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Biomedical subjects

F S Prato

Publications and source records attributed to F S Prato.

At least 19 recordsLinked to original sources

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

Serial nuclear magnetic resonance imaging of acute myocardial infarction with and without reperfusion.

To compare nuclear magnetic resonance (NMR) image-derived T1 and T2 changes during evolving infarction, 14 dogs were studied serially: (1) 1 to 2 hours after left anterior descending coronary occlusion, (2) 2 to 3 hours after coronary occlusion (n = 7) or in the first hour after reperfusion following 2 hours of occlusion (n = 7), and (3) 5 days and (4) 21 days after occlusion/reperfusion. In addition, the extent of T1 and T2 abnormalities was compared to the extent of infarction as determined histologically for each set of images. With sustained coronary occlusion, an increase versus control values (T1 = 351 +/- 11 msec; T2 = 41 +/- 2 msec) was observed in the second hour after occlusion (T1 = 448 +/- 51 msec; T2 = 51 +/- 8 msec), gradually reaching a maximum by day 5 (T1 = 490 +/- 64 msec; T2 = 63 +/- 9 msec). By 21 days, T1 had decreased to 427 +/- 43 msec and T2 to 55 +/- 11 msec. However, with myocardial reperfusion, an abrupt increase in both T1 and T2 occurred compared to prereperfusion values in the first hour after release of occlusion, from 445 +/- 32 msec to 555 +/- 65 msec and from 52 +/- 5 msec to 65 +/- 8 msec, respectively. Subsequently, T1 remained elevated whereas T2 normalized. Only on day 21 images was there a good correlation between the extent of T1 and T2 abnormalities and infarct size, in both nonreperfused (r = 0.87; p less than 0.05), and reperfused (r = 0.89; p less than 0.01) dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of the biodistribution of gadolinium-153 DTPA and technetium-99m DTPA in rats.

Twenty-three mature Sprague-Dawley male and female rats were simultaneously injected with trace quantities of [153Gd]DTPA and [99mTc]DTPA and 0.5 mmol/kg of nonradioactive gadolinium DTPA. Rats were killed at 1 min, 5 min, 10 min, 15 min, and 30 min after the intracardiac bolus injection. The heart, lungs, liver, brain, kidney, and blood were excised and counted in a well-counter to determine the amount of the injected material in each organ and blood. In order for the percent of total injected activity to be determined, a technique was developed which allowed discrimination of the 140 keV gamma-ray of 99mTc from sum peaks of 153Gd when the latter is counted in a well-counter with 4 pi geometry. Although the distribution of the two DTPA compounds was qualitatively similar, statistical analysis indicated that the amount of 99mTc deposited in the lungs was higher than 153Gd (p = 0.03), the amount of 99mTc deposited in the kidneys was lower than 153Gd (p = 0.0004) and the amount of 99mTc in the blood was higher than 153Gd (p = 0.0022). This may be due to the greater binding of [99mTc]DTPA or its minor impurities to plasma proteins.

Animals

Diagnostic applicability of magnetic resonance imaging in assessing human cardiac allograft rejection.

To assess the diagnostic applicability of magnetic resonance imaging (MRI) for diagnosis of cardiac allograft rejection, 25 patients who recently underwent cardiac transplantation were studied on a 0.15-tesla resistive system within 24 hours of endomyocardial biopsy. Ten normal volunteers and 4 patients who had recent (within 2 weeks) nontransplant cardiac surgery were also studied. In the 19 transplant patients imaged within 24 days of graft implantation, only 1 had evidence of graft rejection on biopsy. However, all nonrejecting grafts had increased T1 and T2 values, 501 +/- 22 and 61 +/- 6 ms, respectively (mean +/- standard deviation) and the only rejecting graft had values of 496 and 60 ms, respectively. In the normal volunteers mean T1 was 352 +/- 18 ms and T2 was 35 +/- 6 ms. There was no significant difference in T1 and T2 values between patients who underwent nontransplant surgery and control subjects. In patients with nonrejecting transplants who were imaged more than 25 days after surgery, the T1 and T2 values had normalized to 359 +/- 17 ms and 36 +/- 7 ms, respectively (n = 28 images in 20 patients). However, in those grafts with rejection, T1 and T2 were both elevated to 502 +/- 21 ms and 62 +/- 6 ms, respectively (n = 15 in 13 patients); wall thickness was also increased. Fourteen of 15 late rejection events (more than 25 days after surgery) were correctly identified on the basis of increases in T1 and T2 to more than 2 standard deviations above normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Magnetic resonance imaging temporarily alters blood-brain barrier permeability in the rat.

Exposure to a short (23.2 min) standard clinical magnetic resonance imaging (MRI) procedure elicits a temporary dysfunction of the blood-brain barrier in rats. Monitoring of the increased permeability of rat brain frontal cortex microvessels with the protein tracer horseradish peroxidase and freeze-fracture electron microscopy, revealed an amplified vesicle-mediated transport of tracer across the microvessel endothelium to the albuminal basal lamina and extracellular compartment of the brain parenchyma. Recovery of normal blood-brain function, as evidenced by exclusion of protein tracer from subendothelial basal lamina and neuropil extracellular milieu, was complete 15-30 min following cessation of the MRI exposure. These findings raise the possibility that exposure to clinical MRI procedures may also temporarily alter central blood-brain permeability in human subjects.

Animals

Cardiac T1 calculations from MR spin-echo images.

Normally, cardiac triggering in MR spin-echo imaging restricts repetition times (TR) to integral values of the cardiac period (TC), and introduces irregularities in TR due to variations in TC. We have investigated how much these restrictions decrease the accuracy and precision of spin-lattice relaxation (T1) values of the myocardium calculated from two cardiac-triggered spin-echo images. By introducing additional excitation pulses, TR can effectively be reduced to a fractional value of TC and considerable improvement in T1 precision is possible. For TC = 800 ms, the improvement in T1 precision is 30% when two spin-echo images of TR = 1/2 X TC and TR = 2 X TC are used to calculate T1 instead of two images with TR = TC and TR = 2 X TC. The irregularities in TR decrease both T1 precision and accuracy. Irregularities of the order of 15% in a mean TR of 800 ms produce a fourfold decrease in precision. Since irregularities in TC easily exceed 15%, MRI data should be acquired when individual TR values are approximately within +/- 15% of the subject's mean TC.

Animals

An optimized head coil design for MR imaging at 0.15 T.

Receive-only head coils employing a modified solenoid design were developed for a 0.15-T imager with horizontal main static and radiofrequency transmit fields. This coil design uses three or five identical horseshoe-shaped elements, constructed of 1/2-in. outside diameter copper tubing, lying one above the other in equally spaced horizontal planes. Coils of this design were compared to the half-saddle coil supplied with our imager and to the Hammersmith Hospital spherical coil (G.M. Bydder et al., J. Comput. Assist. Tomogr. 9, 987 (1985]. Compared to the half-saddle coil, one of our new head coils has the same field of view while improving the signal-to-noise ratio (S/N) by 80% in the upper brain and 20% in the cervical vertebrae; compared to the spherical coil the S/N was up to 60% lower but the field of view was larger and patient comfort was better.

Brain

The effect of magnetic resonance imaging on human cognition.

Potential effects of MRI exposure on aspects of human cognition were investigated out of concern that possible safety hazards associated with the procedure may exist. One hundred and fifty-seven volunteer subjects were randomly assigned to either an imaged, sham-imaged or nonimaged control condition. The following psychological tests were administered in a double blind procedure at pretreatment, post-treatment and follow-up time periods: the Wechsler Adult Intelligence Scale-Revised (Digit Span, Block Design and Digit Symbol), the Wechsler Memory Scale Paired Associate Learning test, the Benton Revised Visual Retention test, the Vandenberg Mental Rotation test, the Sternberg memory scanning paradigm and the State Anxiety Inventory. The overall analysis of results indicated that MRI at 0.15 T has no significant effect upon the cognitive functions assessed.

Adolescent

Attenuation of morphine-induced analgesia in mice by exposure to magnetic resonance imaging: separate effects of the static, radiofrequency and time-varying magnetic fields.

Exposure of adult male mice to a magnetic resonance imaging (MRI) procedure has been shown to abolish the nocturnal analgesic responses observed following treatment with morphine. The field component(s) responsible for this inhibitory effect were examined by exposing mice to either the static, time-varying or rf magnetic field components associated with an MRI procedure. In the middle of the night portion of their day-night cycle, mice were exposed for 23.2 min to one of the above field components, intraperitoneally injected with morphine sulphate (10 mg/kg) and then exposed to the field conditions for another 23.2 min, after which analgesic responses were determined. Analgesia was quantitated by determining the length of time mice were content to be on a hot surface (50 degrees C) before they showed discomfort by licking their paws. It was observed that the time-varying magnetic field completely abolished, the rf field significantly reduced, while the static field component (0.15 T) had no evident effect on morphine-induced analgesia. These results indicate that the time-varying, and to a lesser extent the rf, fields associated with the MRI procedure inhibit morphine-induced analgesia in mice. These data also raise the possibility that exposure in humans to some of the magnetic field components associated with MRI may have clinically relevant effects on the actions of narcotic drugs such as morphine.

Animals

Survivability and long-term stress reactivity levels following repeated exposure to nuclear magnetic resonance imaging procedures in rats.

The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on survivability and long-term stress reactivity levels was examined in male rats. Rats in the experimental condition were exposed to MRI for 22.5 minutes for five successive days (Expt. 1) or 23.3 minutes for twenty-one successive days (Expt. 2). Sham field exposed animals received the identical treatment as the exposed animals except that the magnetic and radio-frequency fields were absent. Control rats were also maintained. Thirteen to twenty-two months after the exposure procedure the remaining rats were sacrificed and their whole body, spleen, heart, thymus, and adrenal weights were recorded. Blood samples were taken for measurements of red and white blood cell counts, hemoglobin content, as well as adrenocorticotrophin and corticosterone levels. The results fail to provide any evidence for changes in survivability and long-term stress reactivity levels in rats exposed to MRI and thus give no grounds to challenge the view that MRI is a safe diagnostic procedure.

Adrenocorticotropic Hormone