Impedance cardiography (ICG) is a method to evaluate cardiac-stroke volume and cardiac-output by measuring the cardiac-synchronous changes in the dynamic trans-thoracic electrical impedance (ΔZ). Clinical evaluations on the accuracy of ICG showed varying results. Consequently, the classic assumption in ICG-the aorta as a main source of ΔZ-is questioned and subsequently investigated in simulation studies using mathematical models of the electrical resistivity of the human body. The aim is to review the consensus in mathematical modelling studies that investigate the origin of the ΔZ as measured in ICG. In a systematic literature search, studies were identified and surveyed with reference to characteristics, such as included organs and their resistivity and geometries, electrode positions and calculation of ΔZ, to review the consensus between mathematical modelling studies that investigate the origin of the ΔZ as measured in ICG. Thirteen papers showed considerable variation in the model's characteristics with varying or contradicting outcomes for the ΔZ 's origin. For instance, 11 studies excluded perfused muscle tissue, implying implicitly their insignificance, while 3 other studies included muscle tissue and indicated it as the most important origin of ΔZ. In conclusion, the reviewed papers show a lack of consensus with respect to both the modelled characteristics as well as the model outcomes and, as a result, these studies failed to settle the controversy on ΔZ 's origin. Recommendations have been added to improve future mathematical model studies.

Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during non-specific general tasks, is a hemodynamic effect caused by heart rate variations. Of fifteen healthy controls ECG, EEG and fMRI were co-registered. Slice time dependent heart rate regressors were derived from the ECG data and correlated to fMRI using a linear correlation analysis where the impulse response is estimated from the data. It was found that in most subjects substantial correlations between heart rate variations and fMRI exist, both within the brain and at the ventricles. The brain areas with high correlation to heart rate are different from the "default network" and the response functions deviate from the canonical hemodynamic response function. Furthermore, a general negative correlation was found between heart beat intervals (reverse of heart rate) and alpha power. We interpret this finding by assuming that subject's state varies between drowsiness and wakefulness. Finally, given this large correlation, we re-examined the contribution of heart rate variations to earlier reported fMRI/alpha band correlations, by adding heart rate regressors as confounders. It was found that inclusion of these confounders most often had a negligible effect. From its strong correlation to alpha power, we conclude that the heart rate variations contain important physiological information about subject's resting state. However, it does not provide a full explanation of the behaviour of the "default network". Its application as confounder in fMRI experiments is a relatively small computational effort, but may have a substantial impact in paradigms where heart rate is controlled by the stimulus.

The brain's resting state is studied with the analysis of co-registered fMRI/EEG/ECG. In particular, it was investigated whether spontaneous heart rate fluctuations are correlated to fMRI-signals. This might be the case because of a direct hemodynamic coupling, or due to an indirect coupling between heart rate and alpha band power, which are both hall marks of the resting state. It was found that (1) higher alpha power coincides with a higher heart rate, (2) heart rate regressors are in many subjects strongly coupled to fMRI, and (3) inclusion of heart rate confounders hardly affects earlier reported correlations between alpha band and fMRI.

In thoracic impedance cardiography (TIC) measurements the neck electrodes are often positioned at the basis of the neck, close to the neck-thorax transition. Theoretically, this neck-thorax transition will cause inhomogeneities in the current density and potential distribution. This was simulated using a 3D finite element method, solely representing the geometrical neck-thorax transition. The specific conductivity was 7 10−3 (Ωcm)−1 and the injected current was 1 mA. As expected, the model generated inhomogeneities in the current distribution at the neck-thorax transition, which reached as far as 5 cm into the neck and 20 cm into the thorax. These results are supported by in vivo measurements performed in 10 young male subjects, in which the position of the neck electrodes was varied. A two-way ANOVA revealed that the stroke volume of the lowest neck position was significantly different from the other positions. Small shifts in the position of the neck electrode resulted in large changes in impedance and stroke volume (127 to 82 ml for the Kubicek equation). To standardise the electrode position, the authors strongly recommend placement of the neck electrodes at least 6 cm above the clavicula.

At relatively high frequencies, the application of an alternating current through the body or a body segment results in electromagnetic stray fields which reduce the amount of current actually injected into the tissue under study. This radiation effect can be reduced by use of a symmetrical configuration current source. The symmetry of such an arrangement, however, depends on the stray capacitances of the source with respect to surrouding equipment. To minimise these effects, it is required that the source is electrically isolated from the surrounding equipment and the subject under study. In this manner stray capacitances with respect to elements of the current source are reduced. In such a configuration common mode voltages to the input amplifier of the measuring system are also reduced. The paper describes design considerations and the implementation of a wideband current source capable of injecting alternating current in the order of 300μARMS into biological tissue having impedances up to 1kΩ. Current stabilisation is obtained by means of a control circuit which measures the actual current passing through the tissue under study. Leakage currents arising from shielding and stray capacitances are compensated for. The usable frequency range is between 4 kHz and 1024 kHz and current stability is better than 0.2%. Through the use of a symmetrical, floating circuit a configuration is obtained which substantially reduces stray effects. The current source is connected to other circuits by means of two isolation ports: (1) a transformer coupling for the carrier frequency; and (2) an opto-coupler to transfer a phase reference signal obtained from current measurement. The current amplitude can be modulated by controlling the reference input to the control loop by means of a third auxiliary isolation port for transfer of the modulating signal.

The study investigates the effects of non-cardiogenic oedema, especially the accumulation of protein in extracellular fluid, on thoracic impedance and proposes a new method of oedema measurement based on an impedance ratio from a dual-frequency measurement. In vitro measurements in a cell containing an albumin-in-saline solution yield a resistance increase when the albumin concentration increases. Subsequently, 13 patients having acute respiratory failure are measured. The single-frequency Z0 measurements and the proposed impedance ratio are compared with extravascular lung water (EVLW) determined by the double indicator dilution method. The single-frequency measurement correlates poorly with EVLW (r=−0.24, p=0.56). In some patients, a total thoracic impedance increase is found with increasing EVLW. The correlation between the impedance ratio and EVLW is r=−0.79 (p<0.0005). The ratio decreases as EVLW increases. Thus, when oedema is measured using bio-impedance, cardiogenic and noncardiogenic oedema yield different results. It is well recognised that cardiogenic oedema decreases total thoracic impedance. In non-cardiogenic oedema, however, protein accumulation causes an impedance increase. The decrease in the impedance ratio as EVLW increases can be explained by the accumulation of albumin in the extracellular compartment.

Design considerations and implementation of a multifrequency measuring channel for application in the field of bio-impedance measurement are discussed in this paper. The input amplifier has a differential configuration which is electrically isolated from the remaining circuits. Transformer coupling provides improved common mode rejection when compared to non-isolated input stages. The frequency characteristic of the section between input and demodulator is flat within ±0.1 dB between 4kHz and 1024 kHz. The synchronous demodulator is based on a wideband switched video amplifier. In contrast to commonly used lock-in techniques, the carrier for demodulation is recovered from the input signal by means of a phase-locked loop. This method ensures zero phase shift with respect to the input signal and improves the accuracy of measurement. The system has been developed primarily for thoracic impedance cardiography (TIC) but has also succesfully been applied in the field of total body bio-impedance analysis (BIA). At present an electrical impedance tomograph is under development based on the instrumentation described. Results regarding the measurement range and accuracy are given and some recordings of patient data are shown.

Beat-to-beat cardiovascular signals, e.g. a series of systolic pressure values, can be considered as time series which are pulse amplitude modulated (PAM) and pulse frequency modulated (PFM). The latter process, due to variations in heart rate, causes the series to become non-uniformly spaced in time. If PAM is to be quantified by spectral analysis, the influence of PFM must be known. An analytical expression is therefore derived for the spectrum of sinusoids which are sampled according to the output event series of a linear integral pulse frequency modulator (IPFM). We conclude that two spectral components arise at the difference and sum of the PFM and PAM frequencies, fp±fx, with amplitudes proportional to the PFM modulation depth. These components appear as a DC component and as a first harmonic if both modulating frequencies are equal. In addition, a cluster of spectral components appears around the mean pulse frequency fo (i.e. mean heart rate), at frequencies fo-nfp±fx, which may leak into the signal band. From these theoretical considerations, we conclude that the amplitude spectrum of a sinusoidally varying systolic blood pressure series can contain up to 20–30% spurious components, owing to the heart rate modulation process.

For three direct Fourier transform algorithms we quantified the influence of pulse frequency modulation (PFM) on the spectral estimation of pulse amplitude modulation (PAM). The simulation study is based on sinusoid functions sampled according to a pulse sequence which is the output of an integral pulse frequency modulator (IPFM). One algorithm exactly reproduces the theoretical spectrum derived in Part 1. The other two, including the classical FFT, scale all PFM-induced components in a different way, and in addition, generate higher modulating frequency harmonics. For a PFM depth below 30%, the sum of spurious PFM components is almost linearly dependent on this modulation depth, for all three algorithms. Dividing the effect of PFM in a 'harmonic' and 'aliasing' distortion, we found that the FFT has a relatively high harmonic distortion, compared to an algorithm that takes into account the non-uniform character of the data. In the cardiovascular (worst) case of 30% modulation in heart rate (PFM) at a frequency of 0.1 Hz, the FFT spectrum of beat-to-beat systolic blood pressure variations contains approximately 20% of spurious components caused solely by the modulation in time occurrences of the blood pressure samples. The 'non-uniform' algorithm performs twice as well in this case.

Simple formulae are presented for designing filters based on repeatedly applied moving average operations with unit coefficients. Design formulae are derived to synthesise the filter in a way that satisfies specified passband and stopband specifications. These filters are attractive because of the reasonable frequency characteristics, the computational efficiency of the design and filter algorithms, and the uncomplicated implementation in software.