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A piperidinyl nitroxide stable free radical derivative, TES, was tested as an NMR contrast enhancer of renal structures in normal animals and animals with experimentally induced unilateral renal ischemia, renal vascular congestion, and hydronephrosis. Physiologic measurements indicated that TES is rapidly excreted in the urine with a clearance rate equal to the glomerular filtration rate. Because the compound is strongly paramagnetic, it increases the observable NMR intensity within the kidneys and urine in relatively low doses (0.04 to 0.9 g/kg). TES-enhanced spin echo renal images clearly demonstrated the presence of disease and functional abnormalities in diseased kidneys. These abnormalities were either not evident or only indirectly suggested on nonenhanced NMR images.

Acute myocardial infarctions were produced in 11 dogs by ligation of the left anterior descending coronary artery. Twenty-four hours after ligation, 0.35 millimoles per kilogram of Gd-DTPA was injected intravenously, followed by cardiectomy either 90 seconds (3 dogs) or 5 minutes (5 dogs) later. The remaining 3 dogs had cardiectomy without injection of Gd-DTPA at 24 hours after coronary occlusion. The 3 dogs that did not receive Gd-DTPA had longer T1 and T2 relaxation times in infarcted myocardium than in normal myocardium, as measured by a 10.7-MHz magnetic resonance (MR) spectrometer. The T1 and T2 relaxation times of normal myocardium at 90 seconds postinjection of Gd-DTPA were significantly shorter (p less than 0.05) than those of the normal myocardium of animals that did not receive Gd-DTPA. At five minutes postinjection, significantly (p less than 0.01) greater T1 shortening was exhibited in the infarcted myocardium compared with adjacent normal myocardium in the dogs injected with Gd-DTPA. Thus, Gd-DTPA has differential and time-varying effects on relaxation times of normal and infarcted myocardium.

OBJECTiVE.The purpose of this prospective study was to compare MR angiography of the carotid artery from the aortic arch through the circle of Willis using maxi-

Tissue deposits of hemosiderin, a paramagnetic iron-protein complex, resulted in marked abnormalities of magnetic resonance (MR) spin-echo signal intensity within the viscera of three children with transfusional hemosiderosis and thalassemia major. In all patients the liver and bone marrow demonstrated abnormally low spin-echo intensities and the kidneys and muscles had abnormally high intensities. These observations correlate with in vitro MR observations of ferric (Fe+3) solutions, in which concentrations of ferric salts greater than 20 mmol yielded a low MR intensity signal and ferric concentrations less than 15 mmol yielded higher intensities than did water alone. MR imaging is sensitive to the tissue deposition of hemosiderin, and MR intensity appears to provide a rough measure of the amount of iron deposited.

Contrast-enhancing agents for demonstrating abnormalities of the blood-brain barrier may extend the diagnostic utility of proton nuclear magnetic resonance (NMR) imaging. "TES," a nitroxide stable free radical derivative, was tested as a central nervous system contrast enhancer in dogs with experimentally induced unilateral cerebritis or radiation cerebral damage. After intravenous injection of TES, the normal brain showed no change in NMR appearance, but areas of disease demonstrated a dramatic increase (up to 45%) in spin-echo intensity and a decrease in Ti relaxation times. The areas of disease defined by TES enhancement were either not evident on the nonenhanced NMR images or were better defined after contrast administration. In-depth tests of toxicity, stability, and metabolism of this promising NMR contrast agent are now in progress.Contrast-enhancing pharmaceutical agents may extend the diagnostic capa bilities of nuclear magnetic resonance (NMR) imaging. Paramagnetic substances tested as NMR contrast agents include the ions of manganese and iron and nitroxide stable free radicals (NSFRs) [1,2]; all have been shown to decrease proton relaxation times, namely T, and T2 [3]. Thus, paramagnetic substances enhance contrast differences between those tissues containing the contrast agent and magnetically similar tissues without it.In separate reports we have described the relative advantages and disadvan tages of various methods to manipulate NMR contrast [2,4] and the potential to directly evaluate renal function in experimental animals using NSFRs as uro graphy NMR contrast agents [2,5].NSFRs are a group of synthetic, strongly paramagnetic organic compounds that for two decades have been used as "spin labels" for in vitro biologic studies[6], A water-soluble piperidinyl NSFR derivative, "TES," is rapidly excreted into the urine after intravenous administration, an excretion pattern useful for NMR urographic studies [2,5]. TES demonstrates additional properties suggesting promise as a clinically useful NMR contrast agent; these include chemical stability of solutions over a broad range of pH and temperature, limited in vivo metabolism, and broad chemical versatility [2,6]. The ability to chemically attach TES to a variety of biomolecules, drugs, and particles may permit the synthesis of tissuespecific NMR contrast agents. Preliminary toxicity studies of NSFRs, the subject of future reports, are also favorable for the continued development of NSFRs as pharmaceuticals.In this study we examined the potential of TES to enhance NMR contrast within the brains of animals having experimentally induced cerebritis or radiation damage. Living dogs were imaged by NMR before and after intravenous admin istration of TES. Loci of brain injury were more clearly identified on the postcontrast images; TES appears to cross the blood-brain barrier (BBB) only at sites of disease and thereby increases the diagnostic yield from the NMR imaging examination. Brain Nuclear Magnetic Materials and Methods Experimental AnimalsAlpha-strep...

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 < .01). The T2 (spin-spin) relaxation time was 69 + 3% longer in the infarcted myocardium as compared with normal myocardium (p < .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 spinecho 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. Circulation 69, No. 1, 125-130, 1984. TOMOGRAPHIC IMAGING of the hydrogen nucleus by proton nuclear magnetic resonance (NMR) techniques offers potential advantages for imaging the cardiovascular system. The lumen of blood vessels and the cardiac chambers display essentially no NMR signal by the spin-echo imaging technique' because of the high velocity of the protons in blood. This allows a high degree of signal contrast between moving blood and the walls of blood vessels and cardiac chambers without the need for intravenous paramagnetic contrast media. NMR imaging also offers the potential for characterization of tissues and biological fluids by Tl and T2 relaxation times, spin (hydrogen) density, and possibly spin-diffusion constants. Many pathologic processes, including acute myocardial infarction, are associated with an increased regional water content. -' Previous NMR spectrometric studies of tissue samples in vitro have demonstrated prolonged Tl relaxation times in infarcted myocardium relative to normal myocardium.5 6 Although an early report of experiments with hearts ex situ suggested that acute myocardial infarctions could be discriminated from normal myocardium only in the presence of a paramagnetic contrast medium,8 more recent reports suggest that infarcts can be detected without contrast media.9 " Previous investigations with proton NMR imaging in our laboratory have also demonstrated prolonged TI and T2 relaxation times of acutely infarcted skeletal muscle...

Perflubron is safe, and its efficacy was unaffected by pulse sequences, magnetic field strength, or time delay.