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F S Prato

Publications and source records attributed to F S Prato.

At least 19 recordsLinked to original sources

Shielding, but not zeroing of the ambient magnetic field reduces stress-induced analgesia in mice.

Magnetic field exposure was consistently found to affect pain inhibition (i.e. analgesia). Recently, we showed that an extreme reduction of the ambient magnetic and electric environment, by mu-metal shielding, also affected stress-induced analgesia (SIA) in C57 mice. Using CD1 mice, we report here the same findings from replication studies performed independently in Pisa, Italy and London, ON, Canada. Also, neither selective vector nulling of the static component of the ambient magnetic field with Helmholtz coils, nor copper shielding of only the ambient electric field, affected SIA in mice. We further show that a pre-stress exposure to the mu-metal box is necessary for the anti-analgesic effects to occur. The differential effects of the two near-zero magnetic conditions may depend on the elimination (obtained only by mu-metal shielding) of the extremely weak time-varying component of the magnetic environment. This would provide the first direct and repeatable evidence for a behavioural and physiological effect of very weak time-varying magnetic fields, suggesting the existence of a very sensitive magnetic discrimination in the endogenous mechanisms that underlie SIA. This has important implications for other reported effects of exposures to very weak magnetic fields and for the theoretical work that considers the mechanisms underlying the biological detection of weak magnetic fields.

Analgesia↗

Human electrophysiological and cognitive effects of exposure to ELF magnetic and ELF modulated RF and microwave fields: a review of recent studies.

The investigation of weak (<500 microT), extremely low frequency (ELF, 0-300 Hz) magnetic field (MF) exposure upon human cognition and electrophysiology has yielded incomplete and contradictory evidence that MFs interact with human biology. This may be due to the small number of studies undertaken examining ELF MF effects upon the human electroencephalogram (EEG), and the associated analysis of evoked related potentials (ERPs). Relatively few studies have examined how MF exposure may affect cognitive and perceptual processing in human subjects. The introduction of this review considers some of the recent studies of ELF MF exposure upon the EEG, ERPs and cognitive and perceptual tasks. We also consider some of the confounding factors within current human MF studies and suggest some new strategies for further experimentation.

Cognition↗

A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls exposed to a pulsed (200 microT) magnetic field: effects on normal standing balance.

Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF's on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.

Adaptation, Physiological↗

Human standing balance is affected by exposure to pulsed ELF magnetic fields: light intensity-dependent effects.

There is evidence in animals that behavioral and physiological responses to static and extremely low frequency magnetic fields (ELFMF) is affected by the presence of light during magnetic field exposures. Here we report that the effect of a specific pulsed ELFMF (PEMF) on human standing balance is modulated by light intensity during exposure. Under a low light condition (0.12 W/m2), nine healthy human volunteers stood on a 3D forceplate, throughout four 2 min exposures (eyes open/eyes close, sham/PEMF of 200 +/- 1 microTpk, order randomized). There was a significant increase in standing movement during PEMF exposure during eyes closed. In a second experiment on 26 normal subjects exposed to the identical protocol, but at greater light intensities (0.51 W/m2), a significant but opposite effect was observed.

Adult↗

Human subjects exposed to a specific pulsed (200 microT) magnetic field: effects on normal standing balance.

Static and time-varying magnetic fields have been shown to alter animal and human behaviors, such as directional orientation, learning, pain perception (nociception or analgesia) and anxiety-related behaviors. Human volunteers (12 male, 12 female, 18-34 years old) stood on a force plate while within three square magnetic field coil pairs (2, 1.75 and 1.5 m) arranged orthogonal with the uniform magnetic field volume centered at head level. Analysis of the data shows a significant improvement of normal standing balance or center of pressure, with eyes open or eyes closed, by a specific pulsed 200 microT(pk) magnetic field (PEMF). There was no significance found in control condition testing, such as sham-sham exposure of subjects or sham/PEMF exposure of a 60 kg saline phantom. There were no significant effects of gender or age.

Adolescent↗

Modeling tissue contrast agent concentration: a solution to the tissue homogeneity model using a simulated arterial input function.

The tissue homogeneity model, which describes tissue in terms of two compartments, one intravascular (iv) and one extravascular (ev), is solved by Laplace transformation of two coupled differential equations. By assuming a functional form for the arterial input function (AIF), or by fitting to an experimentally determined AIF, this function is introduced into the solution as a boundary condition describing the time dependent input to the capillary. The solution to the tissue homogeneity model equations in Laplace space are numerically inverted to obtain the concentration of tracer in the ev space as a function of time and in the iv space as a function of both position and time. Magn Reson Med 45:42-45, 2001.

Computer Simulation↗

Magnetic field exposure and behavioral monitoring system.

To maximize the availability and usefulness of a small magnetic field exposure laboratory, we designed a magnetic field exposure system that has been used to test human subjects, caged or confined animals, and cell cultures. The magnetic field exposure system consists of three orthogonal pairs of coils 2 m square x 1 m separation, 1.751 m x 0.875 m separation, and 1.5 m x 0.75 m separation. Each coil consisted of ten turns of insulated 8 gauge stranded copper conductor. Each of the pairs were driven by a constant-current amplifier via digital to analog (D/A) converter. A 9 pole zero-gain active Bessel low-pass filter (1 kHz corner frequency) before the amplifier input attenuated the expected high frequencies generated by the D/A conversion. The magnetic field was monitored with a 3D fluxgate magnetometer (0-3 kHz, +/- 1 mT) through an analog to digital converter. Behavioral monitoring utilized two monochrome video cameras (viewing the coil center vertically and horizontally), both of which could be video recorded and real-time digitally Moving Picture Experts Group (MPEG) encoded to CD-ROM. Human postural sway (standing balance) was monitored with a 3D forceplate mounted on the floor, connected to an analog to digital converter. Lighting was provided by 12 offset overhead dimmable fluorescent track lights and monitored using a digitally connected spectroradiometer. The dc resistance, inductance of each coil pair connected in series were 1.5 m coil (0.27 Omega, 1.2 mH), 1.75 m coil (0.32 Omega, 1.4 mH), and 2 m coil (0.38 Omega, 1.6 mH). The frequency response of the 1.5 m coil set was 500 Hz at +/- 463 microT, 1 kHz at +/- 232 microT, 150 micros rise time from -200 microT(pk) to + 200 microT(pk) (square wave) and is limited by the maximum voltage ( +/- 146 V) of the amplifier (Bessel filter bypassed).

Animals↗

Examining a canine model of stunned myocardium with Gd-DTPA-enhanced MRI.

It has previously been shown that the distribution volume of Gd-DTPA (lambda) in infarcted, canine myocardium is higher than that of normal tissue. The purpose of this study was to determine whether stunned myocardium exhibits increased lambda. Stunning was produced in beagles by means of 30 min LAD occlusion followed by 3 weeks (n = 4) reperfusion. Gd-DTPA was infused at each imaging session and lambda determined in vivo using a saturation recovery turboFLASH sequence; cine imaging was used to assess ventricular wall thickening (%WT). (201)Tl uptake was used as an independent assessment of viability. %WT data confirmed that the brief insult caused prolonged, yet reversible, regional contractile dysfunction in each animal. %WT was not significantly different from baseline values by 3 weeks post-reflow. Normal (201)Tl uptake confirmed the absence of infarction. The lambda of stunned tissue (lambda = 0.381 +/- 0.030 ml/g) was not elevated above that of normal tissue (lambda = 0.398 +/- 0.027 ml/g, P = NS), at any time point studied, in vivo. These data suggest that an increase in lambda is a specific indicator of irreversible damage.

Animals↗

Gd-DTPA bolus tracking in the myocardium using T1 fast acquisition relaxation mapping (T1 FARM).

MRI methods currently used for bolus tracking in the myocardium, such as saturation recovery turbo-fast low-angle shot (FLASH) (srTFL), are limited by signal intensity (SI) saturation at high contrast agent (CA) concentrations. By using T1 fast acquisition relaxation mapping (T1 FARM), a Gd-DTPA bolus (0.075 vs. 0.025 mmol/kg) may be injected without causing saturation. This study tested the feasibility of in vivo T1 FARM bolus tracking under rest/stress conditions in seven beagles with multiple permanently occluded branches of the left anterior descending (LAD) coronary artery. Although it underestimated the myocardial perfusion reserve (MPR) measured ex vivo using radioactive microspheres (mean +/- SEM; 3.60 +/- 0.26), the MPR determined upon application of the modified Kety model (1.86 +/- 0.10) enabled distinction between normal and infarcted tissue. The partition coefficient (lambda) estimated at rest and stress using the modified Kety model underestimated ex vivo radioactive measurements in infarcted tissue (0.25 +/- 0.01 vs. 0.26 +/- 0.01 vs. 0.79 +/- 0.08 ml/g, P < 0.0001) yet was accurate in normal tissue (0.28 +/- 0.01 vs. 0.30 +/- 0.01 vs. 0.33 +/- 0.01 ml/g, P = NS). Thus, although unsuitable for myocardial viability assessment, T1 FARM bolus tracking shows potential for assessment of myocardial perfusion.

Animals↗

A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field.

The open field test (OFT) is a widely used procedure for examining the behavioral effects of drugs and anxiety. Detailed ethological assessments of animal behavior are lacking. Here we present a detailed ethological assessment of the effects of acute treatment with the benzodiazepines, diazepam (DZ, 1.5mg/kg) and chlordiazepoxide (CDP, 5.0 and 10.0mg/kg), as well as exposure to a non-pharmacological agent, a specific pulsed extremely low frequency magnetic field (MAG) on open field behavior. We examined the duration, frequency and time course of various behaviors (i.e. exploration, walk, rear, stretch attend, return, groom, sit, spin turn, jump and sleep) exhibited by male mice in different regions of a novel open field. Both DZ and CDP consistently reduced the typical anxiety-like behaviors of stretch attend and wall-following (thigmotaxis), along with that of an additional new measure: 'returns', without producing any overall effects on total locomotion. The drugs also differed in their effects. CDP elicited a shift in the locomotor pattern from a 'high explore' to a 'high walk', while DZ mainly elicited alterations in sit and groom. The MAG treatment was repeated twice with both exposures reducing horizontal and vertical (rearing) activity and increasing grooming and spin turns. However, the anxiety-like behaviors of stretch attend and return were marginally reduced by only the first exposure. We conclude that a detailed ethological analysis of the OFT allows not only the detection of specific effects of drugs and non-pharmacological agents (i.e. pulsed magnetic field) on anxiety-like behaviors, but also permits the examination of non-specific effects, in particular those on general activity.

Animals↗

Extremely low frequency magnetic fields can either increase or decrease analgaesia in the land snail depending on field and light conditions.

Results of prior investigations with opioid peptide mediated antinociception or analgaesia have suggested that these extremely low frequency (ELF) magnetic field effects are described by a resonance mechanism rather than mechanisms based on either induced currents or magnetite. Here we show that ELF magnetic fields (141-414 microT peak) can, in a manner consistent with the predictions of Lednev's parametric resonance model (PRM) for the calcium ion, either (i) reduce, (ii) have no effect on, or (iii) increase endogenous opioid mediated analgaesia in the land snail, Cepaea nemoralis. When the magnetic fields were set to parameters for the predictions of the PRM for the potassium ion, opioid-peptide mediated analgaesia increased and there was evidence of antagonism by the K(+) channel blocker, glibenclamide. Furthermore, these effects were dependent on the presence of light; the effects were absent in the absence of light. These observed increases and decreases in opioid analgaesia are largely consistent with the predictions of Lednev's PRM.

Analgesia↗

Contrast-enhanced MRI for the assessment of myocardial viability after permanent coronary artery occlusion.

Previous studies in a model of ischemia/reperfusion using a constant infusion of Gd-DTPA have shown that distribution volume (lambda) is increased in infarcted myocardial tissue. This study examined this technique in the setting of permanent coronary artery occlusion. Ten beagles underwent permanent occlusion of a coronary artery for 2 days (N = 3), 1 week (N = 4), or 3 weeks (N = 3). Imaging was performed at 2 days and, depending on the length of occlusion, 1 week, 2 weeks, and 3 weeks to follow changes in lambda in vivo. At sacrifice, (201)Tl was injected and the extent of the hyperenhanced region was compared to pathology. lambda was increased in infarcted tissue by 2 days post occlusion and this increase persisted for 3 weeks. At sacrifice, lambda correlated strongly with (201)Tl uptake (r = -0.86 to -0.95, P < 0.05; i.e., lambda increased in infarcted tissue) and the size of the hyperenhanced region was comparable to pathological infarct size (slope 1.006, r = 0.96, P < 0.0001). Thus, beyond 2 days after coronary occlusion, MRI, during a constant infusion of Gd-DTPA, can assess myocardial viability regardless of the success of reperfusion. Magn Reson Med 44:309-316, 2000.

Analysis of Variance↗

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA.

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution 201Thallium (201Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between 201Tl uptake and MRI signal intensity, i.e. infarcted tissue (low 201Tl uptake) had increased MR signal intensity. Segments were separated into normal (201Tl uptake > 90%) and infarcted (< 601%). lnfarcted MRI segments had greater signal intensity than normal segments (179 +/- 50 vs. 102 +/- 14%; P < 0.0001). WTI in normal segments increased by 18 +/- 8.5% (P < 0.0001) from baseline to 10 microg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8 +/- 7.2% (P = 0.17). Thus regions of myocardium that were infarcted as defined by reduced 201Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.

Adult↗

T(1) fast acquisition relaxation mapping (T(1)-FARM): optimized data acquisition.

A theoretical procedure for estimating the precision of the T(1) Fast Acquisition Relaxation Mapping sequence as a function of a number of acquisition parameters has been validated by both simulations and experimental results. These results have clarified the selection of sequence parameters to give optimal accuracy and precision in the R(1)* measurements. There is excellent agreement between theory, simulation, and experiment except for flip angles greater than 9 degrees, at which point slice profile imperfections significantly degrade the precision of the technique. The experimental results indicate that over a range of T(1)s that would be seen in a bolus tracking experiment (25-1200 ms), T(1) Fast Acquisition Relaxation Mapping can be used to obtain 64 x 128 R(1)* maps at a rate of 1 map/s, with a precision of 10% or better.

Calibration↗

Scatter and attenuation correction for brain SPECT using attenuation distributions inferred from a head atlas.

UNLABELLED: Sequential transmission scanning (TS)/SPECT is impractical for neurologically impaired patients who are unable to keep their heads motionless for the extended duration of the combined scans. To provide an alternative to TS, we have developed a method of inferring-attenuation distributions (IADs), from SPECT data, using a head atlas and a registration program. The validity of replacing TS with IAD was tested in 10 patients with mild dementia. METHODS: TS was conducted with each patient using a collimated 99mTc line source and fanbeam collimator; this was followed by hexamethyl propyleneamine oxime-SPECT. IAD was derived by deformably registering the brain component of a digital head atlas to a preliminary SPECT reconstruction and then applying the resulting spatial transformation to the full head atlas. SPECT data were reconstructed with scatter and attenuation correction. Relative regional cerebral blood flow was quantified in 12 threshold-guided anatomic regions of interest, with cerebellar normalization. SPECT reconstructions using IAD were compared with those using TS (which is the "gold standard") in terms of these regions of interest. RESULTS: When we compared all regions of interest across the population, the correlation between IAD-guided and TS-guided SPECT scans was 0.92 (P < 0.0001), whereas the mean absolute difference between the scans was 7.5%. On average, IAD resulted in slight underestimation of relative regional cerebral blood flow; however, this underestimation was statistically significant for only the left frontal and left central sulcus regions (P = 0.001 and 0.002, respectively). Error analysis indicated that approximately 10.0% of the total error was caused by IAD scatter correction, 36.6% was caused by IAD attenuation correction, 27.0% was caused by discrepancies in region-of-interest demarcation from quantitative errors in IAD-guided reconstructions, and 26.5% was caused by patient motion throughout the imaging procedure. CONCLUSION: SPECT reconstructions guided by IAD are sufficiently accurate to identify regional cerebral blood flow deficits of 10%, which are typical in moderate and advanced dementia.

Brain↗

Light-dependent effects of magnetic fields on nitric oxide activation in the land snail.

The attenuation of opioid analgaesia is a well established effect of extremely low frequency (ELF) magnetic fields with light having a modulatory role in these effects such that when the ELF exposures are carried out in the dark, the inhibitory effects on analgesia are reduced. Here, we considered the light dependency of the effects of exposure to an ELF magnetic field prior to the induction of opioid analgesia. Brief exposure to a 60 Hz field potentiated in a light dependent manner the inhibitory effects of the nitric oxide (NO) precursor L-arginine on the level of subsequent opioid-induced analgesia in the land snail Cepaea nemoralis. This suggests a general light dependency of the actions of magnetic fields and the involvement of NO in the mediation of the effects of magnetic fields.

Analgesics↗

Fast acquisition of quantitative T2 maps.

A rapid new technique called T2 fast acquisition relaxation mapping (T2 FARM) was developed to allow T2 maps to be reconstructed directly from k-space data acquired in 3 sec. A single acquisition measured two sets of k-space data, the first with T1 and T2 weighting independent of phase encode position, and the second with T2 weighting varying with phase encode position. These data were processed using an iterative least squares algorithm to produce a quantitative T2 map from the k-space data. T2 values of phantoms and an egg were determined from T2 FARM maps and spectroscopic Carr-Purcell-Meiboom-Gill (CPMG) measurements, demonstrating the validity of the new technique.

Algorithms↗

Improved contrast agent bolus tracking using T1 FARM.

Current MRI bolus tracking techniques, such as saturation recovery Turbo-FLASH (srTFL), suffer from signal saturation at high contrast concentrations. In this study T1 Fast Acquisition Relaxation Mapping (T1 FARM) was compared to srTFL. In phantoms, T1 FARM maps were linear with [Gd-DTPA] up to 7.0 mmol/L while srTFL images saturated above 2.0 mmol/L. In the canine left ventricle, blood concentration curves determined from T1 FARM saturated with bolus injections exceeding 0.075 mmol/kg, while srTFL curves saturated above 0.025 mmol/kg of Gd-DTPA. Also, T1 FARM improved contrast-to-noise ratio in tissue concentration curves since higher contrast concentrations could be measured without saturating.

Animals↗