Current status of magnetic resonance imaging.
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Animals↗
Biomedical subjects
J A Clanton
Publications and source records attributed to J A Clanton.
Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue.
Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow.
Animals↗
Dynamic fluctuations in blood and spleen radioactivity: splenic contraction and relation to clinical radionuclide volume calculations.
Alterations in the blood radioactivity affect ventricular volume calculations using count-based radionuclide ventriculography. To study this phenomenon, the effect of time, posture and supine exercise on blood radioactivity, red blood cell count and splenic radioactivity was evaluated. The red blood cell count, and blood, splanchnic and splenic radioactivity remained stable in five patients studied at rest in the supine position. On standing, blood radioactivity increased 10 +/- 3% (standard error of the mean), and abdominal radioactivity decreased 14.5 +/- 6.5% (both p less than 0.05). In 10 patients, splenic radioactivity decreased after supine exercise by 49 +/- 7%, while blood radioactivity increased 10.5 +/- 1.5% and red blood cell count increased 7.5 +/- 1.5% (all p less than 0.001). Splenic radioactivity increased gradually after exercise and decreased after a second exercise period. In the exercising patients, blood radioactivity increased by 14.5% and correlated with an increase in the red blood cell count (r = 0.57, p = 0.01, 19 samples from 10 patients). Reduction in splenic radioactivity also correlated with the increase in red blood cell count (r = -0.51, p = 0.025). The data demonstrate splenic shrinkage in human beings and an inverse relation between changes in splenic and blood radioactivity. These dynamic fluctuations emphasize the need for simultaneous blood sampling for accurate calculation of left ventricular volume and high-light the importance of regional volume shifts during exercise.
Animals↗
Respiratory gating in magnetic resonance imaging at 0.5 Tesla.
A device for gating the acquisition of magnetic resonance images with chest wall motion was developed, and the effects of respiratory gating upon image quality were studied. Images of respiratory gated examinations were compared with those of ungated examinations in 16 subjects. In a subset of four of those subjects, combined respiratory and cardiac gated images were obtained. Respiratory gating removed gross motion artifacts from magnetic resonance images of the chest and abdomen. Resolution of small normal tissue structures, such as the portal and hepatic veins, is improved. In cardiac studies, respiratory gating improved the visualization and definition of the atria and ventricles.
Abdomen↗
Contrast enhancement of magnetic resonance images by chromium EDTA: an experimental study.
Chromium EDTA was evaluated as an intravenous contrast agent for magnetic resonance (MR) imaging in vitro and in vivo in rabbits and rats. The effect of Cr EDTA on T1 and T2 values in vitro was first quantitated by spectroscopy at 2.5 MHz, followed by animal trials in which the effects of intravenous injection of Cr EDTA on calculated T1 MR images (obtained by the spin- warp technique at 1.7 MHz) were determined. Following administration of chromium EDTA, differences in T1 values between normal and abnormal kidneys were noted, renal hydronephrosis and renal ischemia were readily identified by the pattern of change in T1, and changes were observed in the normal rabbit brain and in tumors implanted in rats. It is concluded that the use of stable paramagnetic metal ion chelates, such as Cr EDTA, as intravenous contrast agents in MR imaging is feasible and that such agents would make possible the observation of tissue vascularity, breakdown of the blood-brain barrier, and renal function.
Animals↗
Intravascular contrast agents suitable for magnetic resonance imaging.
Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging (MR) using a 0.5-T superconducting scanner. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.
Animals↗
The female chaplain's contributions to breast cancer management.
Maintains that a female chaplain's ministry to women breast cancer patients holds unique qualities because of the chaplain's ease of achieving physical and psychological identification with the mastectomy patient. Notes particularly how a female chaplain can provide a relationship for affirmation of self-esteem, confession, and repentance. Illustrates with actual cases ways the female chaplain can share in the feminine identity crisis, participate in the struggle to claim God-given dignity and worth, and be genuinely present for healing the resentment and guilt often accompanying the mastectomy patient's loss.
Chaplaincy Service, Hospital↗
Evaluation of neutrophil labeling techniques using the chemotaxis radioassay.
Neutrophils isolated from human blood were labeled by various methods and exposed to a chemotactic gradient. The chemotactically functional cells that migrated into the gradient were isolated. The portion of radioactivity of the original cell suspension carried with the chemotactically responsive cells was related to the relative number of migrating cells as determined microscopically. Of the radionuclides used, P-32 diisopropylfluorophosphate (DFP), In-111 oxine, and Tc-99m sulfur colloid provided cell preparations with the highest relative portion of radioactivity confined to functionally intact (chemotactic) neutrophils. Results with Na2(51)CrO4 and with SnCl2-reduced 99mTcO4- were less than optimal. Neutrophils exposed to Ga-67 citrate apparently took up the label and retained chemotactic responsiveness. However, little or no radioactivity was detected in the neutrophils that migrated from the suspensions of Ga-67-labeled cells. The results indicate that the chemotaxis radioassay can yield unique information pertaining to the extent to which a radiotracer is specifically associated with viable neutrophils in a suspension of labeled cells.
Chemotaxis, Leukocyte↗
Paramagnetic contrast agents in magnetic resonance imaging: research at Vanderbilt University.
Experimental studies in animals have demonstrated the application of particulate and chelated paramagnetic oral contrast agents in magnetic resonance imaging (at 0.5 tesla). The ability of a soluble paramagnetic species, ferrous gluconate, to improve imaging studies of the pancreas presently is being evaluated in clinical trials. Two paramagnetic metal ion chelates, Cr EDTA and Gd DTPA, have been evaluated extensively as potential intravascular contrast agents. Renal function, tissue vascularity, abnormalities of the blood-brain barrier, and infarction of myocardial tissue may all be assessed with IV contrast enhanced magnetic resonance imaging. The contrast materials tested all represent first generation compounds. Improved relaxation characteristics, toxicity, distribution, and flexibility will result from development of second generation agents, primarily within the particulate and chelate classes.
Animals↗
Lymphoscintigraphy as an adjunctive procedure in the perioperative assessment of patients undergoing microlymphaticovenous anastomoses.
Microlymphaticovenous anastomoses provide a potential for reducing lymphedema of the upper extremity complicating radical mastectomy or irradiation. Lymphoscintigraphy is a valuable investigative modality in the perioperative evaluation of patients undergoing this surgical procedure. The radionuclide studies provide information regarding structural change and physiologic derangement with a low radiation dose to the patient. It is a simple, painless procedure requiring minimal skill and no surgical intervention. In addition, a reproducible method for preparing a radiocolloid suitable for lymphatic imaging using an approved drug as a precursor has been developed.
Arm↗
Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice.
Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease.
Animals↗
Work in progress: potential oral and intravenous paramagnetic NMR contrast agents.
The potential use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents was examined in vitro. The T1 relaxation times for serial dilutions of Cu2+, Cr3+, Fe3+, and Mn2+ ions in saline, gadolinium oxalate (a potential oral contrast agent) in suspension, and chromium EDTA (a potential intravenous contrast agent) in solution were determined. The effect on T1 of increasing the concentration of oxygen in solution was also examined. The relative magnitude of the decrease in T1 was, as expected, proportional to both the concentration of the paramagnetic substance and its effective magnetic moment. Thus NMR has the potential to detect differences in tissue oxygenation. By incorporating paramagnetic metal ions into insoluble compounds or stable complexes, toxicity can be dramatically reduced while maintaining a significant paramagnetic effect. Highly insoluble paramagnetic compounds or stable paramagnetic ion complexes can thus be utilized as effective NMR contrast agents with significantly diminished toxicity.
Administration, Oral↗
Neutrophil labeling with indium-111: tropolone vs. oxine.
This study was undertaken to compare tropolone with oxine (8-hydroxy-quinoline) for labeling human neutrophils with In-111. Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis. In contrast, no impairment of neutrophil chemotaxis was observed using In-111 oxine. Labeling efficiencies obtained with In-111 tropolone under optimal conditions were consistently less than those obtained with In-111 oxine. We evaluated cells labeled by the two methods using chemotaxis radioassay to assess the chemotatic potential of labeled cells. The results led to the conclusion that the oxine technique is preferable to tropolone for labeling human neutrophils with In-111.
Chemotaxis, Leukocyte↗
Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction.
The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.
Animals↗
The effects of RO-22-4679, a thromboxane synthetase inhibitor, on ventricular fibrillation induced by coronary artery occlusion in conscious dogs.
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Animals↗
Nuclear magnetic resonance of iron and copper disease states.
The tissue levels of paramagnetic ions are an important factor in the determination of T1 values as observed by nuclear magnetic resonance (NMR) imaging. The increased levels of iron present in human disease states such as hemochromatosis lead to decreased T1 values. The mean liver T1 of three patients with iron storage disease was determined to be 130 msec, significantly different from the value of 154 msec, the mean for 14 normal controls. Whether NMR will be able to detect the increased copper levels in liver and brain in Wilson disease remains for further clinical trials to evaluate. NMR imaging, however, does serve as a noninvasive method for the diagnosis of states of iron overload and as a technique to follow progression of disease or response to medical therapy.
Abdomen↗
Paramagnetic agents for contrast-enhanced NMR imaging: a review.
The use of paramagnetic agents for contrast enhancement may extend the diagnostic potential of nuclear magnetic resonance (NMR) imaging. Proton relaxation is enhanced in targeted organ systems after either oral or intravenous administration of suitable paramagnetic agents. A decrease in T1 and T2, the spin-lattice and spin-spin relaxation times, can then be observed as an increase in signal intensity on NMR imaging. Initial investigations have focused on development of agents incorporating either paramagnetic ions or stable free radicals. Principles in development and application are illustrated with examples from experiments using the Vanderbilt Technicare 0.5 T NMR imager.
Animals↗
Arachidonic acid metabolism in the murine eosinophil. III. Effect of nonsteroid anti-inflammatory drugs on lymphokine-directed eosinophil migration in vivo.
In vitro studies of murine eosinophils indicated that lymphokine-stimulated metabolism of arachidonic acid by a lipoxygenase pathway was required for a migration response. In this study we tested the effects of drugs that affect arachidonic acid metabolism on lymphokine-dependent eosinophil accumulation in vivo by the use of 111In-labeled eosinophils. Indomethacin at different dosages either stimulated (1 mg/kg) or partially inhibited (5 to 25 mg/kg) eosinophil accumulation. Aspirin had no significant effects in doses up to 50 mg/kg. BW755C, a drug that inhibits both cyclooxygenase and lipoxygenase, dramatically inhibited eosinophil accumulation at 25 to 125 mg/kg. Pretreatment in vitro of 111In-labeled eosinophils with some drugs known to inhibit lipoxygenase reduced their subsequent accumulation at a lymphokine-injected site in vivo, but the high concentrations required for inhibition suggested that the effects of the drugs were at least partially reversible. Pretreatment with indomethacin did not inhibit the ability of 111In-labeled eosinophils to accumulate at the site of lymphokine injection in vivo. It may be anticipated from these results that drugs inhibiting lipoxygenase will have critical effects on manifestations of immunologic reactions that recruit eosinophils.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗