George E. Wesbey

Imaging and characterization of acute myocardial infarction in vivo by gated nuclear magnetic resonance.

Imaging by nuclear magnetic resonance (NMR) techniques has been shown to provide high-contrast resolution between soft tissues and characterization of normal and pathologic tissues by differences in magnetic relaxation times. The current study was designed to determine whether electrocardiogram (ECG)-gated NMR imaging of the canine heart in vivo could distinguish normal from infarcted myocardium without the use of intravenous paramagnetic contrast agents. Seven dogs were studied by ECG-gated NMR imaging in vivo (spin-echo technique) with a 0.35 Tesla superconducting magnet at 2 to 7 days after ligation of the left anterior descending coronary artery. In six of the seven dogs, signal intensity was increased in the anterior wall compared with the remainder of the left ventricle; this region of high signal intensity corresponded to the area of myocardial infarction demonstrated at postmortem examination. The signal intensity of the infarcted region was 66 +/- 27% greater than that of normal myocardium (p less than .01). The T2 (spin-spin) relaxation time was 69 +/- 3% longer in the infarcted myocardium as compared with normal myocardium (p less than .01). The NMR images from the seventh dog had uniform signal intensity throughout the myocardium of the left ventricle. An infarct was not evident on postmortem examination in this dog. Thus gated NMR imaging in vivo by the spin-echo technique displays acute myocardial infarctions as regions of high signal intensity without the use of contrast media. The infarct is characterized by a prolonged T2 relaxation time.

Translational molecular self-diffusion in magnetic resonance imaging. II. Measurement of the self-diffusion coefficient.

By varying slice-selective gradients in successive data acquisitions, the first in vitro measurements of molecular self-diffusion coefficients were performed in a magnetic resonance imager at 0.35 Tesla. Reasonably accurate measurements were found by the MRI method in comparison with 2.3 T NMR spectrometer measurements on the same samples, and in comparison to reported literature values. Thus, in addition to T1, T2, mobile proton density, flow velocity, magnetic susceptibility, and chemical shift, molecular self-diffusion coefficients are now added to the list of biophysical parameters measurable by magnetic resonance imaging in the noninvasive characterization of biological systems.

Pharmacokinetics and Metabolic Fate of Two Nitroxides Potentially Useful as Contrast Agents for Magnetic Resonance Imaging

Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in magnetic resonance imaging (MRI) experiments in animals. Preliminary information on the metabolic fate, pharmacokinetic behavior, stability in tissues, and chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in vivo to their corresponding hydroxylamines. No other metabolite was observed. Measured reducing activity in tissue homogenates was greater in liver or kidney than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA was also more resistant to reduction by ascorbic acid at physiologic pH. These preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a piperidinyl nitroxide, for MRI contrast enhancement.

Dilute oral iron solutions as gastrointestinal contrast agents for magnetic resonance imaging; Initial clinical experience

Delineation of the gastrointestinal tract in magnetic resonance imaging (MRI) remains a problem. Ferric ammonium citrate is paramagnetic, producing a high MRI signal intensity by virtue of its spin-lattice (T1) relaxation rate enhancement properties. Water is diamagnetic, producing a low MRI signal intensity, especially with short TR and TE times. To compare efficacy for gastrointestinal contrast alteration, ferric ammonium citrate was administered to 18 patients and water was given to 10 patients. Spin-echo imaging at 0.35T was performed after administration of these agents. Ferric ammonium citrate produced high signal intensity within the esophagus, stomach, duodenum, and small intestine that aided in the differentiation of the gastrointestinal tract from adjacent tumors, vessels, and viscera. Delineation of the gut wall was superior using ferric ammonium citrate compared to that produced by water. Delineation of the margins of the pancreas, liver, and kidney from adjacent gastrointestinal tract was also better with ferric ammonium citrate. Optimal distinction between bowel and fat was better with water. Longer TE times (75 to 200 ms) may allow improved contrast between gut and intrabdominal fat using ferric ammonium citrate.

Enhanced MRI of tumors utilizing a new nitroxyl spin label contrast agent

Nitroxyl spin labels have been shown to be effective in vivo contrast agents for magnetic resonance imaging (MRI) of the central nervous system, myocardium, and urinary tract. A new pyrrolidine nitroxyl contrast agent (PCA) with better resistance to in vivo metabolic inactivation than previously tested agents was studied for its potential to enhance subcutaneous neoplasms in an animal model. Twenty-two contrast enhancement trials were performed on a total of 15 animals 4-6 weeks after implantation with human renal adenocarcinoma. Spin echo imaging was performed using a .35 T animal imager before and after intravenous administration of PCA in doses ranging from 0.5 to 3mM/kg. The intensity of tumor tissue in the images increased an average of 35% in animals receiving a dose of 3 mM/kg. The average enhancement with smaller doses was proportionately less. Tumor intensity reached a maximum within 15 min of injection. The average intensity difference between tumor and adjacent skeletal muscle more than doubled following administration of 3 mM/kg of PCA. Well-perfused tumor tissue was more intensely enhanced than adjacent poorly perfused and necrotic tissue.

Translational molecular self-diffusion in magnetic resonance imaging. I. Effects on observed spin-spin relaxation

The reduced T2 (spin-spin) relaxation times (T2obs less than 200 ms) measured on pure fluids on our 0.35T magnetic resonance imagers stimulated an investigation into this phenomenon. The cause for the short T2obs of fluids was found to be translational molecular self-diffusion of hydrogen nuclei through the pulsed slice-selective magnetic gradient in the imagers. Similar reductions in biological tissue T2obs were also attributed to molecular self-diffusion.

Nuclear magnetic resonance imaging of the brain in children

Nuclear magnetic resonance imaging of the hydrogen nucleus provides a unique noninvasive display of proton dynamics in biologic tissues and fluids as well as internal anatomy in a sectional imaging format. No ionizing radiation is utilized. Our experience with NMR imaging of the brain in 14 pediatric patients is presented and compared with computed tomography. The major advantages of NMR over CT include its greater sensitivity to blood flow, edema, hemorrhage, and myelinization and its lack of beam-hardening artifacts. In addition, the potential for tissue characterization exists by determination of T1 and T2 relaxation times and of mobile proton density. Disadvantages of NMR over CT include its failure to demonstrate calcification and bone detail and longer data acquisition times.

Magnetic resonance applications in atherosclerotic vascular disease

Magnetic resonance imaging of the cardiovascular system offers great promise in the detection and characterization of the anatomic, physiologic, and biochemical consequences of atherosclerosis. This review will focus on the potential applications of MRI for evaluating atherosclerosis of the abdominal aorta and iliofemoral vessels.

Magnetic field dependence of spin-lattice relaxation enhancement using piperidinyl nitroxyl spin-labels

We examined the magnetic resonance properties of 12 paramagnetic piperidinyl nitroxyls in water and plasma solutions. Paramagnetic contributions to proton relaxation times were measured using 10.7 and 100 MHz spectrometers. Proton relaxation enhancement from nitroxyls increased with ascending molecular weight, in plasma solutions versus equimolar aqueous solutions, and with measurements at 10.7 MHz compared to 100 MHz. Relaxation rates were observed to approximately double at 10.7 MHz compared to 100 MHz and from water to plasma solutions. The data indicate that proton spin-lattice relaxation enhancement is magnetic field-dependent, and increases using nitroxyls of large molecular weight and with chemical substitutents that increase the microviscosity of solvent water molecules. The development of nitroxyls for diagnostic MRI will be aided by understanding these in vitro physical characteristics and trends.

Magnetic resonance imaging of acute myocardial infarction using a nitroxyl spin label (PCA).

The effects of an intravenously administered nitroxyl spin label (PCA) on the magnetic resonance imaging (MRI) appearance and relaxation times of acute canine myocardial infarctions were studied. Twenty-four hours after ligation of the left anterior descending coronary artery (LAD), animals were either sacrificed immediately (three dogs) or injected with 3.0 mmol/kg of PCA prior to sacrifice (six dogs). The PCA group dogs were sacrificed at either 5 minutes postinjection (three dogs) or 15 minutes postinjection (three dogs). Magnetic resonance imaging (0.35 T) using spin-echo techniques demonstrated high signal intensity in the infarct relative to normal myocardium in all three groups. In the control group, the T1 and T2 relaxation times were longer in infarcted compared with normal myocardium, but only the measure in T2 reached statistical significance (P less than .05). PCA produced infarct-avid T1 shortening in the six dogs that received it. Contrast in the group sacrificed at 15 minutes postcontrast administration was greater than that in the control group due to T1 shortening in the infarct. Thus, PCA produces differential effects on normal and infarcted myocardium. Between 5 and 15 minutes after IV administration, it causes greater changes in the infarct due to prolonged retention in this region.