Klaes Golman

Lund University | LU · Department of Diagnostic Radiology

The objectives of this clinical trial of orally administered manganese in magnetic resonance imaging (MRI) of the liver were to assess signal enhancements in the liver with and without the addition of an uptake promoter, ascorbic acid, and to evaluate acute safety. A total of 18 healthy adult males were enrolled in the present trial. Contrast mediu...

Blood samples were taken from 21 subjects at 2 to 4 hours after simultaneous injection of contrast medium (metrizoate) for urography and 51Cr-EDTA. Clearance calculations were performed using the single injection (single slope) technique. The plasma concentrations of 51Cr-EDTA and contrast medium were measured by gamma counting and X-ray fluorescen...

As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue...

Pyruvate is included in the energy production of the heart muscle and is metabolized into lactate, alanine, and CO(2) in equilibrium with HCO(3) (-). The aim of this study was to evaluate the feasibility of using (13)C hyperpolarization enhanced MRI to monitor pyruvate metabolism in the heart during an ischemic episode. The left circumflex artery o...

To prospectively compare nephrotoxicity and radiodensity of plasma hyperosmotic gadolinium chelates (attenuation-osmotic ratio of 1:1) with those of plasma iso-osmotic iodine-based contrast media (attenuation-osmotic ratio of 3:1 or 6:1) after renal arteriography in ischemic porcine kidneys. The local animal care committee approved this study. The...

Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured usi...

Interventional procedures in MRI can be performed preclinically using active or passive catheter-tracking methods. A novel passive nonproton technique is suggested that uses a catheter filled with a hyperpolarized (13)C contrast agent. A prototype three-lumen catheter was built with two closed lumens containing a flowing hyperpolarized (13)C contra...

The study of lung perfusion in normal and diseased subjects is of great interest to physiologists and physicians. In this work we demonstrate the application of a liquid-phase hyperpolarized (HP) carbon-13 ((13)C) tracer to magnetic resonance imaging (MRI) of the pulmonary vasculature and pulmonary perfusion in a porcine model. Our results show tha...

The "Warburg effect," an elevation in aerobic glycolysis, may be a fundamental property of cancer cells. For cancer diagnosis and treatment, it would be valuable if elevated glycolytic metabolism could be quantified in an image in animals and humans. The pyruvate molecule is at the metabolic crossroad for energy delivery inside the cell, and with a...

A study was undertaken of the role of osmotoxicity in gadolinium (Gd) and iodine contrast media (CM) nephrotoxicity in ischemic porcine kidneys. Test solutions: mannitol iso-osmotic to 0.5 M: gadopentetate (1.96 Osm/kg H2O), 0.5 M: gadodiamide (0.78 Osm/kg H2O) and 0.5 M: iohexol (190 mg I/ml, 0.42 Osm/kg H2O). Each solution was injected [3 ml/kg b...

The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the...

A new diagnostic application of a water-soluble contrast medium (CM) based on the hyperpolarization of a 13C substance is introduced. The degree of polarization achieved is >30%, which is about a factor of 10(5) higher than the thermal equilibrium polarization level at 1.5 T. Imaging of hyperpolarized (HP) CM during a cardiac interventional MRI pro...

The evolution of magnetic resonance imaging (MRI) has been astounding since the early 1980s, and a broad range of applications has emerged. To date, clinical imaging of nuclei other than protons has been precluded for reasons of sensitivity. However, with the recent development of hyperpolarization techniques, the signal from a given number of nucl...

A recently developed method for quantitative assessment of regional lung ventilation was employed for the study of posture-dependent ventilation differences in rats. The measurement employed hyperpolarized (3)He MRI to detect the build-up of the signal intensity after increasing numbers of (3)He breaths, which allowed for computation of a regional...

A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time a...

A method to generate strongly polarized nuclear spins in solution has been developed, using Dynamic Nuclear Polarization (DNP) at a temperature of , and at a field of , corresponding to an electron spin resonance frequency of . Trityl radicals are used to directly polarize and other low-γ nuclei. Subsequent to the DNP process, the solid sample is d...

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on tr...

Extract: Two major applications exist for Nuclear Magnetic Resonance (NMR): spectroscopy and imaging. NMR spectroscopy has gained acceptance as one of the major analytical techniques, due to the detailed information that can be obtained about molecular structure, dynamics and intra- and inter-molecular interactions. Magnetic resonance imaging (MRI)...

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized (129)Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with (129)Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit...

Dynamic nuclear polarization has enabled hyperpolarization of nuclei such as 13C and 15N in endogenous substances. The resulting high nuclear polarization makes it possible to perform subsecond 13C MRI. By using the dynamic nuclear polarization hyperpolarization technique, 10% polarization was obtained in an aqueous solution of 100 mM 13C-labeled u...

A method for obtaining strongly polarized nuclear spins in solution has been developed. The method uses low temperature, high magnetic field, and dynamic nuclear polarization (DNP) to strongly polarize nuclear spins in the solid state. The solid sample is subsequently dissolved rapidly in a suitable solvent to create a solution of molecules with hy...

MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity of this modality has limited the clinical use to imaging of water protons. With hyperpolarization techniques, the signal from a given number of nuclear spins can be raised more than 100 000 times. The strong signal enhancement enables imaging of nuclei other than proton...

The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with res...

The feasibility of hyperpolarized 129Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique. Hyperpolarized Xe gas was dissolved in ethanol, a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times. The dissolved Xe was injected as a bolus into a flow phantom wh...

The practicability of using Overhauser enhancement of saline in interventional MRI was investigated. Saline was used as a means of marking the path taken by a fluid-filled cavity, similar to that formed by a needle, catheter, or cannula during interventional MRI procedures. A prototype device was designed and constructed for saturation and propulsi...

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium-3 (3He) MRI has been developed. The method employs the build-up of the signal intensity after a variable number of (3)He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fract...

Gadolinium chelates, intended as intravenous contrast media for magnetic resonance imaging, have been regarded as nonnephrotoxic and recommended to replace iodinated contrast media in patients with azotemia who are undergoing digital subtraction angiography (DSA). High intraarterial doses (up to 220 mmol of gadodiamide) have been used, with a 40% i...

Our arguments indicate that iodinated contrast media may in fact represent a lower toxic load on the body than equal-attenuating doses of gadolinium-based media.

An efficient noninvasive method for in vivo imaging of tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on tumor-bearing mice (squamous ce...

The gelation of sodium alginate by calcium ions is studied by proton-electron double resonance imaging in a magnetic field of only 16 mT using a newly developed free radical. The high sensitivity of the Overhauser enhancement to small variations in water mobility permits the detection of minute changes in gel composition. Spatial inhomogeneity and...

High nuclear spin polarization of (13)C was reached in organic molecules. Enhancements of up to 10(4), compared to thermal polarization at 1.5 T, were achieved using the parahydrogen-induced polarization technique in combination with a field cycling method. While parahydrogen has no net polarization, it has a high spin order, which is retained when...

A noninvasive method for in vivo measurement of the oxygen concentration has been developed. By introducing a novel contrast medium (CM) based on a single electron substance, it is possible to enhance the proton signal through the Overhauser effect. A low-field magnetic resonance scanner is used to image the proton nuclei of the object. The electro...

The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula (I) wherein n is 0 or 1; X is an amide group linked to the phenyl ring either by the nitrogen atom or by the carbon of the carbonyl group; R is H or a C1-4 alkyl group substituted by two or more -OH groups; R' is a C1-4 alkyl group optionally...

Parameters of relevance to oximetry with Overhauser magnetic resonance imaging (OMRI) have been measured for three single electron contrast agents of the triphenylmethyl type. The single electron contrast agents are stable and water soluble. Magnetic resonance properties of the agents have been examined with electron paramagnetic resonance (EPR), n...

To evaluate a new single-electron contrast agent for Overhauser-enhanced MR imaging. The contrast agents that are currently available give enhancement factors that are too low to make the technique a valid option for routine clinical use. MR images were generated directly following the injection of the substance into rats. The MR scanner was operat...

The invention relates to a modification of electron spin resonance enhanced magnetic resonance imaging (ESREMRI) in which two magnetically responsive materials (contrast agents) are introduced into the sample being investigated, one contrast agent serving as an ESREMRI free induction decay signal enhancing agent and the other as enhancement suppres...

The present invention provides the use of a persistent π-system free radical for the manufacture of a contrast medium for use in magnetic resonance imaging, wherein the electron delocalising π-system of said radical comprises at least one homo or heterocyclic ring, said radical being other than the chloranil semiquinone anion radical or a trityl ra...

Rationale and objectives: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. Methods...

The effects of the new nonionic dimeric hexa-iodinated contrast media (CM) iodixanol on renal function and morphology were investigated in 7 independent studies in rats, rabbits and monkeys and compared with other iodinated CM. No significant effect on serum creatinine levels was seen at doses up to and including 5 g I/kg in rats and 10.5 g I/kg in...

An attempt was made to assess the usefulness of using animal models to predict the neural tolerability in man of iodinated contrast media (CM) in general, and of the new nonionic dimer iodixanol in particular. For this purpose, the results from 6 animal experiments evaluating excitative and depressive effects of subarachnoidally injected CM in nona...

Previous studies showed that both high-osmolality and low-osmolality iodinated contrast media cause temporary albuminuria and enzymuria (presence of enzymes in urine) in normal rats. Whether the same is true with ionic high-osmolality and nonionic low-osmolality magnetic resonance (MR) contrast media is unknown. We studied urine profiles and histol...

Golman K, Grynne BH. Nonionic dimer x-ray contrast media: will they be of clinical benefit? Invest Radiol 1994;29:S230-S231.

Higher contrast between normal and pathologic tissues in the liver may enable detection of smaller lesions in computed tomography (CT). This can be obtained using a liver-specific contrast medium. The authors evaluate a new agent, IEEC (1'-Ethyloxycarbonyloxy)-ethyl-5-acetylamino-3-(N-methyl-acetylami no)-2,4,6- triiodo-benzenecarboxylate), in an a...

Previous studies have shown that iodinated contrast media may cause further renal dysfunction in tubulointerstitial nephropathy induced by gentamicin. The current investigation was undertaken to study whether the dysfunction after intravenous injection of a low-osmolar contrast medium is due to a chemotoxic and/or an osmotic effect. Urine profiles...

An MRI simulation method, together with a corresponding computer program, using the k-space formalism has been developed. It uses a FFT algorithm to generate the ideal NMR signal from a user defined object. The k-space trajectory given by a pulse sequence is calculated. And it is used to select elements from the ideal NMR signal. This selection of...

Contrast medium induced nephropathy may be defined as an acute impairment of renal function that follows exposure to radiographic contrast materials, and for which alternative etiologies have been excluded. Acute renal insufficiency has been reported following exposure to contrast media administered by intravenous and intra-arterial routes. Contras...

The authors compared the physiologic and nephrotoxic effects of the magnetic resonance imaging contrast medium gadopentetate with two conventional radiographic contrast media. Rabbits were injected intravenously with one of the following solutions: 1) gadopentetate (0.1 M); 2) iohexol (300 mg I/mL); 3) metrizoate (300 mg I/mL); and 4) NaCl (0.9%)....

Plasma clearance of nonionic iopamidol (300 mg I/ml) was measured in 50 patients in connection with enhanced CT. Before injection of either 50 or 100 ml of the contrast medium, S-creatinine and urine osmolality were measured. Employing Renalyzer PRX 90, the plasma concentration of iodine was determined in blood samples drawn approximately 3 and 4 h...

Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoa...

Thomsen HS, Vestergaard A, Nielsen SL, Fogh-Andersen N, Golman K, Dorph S. Renal clearance of an ionic high-osmolar and a nonionic low-osmolar contrast medium. Invest Radiol 1991;26:564-568. One hundred patients with normal serum creatinine concentration underwent intravenous urography with either an ionic high-osmolar (diatrizoate) or a nonionic l...

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme cr...

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got sal...

The authors investigated in a rat model the efficacy of magnetic resonance imaging (MRI) contrast media for evaluating the liver in conditions of acute biliary obstruction. Two liver-specific MRI contrast media, Cr-DEHIDA and Mn-DPDP, and the nonspecific agent Gd-DTPA were studied in normal rats and in rats whose bile ducts had been ligated before...

The nonionic iodinated contrast medium, iohexol, introduced for clinical urography, is eliminated from the human organism mainly by glomerular filtration. The aim of this study was to analyze the applicability of iohexol for glomerular filtration rate (GFR) measurement by comparing the plasma clearance of iohexol to the plasma clearance of the trad...

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly...

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused furthe...

Thirty-two children were given either metrizoate or iohexol for urography in a double blind study. Mild to moderate adverse reactions were observed in all patients receiving metrizoate (15/15) and in 4 receiving iohexol (4/17). Alkaline phosphatase in urine was significantly increased 4 hours after the injection of both media, but had returned to p...

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of th...

The effect of diatrizoate on the renal extraction of para-amino hippurate (EPAH) was studied in 8 healthy male volunteers. The contrast medium was injected into an antecubital vein and into a renal vein in each individual. A single-injection technique for the determination of EPAH was used and EPAH was measured before and over a period of 30 min af...

It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given...

Thirty-two children were given either metrizoate or iohexol for urography in a double blind study. Mild to moderate adverse reactions were observed in all patients receiving metrizoate (15/15) and in 4 receiving iohexol (4/17). Alkaline phosphatase in urine was significantly increased 4 hours after the injection of both media, but had returned to p...

A pharmacokinetic investigation of a paramagnetic Cr-HIDA derivative was performed. Blood, bile, and urine were collected during the first 2 hours after injection of Cr-HIDA 0.01, 0.05, and 0.25 mmol/kg in rats or rabbits. The pharmacokinetics of the substance were found to be similar to those of the biliary iodinated contrast media in common use....

This review deals with some recent animal and clinical investigations that show that small amounts of intravascular contrast media (CM) that remain in the body at the time of surgery and are the residual from a preoperative roentgen examination may increase (potentiate) the renal injury resulting from temporary intraoperative renal artery occlusion...

The acute intravenous toxicity (i.v. LD50) of solutions of the ratio 1.5 contrast media metrizoate or diatrizoate and the ratio 3.0 contrast medium metrizamide was determined in mice with and without the addition of local anesthetics to the solutions. The two local anesthetics mepivacaine or lidocaine were added to final concentrations up to 2.0 mg...

The relaxant effects of the ionic contrast media diatrizoate and ioxaglate and the nonionic agent iohexol on the vascular wall were examined by a sensitive in vitro system. Control solutions of NaCl and mannitol were used to evaluate the relative importance of osmolality to the vasodilation response. The rabbit central ear artery and the basilar ar...

Effects of equiosmolar solutions (osmolality 1.35 mol/kg) of the ratio 1.5 contrast medium metrizoate (250 mg I/ml) containing either the local anesthetic mepivacaine or saline were evaluated on subjective discomfort, aortic blood pressure and heart rate in 17 patients referred for aortofemoral angiography due to intermittent claudication. Each pat...

The metabolism of iopentol was examined in pigs. The search was focused on the urine and bile excreted during the first day after intravenous injection of a high dose. Chromatographic methods (both TLC and HPLC) indicated that the maximum amount of metabolites was less than 1 per cent of the given dose in urine and less than 0.3 per cent in the bil...

The potential usefulness in urography of two new non-ionic dimeric ratio 6 contrast media (iodixanol and cpd. 2-5410-4A) and a new non-ionic monomeric ratio 3 contrast medium, iopentol, was investigated in a rabbit model and compared with iohexol. Urinary iodine concentrations, urine flow, estimated attenuation capacity and radiographic scoring by...

The degree of albuminuria after selective nephroangiography was investigated in anaesthetized rats. Iopentol, iopromide, iodixanol and compound 2-5410-4A all caused a slight but not statistically significant increase in albuminuria when compared with the control group. After ioxaglate injection a high degree of albuminuria was observed which was st...

Contrast media are used in diagnostic radiology to enhance the X- ray attenuation between a body structure of interest and the surrounding tissue. A detail becomes perceptible on a roentgenogram only when its contrast exceeds a minimum value in relation to the background. Small areas of interest must have higher contrast than the background1. The c...

The non-ionic contrast medium metrizamide (370 mg I/ml) was injected into the cisterna magna of rabbits at 2 dose levels (0.1 ml/kg and 0.5 ml/kg) to investigate whether visually evaluated EEG can detect neurotoxicity at a lower dose level than a method based on observation and ranking of signs of excitation and depression in animal behaviour. Half...

Acute renal failure is a serious complication of reconstructive aortoiliac surgery. The question was raised whether its etiology includes interaction between preoperative angiographic contrast medium and intra-operative clamping of the renal arteries. Renal arteries of 180 rats were bilaterally clamped 10 to 120 min and serum urea was determined fr...

The contrast enhancement of low-osmolality (iohexol) and high-osmolality (diatrizoate) contrast media was compared in 18 pigs following intravenous bolus administration. Liver and blood attenuation and blood sample iodine concentration were measured during the first 3 minutes after injection. Iohexol produced a significantly higher contrast enhance...

Iohexol and meglumine-sodium diatrizoate were injected intravenously into 18 pigs as either a 99:1 or 1:99 mixture. Blood samples were taken for 30 minutes and the concentration of each of the two contrast media was measured by means of a double labeling technique with 125I and 131I. Relative concentrations of iohexol were significantly higher duri...