical assumptions, acoustic wave propagation through human thoracic tissue. Presented here are preliminary modeling results that are indicative of dominant lung resonances at specific frequencies. These resonant modes strongly impact pressure distribution in the tissue as well as the pressure and acceleration at the tissue-air interface. Under the modeling conditions, the effect of these lung resonant modes outweighs that of bones on acoustic waves at these frequencies.