Electrolyte disturbances caused by intravenous contrast media.

The changes in serum electrolytes (sodium, potassium, ionized calcium, and total calcium) produced by high-dose (3 ml/kg) intravenous contrast media were investigated in Japanese white rabbits. The test solutions included sodium/meglumine diatrizoate (370 mgI/ml), sodium/meglumine ioxaglate (320 mgI/ml), iohexol (350 mgI/ml), iopamidol (370 mgI/ml), 20% mannitol, and isotonic saline. The alterations in serum ionized calcium were relatively small and transient, and correlated with changes in the hematocrit. Diatrizoate caused a significant decrease in ionized calcium in comparison with other contrast media and mannitol. The ratio of ionized calcium to total calcium showed no significant decrease in any group. The changes in potassium did not correlate with those in hematocrit. Diatrizoate caused a smaller decrease in potassium than low-osmolality contrast media, which may suggest that diatrizoate caused a shift in potassium from extravascular space to intravascular space. In conclusion, intravenous infusion of high doses of low-osmolality contrast media did not cause clinically significant alterations in serum electrolytes.     

Measurement of serum calcium concentration after administration of gadoversetamide in dogs

PURPOSE: To measure serum calcium concentration with three different analytic methods after administration of gadoversetamide and three other gadolinium chelates in dogs. MATERIALS AND METHODS: Six dogs were injected with 0.1-, 0.3-, 1.0-, and 3.0-mmol/kg doses of gadoversetamide; 1.0-mmol/kg doses of gadodiamide, gadopentetate, and gadoteridol; and a 6-mL/kg dose of saline. Baseline blood samples were collected before injection; 5, 15, 30, and 60 minutes after each treatment; and 2, 4, 6, 12, and 24 hours after each treatment. Serum calcium levels were measured with inductively coupled plasma mass spectrometry, an arzenazo III dye assay, and an orthocresolphalthalin (OCP) complexone system. Analysis of variance coupled with the Dunnett procedure was used to compare serum calcium concentrations at different time points after injection with baseline values. RESULTS: Administration of gadoversetamide caused no decrease in serum calcium levels, as measured with inductively coupled plasma mass spectrometry or arzenazo III analytic techniques. In contrast, OCP assays showed a significant (P <.05) decrease in serum calcium values after administration of gadoversetamide. The decrease in serum calcium values peaked immediately after injection, and serum calcium values quickly returned to baseline. Injection of gadodiamide caused a significant (P <.05) decrease in the value of serum calcium when analyzed with the OCP technique but not when analyzed with inductively coupled plasma mass spectrometry or arzenazo III assays. In contrast, administration of gadopentetate or gadoteridol produced no significant change in serum calcium values, regardless of analytic method. CONCLUSION: Gadoversetamide and gadodiamide caused a transient artifact in measurement of serum calcium levels with an OCP assay but not with an arzenazo III technique or inductively coupled plasma mass spectrometry. The presence of gadopentetate or gadoteridol in the blood did not affect measurement of serum calcium levels.     

Local tissue toxicity in response to extravascular extravasation of magnetic resonance contrast media

RATIONALE AND OBJECTIVES: The relative toxicities of the gadolinium chelates currently available in the United States were compared when extravasated in soft tissue. The increasing use of these contrast agents in higher volumes and at faster injection rates, often with a power injector, was a principal motivation for this research. METHODS: Gadopentetate dimeglumine (Magnevist), gadoteridol (ProHance), gadodiamide (Omniscan), and gadoversetamide (Optimark) were evaluated at standard concentration and compared with a control (physiologic saline) and the conventional ionic radiographic contrast medium meglumine diatrizoate (Renografin 60). Each mouse received a subcutaneous injection in the hindlimb of 0.3 mL of contrast or saline. There were 6 experimental groups, with 15 animals in each group. The individual performing the injection was blinded to the identity of the contrast agent used in each mouse. After 48 hours, the mice were killed and tissue samples obtained for histopathology. A veterinary pathologist, also blinded to the agent injected, graded the degree of damage seen on microscopic examination. RESULTS: Of the four MR contrast agents, gadopentetate dimeglumine caused the greatest tissue damage, and gadoteridol and gadodiamide-the two lowest osmolar agents-the least. The difference was statistically significant in terms of both inflammation (P = 0.0008 for gadoteridol, and P = 0.006 for gadodiamide) and necrosis (P = 0.0067 for gadoteridol, and P = 0.031 for gadodiamide), when these agents were compared with gadopentetate dimeglumine. In regard to the control experiments, for all three variables (necrosis, edema, and inflammation), there was no statistically significant difference between the results with gadoteridol or gadodiamide and those with saline. In terms of both edema and inflammation, the effect of gadopentetate dimeglumine, although less, could not be differentiated with any statistical significance from that of meglumine diatrizoate. Gadoversetamide, which has an osmolality between the ionic agent (gadopentetate dimeglumine) and the other two nonionic agents, caused a reaction that could not be differentiated from that seen with gadopentetate dimeglumine for both necrosis and edema. Only in the scoring of inflammation was the effect less using gadoversetamide compared to gadopentetate dimeglumine with any statistical significance (P = 0.021). CONCLUSIONS: The risk of tissue damage due to extravasation is not widely appreciated for the gadolinium chelates. Care should be exercised during contrast injection, to avoid inadvertent extravasation and its deleterious consequences, in particular with the two higher osmolar agents (gadopentetate dimeglumine and gadoversetamide).     

Effects of gadopentetate dimeglumine and gadodiamide on serum calcium, magnesium, and creatinine measurements

PURPOSE: To investigate the in vivo effects of gadodiamide (Gd-DTPA-BMA) and gadopentetate dimeglumine (Gd-DTPA) on the laboratory measurements of serum calcium, magnesium, and creatinine. MATERIALS AND METHODS: Medical records from 1993 to 2004 were reviewed to identify inpatients for whom laboratory data were available regarding serum calcium, creatinine, and magnesium levels before and within one day after gadodiamide and gadopentetate dimeglumine enhanced MRI. Patients who underwent both gadolinium (Gd)-enhanced MRI and iodinated contrast-enhanced examinations on separate days within a six-month period were also identified to compare changes in serum creatinine. RESULTS: Serum creatinine did not increase in 2788 cases following gadopentetate dimeglumine and gadodiamide injection. By comparison, serum creatinine increased from 1.21 to 1.28 mg/dL following iodinated contrast, and there were 20 cases (2.6%) of contrast-induced nephrotoxicity (P < 0.01). Gadopentetate dimeglumine did not affect serum calcium or magnesium measurements. Following 1157 gadodiamide-enhanced examinations, measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL (P < 0.0001) and 34 patients had spurious critical hypocalcemia (<6 mg/dL). Of 60 patients with high-dose gadodiamide injection and renal insufficiency, 36.7% (N = 22) had spurious critical hypocalcemia immediately post MRI. In 216 patients with renal insufficiency, the mean serum magnesium level increased slightly from 1.69 to 1.77 mEq/L following gadodiamide injection (P < 0.0001). CONCLUSION: Gd-based contrast agents are safe for MRI and MR angiography (MRA), and do not induce nephrotoxicity. However, gadodiamide interferes with serum calcium and magnesium measurements-particularly at high doses and/or with renal insufficiency.     

Effect of field strength on gadolinium enhancement in MR imaging

This studv was designed to evaluate the influence of magnetic field strength on the relative enhancement effect (RE) of gadolinium (Gd)-chelates. Dilution series of two paramagnetic contrast agents (Gd-DTPA and Gd-DOTA) were examined in three commercially available MR systems. operating at different field strengths (02 T, 1. T, and 1.5 T). The RE was plotted against Gd concentration. The highest increases in signal intensity occurred with Gd concentrations of approximately L.0 mmol/L. No significant difference in RE was observed between MR systems ranging in field strength from 0.? T to 1.5 T. The RE of Gd-DTPA and Gd-DOTA was found to he equivalent.     

Effects of ionic and non-ionic paramagnetic contrast media on brain bio-electric activity

The potential neurotoxic effects of gadolinium (Gd)-based compounds for enhanced MRI are not completely understood. We investigated electroencephalography changes induced by ionic and non-ionic Gd-based compounds administered intravenously in patients affected by lesions of the central nervous system (CNS) characterized by breakdown of the blood–brain barrier. This double-blind, randomized, study of two parallel groups involved 40 patients scheduled for an MRI examination with contrast medium for known CNS lesions. Twenty patients were randomly allocated to receive non-ionic Gd-DTPA-BMA/gadodiamide and 20 patients were randomly allocated to receive ionic Gd-DTPA/gadopentetate. For both groups the intravenous dose was 0.1 mmol/kg body weight. Three electroencephalography recordings were performed: immediately before, during, and 15 min after contrast medium injection. Mean and peak frequencies of the beta band and absolute power of the delta and/or theta bands of the electroencephalograms (EEGs) were noted. Each EEG was also evaluated to detect any alterations. The values of the 8–12 Hz band showed a significant increase during and after injection versus baseline in the gadopentetate group (P<0.05) and a significant decrease during injection in the gadodiamide group (P<0.05). The values of the 12–16 Hz band showed a significant increase versus baseline during and after injection in the gadopentetate group (P<0.05). The electrophysiological method based on computerised spectral analysis is a sensitive tool for evaluating effects of contrast media on brain bio-electric activity. EEG changes are detectable, even in the absence of any clinical evidence. It would appear that there might be clinical advantages in the use of non-ionic compounds.     

Renografin-60 for urography: effect on serum electrolytes and proteins in adults

A prospective study was done on 27 adults to assess the changes in serum electrolytes and proteins induced by bolus administration of 100 ml of the ionic contrast medium diatrizoate meglumine and sodium (Renografin-60) for IV urography. Statistically significant changes in serum sodium, chloride, potassium, calcium, bicarbonate, phosphate, total proteins, and albumin were shown at 5 min postinjection. The mean percentage decreases were sodium 2%, chloride 2%, potassium 9%, calcium 13%, bicarbonate 9%, phosphate 10%, and proteins 15%. A mean 3% increase in serum osmolality was observed. By 30 min, sodium and chloride levels had returned to baseline; potassium, calcium, and albumin values were incompletely recovered; bicarbonate was not significantly changed from 5 min; and phosphate values continued to decrease. An in vitro dialysis experiment in which different volumes of Renografin-60 were dialysed against an electrolyte solution (pseudoserum) produced a dilutional factor of 5 to render a given volume of the contrast isoosmotic with plasma. The observed changes from the baseline values of the electrolytes and proteins up to 10% are therefore assumed to be due to hemodilution resulting from movement of fluid from the extravascular to the intravascular compartment. This study confirms alterations in serum levels of several electrolytes after the use of ionic contrast media beyond simple hemodilution. Although these changes appear not to be clinically significant in this investigation, the alterations in potassium and calcium may contribute to arrhythmias, particularly when hypokalemia or hypocalcemia preexists.     

Cardiovascular effects caused by rapid administration of gadoversetamide injection in anesthetized dogs

RATIONALE AND OBJECTIVES: This study assessed the cardiovascular effects of gadoversetamide and other gadolinium chelates administered at high rates of injection. METHODS: Anesthetized beagles were instrumented to record the electrocardiogram and to measure arterial blood pressure. In part 1, each animal was injected with gadoversetamide at rates of 1.0, 3.0, and 10 mL/s. In part 2, each animal was injected with gadoversetamide, gadopentetate dimeglumine, gadodiamide, and gadoteridol at a dose of 0.6 mmol/kg delivered at a rate of 3.0 mL/s. RESULTS: Intravenous administration of gadoversetamide caused transient decreases in both heart rate and blood pressure. The rate of injection did not affect the magnitude of the heart rate or blood pressure changes. Administration of gadoversetamide, gadopentetate dimeglumine, and gadodiamide elicited equivalent changes in cardiovascular function. Injection of gadoteridol caused a similar degree of hypotension, but the changes lasted longer. CONCLUSIONS: Rapid administration of gadoversetamide caused no potentiation in cardiovascular changes. Our data support the initiation of a clinical trial to demonstrate the safety of rapidly administering gadoversetamide with the use of a power injector.     

Extracellular gadolinium contrast agents: differences in stability

Extracellular gadolinium contrast agents (Gd-CA) are either linear or macrocyclic chelates available as ionic or non-ionic preparations. The molecular structure whether cyclic or linear and ionicity determines the stability of Gd-CA. Linear chelates are flexible open chains which do not offer a strong binding to Gd³⁺. In contrast, the macrocyclic chelates offer a strong binding to Gd³⁺ by the virtue of being preorganized rigid rings of almost optimal size to cage the gadolinium atom. Non-ionic preparations are also less stable in comparison to the ionic ones as the binding between Gd³⁺ with the negatively charged carboxyl groups is stronger in comparison to that with amides or alcohol in the non-ionic preparations. According to stability constants and kinetic measurements, the most stable Gd-CM is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents are the non-ionic linear chelates gadodiamide and gadoversetamide. In vivo data confirmed the low stability of non-ionic linear chelates but no significant difference was observed amongst the macrocyclic agents whether ionic (Gd-DOTA) or non-ionic such as Gd-HP-DO3A and Gd-BT-DO3A. The stability of Gd-CA seems to be an important factor in the pathogenesis of the serious complication of nephrogenic systemic fibrosis. Gd-CA of low stability are likely to undergo transmetallation and release free Gd ions that deposit in tissue and attract circulating fibrocytes to initiate the process of fibrosis. No cases of NSF have been observed so far after the exclusive use of the stable macrocyclic Gd-CA.     

A preclinical study to investigate the development of nephrogenic systemic fibrosis: a possible role for gadolinium-based contrast media

OBJECTIVES: Several recent publications have suggested an association between the administration of gadolinium (Gd)-based contrast agents and the occurrence of Nephrogenic Systemic Fibrosis (NSF), an acquired disorder marked by skin thickening and fibrosis occurring in patients with severe renal dysfunction. The aim of this study was to establish a preclinical experimental setting to investigate the possible link between NSF and Gd-based contrast agents, and specifically the role of Gd and/or depletion of endogenous metal ions as possible triggers for NSF. MATERIALS AND METHODS: Thirty-five healthy male rats received repeated intravenous injections of Magnevist (gadopentetate dimeglumine; Gd-DTPA), Omniscan (gadodiamide; Gd-DTPA-BMA), or gadodiamide without caldiamide at a dose of 2.5 mmol Gd/kg body weight over at least 20 days to simulate the exposure to Gd-containing contrast agents in patients with severe renal dysfunction. In addition, caldiamide (the excess ligand in Omniscan) and Gd-ethylenediamine tetraacetic acid (Gd-EDTA) as a positive control, and saline as a negative control were studied. Histopathologic and immunohistochemical analysis of the skin was performed. Gd and zinc concentrations were measured in skin, femur, and liver tissue by atomic emission spectrometry. RESULTS: Rats receiving Gd-EDTA, gadodiamide without caldiamide, and Omniscan developed epidermal ulceration and acanthosis, dermo-epidermal clefts, minimal-to-slight dermal fibrosis, and increased dermal infiltration of different cells, partly positive for CD34 fibrocytes. No such NSF-like macroscopic lesions were observed in the saline, caldiamide, and Magnevist groups. High Gd concentrations in the skin were found in the Gd-EDTA, gadodiamide without caldiamide, and Omniscan groups. In the Magnevist group, Gd levels in the skin were 10-times lower than in the Omniscan-treated animals but elevated compared with saline. CONCLUSIONS: A preclinical experimental setting has been established where NSF-like lesions could be observed. The link between the application of Gd-based contrast media and the induction of NSF-like lesions was established. The data indicate that the observed skin lesions are related to the release of Gd and not to the depletion of endogenous ions. The investigations further suggest potential importance of the stability of Gd-based contrast agents.     

Gadolinium-DOTA enhanced MR imaging of intracranial lesions

Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (Gd-DOTA) is the first of a new class of macrocyclic paramagnetic magnetic resonance (MR) contrast agents (gadolinium cryptelates) to be used in clinical practice. Gadolinium-DOTA possesses relaxation properties similar to those of gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). We report our initial clinical experience in 38 patients with intracranial lesions studied with MR before and after injection of Gd-DOTA. Diseases included primary and metastatic brain tumor, cerebral infarct, vascular malformation, meningioma, hemangiopericytoma, schwannoma, and pituitary macroadenoma. Gadolinium-DOTA was administered intravenously in a dosage of 0.1 mmol/kg body weight. All studies were performed on a superconductive 0.5 T system. As compared to noncontrast T1- and T2-weighted images (WI), Gd-DOTA enhanced T1 WI were useful in defining the anatomy of malignant intraaxial tumors (high-grade glioma, metastasis) and in tumor versus edema differentiation. Low-grade gliomas did not enhance; in these cases the precontrast T2-weighted sequence was found to be more informative. In post-operative patients, Gd-DOTA allowed us to demonstrate residual tumor or tumor recurrence. Extraaxial tumors (meningioma, hemangiopericytoma, neuroma) enhanced markedly, presumably reflecting tumor vascularity. In our experience, the use of Gd-DOTA improves the anatomic definition of cerebral lesions and in some cases increases both MR sensitivity and specificity. We found Gd-DOTA to be a well tolerated and effective paramagnetic contrast agent. Gadolinium-DOTA can be considered as an alternative water-soluble MR contrast agent to Gd-DTPA.     

Intraindividual comparison of gadopentetate dimeglumine,gadobenate dimeglumine,and gadobutrol for pelvic 3D magnetic resonance angiography

RATIONALE AND OBJECTIVES: To compare the effect on image quality of a 1.0 mol/L gadolinium chelate with that of two 0.5 mol/L gadolinium compounds. MATERIALS AND METHODS: Five healthy volunteers underwent a mono-station 3D MRA exam (Siemens SONATA, Erlangen, Germany) four times using four separate gadolinium preparations. All subjects first received a fixed volume of undiluted gadobutrol (1 mol/L), which corresponded to a dose between 0.1 and 0.15 mmol/kg body weight. This gadobutrol dosage was then diluted with saline into twice the volume and administered as a bolus at twice the injection rate. For Gd-DTPA and Gd BOPTA, because these contrast agents are 0.5 mol/L preparations, the volume and flow rate were doubled to match diluted gadobutrol volume and concentration. Quantitative and qualitative analysis of the angiographic data sets was performed on nine arterial segments. RESULTS: Image quality was rated diagnostic for all image data sets without statistically significant differences between any of the compounds (P > 0.3). Quantitative measurements of Gd BOPTA (SNR: 81.15; CNR: 68.91) and both standard and diluted forms of gadobutrol (SNR: 84.33; CNR: 71.62; SNR(diluted): 79,23; CNR(diluted): 66.26) yielded significantly higher results (P < 0.02) in comparison with Gd-DTPA (SNR: 49.55; CNR: 38.24). The difference between either form of gadobutrol and Gd BOPTA was not shown to be statistically significant (P > 0.3), whereas both the SNR and CNR of standard gadobutrol were significantly higher than diluted gadobutrol. CONCLUSION: Gadobutrol- and Gd BOPTA-MRA exams lead to improved delineation of the pelvic arterial morphology compared with MRA exams performed with Gd-DTPA.     

Enhancement of intervertebral disks with gadolinium complexes: comparison of an ionic and a nonionic medium in an animal model.

PURPOSETo compare MR contrast enhancement of intervertebral disk tissue after intravenous administration of equimolar doses of an ionic and of a nonionic gadolinium complex.METHODSContrast enhancement was measured on MR in lumbar intervertebral disks for 120 minutes after intravenous injection of gadoteridol or gadopentetate dimeglumine, 0.3 mmol/kg. MR studies were performed with each contrast medium in four rabbits. Contrast enhancement was measured in intervertebral disks as a function of time and contrast medium.RESULTSWith both contrast media, enhancement of normal intervertebral disks was detected. Enhancement of disks was significantly greater with gadoteridol than with gadopentetate dimeglumine.CONCLUSIONThe enhancement of cartilage is influenced by the molecular structure of the gadolinium complex. The negative charge of gadopentetate dimeglumine may give it a slower rate of diffusion into disk cartilage than a nonionic complex.     

Comparison of iron oxide particles (AMI 227) with a gadolinium complex (Gd-DOTA) in dynamic susceptibility contrast MR imagings (FLASH and EPI) for both phantom and rat brain at 1.5 Tesla

The goal of the study was to compare, in phantom and normally perfused rat brain tissue, a superparamagnetic iron oxide particle-based contrast agent (AMI 227) with a low-molecular-weight gadolinium chelate, gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA), in two susceptibility contrast magnetic resonance imaging (MRI) modes [fast low-angle shot sequence (FLASH) and echoplanar imaging (EPI)]. A phantom consisting of dilution series of both contrast agents was manufactured. Dilutions were obtained with isotonic serum from the available agent solutions (0.5 mmol Gd/mL Gd-DOTA; 350 mumol Fe/mL AMI 227). Eighteen rats were studied. Contrast agent (0.1 mL) was bolus injected in each rat, and dynamic MRI was performed (first pass of the contrast agent) in rat brain. The doses of AMI 227 injected were extrapolated from the phantom experiment: 0.2 mmol/kg body weight of Gd-DOTA and 7, 14, and 28 mumol Fe/kg body weight of AMI 227 were injected. For both sequences, signal-to-noise ratios (S/N) were measured on each tube of the phantom and on rat brain from each image of the dynamic imaging. S/N was plotted versus contrast dilution (phantom) and versus time (rats). In the FLASH sequence, a well-shaped curve (S/N decrease, S/N peak decrease, S/N increase) of the first pass of the contrast agent was demonstrated for Gd-DOTA and for AMI 227 (7 mumol Fe/kg body weight). In the EPI sequence, a well-shaped curve was demonstrated for Gd-DOTA, and a plateau effect was noted for both concentrations of AMI 227. With the FLASH technique, dynamic susceptibility contrast imaging of rat brain can be performed with very low concentrations of AMI 227 compared with the Gd-DOTA concentration (0.2 mmol Gd/kg body weight) used in clinical practice. This could be of interest in perfusion imaging, because it may allow for first-pass susceptibility imaging after administration of a small volume in a narrow bolus.     

Vascular response to gadolinium-containing contrast media in an ex vivo rabbit arterial model

RATIONALE AND OBJECTIVES: To assess the influence of gadolinium-containing magnetic resonance contrast agents on contractility of the arterial vessel wall. METHODS: Bilateral segments of rabbit carotid arteries were mounted in flow chambers, surrounded by aerated (95% O2, 5% CO2) Krebs' solution, and perfused at a constant rate by separated and aerated Krebs' solution. Therefore, changes in pressure of the circulating Krebs' solution indicated alterations of vessel wall contractility. Viability of the artery was tested by 124 mmol/L KCl, 3 x 10-5 mol/L phenylephrine, and 10-5 mol/L acetylcholine. After a washout phase, gadopentate (n = 10) or gadoteridol (n = 10) was added to the perfusate of one carotid artery in increments of 0.1, 0.3, and 0.6 mmol/L. Concentrations up to 0.9 mmol/L and 1.2 mmol/L were tested, respectively. The contralateral artery served as a control. To assess potential relaxing effects of the media, vessels were brought into a contracted status with 3 x 10-5 mol/L phenylephrine and then received gadolinium chelates. RESULTS: Potassium chloride and phenylephrine increased and acetylcholine decreased the pressure, indicating vasoconstriction and vasodilatation, respectively. After gadopentate and gadoteridol infusion, no statistically significant pressure changes could be detected, ruling out any vasoconstrictor or vasodilator effect. CONCLUSIONS: Gadopentetate and gadoteridol in doses of up to 1.2 mmol/L did not alter vessel wall tone. The impact of contrast media on blood pressure, as has been shown in some clinical trials, probably is not due to direct changes in arterial wall tone.     

Ionic versus nonionic MR imaging contrast media: operational definitions.

An experimental rationale is provided to differentiate between the terms ionic and nonionic for magnetic resonance (MR) imaging contrast media such as gadodiamide and gadopentetate dimeglumine. Four independent types of physical measurements (electric conductivity, osmolality, electrophoresis, and ion exchange) were performed on a range of test compounds, including D-glucose, iohexol, gadopentetate dimeglumine, and gadodiamide. Iohexol, D-glucose, and gadodiamide are shown to be nonionic species at physiologic pH (7.4), not measurably dissociating in solution. A range of gadopentetate salts behave as electrolytes, dissociating into constituent charged ions in aqueous media. Operational definitions for the terms ionic and nonionic are provided, and the terms neutral and net zero charge are compared with nonionic for accuracy. The nomenclature nonionic and ionic is deemed appropriate for differentiating MR imaging contrast media.     

Ionized calcium levels in coronary sinus blood during coronary angiography: effects of four contrast media.

The changes in ionized calcium level in the coronary sinus during coronary angiography were compared for four contrast media (meglumine sodium diatrizoate, iohexol, iopamidol, and meglumine sodium ioxaglate) in 44 subjects. Blood samples were collected before and 5, 15, and 30 seconds after injection of contrast medium into the left coronary artery. The hematocrit and ionized calcium level of each specimen were measured. Meglumine sodium diatrizoate produced the largest changes in hematocrit and ionized calcium level. The time-concentration curve of the hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease of ionized calcium. The cause of this is not clear, but the phenomenon may be related to differences of ionic status among the contrast media. With respect to maintenance of the ionized calcium level, nonionic low-osmolality contrast medium with added calcium may be preferable for coronary angiography.     

Gadodiamide administration causes spurious hypocalcemia

PURPOSE: To evaluate the prevalence of spurious hypocalcemia after gadodiamide-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eight hundred ninety-six inpatients with available serum calcium data obtained before and after gadodiamide-enhanced MR imaging were identified. Changes in serum calcium measurements following gadodiamide administration in 1,049 MR imaging examinations performed in these patients were correlated with gadodiamide dose, renal function, and time between gadodiamide administration and phlebotomy. RESULTS: Following 42 gadodiamide-enhanced examinations, serum calcium measurements spuriously decreased by more than 2 mg/dL (0.5 mmol/L), resulting in laboratory reports of "critical" hypocalcemia (ie, calcium level < 6 mg/dL [1.5 mmol/L]) in 25 examinations. These reduced calcium measurements were correlated with serum creatinine level (r = 0.39, P <.001), gadodiamide dose (r = 0.37, P <.001), and time between gadodiamide injection and phlebotomy (r = -0.28, P <.001). Spurious reductions in calcium measurements after administration of 0.1 mmol of gadodiamide per kilogram of body weight were greater in patients with renal insufficiency (0.6 mg/dL [0.15 mmol/L] +/- 0.5 [0.125, SD]) than in those with normal renal function (0.14 mg/dL [0.035 mmol/L] +/- 0.4 [0.1]) (P <.001). After administration of more than 0.2 mmol/kg of gadodiamide, spurious calcium measurement decreases were greater in patients with renal insufficiency (2.4 mg/dL [0.6 mmol/L] +/- 3.6 [0.9]) than in those with normal renal function (0.4 mg/dL [0.1 mmol/L] +/- 0.7 [0.175]) (P <.001). Patients with renal insufficiency had spuriously low calcium measurements up to 4(1/2) days after gadodiamide administration. Seven patients were inappropriately treated with intravenous calcium and eleven with oral calcium in response to false-positive laboratory reports of critical hypocalcemia. No patient had characteristic symptoms of hypocalcemia or injuries attributed to the inappropriate medical treatment. CONCLUSION: Gadodiamide administration causes spurious hypocalcemia, particularly at doses of 0.2 mmol/kg or higher and in patients with renal insufficiency.     

Effect of tamoxifen in an experimental model of breast tumor studied by dynamic contrast-enhanced magnetic resonance imaging and different contrast agents

OBJECTIVES: The aim of this study was to compare the efficacy of gadoteridol, B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37-albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor implanted in rats. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10 mammary adenocarcinoma cells (13762 MAT B III). Treatment with tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and, 24 hours later, using (Gd-DTPA)37-albumin. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging data showed that tamoxifen treatment decreased vascular permeability to B22956/1, whereas no difference was detectable in permeability to gadoteridol or to (Gd-DTPA)37-albumin. No effect on fractional plasma volume was detected with either of contrast agents. CONCLUSIONS: B22956/1 is superior to both small Gd chelates and macromolecular contrast agents in the assessment of the effect of tamoxifen treatment on tumor vasculature.     

Alteration of the ionized calcium level in coronary sinus blood during coronary arteriography]

Injection of contrast medium into the coronary circulation produces a decrease in the concentration of ionized calcium in blood and thus causes a deterioration of myocardial contractility. In this study, changes in the ionized calcium level in the coronary sinus during coronary arteriography were compared for four different contrast media in human subjects. The contrast media used were meglumine sodium diatrizoate, iohexol, iopamidol and meglumine sodium ioxaglate. Blood samples were collected from the coronary sinus before and 5, 15 and 30 seconds after the first injection of contrast medium into the left coronary artery. The ionized calcium level of each specimen was measured using an ion specific electrode, and hematocrit was measured using the centrifuge method. Diatrizoate produced the greatest changes in both hematocrit and ionized calcium. The time concentration curve of hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease in ionized calcium. The cause of this phenomenon is not clear, but it may be related to differences in the ionic status of the contrast media. Nonionic low-osmolality contrast media with added calcium may be preferable for coronary arteriography with respect to maintenance of the ionized calcium level.