Methods and evaluations of MRI content-adaptive finite element mesh generation for bioelectromagnetic problems.

In studying bioelectromagnetic problems, finite element analysis (FEA) offers several advantages over conventional methods such as the boundary element method. It allows truly volumetric analysis and incorporation of material properties such as anisotropic conductivity. For FEA, mesh generation is the first critical requirement and there exist many different approaches. However, conventional approaches offered by commercial packages and various algorithms do not generate content-adaptive meshes (cMeshes), resulting in numerous nodes and elements in modelling the conducting domain, and thereby increasing computational load and demand. In this work, we present efficient content-adaptive mesh generation schemes for complex biological volumes of MR images. The presented methodology is fully automatic and generates FE meshes that are adaptive to the geometrical contents of MR images, allowing optimal representation of conducting domain for FEA. We have also evaluated the effect of cMeshes on FEA in three dimensions by comparing the forward solutions from various cMesh head models to the solutions from the reference FE head model in which fine and equidistant FEs constitute the model. The results show that there is a significant gain in computation time with minor loss in numerical accuracy. We believe that cMeshes should be useful in the FEA of bioelectromagnetic problems.

Should transcranial magnetic stimulation research in children be considered minimal risk?

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a neurophysiologic technique with research applications. Institutional Review Boards (IRBs) must carefully consider potential risks and possible benefits in research involving children. The purpose of this study is to provide concise information for investigators and IRBs about the safety of single and paired pulse TMS research in children. METHODS: This paper has 4 sections: (I) Regulations governing research in children are reviewed and applied to the use of TMS. (II) Energy imparted by TMS is assessed in terms of theoretical biological risks to human subjects. (III) Through MEDLINE review, the empirical evidence of risk from TMS is assessed. Reported adverse events, including issues related to risk of seizures and of hearing loss, are summarized. (IV) Safety data are presented from a study of TMS in children with Tourette Syndrome. RESULTS: No published or empirical evidence was found to suggest that single or paired pulse TMS is associated with more than minimal risk in children. CONCLUSIONS: IRBs may consider well-designed studies using single and paired pulse TMS protocols similar to those described in this study as bearing minimal risk to children. SIGNIFICANCE: This manuscript may be useful as a reference to IRBs and TMS investigators.

Patterns of abnormal motor cortex excitability in atypical parkinsonian syndromes.

OBJECTIVE: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal-ganglionic degeneration (CBGD) are all clinically characterized by an akinetic-rigid syndrome together with a variety of additional signs. We hypothesised that these atypical parkinsonian syndromes (APS) will show distinctive patterns in their motor output upon transcranial magnetic stimulation (TMS) due to their different underlying anatomico-functional deficits. METHODS: We performed single and paired-pulse TMS and assessed inhibitory and excitatory response parameters from the first dorsal interosseus muscles in 13 patients with MSA, 18 with PSP, 13 with CBGD, 15 patients with Parkinson's disease and 17 healthy subjects. RESULTS: PSP and MSA patients had significantly enlarged response amplitudes at rest, reduced intracortical inhibition (ICI) and prolonged ipsi- and contralateral silent periods, whereas CBGD patients showed significantly increased motor thresholds, smaller response amplitudes at rest, shortened contralateral silent period, reduced transcallosal inhibition and a reduced ICI. In 22% of APS patients ipsilateral motor responses occurred in upper limb muscles irrespective of the underlying disease. CONCLUSIONS: Our results indicate that motor cortex disinhibition is predominant in patients with PSP and MSA. In CBGD more severe neuronal cell loss in the motor cortex itself may lead to hypoexcitability of corticospinal and transcallosal pathways.

Decision analysis of the cost-effectiveness of repetitive transcranial magnetic stimulation versus electroconvulsive therapy for treatment of nonpsychotic severe depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant depression. OBJECTIVE: We tested the economic feasibility of this new method compared with electroconvulsive therapy (ECT). METHOD: An economic decision analysis was used to compare the costs of three different treatment strategies for nonpsychotic severe depression. The strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted life years (QALYs) for the three treatment options for all nonpsychotic, severely depressed United States patients who would have otherwise undergone ECT. A sensitivity analysis was performed to test the degree of change in outcome with various parameter changes. RESULTS: The additional cost of using ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted year of life gained. For ECT versus rTMS-to-ECT, there was both an increased cost and a loss of 1,538 QALYs with ECT alone. The sensitivity analysis revealed the model to be robust with various parameter changes. CONCLUSION: If rTMS were to be made widely available clinically in the US, it would offer a substantial economic benefit over ECT in treating resistant depression. Using rTMS-to-ECT offers not only an economic advantage but also an increase in QALYs. This analysis suggests that rTMS would be a cost-effective treatment for depression compared with the current option of ECT alone.

Very high power THz radiation at Jefferson Lab.

We report the production of high power (20 W average, approximately 1 MW peak) broadband THz light based on coherent emission from relativistic electrons. We describe the source, presenting theoretical calculations and their experimental verification. For clarity we compare this source with that based on ultrafast laser techniques, and in fact the radiation has qualities closely analogous to those produced by such sources, namely that it is spatially coherent, and comprises short duration pulses with transform-limited spectral content. In contrast to conventional THz radiation, however, the intensity is many orders of magnitude greater due to the relativistic enhancement.

Effects of ovarian hormones on human cortical excitability.

Ovarian steroids appear to alter neuronal function in women, but direct physiological evidence is lacking. In animals, estradiol enhances excitatory neurotransmission. Progesterone-derived neurosteroids increase GABAergic inhibition. The effect of weak transcranial magnetic stimulation of the motor cortex on the motor evoked potential (MEP) from transcranial magnetic stimulation given milliseconds later is changed by GABAergic and glutamatergic agents. Using this technique previously, we showed more inhibition in the luteal phase relative to the midfollicular menstrual phase, which is consistent with a progesterone effect. To detect the effects of estradiol, we have now divided the follicular phase. We tested 14 healthy women during the early follicular (low estradiol, low progesterone), late follicular (high estradiol, low progesterone), and luteal (high estradiol, high progesterone) phases, with interstimulus intervals from 2 to 10msec (10 trials at each interval and 40 unconditioned trials). We calculated the ratio of the conditioned MEP at each interval to the mean unconditioned MEP: the higher the ratio, the less inhibition and the more facilitation caused by the first stimulus. The combined ratios increased significantly from the early follicular phase to the late follicular phase and then decreased again in the luteal phase. These findings demonstrate an excitatory neuronal effect associated with estradiol and confirm our earlier finding of inhibition associated with progesterone.

Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis.

OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.

Reliability of proxy-reported and self-reported household appliance use.

Exposure assessment presents a major challenge for studies evaluating the association between household exposure to electric and magnetic fields and adverse health outcomes, especially the reliance on proxy respondents when study subjects themselves have died. We evaluated the reliability of proxy- and self-reported household appliance exposure. We recruited 92 healthy couples through either random-digit dialing or newspaper advertisements. Trained interviewers administered questionnaires to each member of a couple independently to assess the reliability of proxy-reported household appliance use. Eighty-five couples completed a second interview 2 months later to assess the reliability of self-reported appliance use. Reliability of proxy-reported appliance exposure was good when we inquired about having any exposure to each of the eight indicator appliances during the past year (range of kappa coefficients = 0.63-0.85; median = 0.76) but was lower with increased time to recall or increased detail. Reliability of self respondents reporting 2 months apart was excellent (range of kappa coefficients = 0.75-0.94; median = 0.87) for having any exposure to the eight indicator appliances during the past year, but reliability was again lower with increased detail. When we used self reports at the first interview as the standard, little systematic over- or underreporting occurred for proxy respondents or for self respondents reporting 2 months later. Because this study did not include cases of specific disease, these findings of no systematic differences in reporting do not refer to case or control status. In summary, reliability of self respondents' reports of appliance use is very good for recent time periods and good for broad aspects of exposure in distant time periods. Proxy respondents can provide information regarding broad aspects of appliance exposure in the past year, but detailed aspects of exposure or exposure in more distant time periods is not reliable.

Is there more than one source for the temporal binding factor for human consciousness?

If the emergence of higher order consciousness is produced by transcerebral electromagnetic processes recreated every 20 msec. to 25 msec., then any frequency band in addition to the 40-Hz range could serve as a binding factor for this process. Second order differences or "derivatives," obtained by lagging differences in real time between adjacent frequency integers, indicate that 20 msec. to 25 msec. intervals could be continuously recreated by shifts in frequency within approximately 6.3 and 7.8 Hz. Higher order differences indicate that variations within very narrow band widths between 5 Hz and 6 Hz would generate continuous recreations of 20-msec. to 25-msec. intervals.

[The effects of different types of pulsed electromagnetic fields on fibroblast cell cultures]. / Efectele diferitelor tipuri de câmp electromagnetic pulsatil asupra unei culturi celulare fibroblastice.

UNLABELLED: The aim of this study is to determine which is the most effective pulsed electromagnetic field (PEMF) on a fibroblastic culture cells. MATERIAL AND METHODS: Five different types of PEMF are generated by a pulsed generator created by the author. The electric signal, received by a reference coil is pulse bursts type. The growth rate of a fibroblastic culture cells is measured with and without different types of PEMF. RESULTS: Comparative results showed the the most effective type of PEMF is characterized by a 15 mV positive amplitude of the signal and a 15 Hz frequency of the bursts. The intermittent stimulation (8 hours/day) was more effective than continuous stimulation.

A cell strain system for small homogeneous strain applications.

A cell culture system has been developed that enables application of well characterized, homogeneously distributed cyclic strains to monolayer cell cultures. Optically clear silicone culture dishes atop Plexiglas base plates are deformed by four-point bending of flexible silicone culture wells driven in user specified strain cycle patterns using computer controlled electromagnetic linear actuators. Cyclic mechano-transduction can be induced in amplitudes of 0 to 3000 mustrain, in frequencies of 0 to 30 Hz and in any specified strain cycle pattern. The cell culture system, which contains six simultaneously driven culture wells, has been mechanically characterized by holographic interferometry, laser displacement sensor recordings of the dish surfaces, strain gauge monitoring of the base plates, and finite element modeling of the dishes on the base plates. The standard deviation of the strain amplitudes among the six simultaneously stimulated culture wells is less than 5%. The cell culture system allows accurate generation of small magnitudes of well characterized, homogeneous strain, easy handling of the culture wells, flexible setting of cyclic strain pattern parameters, simultaneous stimulation of 6 culture wells, and light microscopic observation of the cell cultures.

Coronary heart diseases: assessment of risk associated with work exposure to ultralow-frequency magnetic fields.

The present analysis was stimulated by previous findings on the possible influence of natural ultralow-frequency (ULF; 0.001-10 Hz) geomagnetic field variations on the cardiovascular system and indications of an effect of man-made ULF magnetic fields on the rate of myocardial infarction. In the present study, we considered the occupational health hazards of the strongest ULF magnetic fields in densely populated urban areas. Measurements of ULF magnetic field fluctuations produced by trains powered by DC electricity were performed by means of a computer-based, highly sensitive, three-component magnetometer. We found that the magnitude of magnetic field pulses inside the driver's cab of electric locomotives (ELs) could be > or = 280 microT in the horizontal component perpendicular to the rails and up to approximately 130 microT in the vertical component, and, in the driver's compartment of electric motor unit (EMU) trains, they were approximately 50 and 35 microT, respectively. We have investigated the relationships between the occupational exposure to ULF magnetic field fluctuations produced by electric trains and cardiovascular diseases (CVDs) among railroad workers in the former Soviet Union. We have analyzed medical statistical data for a period of 3 years for approximately 45,000 railroad workers and 4,000 engine drivers. We have also analyzed 3 years of morbidity data for three subgroups of engine drivers (approximately 4,000 in each group) operating different types of trains. We find that EL drivers have a twofold increase in risk (2.00 +/- 0.27) of coronary heart diseases (CHDs) compared with EMU drivers. Because our analysis of major CVDs shows that the examined subpopulations of drivers can be considered to have had equal exposure to all known risk factors, the elevated CHD risk among EL drivers could be attributed to the increased occupational exposure to ULF magnetic fields.

A novel electric design for electromagnetic stimulation--the Slinky coil.

A novel coil design for inductive electromagnetic stimulation of neural cells has been simulated and experimentally tested. This coil improves the focal effect of a magnetic stimulator, and it reduces its inductance, hence the efficiency of the system is improved. The basic structure of the device is derived from the popular "Slinky" toy. The actual device is formed by winding different numbers of loops forming a helical coil on a half torus. The loops are bunched at the axis of the torus. The coil, due to its geometry, generates a unique distribution of eddy currents in nearby tissues which is favorable compared to a solenoid type stimulator. This renders the Slinky coil more selective than conventional coils used for magnetic stimulation. The distribution of eddy currents was analyzed using Matlab, following Faraday's Law of Induction. Improved focality permits the current through the coil to be reduced for the same effect. In addition, the reduced inductance of the Slinky coil decreases the power requirement; thus, the improved efficiency of the system may allow the generation of bursts of pulses, and expand the utilization of the system to possible functional activation of certain neuro-muscular structures when peripheral nerves are stimulated.

Cylindrical tissue model for magnetic field stimulation of neurons: effects of coil geometry.

An analytical solution for the electric field induced in a homogeneous cylindrical conductor under quasi-static conditions from current in a coil is used to model peripheral nerve stimulation with magnetic fields. A variety of coil geometries is analyzed in terms of the spatial derivative of the induced electric field along a long straight nerve, parallel to the axis, in a human-arm model. The results of these computations are found to be in general agreement with conclusions regarding the optimization of stimulating coils derived from analyses of the semi-infinite tissue model. The differences and their physical basis are pointed out.

Determination of vascular impedance in the peripheral circulation by transcutaneous pulsed Doppler ultrasound.

Instantaneous blood flow velocity characteristics and vascular impedance spectra derived noninvasively by pulsed Doppler ultrasound and invasively by electromagnetic flow probe were compared in the canine common femoral artery to validate the pulsed Doppler technique for determination of vascular impedance in the peripheral circulation. Although Doppler ultrasonography is routinely performed to evaluate blood flow velocity patterns in the human peripheral circulation; the validity of this technique to derive peripheral vascular impedance has yet to be investigated. Simultaneous measurements of blood flow velocity were determined by both noninvasive pulsed Doppler ultrasound and surgically implanted electromagnetic flow probe in the common femoral artery of eight dogs and compared in both time and frequency domains. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe and simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were obtained at baseline and after intra-arterial injection of acetylcholine in five additional dogs. During the first 10 to 20% of the cardiac cycle, Doppler ultrasound blood flow velocity was transiently greater than the simultaneously recorded electromagnetic blood flow velocity. During the remainder of the cardiac cycle, the two blood flow velocity waveforms were nearly superimposable. The frequency spectra of the blood flow velocity waveforms derived from Doppler ultrasound and electromagnetic flow probes were similar for harmonies less than 10 Hz. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe with simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were similar at baseline and after regional administration of acetylcholine. Mean vascular resistance (impedance at 0 Hz), characteristic impedance, and the first minima of the impedance modulus derived from Doppler ultrasound and electromagnetic flow probe blood flow velocity measurements were closely correlated at baseline and after dilation with acetylcholine (r > or = 0.89, p < 0.05 for all correlations). Doppler ultrasonography is a convenient and accurate technique for determination of vascular impedance in the peripheral circulation.

Trivial influences: a doubly stochastic Poisson process model permits the detection of arbitrarily small electromagnetic signals.

If a weak, exogenous, extremely low-frequency (ELF) electric or magnetic field is to produce biological sequelae, then there must exist averaging sufficient to lift some primary effect of that field above the endogenous stochastic variations of the biological system. One way in which a field could accomplish this is by changing the intensity of some stochastic operation that controls an important and not trivially reversible biological transformation. In this paper, this operation is modeled as a doubly stochastic Poisson process. It is then shown, first, that (in theory) even a minuscule exogenous influence might appreciably shift the incidence of a sufficiently rare transformation and, second, that this shift might be observable if a trial were allowed to run long enough over a sufficiently large population of exposed entities.

Comparison of cardiac output measurement by continuous thermodilution with electromagnetometry in adult cardiac surgical patients.

A pulmonary artery catheter (PAC) capable of continuous cardiac output (CCO) determination by thermodilution has recently been introduced. The purpose of this study was to compare CCO with two other methods of cardiac output (Ot) determination: electromagnetometry (EM) and standard bolus thermodilution cardiac output (BCO). Following median sternotomy and pericardiotomy, an EM ring probe was placed around the ascending aorta in 25 adult cardiac surgical patients and connected to an EM flowmeter interfaced with a calibrated strip recorder. Measurements were obtained over a 15- to 20-minute interval during a period of stable EM-determined Ot prior to initiation of cardiopulmonary bypass and in the absence of surgical stimulation. The CCO system averages Ot over a 3-minute interval, updating the measurement every 30 seconds. Cardiac output determined by the CCO system was compared with EM Ot averaged from the prior 3-minute period and with BCO obtained immediately after changing the Ot monitor from the continuous to bolus mode. Compared with EM, the bias for CCO was -0.48 L/min, precision 0.56 L/min, and the limits of agreement 1.12 L/min. Bias, precision, and limits of agreement of CCO compared with BCO were 0.41, 0.82, 1.64 L/min, respectively. Correlation between EM and CCO was r = 0.80 and between CCO and BCO r = 0.64. Cardiac output determined by CCO was within 10% of the EM determination for 37 measurements, between 10% and 20% for 17, and greater than 20% for 7 measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult leukemia risk and personal appliance use: a preliminary study.

The hypothesis that use of personal electric appliances may be associated with increased risk of acute nonlymphocytic leukemia in adults was tested using interview data from a previously completed case-control study of 114 cases and 133 controls conducted between 1981 and 1984. Cases were obtained from a population-based cancer registry in western Washington state, and controls were obtained from the same area by random digit dialing. Of 32 electrical home appliances for which data on use were available for adult acute nonlymphocytic leukemia cases and controls, three motor-driven personal appliances (electric razors, hair dryers, and massage units) were selected a priori because their use represents exposure to higher peak magnetic fields than that from most other home appliances. When compared on an "ever used" versus "never used" basis, use of one or more of these appliances was not associated with increased risk of leukemia in the population studied (odds ratio (OR) = 0.71, 95% confidence interval (CI) 0.41-1.24). When the appliances were considered individually, massage units were more likely to have been used by cases than by controls (OR = 3.00, 95% CI 1.43-6.32), while hair dryers were more likely to have been used by controls than cases (OR = 0.38, 95% CI 0.22-0.66). There was a nonsignificant tendency for electric razor use to differentiate the cases from controls (OR = 1.33, 95% CI 0.80-2.23). When reported daily time of use was stratified, there was no overall increased risk with increased time of use except for electric razors (p < 0.05). In addition to the analysis of appliance use data from the case-control study, the authors obtained several models of these motor-driven personal appliances and characterized the magnetic fields they produce. Magnetic field flux density, or the B-field, and spectral measurements showed that partial body exposure from such appliances may exceed 0.5 mTesla (root mean squared) at rates-of-change exceeding 10 Tesla/sec. These epidemiologic data must be interpreted cautiously because the number of cases is limited and because of proxy reporting of appliance use for deceased cases. Nevertheless, the authors believe these data indicate that peak magnetic field exposure from personal appliances warrants further investigation as a possible risk factor for acute nonlymphocytic leukemia in adults.

On the biomagnetic inverse problem in the case of multiple dipoles.

Series of Monte Carlo simulations have been carried out which were based on the assumption that two dipoles with a distance of 0.5-2 cm are located in a homogeneous semi-infinite volume conductor (depth 3 cm), and that the magnetic field component perpendicular to the surface of the volume conductor is recorded by means of a magnetometer with infinitesimal coil diameter. Moving-dipole models (all parameters time-dependent), rotating-dipole models (dipole locations fixed, dipole orientation and amplitudes time-dependent) as well as fixed-dipole models (dipole locations and orientations fixed, amplitudes time-dependent) were considered. The algorithm used to retrieve the model parameters from the simulated field distributions (biomagnetic inverse procedure) was based on a transformation of the standard least-squares fit procedure into a minimization procedure with respect to the nonlinear parameters (dipole locations and orientations), which was solved iteratively by means of the Fletcher-Powell algorithm. It was found that the resolving power of the biomagnetic inverse procedure is highly dependent on the relative orientation of the two dipoles, the temporal overlap of the dipole moments, and the correlation of successive samples of the superimposed noise. The results obtained in this study suggest that the resolving power of the biomagnetic inverse procedure for conditions typically found in the case of auditory evoked magnetic fields is not better than 2 cm for the moving-dipole approach, and not better than 1 cm for the fixed-dipole approach, provided that no additional a priori information is available. In practice, the situation is probably even worse since the depth of the generators is usually larger than assumed in this study.

Automatic model selection for the 'best localization' of cardiac sources.

In the present paper a simulation study on the influence of noise and source model on the accuracy of localization of the sources of biomagnetic fields is presented. Applying a statistical analysis (F test) to the localization results obtained by various models on the simulated maps calculated using different theoretical sources and different noise levels we were able to define a 'best localization' (BL) method. It allows an automatic determination of the particular source model able to represent in the best statistical way a specific field distribution obtaining the best source localization for that distribution. We applied this method to the localization of cardiac sources in the experimental maps of the magnetic field produced by isolated rabbit hearts completely immersed in a conductive medium. The results clearly indicate that the proposed method is very effective in determining the 'best localization' for every particular field distribution while the use of the same source model for every field map often produces a source localization completely in contrast with the position of cardiac structures of the isolated hearts.