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Biomedical subjects

V M Runge

Publications and source records attributed to V M Runge.

At least 109 records · Page 6Linked to original sources

111In-labeled eosinophils: localization of inflammatory lesions and parasitic infections in mice.

Based upon recent development of practical isolation techniques for eosinophils, labeling and in vivo imaging of eosinophils has been achieved. Isolation of cells was performed utilizing a Percoll density gradient. The eosinophils were subsequently labeled by a modified 111In-oxine method. Migration of eosinophils in response to intradermal ear-pinna injections of SEA (soluble schistosoma egg antigen), S. mansoni eggs, E. coli, and turpentine was followed with gamma-ray camera imaging from 4 to 48 h. Maximal localization, determined by Gamma 11 data processing, occurred by 4-h post-injection of radiolabel. SEA and S. mansoni eggs provided a greater stimulus for localization than E. coli or turpentine. Neutrophils did not preferentially accumulate. Tissue distribution of labeled eosinophils was greatest in the spleen, followed by liver and bone. 111In-labeled-eosinophil scans are sensitive to parasitic infections, although somewhat nonspecific.

Animals↗

Initial clinical evaluation of gadolinium DTPA for contrast-enhanced magnetic resonance imaging.

Gadolinium DTPA was evaluated as an intravenous contrast agent for magnetic resonance imaging in 15 patients with primary or secondary intracranial neoplastic disease. T1 and T2 weighted images were obtained prior to contrast administration. T1 weighted spin echo 35/800 (TE/TR) images were utilized to detect enhancement. The increase in signal intensity observed, identifying areas of breakdown of the blood-brain barrier (BBB), was similar in magnitude to the contrast enhancement observed on CT. This permitted differentiation of neoplastic tissue from surrounding cerebral edema on MRI. Direct visualization of otherwise "isomagnetic" lesions was also demonstrated. The use of intravenous contrast media should significantly extend the diagnostic potential and specificity of magnetic resonance imaging.

Brain Edema↗

The use of Gd DTPA as a perfusion agent and marker of blood-brain barrier disruption.

To provide contrast enhancement in magnetic resonance imaging, a new class of compounds has been developed, the paramagnetic metal ion chelates. Gadolinium (Gd) DTPA, a prototype of this class, shows a sufficiently high in vivo stability and low toxicity for use in initial clinical trials. This type of agent, designed for rapid clearance by glomerular filtration, allows the assessment on MRI of renal function, alterations in tissue perfusion, myocardial ischemia, and perhaps most significantly disruption of the blood-brain barrier (BBB). Research at Vanderbilt has demonstrated these applications, with particular emphasis in three areas. Tissue perfusion changes, such as those produced by ligation of the arterial blood supply to portions of the spleen and kidney, cannot easily be detected on unenhanced MRI. These acute tissue infarcts can be readily identified following the administration of Gd DTPA. The question of field strength dependence of Gd DTPA has been addressed by experimentation at 0.15, 0.5, and 1.5 tesla. Furthermore, the ability to detect an alteration of the BBB, when present without associated edema, has been demonstrated with the application of control enhancement. The use of contrast agents in MRI will enhance both the sensitivity and specificity of magnetic resonance imaging.

Animals↗

Gated magnetic resonance imaging of acute myocardial ischemia in dogs: application of multiecho techniques and contrast enhancement with GD DTPA.

ECG gated magnetic resonance images were obtained in six canines prior to and immediately following occlusion of either the LAD or circumflex coronary artery using a surgically placed snare. Multiecho and single-echo acquisition techniques were utilized 0.25 mmol/kg Gd DTPA was injected as an IV bolus 1 hr following coronary artery ligation. In two animals, the region of ischemic myocardium was clearly visualized on multiecho technique without the use of intravenous contrast. The ischemic zone could be best identified on images with a long TE of 120 msec. Contrast enhancement with Gd DTPA enabled visualization of the ischemic myocardium in all six canines. Administration of Gd DTPA, a perfusion agent, improved both detectability and definition of the myocardial lesions.

Animals↗

Contrast enhanced MRI. Evaluation of a canine model of osmotic blood-brain barrier disruption.

An osmotic model of blood-brain barrier (BBB) disruption was studied by magnetic resonance (MR) imaging (0.5 T) in 17 canines. The animals were killed after imaging and the lesions confirmed on gross pathology by the presence of Evans blue dye. No accompanying cerebral edema was demonstrated on histologic examination. The disrupted BBB could be identified in only one of five control animals on unenhanced MRI, despite the use of calculated T1 and T2 images. In a second group of five animals, the area of abnormal vascular permeability was consistently demonstrated after IV injection of 0.25 mmol/kg Gd DTPA. The time course of enhancement was evaluated in four additional animals. The brain tissue concentration of the gadolinium ion responsible for the observed enhancement was determined by ion coupled plasma analysis in the last three canines. In a study of pulse techniques, spin echo sequences with both short TRs and TEs (ie, SE 500/30) and inversion recovery techniques proved to be most efficacious for the detection of contrast enhancement. However, contrast could be demonstrated on more T2 weighted sequences.

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↗

Magnetic resonance imaging of multiple sclerosis: a study of pulse-technique efficacy.

Forty-two patients with the clinical diagnosis of multiple sclerosis were examined by proton magnetic resonance imaging (MRI) at 0.5 T. An extensive protocol was used to facilitate a comparison of the efficacy of different pulse techniques. Results were also compared in 39 cases with high-resolution x-ray computed tomography (CT). MRI revealed characteristic abnormalities in each case, whereas CT was positive in only 15 of 33 patients. Milder grades 1 and 2 disease were usually undetected by CT, and in all cases, the abnormalities noted on MRI were much more extensive than on CT. Cerebral abnormalities were best shown with the T2-weighted spin-echo sequence (TE/TR = 120/1000); brainstem lesions were best defined on the inversion-recovery sequence (TE/TI/TR = 30/400/1250). Increasing TE to 120 msec and TR to 2000 msec heightened the contrast between normal and abnormal white matter. However, the signal intensity of cerebrospinal fluid with this pulse technique obscured some abnormalities.

Adult↗

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↗

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↗

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↗

Phase III clinical evaluation of Gd-HP-DO3A in head and spine disease.

As part of a phase III clinical trial, 25 patients with suspected intracranial or spinal disease underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg Gd-HP-DO3A (1,4,7-tris[carboxymethyl]-10-[2' hydroxypropyl]-1,4,7,10- tetraazacyclododecane), a neutral (nonionic) gadolinium chelate. Laboratory analysis included a complete blood count; blood chemistry; measurement of electrolyte levels; hepatic function, clotting function, and iron metabolism panels; and urinalysis both before and 24 hours after contrast agent administration. No statistically significant changes related to contrast agent administration were noted in laboratory values after administration of the contrast agent. In this selected group of patients, the contrast agent-enhanced study provided greater diagnostic information than did the precontrast study in 69% of head cases and 67% of spine cases. These initial clinical trials demonstrate that Gd-HP-DO3A is a safe, efficacious agent for head and spine examinations.

Adult↗

Clinical comparison of three-dimensional MP-RAGE and FLASH techniques for MR imaging of the head.

Three-dimensional (3D) MP-RAGE (magnetization-prepared rapid gradient-echo) imaging was evaluated as a high-resolution 3D T1-weighted brain imaging technique for patients with suspected neurologic disease. Fourteen patients were studied. In five, 3D MP-RAGE images were compared with 3D FLASH (fast low-angle shot) images. Signal difference--to-noise ratios and T1 contrast were not statistically different for 3D MP-RAGE images as opposed to 3D FLASH images. Advantages intrinsic to the application of 3D MP-RAGE sequences include decreased imaging time and decreased motion artifact. With this technique, it is possible to perform a relatively motion-insensitive, T1-weighted screening brain study with voxel resolution of 1.0 x 1.4 x 2.0 mm or smaller, in an imaging time of 5.9 minutes or less--permitting offline (poststudy) reconstruction of high-resolution images in any desired plane.

Brain↗