Effects of polarization and apodization on laser induced optical breakdown threshold.

We investigated the influence of polarization and apodization on laser induced optical breakdown threshold in transparent and diffuse media using linearly and radially polarized light. We demonstrate a lower irradiance threshold for optical breakdown using radially polarized light. The dominance of radial polarization in higher-order multiphoton ionization has important medical applications where a lower irradiance threshold may allow reaching deeper layers inside the skin with less risk of collateral damage and thereby improving safety and efficacy of treatment.

Experimental thresholds of magnetically induced currents via a figure-of-eight coil up to 25 kHz.

Magnetic particle imaging, uses magnetic fields of frequencies in the kilo-hertz range. Little research has been carried out upon effects on excitable tissue caused by time-varying magnetic fields in that frequency range. To learn about magnetic stimulation thresholds, a system that is capable of generating a very focused magnetic field strong enough to induce a muscular reaction was built. Stimulation thresholds at 7.38, 12.04, 16.5, and 25.27 kHz have been recorded in 31 trial participants. It has been proved that magnetic stimulation is possible up to even 25 kHz, and respective thresholds have been determined. This article presents the trial setup, procedure, and evaluation of field quantities.

Numerical prediction of frequency dependent 3D maps of mechanical index thresholds in ultrasonic brain therapy.

PURPOSE: Therapeutic ultrasound has been used in the brain for thrombolysis and high intensity focused ultrasound (HIFU) therapy. A low-frequency clinical study of sonothrombolysis, called the transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia (TRUMBI), has revealed an increased incidence of hemorrhage, which may have been caused by cavitation. The goal of this study is to determine if there is a comparable risk of generating cavitation during HIFU brain therapy at different frequencies. METHODS: Two approaches are used to transmit acoustic energy through the skull to the brain: low-frequency ultrasound, with a wavelength that is larger than the skull thickness, and high frequency ultrasound, that is sensitive to aberrations and must use corrective techniques. At high frequency, the mechanical index (MI) is lower, which translates to a higher cavitation threshold. In addition to the nonfocused geometry of the 300 kHz sonothrombolysis treatment device, two types of focused therapeutic transducers were modeled: a low frequency 220 kHz transducer and a 1 MHz transducer that required aberration correction with a time-reversal approach, representing the lowest and highest frequencies currently used. The acoustic field was modeled with a finite difference fullwave acoustic code developed for large scale computations, that is, capable of simulating the entire brain volume. Various MI thresholds and device geometries were considered to determine the regions of the brain that have an increased probability of cavitation events. RESULTS: For an equivalent energy deposition rate, it is shown that at a low frequency there is a significant volume of the brain that is above the MI thresholds. At a high frequency, the volume is over 3 orders of magnitude smaller, and it is entirely confined to a compact focal spot. CONCLUSIONS: The significant frequency dependence of the volumes with an increased probability of cavitation can be attributed to two factors: First, the volume encompassed by the focal region depends on the cube of the frequency. Second, the heat deposition increases with frequency. In conclusion, according to these simulations, the acoustic environment during HIFU brain therapy at 1 MHz is not conducive to a high probability of cavitation in extended regions of the brain.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Acute dosimetry and estimation of threshold-inducing behavioral signs of thermal stress in rabbits at 2.45-GHz microwave exposure.

In the current international guidelines and standards for human exposure to microwaves (MWs), the basic restriction is determined by the whole-body average specific absorption rate (SAR). The basis for the guidelines is the adverse effect such as work stoppage in animals for whole-body average SARs above a certain level. Although it is known that absorbed MW energy causes the behavioral sign of thermal stress, the relationship of whole-body average SAR with temperature/temperature elevation has not been sufficiently investigated. In the present study, we performed experiments on rabbits exposed to 2.45-GHz MWs. A total of 24 measurements were conducted for power densities from approximately 100 to 1000 W/m(2). Our computational code for electromagnetic-thermal dosimetry was used to set the exposure time duration and incident power density. Our experimental results suggest that a core temperature elevation of 1 degrees C is an estimate of the threshold-inducing complex behavioral signs of MW-induced thermal stress in rabbits for different whole-body average SARs and exposure time durations. The whole-body average SAR required for MW-induced behavioral sign in rabbits was estimated as approximately 1.3 W/kg for 2.45-GHz MWs.

Short term effects of magnetic resonance imaging on excitability of the motor cortex at 1.5T and 7T.

RATIONALE AND OBJECTIVES: The increasing spread of high-field and ultra-high-field magnetic resonance imaging (MRI) scanners has encouraged new discussion of the safety aspects of MRI. Few studies have been published on possible cognitive effects of MRI examinations. The aim of this study was to examine whether changes are measurable after MRI examinations at 1.5 and 7 T by means of transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: TMS was performed in 12 healthy, right-handed male volunteers. First the individual motor threshold was specified, and then the cortical silent period (SP) was measured. Subsequently, the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using standard sequences. The MRI examination was immediately followed by another TMS session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete setting was repeated using a 7-T scanner. Control conditions included lying in the 1.5-T scanner for 63 minutes without scanning and lying in a separate room for 63 minutes. TMS was performed in the same way in each case. For statistical analysis, Wilcoxon's rank test was performed. RESULTS: Immediately after MRI exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and 7 T. The motor threshold was significantly increased. Fifteen minutes after the examination, the measured value tended toward normal again. Control conditions revealed no significant differences. CONCLUSION: MRI examinations lead to a transient and highly significant alteration in cortical excitability. This effect does not seem to depend on the strength of the static magnetic field.

Infrared skin damage thresholds from 1940-nm continuous-wave laser exposures.

A series of experiments are conducted in vivo using Yucatan mini-pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1940-nm continuous-wave thulium fiber laser irradiation. Experiments employ exposure durations from 10 ms to 10 s and beam diameters of approximately 4.8 to 18 mm. Thermal imagery data provide a time-dependent surface temperature response from the laser. A damage endpoint of minimally visible effect is employed to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Results are compared with current exposure limits for laser safety. It is concluded that exposure limits should be based on data representative of large-beam exposures, where effects of radial diffusion are minimized for longer-duration damage thresholds.

Thresholds for transverse stimulation: fiber bundles in a uniform field.

Cable theory is used to model fibers (neural or muscular) subjected to an extracellular stimulus or activating function along the fiber (longitudinal stimulation). There are cases however, in which activation from fields across a fiber (transverse stimulation) is dominant and the activating function is insufficient to predict the relative stimulus thresholds for cells in a bundle. This work proposes a general method of quantifying transverse extracellular stimulation using ideal cases of long fibers oriented perpendicular to a uniform field (circular cells in a 2-D extracellular domain). Several methods are compared against a fully coupled model to compute electrical potentials around each cell of a bundle and predict the magnitude of applied plate potential (Phi(p)) needed to activate a given cell (Phi(pact)). The results show that with transverse stimulation, the effect of cell presence on the external field must be considered to accurately compute Phi(pact). They also show that approximating cells as holes can accurately predict firing order and Phi(pact) of cells in bundles. Potential profiles from this hole model can also be applied to single cell models to account for time-dependent transmembrane voltage responses and more accurately predict Phi(pact). The approaches used herein apply to other examples of transverse cell stimulation where cable theory is inapplicable and coupled model simulation is too costly to compute.

Stimulation threshold comparison of time-varying magnetic pulses with different waveforms.

PURPOSE: To clarify whether sinusoidal pulses possess lower thresholds than rectangular ones at perception threshold, a statement often made that contradicts the theory of stimulation. MATERIALS AND METHODS: The results of a nerve stimulation study with 65 volunteers and with trapezoidal and sinusoidal gradient pulses were used to apply the combination of the electric field, induced in the tissue of the human body, with the "Fundamental Law of Electrostimulation." This law claims that the waveshape of a pulse is not essential as long as the amplitude of the pulse does not decrease below rheobase (rheobase condition). RESULTS: If the rheobase condition is applied to sinusoidal waveforms and the pulse duration and amplitude is corrected accordingly, both trapezoidal and sinusoidal gradient pulses have identical threshold amplitudes as a function of pulse duration. CONCLUSION: The "Fundamental Law of Electrostimulation," including the "rheobase condition," proved to be a good basis for describing magnetic field stimulation (magnetostimulation) and that application of it to magnetostimulation is suitable as the basis for describing magnetic field stimulation with various waveforms. For nonrectangular pulses, pulse durations and pulse amplitudes must be corrected according to the "rheobase condition." The exponential Blair Equation is less suited to be applied in magnetostimulation.

Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex.

OBJECTIVE: Although transcranial magnetic stimulation (TMS) has been widely used to study motor cortex organization and excitability, the reliability of this technique has not been thoroughly investigated. Furthermore, previous reports of TMS reliability have been restricted to upper limb musculature. We sought to determine the test-retest reliability for TMS mapping of motor representations for swallowing musculature. METHODS: Twenty healthy volunteers were tested twice over two weeks using TMS to determine motor threshold, map area, map volume, maximal MEP site location and maximal MEP site size for the suprahyoid complex and pharyngeal musculature. RESULTS: Good test-retest reliability was found in both swallowing muscle sites for the following test parameters: motor map area, maximal MEP site location: lateral coordinate, maximal MEP site size and motor threshold (ICC=0.76-0.98). Moderate reliability was observed for motor map volume and maximal MEP site location: anterior-posterior coordinate (ICC=0.68-0.74). CONCLUSIONS: TMS assessments of motor representation size, location and excitability appear to be highly reproducible, although the reliability of these measures may vary according to the specific muscle under investigation. SIGNIFICANCE: These works provide much needed psychometric data to validate the use of TMS to assess the cortical representation of swallowing musculature.

Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF).

OBJECTIVE: Short-interval intracortical inhibition (SICI) is a widely used paired-pulse transcranial magnetic stimulation (TMS) measure to assess inhibition in human motor cortex. However, facilitatory processes may contaminate SICI under certain conditions. Here, we specifically address the contribution of short-interval intracortical facilitation (SICF). METHODS: A SICF interstimulus interval (ISI) curve was obtained in nine healthy subjects according to an established paired-pulse TMS protocol [Ziemann U, Tergau F, Wassermann EM, Wischer S, Hildebrandt J, Paulus W. Demonstration of facilitatory I-wave interaction in the human motor cortex by paired transcranial magnetic stimulation. J Physiol (Lond) 1998a;511:181-190]. The individual ISI leading to SICF peak1, trough1, peak2, trough2 and peak3 was selected for the subsequent measurement of SICI intensity curves (SICI(peak1), SICI(trough1), SICI(peak2), SICI(trough2), SICI(peak3)) using intensity variation of the first stimulus (S1) from 50% to 120% of active motor threshold (AMT) in the first dorsal interosseous muscle. RESULTS: SICI(peak1) (mean ISI, 1.54ms) and SICI(trough1) (mean ISI, 1.97ms) showed a sigmoid SICI increase with S1 intensity. SICI(trough1) reached the strongest SICI and was therefore chosen for comparison with the other SICI curves. SICI(peak2) (mean ISI, 2.61ms) was U-shaped with a similar increase at low S1 intensities, but a decrease when S1 intensity exceeded 90% AMT. Correlation analyses suggested that this decrease was caused by SICF. SICI(trough2) (mean ISI, 3.50ms) and SICI(peak3) (mean ISI, 4.26ms) showed considerably less inhibition than SICI(trough1) over the whole range of S1 intensities. CONCLUSIONS: Findings show that commonly accepted protocols of testing SICI (ISI of 2-3ms, S1 intensity approximately 95% AMT) bear the risk of measuring net inhibition contaminated by SICF. SIGNIFICANCE: SICF may contribute to apparently reduced SICI in patients with neurological or psychiatric disorders.

Wavelength dependence of femtosecond laser ablation threshold of corneal stroma.

We measure the surface ablation threshold fluence of porcine corneal stroma for 100 fs laser pulses, with wavelengths between 800 nm and 1450 nm, generated by a Ti:sapphire-pumped optical parametric amplifier. The ablation threshold was found to vary only slightly within this wavelength range, between 1.5 and 2.2 J/cm(2). The data suggest a rapid increase of the ablation threshold for wavelengths up to about 1000 nm, followed by a plateau for longer wavelengths. This behavior is partly confirmed by a simple theoretical model of the ablation process. The influence of the wavelength on the physics of surface ablation is discussed on the basis of the model.

Efficient reduction of stimulus artefact in TMS-EEG by epithelial short-circuiting by mini-punctures.

OBJECTIVE: We aimed at comparing the effects of two different electrode-to-skin contact preparation techniques on the stimulus artefact induced by transcranial magnetic stimulation (TMS) in electroencephalography (EEG) signals. METHODS: Six healthy subjects participated in a combined navigated brain stimulation (NBS) and EEG study. Electrode contacts were first prepared in the standard way of rubbing the skin using a wooden stick with a cotton tip. The location of hand motor area and the motor threshold (MT) was determined for each subject. Then, the TMS-induced artefact was measured at 60%, 80%, 100% and 120% of the MT. Subsequently, the epithelium under the electrode contacts was electrically short-circuited by puncturing with custom-made needles and the stimulation sequences were replicated. The artefact was compared between the preparation techniques. RESULTS: The TMS-induced artefact was significantly reduced after puncturing. In addition, the size and duration of the artefact depended on the applied stimulation intensity. The reduction of the artefact was largest in electrodes at and close to the stimulation site. CONCLUSIONS: Mini-puncturing technique enables more accurate analysis of TMS-induced short-latency phenomena in EEG during NBS, and it may aid in the examination of the short distance neural connectivity beneath and close to the stimulation site. SIGNIFICANCE: This study describes a practical skin preparation method that significantly improves the utility of TMS-EEG method in studying short-latency cortical connectivity.

Effect of electrode surface area on thresholds for AC stimulation and ventricular fibrillation.

Unintended, weak AC stimulation (leakage currents) from medical devices can cause blood pressure collapse and ventricular fibrillation (VF), potentially even death. Yet, little is understood about AC cardiac stimulation. The objective of this paper is to establish the relationship between the stimulation and VF thresholds for electrode size and stimulation frequency. Twenty-four retired male breeder guinea pigs were anesthetized with isoflurane, a tracheotomy and thoracotomy were performed, and vitals were monitored using the lead II ECG and an optical plethysmograph. The circular flat ends of eleven stainless steel rods were used as electrodes with areas ranging from 0.1 to 26.79 mm2. In the first study, 60-Hz AC stimuli of 5 s duration were delivered with strengths from 25-3000 microA or until VF was induced. In the second group, the current thresholds at 20, 40, 80, and 160 Hz were determined at electrode areas of 0.2, 2.01, and 16.4 mm2. Reactions were categorized as having no effect, having some effect (EFFECT, typically blood pressure collapse), and inducing VF. On a log-log scale, electrode radii had a piecewise-linear relationship with the current thresholds for EFFECT (p < 0.005) and VF (p < 0.01). The liminal area determined by the piecewise-linear fit was 2.0 and 2.84 mm2 for EFFECT and VF, respectively. Above the liminal area, the threshold increased proportional to r(1.25) and r(0.95) (r = radius of electrode), for EFFECT and VF, respectively. Based on these experimental results, we present a theoretical framework to explain the electrode size-stimulation threshold variation for both low strength AC stimulation and VF initiation.

Damage thresholds for cultured retinal pigment epithelial cells exposed to lasers at 532 nm and 458 nm.

The determination of safe exposure levels for lasers has come from damage assessment experiments in live animals, which typically involve correlating visually identifiable damage with laser dosimetry. Studying basic mechanisms of laser damage in animal retinal systems often requires tissue sampling (animal sacrifice), making justification and animal availability problematic. We determined laser damage thresholds in cultured monolayers of a human retinal pigment epithelial (RPE) cell line. By varying exposure duration and laser wavelength, we identified conditions leading to damage by presumed photochemical or thermal mechanisms. A comparison with literature values for ocular damage thresholds validates the in vitro model. The in vitro system described will facilitate molecular and cellular approaches for understanding laser-tissue interaction.

Influence of a 902.4 MHz GSM signal on the human visual system: investigation of the discrimination threshold.

The proximity of a mobile phone to the human eye raises the question as to whether radiofrequency (RF) electromagnetic fields (EMF) affect the visual system. A basic characteristic of the human eye is its light sensitivity, making the visual discrimination threshold (VDThr) a suitable parameter for the investigation of potential effects of RF exposure on the eye. The VDThr was measured for 33 subjects under standardized conditions. Each subject took part in two experiments (RF-exposure and sham-exposure experiment) on different days. In each experiment, the VDThr was measured continuously in time intervals of about 10 s for two periods of 30 min, having a break of 5 min in between. The sequence of the two experiments was randomized, and the study was single blinded. During the RF exposure, a GSM signal of 902.4 MHz (pulsed with 217 Hz) was applied to the subjects. The power flux density of the electromagnetic field at the subject location (in the absence of the subject) was 1 W/m(2), and numerical dosimetry calculations determined corresponding maximum local averaged specific absorption rate (SAR) values in the retina of SAR(1 g) = 0.007 W/kg and SAR(10 g) = 0.003 W/kg. No statistically significant differences in the VDThr were found in comparing the data obtained for RF exposure with those for sham exposure.

Threshold level of p53 required for the induction of apoptosis in X-irradiated MOLT-4 cells.

PURPOSE: To determine the threshold level for the initiation of apoptosis by studying the quantitative aspect of p53 response to DNA damage in individual cells, to better understand the process in X-ray-induced p53-dependent apoptosis. METHODS AND MATERIALS: Time-sequential changes in p53 protein level were obtained for X-irradiated MOLT-4 cells using flow cytometry and analyzed. RESULTS: The changes in the cellular frequency distribution pattern of p53 content could be divided into two parts at a certain p53 level. The p53 vs. side-scatter in flow cytometry showed the sequential changes of p53 increase followed by an increase in cell death. On the basis of these results we determined a threshold level of p53 for the initiation of apoptosis. The level was estimated to be (1.08 +/- 0.05) x 10(5) molecules per cell, which was approximately threefold higher than the mean content of control cells. The minimum times for p53 level to reach this threshold level were independent of X-ray dose and 1.4-1.6 h. The times for the signal transduction from the p53 accumulation to disruption of the mitochondrial membrane potential, caspase-3 activation, and cell death were 1.6, 2.1, and 2.8 h, respectively. CONCLUSIONS: The threshold level of p53 for the initiation of apoptosis and the time sequence in the course of apoptotic events were determined in X-irradiated MOLT-4 cells.

Changes in measures of motor axon excitability with age.

OBJECTIVE: Threshold tracking is a novel technique that permits examination of the excitability of human axons in vivo. Protocols have been validated for sensory and motor axons, but there are limited data on the changes in the excitability of motor axons with age. This study aimed to determine such changes from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79, 10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold-tracking program to assess motor axon function. The median nerve was stimulated at the wrist and the compound muscle action potential was recorded from the thenar muscles. RESULTS: There was an increase in threshold in elderly subjects, associated with a decrease in slope of the stimulus-response curves. Strength-duration time constant and threshold electrotonus to depolarising and hyperpolarising currents of up to 40% did not change significantly with aging. The current-threshold relationship was similar across all decades for subthreshold depolarising currents, but the slope of the current-threshold relationship was significantly steeper the older the subjects for hyperpolarising currents, particularly those greater than 40% of threshold. There was also a significant decrease in supernormality in the recovery cycle with increasing age. CONCLUSIONS: The threshold of axons increases with age and the extent of supernormality decreases. There may also be greater inward rectification in motor axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated conductance, though this is only significant with hyperpolarising currents greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal excitability, such as strength-duration time constant, the relative refractory period, late subnormality, threshold electrotonus and the depolarising side of the current-threshold relationship, do not change significantly with age. For other indices, age-related changes may be due to a combination of non-neural factors that alter current access to the node of Ranvier, changes in the axon and its myelination and, possibly, changes in channel activity and/or changes in extracellular [K(+)](o).

Changes in cortical excitability differentiate generalized and focal epilepsy.

OBJECTIVE: Different pathophysiological mechanisms related to the balance of cortical excitatory and inhibitory influences may underlie focal and generalized epilepsies. We used transcranial magnetic stimulation to search for interictal excitability differences between patients with idiopathic generalized epilepsy (IGE) and focal epilepsy. METHODS: Sixty-two drug-naive patients with newly diagnosed epilepsy (35 IGE, 27 focal epilepsy) were studied. In the latter group, the seizure focus was not located in the motor cortex. Motor threshold at rest, cortical silent period threshold, recovery curve analysis using paired-pulse stimulation at a number of interstimulus intervals), and cortical silent period were determined. Results were compared with those of 29 control subjects. RESULTS: Hyperexcitability was noted in the recovery curves at a number of interstimulus intervals in both hemispheres in patients with IGE and in the hemisphere ipsilateral to the seizure focus in those with focal epilepsy compared with control subjects and the contralateral hemisphere in focal epilepsy. Motor threshold and cortical silent period threshold were higher in the ipsilateral hemisphere in focal epilepsy compared with the contralateral hemisphere. No other intragroup or intergroup differences were found in the other measures. INTERPRETATION: The disturbance of cortical excitatory/inhibitory function was found to be bilateral in IGE, whereas in focal epilepsy it spread beyond the epileptic focus but remained lateralized. This finding confirms that there are differences in cortical pathophysiology comparing the two major types of epilepsy.

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. METHODS: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. RESULTS: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. CONCLUSION: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. SIGNIFICANCE: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.