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Biomedical subjects

F S Prato

Publications and source records attributed to F S Prato.

At least 55 records · Page 3Linked to original sources

Spatial learning in deer mice: sex differences and the effects of endogenous opioids and 60 Hz magnetic fields.

We examined the effects of brief exposure to weak 60 Hz extremely low frequency (ELF) magnetic fields and opioid systems on spatial behavior and learning in reproductive adult male and female deer mice, Peromyscus maniculatus. Sex differences were evident in spatial performance, with male deer mice displaying significantly better performance than female mice in the Morris water maze, whereby animals had to acquire and retain the location of a submerged hidden platform. Brief (maximum 5 min) exposure to weak (100 microT) 60 Hz magnetic fields during task acquisition significantly improved female performance, eliminating the sex differences in acquisition. The opiate antagonist, naltrexone, also improved female acquisition, though significantly less than the magnetic fields. These facilitatory effects involved alterations of "non-spatial" (task familiarization and reduction of related anxiety/aversive related behaviors) and possibly "spatial" aspects of the task. Enhancement of enkephalin activity with the enkephalinase inhibitor, SCH 34826, significantly reduced task performance by male deer mice. Both naltrexone and the 60 Hz magnetic fields attenuated the enkephalin mediated reductions of spatial performance. These findings indicate that brief exposure to 60 Hz magnetic fields can enhance water maze task acquisition by deer mice and suggest that these facilitatory effects on spatial performance involve alterations in opioid activity.

Analgesics↗

Possible mechanisms by which extremely low frequency magnetic fields affect opioid function.

Although extremely low frequency (ELF, < 300 Hz) magnetic fields exert a variety of biological effects, the magnetic field sensing/transduction mechanism (or mechanisms) remain to be identified. Using the well-defined inhibitory effects that magnetic fields have on opioid peptide mediated antinociception or "analgesia" in the land snail Cepaea nemoralis, we show that these actions only occur for certain frequency and amplitude combinations of time-varying sinusoidal magnetic fields in a manner consistent with a direct influence of these fields. We exposed snails with augmented opioid activity to ELF magnetic fields, which were varied in both amplitude and frequency, along with a parallel static magnetic field. When the peak amplitude (0-547 microT) of a magnetic field of 60 Hz was varied systematically, we observed a nonlinear response, i.e., a nonlinear reduction in analgesia as measured by the latency of a defined response by the snails to a thermal stimulus. When frequency (10-240 Hz) was varied, keeping the amplitude constant (141 microT), we saw significant inhibitory effects between 30 and 35 Hz, 60 and 90 Hz and at 120 and 240 Hz. Finally, when the static field was varied but the amplitude and frequency of the time-varying field were held constant, we observed significant inhibition at almost all amplitudes. This amplitude/frequency "resonance-like" dependence of the magnetic field effects suggests that the mechanism (or mechanisms) of response to weak ELF fields likely involves a direct magnetic field detection mechanism rather than an induced current phenomenon. We examined the implications of our findings for several models proposed for the direct sensing of ELF magnetic fields.

Analgesia↗

The geometric modulation transfer function of a transmission imaging system that uses a SPECT scintillation camera and parallel hole collimation.

An analytic expression has been derived to calculate the geometric modulation transfer function of a transmission imaging system that uses parallel hole collimation for both the source and the SPECT camera. This expression describes the resolution of the transmission imaging system and replaces the need to use computer intensive Monte Carlo simulations for the system design. The geometric modulation transfer function, denoted as MTFg(rho) = [A2sc(Ssc rho)**A2cc(Scc rho)]D(rho), where ** denotes two-dimensional convolution; Asc(rho) and Acc(rho) are the Fourier transforms (FT) of the aperture functions for the parallel hole source collimator (SC) and the camera collimator (CC) holes, respectively; D(rho) is the FT of the camera response; and ssc and scc are scaling constants that depend on the respective collimator dimensions, the system dimensions, the object distance above camera collimator and whether MTFg(rho) is calculated for the object or image plane. The theoretical MTFg(rho) was verified with Monte Carlo simulations and experimental results. The formalism shows that the system resolution is characterized by the camera resolution and a combination of the resolutions of the source and camera collimators. This expression can be used to optimize the design of transmission imaging systems to be used in nuclear medicine.

Fourier Analysis↗

Transmission computed tomography imaging of the head with a SPECT system and a collimated line source.

UNLABELLED: Transmission images of relatively high resolution as compared to SPECT are needed for brain SPECT quantification to provide skull thickness, attenuation coefficients and anatomical correlation. Consequently, a technique to acquire transmission CT images with a SPECT system by using a collimated line source positioned at the focal line of a fanbeam collimator (FBC) has been developed. METHODS: Computer simulations that model the transmission imaging system optimized the system resolution and tested the validity of a equation for the geometric efficiency of the line source collimator (LSC). Based on the computer simulations, a LSC was constructed with tantalum septa 100 mm long, 0.5 mm thick and spaced 1.0 mm apart. A 600-mm focal length FBC was used. Experiments were conducted to measure the system resolution and to determine the effect of the LSC on the amount of detected scatter. RESULTS: The simulations showed that without a LSC the transmission images have a longitudinal resolution (LR) characterized by the resolutions of the FBC (depth-dependent, approximately 8 mm FWHM at 150 mm) and the detector (approximately 4 mm). However, with an optimally designed LSC, the contribution of the FBC to the system resolution can be made negligible, creating a system with a LR that is comparable to the detector resolution and independent of object depth. Resolution experiments conducted with a lucite rod phantom showed that the LR and TR are better than 4.8 mm and confirmed the results of the computer simulations. CONCLUSION: Brain transmission images of relatively high isotropic resolution can be obtained using a SPECT system, a FBC and an optimized LSC.

Brain↗

Blood-brain barrier permeability in rats is altered by exposure to magnetic fields associated with magnetic resonance imaging at 1.5 T.

We have previously reported that exposure of rats to low-field (0.15 T) magnetic resonance imaging (MRI) increases blood-brain barrier (BBB) permeability. However, a number of investigators have failed to observe this effect when high-field MRI (1.5 T or higher) is used. Therefore, we investigated whether or not we would observe changes using our technique at these higher fields. Adult male Sprague-Dawley rats were anaesthetised and then exposed to a 22.5 min imaging or sham procedure. Immediately following exposure, rats were injected with 1 MBq of 153Gd-DTPA intracardially and then immediately re-exposed for an additional 22.5 min. The rats were killed 1h following the second MRI exposure, at which time the brain was resected and 3 ml of venous blood collected. The ratio of radioactivity per gram of brain to radioactivity per milliliter of blood, known as the brain-blood partition coefficient, was determined and used as a measure of BBB permeability. Groups of animals had different exposures. Group 1 (n = 9) was exposed to a clinically relevant MRI procedure. Group 2 (n = 20) was exposed to the same procedure except the rf specific absorption rate (SAR) was reduced to 25% and the animals were positioned 15 cm from imager centre to increase the time-varying magnetic field from 0.4 to 2.8 T/s. For the sham exposures (n = 21), the animals were placed in the imager with the static field ramped down to zero and exposed to a sound recording simulating a MRI examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantification of functional deficit in Alzheimer's disease using a computer-assisted mapping program for 99mTc-HMPAO SPECT.

A computer-assisted mapping program was developed to determine changes of cerebral perfusion in normal and pathological aging using single photon emission computer tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HMPAO). The software program outlined the cortex on 14 adjacent brain slices, and superimposed a ring of 12 regions of interest on each slice. Regional/global and regional/cerebellar relative flow values were calculated in 27 patients with clinically diagnosed Alzheimer's disease (AD) (mean age 71 years, SD 7.6) and in 10 normal controls (mean age 73.7 years, SD 7.3). The Dementia Rating Scale (DRS) was used to assess mental status in all subjects. Multiple regression analysis demonstrated a significant correlation between relative flow values and the DRS score. Regional/cerebellar (R = 0.88, p < 0.0001) relative flow values were a better indicator of cortical impairment than regional/global relative flow values (R = 0.68, p = 0.003). Of the brain regions of interest, the left parietal flow values correlated best with the DRS score (r = 0.83, p < 0.0001), a cutoff value of 77 accurately classifying 80% of the normals and 100% of the patients diagnosed as having Alzheimer's disease. The data show that computer-assisted mapping of SPECT can provide semiquantitative flow values with high diagnostic accuracy.

Aged↗

Computing the modulation transfer function of a magnetic resonance imager.

A new method for computing the modulation transfer function (MTF) of magnetic resonance (MR) imagers is presented. Previous attempts to compute the MTF of MR images used nonlinear magnitude reconstructed images, resulting in erroneous MTFs. By using complex domain images, the new method produces predisplay MTFs which describe the spatial frequency transfer characteristics of the entire image formation process, except the magnitude operator, eliminating the artifacts previously found in MR imager MTFs. The use of complex domain images results in two-sided MTFs which differentiate the positive and negative frequencies associated with positive and negative phase encoding or positive and negative time relative to the echo formation. Experimental results are presented which confirm the theoretically predicted form of MR imager MTFs and the need for two-sided MTFs.

Magnetic Resonance Imaging↗

Techniques for the measurement of the local myocardial extraction efficiency for inert diffusible contrast agents such as gadopentate dimeglumine.

We have previously shown that the concentration of Gd-DTPA as a function of time ([Gd-DTPA]t(t)) in the myocardium following an intravenous bolus injection of Gd-DTPA can be modeled using the Modified Kety Equation. Fitting this model to measurements of [Gd-DTPA]t(t) in a region of myocardium would allow the determination of myocardial distribution volume (lambda) and the product of flow (F) and extraction efficiency (E), i.e., FE. Thus, to measure F, E must be known. We describe here techniques developed to measure local values of E in normal and diseased myocardium. These techniques are valid for any inert diffusible MR contrast agent.

Animals↗

Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium.

We have previously shown that the myocardial Gd-DTPA concentration ([Gd-DTPA]t(t)) after a bolus injection of Gd-DTPA can be predicted by the Modified Kety Equation (MKE). If [Gd-DTPA]t(t) can be determined by MRI and the data fit to the MKE, then the distribution volume (lambda) of Gd-DTPA and the myocardial flow (F) times the extraction efficiency (E), i.e., the FE product, can be determined. Therefore F can only be quantified if E is known. We measured the global E in vivo in normal canine myocardium, and measured E and lambda, in vitro, locally in normal, acute ischemic (n = 5; coronary artery occlusion < 4 h), infarcted (n = 4; coronary artery occlusion, 6 days) and reperfused (n = 4; coronary artery occlusion 2 h, and reperfusion 2 h and 6 days) myocardium. Results indicate that E differs with F and with individuals and consequently, F cannot be quantified using the MKE unless the local E is also determined in vivo.

Animals↗

Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease.

In order to clarify the relationship between coronary artery disease (including myocardial infarction) and image contrast in gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI it was decided to model the myocardial tissue distribution and clearance of Gd-DTPA using the modified Kety equation. Using a canine model, myocardial tissue Gd-DTPA concentrations ([Gd-DTPA]m) were measured 1 or 5 min after a bolus injection of Gd-DTPA or immediately after the end of a constant infusion of Gd-DTPA in a total of 35 dogs. It was found that within 5 min of a bolus injection [Gd-DTPA]m is determined primarily by myocardial blood flow (MBF) and after about 10 min primarily by myocardial extracellular volumes (MECV). This study suggests that repeat, rapid (every 2-4 s) measurements of myocardial T1 relaxation rates following the bolus injection of Gd-DTPA are required to calculate MBF (i.e., myocardial tissue perfusion) and MECV.

Animals↗

Correction for attenuation in technetium-99m-HMPAO SPECT brain imaging.

We present a correction technique that uses the effective bone and tissue attenuation coefficients to compensate 99mTc-HMPAO brain SPECT projections for attenuation. Transverse images of a human skull filled with a uniform mixture of 99mTc and gelatin have a greater count density at the center with respect to the periphery when corrected for attenuation with the effective water/tissue coefficient of 0.12 cm-1. An attenuation coefficient of 0.09 cm-1 produces uniform images at the expense of a reduced count density. Additional experiments with phantoms wrapped with aluminum (to simulate bone) indicate that the greater count density at the image center is a result of increased attenuation at the edges of the projections where there is a greater path length through the aluminum (or bone). SPECT projections explicitly corrected for both bone and soft-tissue attenuation result in images of improved uniformity and increased count density.

Brain↗

Effects of dipyridamole infusion on human renal function observed using technetium-99m-DTPA.

Our observation that a prolonged dipyridamole infusion reduced or eliminated blood clearance of Gd-DTPA in dogs led us to investigate if dipyridamole, infused intravenously at rates comparable to those used in thallium myocardial perfusion tests, would alter renal filtration in humans. Renal filtration was assessed using a bolus injection of 10 mCi of 99mTc-DTPA in five males (19-63 yr old) with normal serum urea and creatinine. Twenty minutes following the bolus injection a 10-min intravenous infusion of either dipyridamole (0.14 mg/kg/min) or saline sham was given. Four to 10 min following the start of the dipyridamole infusion, a paradoxical rise in counts in the kidney region of interest was observed and persisted for 10 to 27 min. During this time, a 13% to 52% (mean +/- s.d., 40% +/- 16%, p less than 0.007) reduction in the exponential slope defining the clearance of counts from the cardiac region of interest occurred (implying a reduction of glomerular filtration rate), mean heart rate increased 27 +/- 5 bpm, p less than 0.002 and mean diastolic pressure decreased 12.9 +/- 6.4 mmHg, p less than 0.028. This finding indicates that renal clearance of tracers such as thallium or contrast agents such as Gd-DTPA is reduced during dipyridamole infusion.

Adult↗

A prospective study of magnetic resonance imaging in lymphoma staging.

In this prospective study, magnetic resonance imaging (MRI) was compared with computed tomography (CT) in patients with non-Hodgkin's lymphoma (NHDL), and with CT and laparotomy in patients with Hodgkin's disease (HD). Among 31 patients with NHDL, there was agreement between MRI and CT findings in 21 patients; MRI findings were positive and CT findings were negative in 8 patients; and MRI findings were negative and CT findings were positive in 2 patients. The false-negative findings of MRI included a laparotomy-proven mesenteric mass and a 6.6-cm lesion in the spleen, both shown by CT. In 13 evaluable patients with HD, there was agreement between MRI and laparotomy findings in 8 patients; MRI findings were positive and laparotomy findings were negative in 4 patients; and MRI findings were negative and laparotomy findings were positive in 1 patient. CT findings agreed with laparotomy findings in nine patients; CT findings were positive and laparotomy findings were negative in one patient: and CT findings were negative and laparotomy findings were positive in three patients. This suggested that MRI, although more sensitive than CT, was less specific with more false-positive findings. The spin-lattice relaxation time (T1) for the spleen was generally higher in patients with HD who had pathologically confirmed splenic involvement, and tended to increase with increasing spleen weight. This study was performed on a prototype 0.15 Tesla (Technicare Inc., Solon, OH) resistive unit at a time when methods and reporting for MRI were still being developed. Although MRI appears to have fewer false-negative findings than CT in evaluating the abdomen of lymphoma patients, the lack of a gastrointestinal contrast agent and specificity of T1 elevations in the spleen would not suggest that MRI could replace CT or laparotomy as a staging technique.

Adolescent↗

Magnetic resonance imaging increases the blood-brain barrier permeability to 153-gadolinium diethylenetriaminepentaacetic acid in rats.

In a qualitative electron microscopy study we initially reported that exposure of rats to a standard clinical magnetic resonance imaging (MRI) procedure temporarily increased the blood-brain barrier (BBB) permeability to horseradish peroxidase. In this study, we quantitatively support our initial finding. Rats were injected intracardially with radio-labelled diethylenetriaminepentaacetic acid [( 153Gd]DTPA) in the middle of two sequential 23.2 min MRI exposures. Exposed rats (n = 21) showed significantly greater (29%, P = 0.006) retention of [153 Gd]DTPA than sham-exposed rats (n = 22) 1 h after the end of the last 23.2 min exposure. These findings suggest that magnetic fields may alter BBB permeability.

Animals↗

Time-varying magnetic fields increase cytosolic free Ca2+ in HL-60 cells.

Electromagnetic fields have been reported to cause a variety of biological effects. It has been hypothesized that many of these phenomena are mediated by a primary effect on the concentration of cytosolic free calcium ([Ca2+]i). We investigated the effects of exposure to electromagnetic fields on [Ca2+]i in HL-60 cells using the Ca2(+)-sensitive fluorescent indicator indo-1. Indo-1-loaded cell samples were exposed to a radiofrequency electromagnetic field, a static magnetic field, and a time-varying magnetic field, which were generated by a magnetic resonance imaging (MRI) unit. We found that a 23-min exposure to all three fields, in combination, induced a significant increase in [Ca2+]i of 31 +/- 8 (SE) nM (P less than 0.01, n = 13) from a basal level of 121 +/- 8 nM. Also, cells exposed to only the time-varying magnetic field had a mean [Ca2+]i that was 34 +/- 10 nM (P less than 0.01, n = 11) higher than parallel control samples. Separate exposure to the radio-frequency (6.25 MHz) or static field (0.15 T) had no detectable effects. These results demonstrate that time-varying magnetic fields alter [Ca2+]i and suggest that at least some of the reported biological effects of time-varying magnetic fields may arise from elevation of [Ca2+]i.

Calcium↗

Effects of magnetic resonance imaging (MRI) on the formation of mouse dentin and bone.

The effects of magnetic resonance imaging (MRI) on dentin and bone formation in mice were examined using standard autoradiographic and liquid scintillation procedures. It was observed that exposure to a standard 23.2 min clinical multislice MRI (0.15T) procedure caused a significant increase in the synthesis of the collagenous matrix of dentin in the incisors of mice. There were no significant effects on alveolar and tibial bone matrix synthesis. These results suggest that the magnetic fields associated with MRI can affect the activity of cells and/or tissues that are involved in rapid synthetic activity.

Animals↗

Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice.

The effects of exposure to clinical magnetic resonance imaging (MRI) on analgesia induced by the mu opiate agonist, fentanyl, was examined in mice. During the dark period, adult male mice were exposed for 23.2 min to the time-varying (0.6 T/sec) magnetic field (TVMF) component of the MRI procedure. Following this exposure, the analgesic potency of fentanyl citrate (0.1 mg/kg) was determined at 5, 10, 15, and 30 min post-injection, using a thermal test stimulus (hot-plate 50 degrees C). Exposure to the magnetic-field gradients attenuated the fentanyl-induced analgesia in a manner comparable to that previously observed with morphine. These results indicate that the time-varying magnetic fields associated with MRI have significant inhibitory effects on the analgesic effects of specific mu-opiate-directed ligands.

Analgesia↗