Mario Liehr

Fetal heart rate variability reveals differential dynamics in the intrauterine development of the sympathetic and parasympathetic branches of the autonomic nervous system

The aim of this study was to investigate the hypothesis that fetal beat-to-beat heart rate variability (fHRV) displays the different time scales of sympatho-vagal development prior to and after 32 weeks of gestation (wks GA). Ninety-two magnetocardiograms of singletons with normal courses of pregnancy between 24 + 1 and 41 + 6 wks GA were studied. Heart rate patterns were either quiet/non-accelerative (fHRP I) or active/accelerative (fHRP II) and recording quality sufficient for fHRV. The sample was divided into the GA groups <32 wks GA/>32 wks GA. Linear parameters of fHRV were calculated: mean heart rate (mHR), SDNN and RMSSD of normal-to-normal interbeat intervals, power in the low (0.04-0.15 Hz) and high frequency range (0.15-0.4 Hz) and the ratios SDNN/RMSSD and LF/HF as markers for sympatho-vagal balance. fHRP I is characterized by decreasing SDNN/RMSSD, LF/HF and mHR. The decrease is more pronounced <32 wks GA. Beyond that GA SDNN/RMSSD is predominantly determined by RMSSD during fHRP I and by SDNN during fHRP II. In contrast to fHRP I, during fHRP II, mHR is positively correlated to SDNN/RMSSD instead of SDNN >32 wks GA. LF/HF increases in fHRP II during the first half of the third trimester. Non-accelerative fHRP are indicative of parasympathetic dominance >32 wks GA. In contrast, the sympathetic accentuation during accelerative fHRP is displayed in the interrelations between mHR, SDNN and SDNN/RMSSD. Prior to 32 wks GA, fHRV reveals the increasing activity of the respective branches of the autonomic nervous system differentiating the types of fHRP.

Human fetal heart rate variability-characteristics of autonomic regulation in the third trimester of gestation.

Abstract Aim: To describe developmental aspects of the sympatho-vagal heart rate regulation in the human fetus by applying numerics to visual descriptions of fetal heart rate patterns throughout the third trimester of pregnancy. The focus is to determine potential benefits of this alternative means of assessing the maturation of the fetal autonomic nervous system by analysis of fetal heart rate variability (fHRV). Subjects and methods: The magnetocardiograms of 103 normal fetuses between 24+1 and 41+6 weeks of gestation were studied. Fetal heart beat intervals were determined with a temporal precision of 1 ms. The levels of fetal activity were estimated according to characteristic heart rate patterns (I–III) prior to 32, between 32–35 and beyond 35 (groups 1–3) completed weeks. Mean heart rate (mHR), standard deviation of normal-to-normal beat intervals (SDNN) and root mean square of successive differences of normal beats (RMSSD) served as fHRV indices, mean permutation entropy (PE_Mean) as complexity measure. SDNN/RMSSD was introduced as a potential marker for sympatho-vagal balance. Results: Low activity fHRP (I) were characterized by significantly lower level fHRV indices and higher PE_Mean when compared to fHRP II. We found that SDNN/RMSSD decreases with gestation in fHRP I, which suggests increasing vagal influence. In fHRP III (assigned to active awake fetuses only after 32 weeks), highest level SDNN and mHR are associated with a dramatically reduced complexity. fHRV indices cluster characteristically with the activity levels. Conclusions: We conclude that a combined analysis of fHRV, based on SDNN/RMSSD and PE_Mean, and fHRP is advantageous in the assessment of maturation of the fetal autonomic nervous system.

Magnetic nanoparticle imaging by means of minimum norm estimates from remanence measurements

In magnetic nanoparticle imaging, magnetic nanoparticles are coated and functionalized to bind to specific targets. After measuring their magnetic relaxation or remanence, their distribution can be determined by means of inverse methods. The reconstruction algorithm presented in this paper includes first a dipole fit using a Levenberg–Marquardt optimizer to determine the reconstruction plane. Secondly, a minimum norm estimate is obtained on a regular grid placed in that plane. Computer simulations involving different parameter sets and conditions show that the used approach allows for the reconstruction of distributed sources, although the reconstructed shapes are distorted by blurring effects. The reconstruction quality depends on the signal-to-noise ratio of the measurements and decreases with larger sensor-source distances and higher grid spacings. In phantom measurements, the magnetic remanence of nanoparticle columns with clinical relevant sizes is determined with two common measurement systems. The reconstructions from these measurements indicate that the approach is applicable for clinical measurements. Our results provide parameter sets for successful application of minimum norm approaches to Magnetic Nanoparticle Imaging.

Vortex shaped current sources in a physical torso phantom.

Recent studies reported differential information in human magnetocardiogram and in electrocardiogram. Vortex currents have been discussed as a possible source of this divergence. With the help of physical phantom experiments, we quantified the influence of active vortex currents on the strength of electric and magnetic signals, and we tested the ability of standard source localization algorithms to reconstruct vortex currents. The active vortex currents were modeled by a set of twelve single current dipoles arranged in a circle and mounted inside a phantom that resembles a human torso. Magnetic and electric data were recorded simultaneously while the dipoles were switched on stepwise one after the other. The magnetic signal strength increased continuously for an increasing number of dipoles switched on. The electric signal strength increased up to a semicircle and decreased thereafter. Source reconstruction with unconstrained focal source models performed well for a single dipole only (less than 3-mm localization error). Minimum norm source reconstruction yielded reasonable results only for a few of the dipole configurations. In conclusion active vortex currents might explain, at least in part, the difference between magnetically and electrically acquired data, but improved source models are required for their reconstruction.

Reproducibility of HTS-SQUID magnetocardiography in an unshielded clinical environment

A new technology has been developed which measures the magnetic field of the human heart (magnetocardiogram, MCG) by using high temperature superconducting (HTS) sensors. These sensors can be operated at the temperature of liquid nitrogen without electromagnetic shielding. We tested the reproducibility of HTS-MCG measurements in healthy volunteers. Unshielded HTS-MCG measurements were performed in 18 healthy volunteers in left precordial position in two separate sessions in a clinical environment. The heart cycles of 10 min were averaged, smoothed, the baselines were adjusted, and the data were standardized to the respective areas under the curves (AUC) of the absolute values of the QRST amplitudes. The QRS complexes and the ST-T intervals were used to assess the reproducibility of the two measurements. Ratios (R(QRS), R(STT)) were calculated by dividing the AUC of the first measurement by the ones of the second measurement. The linear correlation coefficients (CORR(QRS), CORR(STT)) of the time intervals of the two measurements were calculated, too. The HTS-MCG signal was completely concealed by the high noise level in the raw data. The averaging and smoothing algorithms unmasked the QRS complex and the ST segment. A high reproducibility was found for the QRS complex (R(QRS)=1.2+/-0.3, CORR(QRS)=0.96+/-0.06). Similarly to the shape of the ECG it was characterized by three bends, the Q, R, and S waves. In the ST-T interval, the reproducibility was considerably lower (R(STT)=0.9+/-0.2, CORR(STT)=0.66+/-0.28). In contrast to the shape of the ECG, a baseline deflection after the T wave which may belong to U wave activity was found in a number of volunteers. HTS-MCG devices can be operated in a clinical environment without shielding. Whereas the reproducibility was found to be high for the depolarization interval, it was considerably lower for the ST segment and for the T wave. Therefore, before clinically applying HTS-MCG systems to the detection of repolarization abnormalities in acute coronary syndromes, further technical development of the systems is necessary to improve the signal-to-noise ratio.

Influence of anisotropic compartments on magnetic field and electric potential distributions generated by artificial current dipoles inside a torso phantom

The purpose of this study is the analysis of the influence of anisotropic conductivity on magnetic fields and electric potentials by means of phantom measurements. An artificial rotating current dipole was placed in the middle of an anisotropic skein arrangement in a torso phantom filled with saline solution. The signal strength and the change of the shape of potential and field patterns due to anisotropic volume conduction were investigated. Different directions of the dipole were compared to corresponding orientations of measured fields and potentials (angle difference). For electric and magnetic data, the angle difference between observed signal orientations and true dipole orientations continuously increased with the angle between dipole and anisotropy (up to 80 degrees ) and then decreased back to zero at their orthogonal orientation. Both signal strengths decreased about 10% with an increasing angle between dipole and anisotropy. While the magnetic field showed a generally stronger shape change, the changed shape of the electric potential showed similarity to an extended source. Our phantom study demonstrated that anisotropic compartments influence directions, amplitudes and shapes of potentials and fields at different degrees. We concluded that anisotropic structures should be considered in volume conductor modelling, when source orientation, extension and strength are of interest.

Fetal heart rate variability in growth restricted fetuses.

Abstract Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.

Alternans of blood pressure and heart rate in dilated cardiomyopathy.

LEDER, U., et al.: Alternans of Blood Pressure and Heart Rate in Dilated Cardiomyopathy. Impaired myocardial performance is known to be associated with electrical and mechanical beat‐to‐beat alternans phenomena. The alternans in blood pressure and heart rate and their interdependency in idiopathic dilated cardiomyopathy (IDC) were studied. The arterial blood pressure and the electrocardiograph (ECG) were continuously recorded in 22 patients suffering from IDC (age 49 ± 13 years, ejection fraction 0.33 ± 0.13, left ventricular diameter of 67 ± 8 mm) and in 21 healthy controls (age 52 ± 15 years). The beat‐to‐beat variations of the interbeat intervals (IBI) and of the blood pressure amplitudes (AMP) were measured. An alternans beat was defined as a beat preceded and followed by beats that had higher or lower values in the respective modality. The percentages of singular and repetitive alternans patterns, and the interdependency of the alternans patterns in AMP and IBI were assessed. The study found significantly more singular and repetitive alternans patterns in the IDC group compared to the control group both in the analysis of AMP and IBI (singular alternans in IBI: 55 ± 11 vs 47 ± 7%, P < 0.01; singular alternans in AMP: 61 ± 15 vs 45 ± 6%, P < 0.01; triple alternans in IBI: 29 ± 18 vs 16 ± 9%, P < 0.01; triple alternans in AMP: 34 ± 24 vs 12 ± 7%, P < 0.01). The amplitudes of the AMP alternans patterns were higher in IDC compared to controls (9 ± 7 vs 4 ± 2% of AMP, P = 0.01) whereas they did not differ in IBI. The correlation analysis revealed a significant interdependency of the alternans pattern in IBI and AMP in 18 of 22 IDC patients and in 12 of 21 controls (r = 0.50 ± 0.21 [IDC]; r = 0.26 ± 0.05 [controls]). The slope of the linear regression (ΔAMP vs ΔIBI) was steeper in the IDC group compared to the control group (62 ± 50 vs 20 ± 22 mmHg/s, P < 0.01). The percentages of alternans patterns appearing in IBI and AMP were positively correlated to the left ventricular diameter (r = 0.70 in the IBI, and r = 0.30 in the AMP). The blood pressure amplitude and the heart rate did not differ between the two groups. Patients suffering from IDC have a higher prevalence, stability, amplitude, and interdependency of alternans patterns in IBI and AMP compared to the control group. The amount of alternans patterns indicates the stage of disease. The alternans analysis may have impact on the functional assessment of patients suffering from heart failure.

The localization of focal heart activity via body surface potential measurements: tests in a heterogeneous torso phantom

The non-invasive localization of focal heart activity via body surface potential measurements (BSPM) could greatly benefit the understanding and treatment of arrhythmic heart diseases. However, the in vivo validation of source localization algorithms is rather difficult with currently available measurement techniques. In this study, we used a physical torso phantom composed of different conductive compartments and seven dipoles, which were placed in the anatomical position of the human heart in order to assess the performance of the Recursively Applied and Projected Multiple Signal Classification (RAP-MUSIC) algorithm. Electric potentials were measured on the torso surface for single dipoles with and without further uncorrelated or correlated dipole activity. The localization error averaged 11 +/- 5 mm over 22 dipoles, which shows the ability of RAP-MUSIC to distinguish an uncorrelated dipole from surrounding sources activity. For the first time, real computational modelling errors could be included within the validation procedure due to the physically modelled heterogeneities. In conclusion, the introduced heterogeneous torso phantom can be used to validate state-of-the-art algorithms under nearly realistic measurement conditions.

Reconstruction of quasi-radial dipolar activity using three-component magnetic field measurements

OBJECTIVE While standard magnetoencephalographic systems record only one component of the biomagnetic field, novel vector-biomagnetometers enable measurement of all three components of the field at each sensing point. Because information content in standard one-component magnetoencephalography (MEG) is often not adequate to reconstruct quasi-radial dipolar activity, we tested the hypothesis that quasi-radial activity can be estimated using three-component MEG. METHODS We stimulated the right median nerve in 11 healthy volunteers and recorded the somatosensory evoked fields over the contralateral hemisphere using a novel vector-biomagnetometer system comprised of SQUID-based magnetometer triplets. Source reconstruction for the early cortical components N20m and P25m was subsequently performed. RESULTS Both tangential and quasi-radial dipolar activity could be reconstructed in 10 of the 11 participants. Dipole locations were found in the vicinity of the central sulcus, and dipole orientations were predominantly tangential for N20m and quasi-radial for P25m. The mean location difference between the tangential and quasi-radial dipoles was 11.9 mm and the mean orientation difference was 97.5°. CONCLUSIONS Quasi-radial dipolar activity can be reconstructed from three-component magnetoencephalographic measurements. SIGNIFICANCE Three-component MEG provides higher information content than does standard MEG.