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Gadolinium, a mechano-sensitive channel blocker, inhibits osmosis-initiated motility of sea- and freshwater fish sperm, but does not affect human or ascidian sperm motility.

Exposure to hypo-osmotic or hyperosmotic environment triggers the initiation of fish sperm motility. In this article, we report that calcium and potassium channel blockers do not influence motility of puffer fish sperm but calmodulin antagonists reversibly decrease it, suggesting that calmodulin-Ca(2+) interactions are prerequisite for the initiation of sperm motility in this species. Gadolinium (a stretch activated ion channel blocker) decreased the motility of puffer fish sperm from 92 +/- 3% to 6 +/- 3% and that of carp sperm from 91 +/- 7% to 3.5 +/- 4.3% in a dose-dependent manner (10-40 micro M). The effect of gadolinium was reversible, suggesting that stretch activated ion channels participate in the initiation of sperm motility of the two species. Gadolinium inhibits changes in the isoelectric point of certain proteins of puffer fish sperm, which occur when sperm motility is initiated in a hypertonic solution. Anisotropy measurements showed that hypo-osmotic treatment, which initiates carp sperm motility, increased membrane fluidity. When hypo-osmotic treatment was given in the presence of gadolinium, the sperm membrane remained as rigid as in quiescent cells, while motility was blocked. By contrast, gadolinium did not influence the motility parameters of Ciona or human sperm. Based on these lines of evidence, we suggest that conformational changes of mechanosensitive membrane proteins are involved in osmolality-dependent but not osmolality-independent sperm.

Animals↗

Wash-in kinetics for gadolinium-enhanced magnetic resonance imaging of carotid atheroma.

PURPOSE: To determine the wash-in kinetics of intravenous gadolinium into the fibrous cap and lipid core of carotid atheroma, and identify the time following gadolinium administration that maximizes contrast between the cap and core. MATERIALS AND METHODS: Seven subjects with carotid artery stenosis were studied. Magnetic resonance (MR) images of the atheroma were acquired using a single-inversion-recovery fast-spin-echo (IR FSE) sequence, which was serially repeated during the first 30 minutes following intravenous gadolinium administration. Postcontrast time was divided into three intervals: <10, 11-20, and >21 minutes. Adjusted signal intensity (SI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) values for postcontrast images were compared to adjusted precontrast values. RESULTS: The mean SNRs of the cap and core were significantly elevated in each postcontrast interval compared with mean precontrast values. The CNRs of the cap vs. the core increased by 19.8% (3.03 to 4.14, P = 0.03) in the first 10 minutes following gadolinium administration, and remained elevated over the next two intervals with a slight decrease in the final interval. CONCLUSION: Increased signal and contrast between the cap and core can be achieved by imaging up to 30 minutes following gadolinium administration, with peak enhancement occurring in the first 10 minutes.

Aged↗

Ionic association and electron spin relaxation rates in aquo gadolinium (III) complexes.

The electron paramagnetic resonance linewidth of aquo gadolinium(III) ion changes with the counter-ion identity and concentration in aqueous solutions. The EPR linewidth of 2 mM gadolinium(III) chloride increases from 49.2 to 89.0 mT when carbonate ion is added and decreases to 17.3 mT when nitrite ion is added. These observations suggest association reactions between aquo gadolinium(III) ion and anions that change the electron spin relaxation rates of the aquo ion. The concentration dependence of the gadolinium(III) EPR linewidth is consistent with binding constants for nitrite and nitrate ion with the aquo gadolinium(III) ion of 37 +/- 6 and 2.3 +/- 0.3 L mol-1 respectively. The decreases in the EPR linewidth factors with these association reactions are difficult to understand unless the anion reactions increase the symmetry of the metal center. Although first-coordination reactions may not be ruled out, the decrease in EPR linewidth is more consistent with an outer-sphere association reaction that also reduces the coordination number of the metal center from 9 to 8.

Animals↗

Liver cysteine proteinases in macrophage depression induced by gadolinium chloride.

Liver lysosomal enzymes during macrophage depression (gadolinium chloride, 7 mg/kg, intravenously) and macrophage stimulation (zymosan, 100 mg/kg, intravenously) have been studied. It was shown that gadolinium chloride treatment of rats reduced the rate of carbon particles phagocytosis at 24 and 48 h after the single administration. Decreased endocytic capacity of Kupffer cells was confirmed also by electron microscopy. Gadolinium chloride induced labilization of liver lysosomes (increased free activity of cathepsins B and L); there was no changes of specific activity of liver cysteine proteinases (24 h). Gadolinium chloride prevented death of rats after administration of non-sonicated particular zymosan particles, resulting to 70% survival, compare with the 17% survival in group with zymosan alone. We can summarize that macrophages depression by gadolinium chloride abolish symptoms of inflammation in zymosan-model, influencing on cysteine proteinases of Kupffer cells.

Animals↗

Mixed micelles containing lipophilic gadolinium complexes as MRA contrast agents.

Mixed micelles for MRA are multicomponent systems containing a phospholipid, a biocompatible non-ionic surfactant (e.g. Synperonic(R) F-108) and a lipophilic gadolinium complex. A variety of lipophilic gadolinium complexes were designed taking into account features such as: (i) nature of ligand (cyclic versus acyclic); (ii) lipophilic moiety; (iii) global charge of the complex; and (iv) nature of bond connecting the complex to the lipophilic moiety. All the lipophilic gadolinium complexes after formulation as mixed micelles show high relaxivities in water and in blood (rat). Mixed micelles containing gadolinium complexes bearing only one aliphatic chain cannot be used as MRA contrast agents because they have a high haemolytic effect. Furthermore, in rats they are quickly eliminated from the blood stream. These drawbacks are completely circumvented using gadolinium complexes bearing two aliphatic chains. Mixed micelles containing such complexes show high relaxivities, no haemolytic effect and long blood permanence. This makes them promising candidates as MRA contrast agents. However, elimination, which occurs exclusively through the liver, is not complete, even after 7 days. Complexes containing labile (e.g. ester) bonds between the lipophilic moieties and the chelate subunit are eliminated through both the liver and the kidneys. However, elimination is still not complete after 7 days.

Animals↗

In vitro studies of gadolinium-DTPA conjugated with monoclonal antibodies as cancer-specific magnetic resonance imaging contrast agents.

The monoclonal antibodies, 9.2.27 against human melanoma cell lines and WM53 against leukemia cell lines, were conjugated with cyclic anhydride gadolinium-diethylenetriaminepenta-acetic acid (Gd-cDTPAa) and used as tumor-specific contrast agents in magnetic resonance imaging (MRI). The data indicate that Gd-DTPA-9.2.27 in solution decreased the T1 relaxation of water protons at 7.0 Tesla (300 MHz) in direct proportion to the gadolinium concentration, and this effect was greater than in Gd-DTPA solutions. These conjugates show high specificity for melanoma and leukemia cell lines. T1 relaxation time at 7.0 Tesla, measured for the melanoma cell line (MM-138) and leukemia cell line (HL-60) after incubation at 37 degrees C for 4 hr, were significantly decreased (approximately 25%) relative to controls. The gadolinium concentration in cells and washing solutions was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). A linear relationship was observed between T1 relaxation rates and gadolinium concentrations obtained by ICP-AES. The ICP-AES results showed no gadolinium uptake in the non-targeted HT-29 colorectal cancer cells.

Animals↗

Improvement of post-gadolinium contrast with magnetization transfer.

Magnetization transfer (MT) provides post-gadolinium contrast improvement through decreasing the tissue signal. Our study had two aims: to analyse the effect of MT qualitatively and quantitatively in 13 patients, and to analyse in vitro the competition between two relaxation phenomena, dipole-dipole which is characteristic of MT and proton - electron which is characteristic of gadolinium. Contrast between lesion and white matter improved from 20.6 % before MT to 65.1 % after MT, enabling new lesions to be detected in two patients. The improvement was due mainly to the proton - electron effect of gadolinium rather than the dipole relaxation of MT. These results are in agreement with those in the literature. The existence of spontaneous high-signal induced by MT in the absence of gadolinium indicates that it is preferable to perform an MT sequence before and after administration of gadolinium.

Adolescent↗

Brain MR post-gadolinium contrast in multiple sclerosis: the role of magnetization transfer and image subtraction in detecting more enhancing lesions.

Our purpose was to evaluate the role of magnetization transfer and image subtraction in detecting more enhancing lesions in brain MR imaging of patients with multiple sclerosis (MS). Thirty-one MS patients underwent MR imaging of the brain with T1-weighted spin echo sequences without and with magnetization transfer (MT) using a 1.5 T imager. Both sequences were acquired before and after intravenous injection of a paramagnetic contrast agent. Subtraction images in T1-weighted sequences were obtained by subtracting the pre-contrast images from the post-contrast ones. A significant difference was found between the numbers of enhanced areas in post-gadolinium T1-weighted images without and with MT (p=0.020). The post-gadolinium T1-weighted images with MT allowed the detection of an increased (13) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. A significant difference was also found between the numbers of enhanced areas in post-gadolinium T1-weighted images without MT and subtraction images without MT (p=0.020). The subtraction images without MT allowed the detection of an increased (10) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. Magnetization transfer contrast and subtraction techniques appear to be the simplest and least time-consuming applications to improve the conspicuity and detection of contrast-enhancing lesions in patients with MS.

Adult↗

Gadolinium-enhanced magnetic resonance angiography in neonates and infants suspected of caval or aortic thrombosis.

BACKGROUND: Gadolinium-enhanced magnetic resonance angiography (MRA)is a well-established technique in older children and adults. No studies have focused on its use in neonates and small infants. OBJECTIVE: Our objective was to study the use of gadolinium-enhanced MRA in neonates and infants suspected of caval or aortic thrombosis. MATERIALS AND METHODS: Gadolinium-enhanced MR angiography was performed on seven neonates and small infants for the evaluation of caval or aortic thrombosis. Gadolinium-DTPA at a dose of 0.3 mmol/kg (minimum dose 1 ml) was injected using a power injector (0.2 ml/s). Contrast-enhanced MRA was performed using a 3-D, fast, radiofrequency spoiled gradient-echo sequence (TR/TE: 4.8/1.1, flip angle 45 degrees , matrix 256 x 128, slice thickness 2.6 mm interpolated to 1.3 mm, FOV variable, NEX=1.0). RESULTS: Diagnostic-quality angiograms were obtained in all seven neonates. Superior vena cava thrombosis was identified in two neonates, and abdominal aortic thrombosis was present in one neonate. CONCLUSION: It is practical to perform gadolinium-enhanced MRA in neonates weighing as little as 600 g for the detection of caval or aortic thrombosis.

Aorta, Abdominal↗

The use of iodinated and gadolinium contrast media during pregnancy and lactation.

The use of iodinated or gadolinium-based contrast media in pregnant or lactating women often causes concerns in the radiology department because of the principle of not exposing a fetus or neonate to any drugs. Because of the uncertainty about the use of contrast media during pregnancy and lactation, the Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and draw up guidelines. An extensive literature search was carried out and summarized in a report. Based on the limited information available, simple guidelines have been drawn up. The report and guidelines were discussed at the 11th European Symposium on Urogenital Radiology in Santiago de Compostela, Spain. Mutagenic and teratogenic effects have not been described after administration of gadolinium or iodinated contrast media. Free iodide in radiographic contrast medium given to the mother has the potential to depress fetal/neonatal thyroid function. Neonatal thyroid function should be checked during the 1st week if iodinated contrast media have been given during pregnancy. No effect on the fetus has been seen after gadolinium contrast media. Only tiny amounts of iodinated or gadolinium-based contrast medium given to a lactating mother reach the milk, and only a minute proportion entering the baby's gut is absorbed. The very small potential risk associated with absorption of contrast medium may be considered insufficient to warrant stopping breast-feeding for 24 h following either iodinated or gadolinium contrast agents.

Contrast Media↗

Value of gadolinium-diethylene-triamine pentaacetic acid dynamics in magnetic resonance imaging of acute myocardial infarction with occluded and reperfused coronary arteries after thrombolysis.

The use of the paramagnetic contrast agent gadolinium-diethylene-triamine pentaacetic acid (DTPA) was evaluated in magnetic resonance imaging (MRI) of 18 patients with an acute myocardial infarction after thrombolysis. The patency of the infarct-related vessel was assessed by coronary angiography. At 58 +/- 9 hours after infarction MRI was performed before and after bolus injection of 0.1 mmol/kg gadolinium-DTPA. Myocardial signal intensities were measured using a circumferential profile. Normal and infarcted myocardium showed a maximum signal intensity enhancement of 35 and 66%, respectively. Signal intensity of infarcted relative to normal myocardium (I/N) increased from 1.06 +/- 0.16 before to a maximum of 1.39 +/- 0.13 after gadolinium-DTPA (p less than 0.001), whereas the contrast between normal myocardium and a pseudo-infarct region in 2 healthy volunteers did not change. Between patients with reperfused infarct-related vessels and occluded vessels without collaterals, maximum I/N did not differ. However, observing I/N as a function of time after injection of gadolinium-DTPA, the reperfusion group differed from the occlusion group on images acquired directly after injection (1.29 +/- 0.10 vs 1.14 +/- 0.05, p less than 0.02). Thus, gadolinium-DTPA enhanced the visualization of acute myocardial infarction on relatively longitudinal (T1)-weighted MR images and its dynamics seem of potential value for the noninvasive assessment of coronary artery reperfusion after thrombolysis.

Adult↗

Determination of optimal gadolinium concentration using SSFP for catheter-directed contrast-enhanced coronary MR angiography.

RATIONALE AND OBJECTIVES: To determine the optimal gadolinium concentration for catheter-directed coronary magnetic resonance angiography (MRA) using magnetization-prepared steady-state free-precession (SSFP) in swine. MATERIALS AND METHODS: In six pigs, we performed real-time MR imaging-guided coronary artery catheterization using a 1.5 T MR scanner. For catheter-directed coronary MRA, we injected 3-4 mL of dilute Gd at 1 mL/second for each tested concentration (4%, 8%, 10%, and 12% Gd). Eleven images per concentration were acquired using electrocardiographic-triggered, magnetization-prepared two-dimensional (2D) projection SSFP. We compared mean relative signal-to-noise ratio (SNR) values for each concentration using two-way analysis of variance. RESULTS: The targeted coronary artery was catheterized under real-time MR guidance in all pigs. Magnetization-prepared 2D projection SSFP successfully depicted the coronary arteries in all 44 injections. Mean relative SNR (+/- standard error) was 7.2 +/- 0.49 for 4%, 8.8 +/- 0.47 for 8%, 9.5 +/- 0.38 for 10%, and 8.8 +/- 0.41 for 12%. Injections of 4% dilute gadolinium yielded significantly less relative SNR than the other tested concentrations (P < .05). There were no statistically significant differences between the remaining concentrations. CONCLUSION: For catheter-directed contrast-enhanced coronary MRA, the ideal gadolinium concentration should maximize relative SNR and limit the total gadolinium dose. Using these criteria, of those concentrations we tested in the swine model, 8% injected gadolinium was superior for catheter-directed SSFP coronary MRA.

Analysis of Variance↗

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy.

BACKGROUND: In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients. AIMS: We prospectively investigated whether the pattern of late gadolinium enhancement correlates with myocardial biopsy findings. METHODS AND RESULTS: 42 patients with DCM and 42 control subjects underwent contrast MRI. In the DCM group, endomyocardial biopsies were performed and evaluated for inflammation and viral genome. None of the control subjects showed late gadolinium enhancement whereas in 29 DCM patients (69%) gadolinium enhancement was detectable (p<0.001). 21 of the DCM patients (50%) showed midwall septal enhancement, 7 patients (17%) showed a patchy distribution of hyperenhancement and 1 patient (2%) showed enhancement typical for ischemic heart disease. In myocardial biopsy analysis, 2 patients (5%) showed persistence of viral genome, 18 patients (43%) showed inflammation and in 22 patients (52%) neither virus nor inflammation was detected. The pattern of late gadolinium enhancement and myocardial biopsy findings were not significantly correlated (p = 0.854). CONCLUSION: MRI as a non-invasive technique cannot replace myocardial biopsy for the differential diagnosis of DCM.

Adult↗

Characterization of radiofrequency ablation lesions with gadolinium-enhanced cardiovascular magnetic resonance imaging.

OBJECTIVES: This study was designed to evaluate the characteristics of gadolinium-enhanced imaging of radiofrequency ablations. BACKGROUND: Gadolinium-enhanced magnetic resonance imaging (MRI) has been used successfully to evaluate tissue necrosis after myocardial infarction. In electrophysiology, radiofrequency energy is used to create a targeted myocardial necrosis for the treatment of various arrhythmias. METHODS: Using a power-controlled, cooled-tip 7-F catheter system, radiofrequency lesions (10 to 40 W for 30 s) were created on the epicardium of the right ventricle in eight mongrel dogs. After injection of 0.225 mmol/kg gadolinium, T1-weighted fast gradient echo images were obtained during a follow-up of 10 h using an intrathoracic high-resolution coil. Radiofrequency ablations were analyzed on the MR images and compared with gross anatomy and histopathology. RESULTS: Four distinct phases of signal enhancement were observed. After gadolinium injection, radiofrequency lesions were delineated clearly as contrast-free areas of low signal intensity (contrast-to-noise ratio [CNR] = -21.1 +/- 19.8). Signal enhancement in the lesion periphery started 4.0 +/- 1.8 min after injection and progressively extended toward the lesion center at a rate of 0.02 mm/min. Full delayed enhancement was observed after 98 +/- 21 min (CNR = +17.8 +/- 9.0). During the follow-up period, CNR started to decrease, but the lesions were detectable for as long as 10 h of follow-up. During the first three phases of enhancement, MRI correlated well with the pathological findings (r = 0.88, r = 0.88, and r = 0.86 [p < 0.001], respectively). CONCLUSIONS: Radiofrequency ablation can be evaluated accurately by using gadolinium-enhanced MRI, which may allow the noninvasive assessment of procedural success. The dissimilar wash-in and wash-out kinetics compared with myocardial infarction suggest a different pathophysiological process with complete loss of microvasculature.

Animals↗

Value of gadolinium in brain MRI examinations for developmental delay.

The aim of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. A computerized retrospective study identified all brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995-2002 for children under the age of 2 years. Review of the clinical records and magnetic resonance imaging reports identified 170 brain magnetic resonance imaging examinations that were performed for developmental delay. Magnetic resonance imaging studies with enhancing lesions were reviewed by two staff neuroradiologists and two radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. In the 107 patients in whom developmental delay was the primary concern, there were no cases in which the findings would have been missed without gadolinium administration. In the 63 patients in whom developmental delay was a secondary concern, there were several cases (11%) where contrast was helpful but not essential in reaching a radiologic diagnosis. In conclusion, intravenous gadolinium has an extremely low yield in children under the age of 2 where developmental delay is the primary concern. In young children for whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly where tumor or infection is clinically suspected.

Age Factors↗

Prevention of primary nonfunction after canine liver allotransplantation: the effect of gadolinium chloride.

PURPOSE: Effective suppression of Kupffer cell function is believed to contribute to the prevention of preservation/reperfusion injury. In this study, effect of gadolinium, a synthetic Kupffer cell suppressant, on the reperfusion injury was examined using a canine partial liver transplantation model. METHODS: About a 70% partial liver segment was harvested and reimplanted in a mongrel recipient dog weighing 20 to 25 kg. Gadolinium chloride (10 mg/kg) was infused via the cephalic vein 24 hours before harvest of the partial liver (gadolinium group, n = 5). Serum aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and morphologic grading of graft were compared with those of a control group (n = 5). Statistical analysis was done with an independent t-test. RESULTS: Average total ischemic time was 4 hours and 27 minutes. At 1 hour after reperfusion, there were no significant differences in AST, ALP, or LDH levels, or pathologic scores. At 48 hours after reperfusion, AST (P = .03) and LDH (P = .05) levels were significantly lower in the gadolinium group. CONCLUSION: Kupffer cell blockade using gadolinium chloride may be effective to reduce ischemia reperfusion injury, but the effect is not evident at an early stage of reperfusion.

Animals↗

Gadolinium-enhanced magnetic resonance angiography for detection of acute pulmonary embolism: an in-depth review.

STUDY OBJECTIVE: To review the published experience with gadolinium-enhanced magnetic resonance angiography (MRA) for the detection of acute pulmonary embolism (PE) in order to test the hypothesis that gadolinium-enhanced MRA may be potentially sensitive and specific enough to include it among diagnostic alternatives in the evaluation of patients with suspected PE. METHODS: Studies were identified by searching MEDLINE for trials that used gadolinium-enhanced MRA to diagnose acute PE based on the visualization of an intraluminal filling defect or a cutoff vessel, using pulmonary angiography as a reference standard. RESULTS: Twenty-eight investigations were identified in which MRA was used to diagnose PE. Only three studies, however, met the criteria for inclusion in the analysis. In these three case series, the sensitivity of gadolinium-enhanced MRA ranged from 77 to 100%, and the specificity ranged from 95 to 98%. CONCLUSION: Gadolinium-enhanced MRA may be a useful diagnostic alternative in some patients with suspected acute PE, particularly if they have an elevated creatinine level, have an allergy to radiographic contrast material, or should, if possible, avoid exposure to ionizing radiation.

Acute Disease↗

Gadolinium neutron-capture therapy using novel gadopentetic acid-chitosan complex nanoparticles: in vivo growth suppression of experimental melanoma solid tumor.

The potential of gadolinium neutron-capture therapy (Gd-NCT) for cancer was evaluated using chitosan nanoparticles as a novel gadolinium device. The nanoparticles, incorporating 1200 microg of natural gadolinium, were administered intratumorally twice in mice bearing subcutaneous B16F10 melanoma. The thermal neutron irradiation was performed for the tumor site, with the fluence of 6. 32x10(12) neutrons/cm(2), 8 h after the second gadolinium administration. After the irradiation, the tumor growth in the nanoparticle-administered group was significantly suppressed compared to that in the gadopentetate solution-administered group, despite radioresistance of melanoma and the smaller Gd dose than that administered in past Gd-NCT trials. This study demonstrated the potential usefulness of Gd-NCT using gadolinium-loaded nanoparticles.

Animals↗