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Biomedical subjects

Lutz Trahms

Publications and source records attributed to Lutz Trahms.

13 recordsLinked to original sources

J-coupling nuclear magnetic resonance spectroscopy of liquids in nT fields.

In ultralow magnetic fields, liquid state nuclear magnetic resonance (NMR) spectra of homonuclear spin systems exhibit line widths dominated by their natural lifetime. Chemical shifts become negligible, and heteronuclear NMR spectra show predominantly the electron-mediated field-independent J-coupling. However, weak polarization and Larmor frequencies down to a few hertz require special detectors, such as Superconducting Quantum Interference Devices (SQUID), that also enable the simultaneous detection of broad band spectra of heteronuclear spin systems. We acquired spectra of 2,2,2-trifluoroethanol and trimethyl phosphate at detection fields varying from 444 nT to 3.34 muT after prepolarizing the sample in a field of 250 muT. Down to a 1H Larmor frequency of 40 Hz, the spectra of trifluoroethanol exhibited four clearly resolvable peaks. The numerical simulation agreed well with the measured spectra. Trimethyl phosphate exhibited two major groups of nonresolved proton lines. At 1H Larmor frequencies below 150 Hz, the separation of the two groups decreased, reflecting the transition from weakly to strongly coupled spin systems. Direct determination of 3J(H,P) from the peak separation is possible only at Larmor frequencies above 150 Hz. The experimental setup allowed an easy adjustment of the detection field over several octaves. This enabled us to adapt the detection field to the best-suited measurement window providing the maximum spectral information. Low-field NMR may open new applications, such as monitoring heteronuclear reactions, low-field imaging, simultaneous NMR/magnetoencephalography measurements, or quantum computing.

Kinetics↗

The influence of amplifier, interface and biological noise on signal quality in high-resolution EEG recordings.

First, the intrinsic random noise sources of a biopotential measurement in general are reviewed. For the special case of an electroencephalographic (EEG) measurement we have extended the commonly used amplifier noise model by biological generated background noise. As the strongest of all noise sources involved will dominate the resulting signal to noise ratio (S/N), we have investigated under which conditions this will be the case. We illustrate experimentally that up to 100 Hz S/N practically depends only on cortical generated background noise, while at a few hundred Hz or more amplifier and thermal noise of interelectrode resistance are the major sources.

Amplifiers, Electronic↗

Tonic neuronal activation during simple and complex finger movements analyzed by DC-magnetoencephalography.

Functional neuroimaging techniques map neuronal activation indirectly via local concomitant cortical vascular/metabolic changes. In a complementary approach, DC-magnetoencephalography measures neuronal activation dynamics directly, notably in a time range of the slow vascular/metabolic response. Here, using this technique neuronal activation dynamics and patterns for simple and complex finger movements are characterized intraindividually: in 6/6 right-handed subjects contralateral prolonged (30 s each) complex self-paced sequential finger movements revealed stronger field amplitudes over the pericentral sensorimotor cortex than simple movements. A consistent lateralization for contralateral versus ipsilateral finger movements was not found (4/6). A subsequent sensory paradigm focused on somatosensory afferences during the motor tasks and the reliability of the measuring technique. In all six subjects stable sustained neuronal activation during electrical median nerve stimulation was recorded. These neuronal quasi-tonic activation characteristics provide a new non-invasive neurophysiological measure to interpret signals mapped by functional neuroimaging techniques.

Adult↗

Impact of the intragastric location of extended release tablets on food interactions.

Gastrointestinal motility and transport as well as concomitant food intake are factors that are known to influence pharmacokinetics derived after intake of extended release dosage forms. However, the mechanisms behind these influencing factors are mostly unknown. In this study the gastrointestinal transit and the in vivo drug release of magnetically labelled extended release tablets containing felodipine were monitored together with the drug absorption phase of pharmacokinetics under fasting and fed conditions in six healthy volunteers using Magnetic Marker Monitoring. It was found that the in vivo drug release profiles of the tablets compared well under fasting and fed conditions. However, the plasma concentration profiles were strongly influenced by concomitant food intake. This could be attributed to elongated residence of the tablets in proximal parts of the stomach, resulting in delayed drug absorption and the occurrence of late high plasma peak concentrations. The lag time until the first appearance of felodipine in plasma and the residence time of the tablets in the proximal stomach, were found to be directly correlated. The study shows that increased plasma peak drug concentrations after intake of extended release formulations together with food can be explained by poor mixing in the proximal part of the stomach and are not necessarily due to failure of the formulation to control drug release (dose dumping).

Adult↗

Magnetic Marker Monitoring: An application of biomagnetic measurement instrumentation and principles for the determination of the gastrointestinal behavior of magnetically marked solid dosage forms.

Magnetic Marker Monitoring offers an alternative to investigate the behavior of solid dosage forms in the organs of the gastrointestinal tract without the need to apply radiation. For Magnetic Marker Monitoring, the dosage form is marked as a permanent magnetic dipole by the incorporation of small amounts of ferromagnetic material, as for example the colorant black iron oxide, and subsequent magnetization. Thereby, the dosage form is labeled as the source of a well defined magnetic field, which can be measured using a measurement technique that is established for biomagnetic investigations. Using the established concepts for magnetic source localization, the three dimensional localization and orientation as well as the strength of the magnetic source can be reconstructed from these magnetic measurement data as a function of time. Furthermore, it is possible to gain quantitative information on the disintegration of dosage forms in vivo. Examples are given for results obtained concerning the esophageal transit, the gastric and the intestinal behavior of capsules and tablets.

Capsules↗

Neurovascular coupling analyzed non-invasively in the human brain.

Most functional brain imaging methods detect neuronal activations indirectly through the accompanying neurovascular response. Here, we demonstrate that a novel methodological approach, the combination of DC-magnetoencephalography (DC-MEG) and near-infrared spectroscopy (NIRS), allows non-invasive assessment of the dynamics of neurovascular coupling in the human brain: detecting directly slow neuronal processes (with time constants of 30s), DC-MEG revealed, even in unaveraged recordings, sustained neuronal activations at pericentral hand cortices contralateral to repetitive finger movements; these were accompanied by the ensuing local vascular response showing similar dynamical features as quantified by simultaneously recorded NIRS. This non-invasive approach opens a new avenue for the understanding of neurovascular coupling during physiological tasks as well as in diseases involving slow neuronal depolarization shifts and alterations of blood flow, such as stroke or migraine.

Adult↗

Non-invasive magnetic detection of human injury currents.

OBJECTIVE: Injury currents are a hallmark of acute lesions in polarized cells. Our objective was to develop a non-invasive technique for monitoring human near-DC injury currents in vivo. METHODS: Using diagnostic muscle biopsy as controlled paradigm, injury-related magnetic DC-fields were mapped for 60 min postsurgery over leg muscle lesions of 9 subjects. A 49-channel magnetometer was used in combination with a mechanical horizontal modulation of the subject beneath the sensor array. RESULTS: Magnetic DC-field maps showed salient differences between biopsy and contralateral legs in 8/9 patients with a characteristic slowly decaying field in all biopsy legs. A variety of anomalous DC-field patterns was recorded over the biopsy sites, corresponding to theoretically predicted geometric variations of equivalent DC-current dipoles, i.e. wound surfaces, pointing into opposing muscle fibre ends. By contrast, all control measurements showed an elongated dipolar DC-field pattern. Additionally, mean global DC-field strengths were significantly higher over biopsy legs compared to the contralateral site. CONCLUSIONS: Our pilot data illustrate that human injury currents can be detected using non-invasive magnetometry. Thus, DC-magnetometry may provide an essential new tool for clinical monitoring of injury currents, possibly also in brain tissue, e.g. in case of anoxic or peri-infarct depolarizations.

Adult↗

MCG to ECG source differences: measurements and a two-dimensional computer model study.

In this work we combine body surface potential map (BSPM) and magnetocardiogram (MCG) measurements with computer simulations in order to elucidate a recent thesis that claims the orthogonality of the main sources of MCG and ECG. Body surface currents and MCG pseudo currents are calculated from measured BSPM and MCG data, respectively. In contrast to the MCG-ECG source orthogonality thesis, we observe the main orientation of the BSPM currents and MCG pseudo currents to have similar axis during most of the depolarization R wave. In an attempt to explain such measurements we simulate a 2D transmural slice of the left ventricle in contact to a volume conductor. The main magnetic source currents along the wave front are indeed orthogonal to the extracellular electric current. However, fiber orientation inhomogeneity through the ventricular wall, volume conductor interface, wave front shape and extra- and intracellular potential distributions, all distort the symmetry of the current loops that contain the wave front currents. The resulting asymmetry rotates the main axis of the pseudo MCG currents away from the orthogonal axis of the body surface currents. Thus, the simulation results could solve the apparent contradiction between the orthogonal source theory and the observed similar ECG and MCG main current axis.

Body Surface Potential Mapping↗

Magnetocardiography for pharmacology safety studies requiring high patient throughput and reliability.

Recent guideline drafts of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) underline the necessity to test nonantiarrhythmic drugs for their potential to prolong the QT or the corrected QT (QTc) interval. The implementation of these guidelines requires a large amount of ECG measurements on animals and humans in preclinical and clinical phases of the drug development process. We propose the use of magnetocardiography (MCG) as a complementary method with particular advantages in high-throughput studies, where signal quality and reliability are key factors. Our proposal is based on a review of recent MCG studies investigating the repolarization phase and results of methodological work assessing QT interval parameters from the MCG. The applicability of MCG for pre-clinical in-vivo studies is demonstrated by the ease of measurement in unrestrained non-anesthetized rabbits, guinea pigs, and hamsters..

Animals↗

Looking for faces: Attention modulates early occipitotemporal object processing.

Looking for somebody's face in a crowd is one of the most important examples of visual search. For this goal, attention has to be directed to a well-defined perceptual category. When this categorically selective process starts is, however, still unknown. To this end, we used magnetoencephalography (MEG) recorded over right human occipitotemporal cortex to investigate the time course of attentional modulation of perceptual processes elicited by faces and by houses. The first face-distinctive MEG response was observed at 160-170 ms (M170). Nevertheless, attention did not start to modulate face processing before 190 ms. The first house-distinctive MEG activity was also found around 160-170 ms. However, house processing was not modulated by attention before 280 ms (90 ms later than face processing). Further analysis revealed that the attentional modulation of face processing is not due to later, for example, back-propagated activation of the M170 generator. Rather, subsequent stages of occipitotemporal object processing were modulated in a category-specific manner and with preferential access to face processing.

Adult↗

Comparison of automatic repolarization measurement techniques in the normal magnetocardiogram.

Multichannel MCG noninvasively measures cardiac magnetic field strength from many sites at the body surface, potentially providing useful regional information about ventricular repolarization. Previous work on ECGs has shown that automatic techniques for repolarization measurement are better than manual measurement at discriminating patients with cardiac conditions from normal subjects. Although automatic repolarization measurement techniques have been quantified for ECGs, no comparative data exists for the MCG. In this study four different automatic repolarization (QT) interval techniques for detecting T wave end in the MCG were compared. The influence of MCG filtering on the automatic algorithms was also quantified. MCGs were obtained at 49 sites over the heart from 23 normal subjects. Automatic measurements of the repolarization (QT) interval were made following the addition of different high pass (0.25, 0.5, 1 Hz) and low pass (100, 60, 40, 30 Hz) filters. There were consistent differences between automatic techniques in the unfiltered data amounting to greatest mean difference of 52.3 ms. Low pass filtering significantly increased the automatic repolarization (QT) interval relative to unfiltered measurement by 6.5 (3.2) ms (mean SD) for 100 Hz, 6.0 (3.0) ms for 60 Hz, 8.1 (3.2) ms for 40 Hz, and 8.8 (3.1) ms for 30 Hz across all techniques. High pass filtering significantly decreased the value by -2.6 (6.0) ms for 0.25 Hz, -5.5 (5.3) ms for 0.5 Hz, and -17.1 (7.8) ms for 1 Hz. Automatic measurements of repolarization (QT) in the MCG differ between techniques and are influenced by filtering. These effects should be considered when comparing results.

Analysis of Variance↗

Errors in repolarization measurement using magnetocardiography.

Multichannel magnetocardiography (MCG) noninvasively measures variations in magnetic field strength from many sites at the body surface, potentially providing useful regional information about ventricular repolarization. MCGs contain features similar to ECGs, and although errors associated with repolarization measurement have been quantified for ECGs, no comparative data exists for MCGs. In this study, errors in manual measurement of repolarization interval in the MCG were determined. Sixteen MCG channels and three ECG leads were recorded simultaneously in eight healthy subjects. Each recording was displayed in a random order on a computer screen, in presentations with different noise levels, time display widths, and amplitude display heights. In total, manual measurement of repolarization intervals in 2,048 (eight subjects x 16 channels x eight presentations x two repeats) MCGs were made by each of four analysts. Measured repolarization intervals were reduced by 3 ms when noise was added and by a further 3 ms when this noise was doubled. Intervals were shortened by 9 ms when the time display width was doubled and by a further 10 ms when the display width was doubled again. Measurements increased by 7 ms for a doubling of amplitude display height, equivalent to a doubling of T wave height. There were also consistent differences between analysts; amounting to a greatest mean difference of 24 ms. Display characteristics, added noise, and different analysts thus affect manual repolarization interval measurements in MCG. The errors detected demonstrate the importance of a standard presentation for repolarization measurement in the MCG.

Electrocardiography↗

Cardiac artifact subspace identification and elimination in cognitive MEG data using time-delayed decorrelation.

To reduce physiological artifacts in magnetoencephalographic (MEG) and electroencephalographic recordings, a number of methods have been applied in the past such as principal component analysis, signal-space projection, regression using secondary information, and independent component analysis. This method has become popular as it does not have constraints such as orthogonality between artifact and signal or the need for a priori information. Applying the time-delayed decorrelation algorithm to raw data from a visual stimulation MEG experiment, we show that several of the independent components can be attributed to the cardiac artifact. Calculating an average cardiac activity shows that physiologically different excitation states of the heart produce similar field distributions in the MEG sensor system. This is equivalent to differing spectral properties of cardiac field distributions in the raw data. As a consequence, the algorithm combines, e.g., the R peak and the T wave of the cardiac cycle into a single component and the one-to-one assignment of each independent component with a physiological source is not justified in this case. To improve the signal quality of visually evoked fields, the multidimensional cardiac artifact subspace is suppressed from the data. To assess the preservation of the evoked signal after artifact suppression, a geometrical and a temporal measure are introduced. The suppression of cardiac and alpha wave artifacts allows, in our experimental setting, the reduction of the number of epochs to one half while preserving the visually evoked signal.

Algorithms↗