Hyperpolarized helium3 encapsulated in microbubbles: a new class of blood pool MRI contrast agent.
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Animals↗
Biomedical subjects
H Tournier
Publications and source records attributed to H Tournier.
MR perfusion imaging using encapsulated laser-polarized 3He.
In this work, the use of a new carrier agent for intravascular laser-polarized 3He imaging is reported. Lipid-based helium microbubbles were investigated. Their average diameter of 3 microm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T2* of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal-to-noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects.
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↗
Vascular and perfusion imaging using encapsulated laser-polarized helium.
In this work, the use of hyperpolarized (HP) 3He for in vivo intravascular imaging on animal is reported. To overcome the problem of the low solubility of helium in blood, we propose an approach based on helium encapsulation in lipid-based carrier agents. The mean diameter of the 3He microbubbles, measured equal to 3.0+/-0.2 microm, makes it possible to conduct in vivo studies. In vitro spectroscopy yielded a longitudinal relaxation time T(1) equal to 90 s and an apparent transverse relaxation time T(2)(*) of 4.5 ms. Angiographic imaging (venous and cardiac cavity visualization), as well as lung perfusion imaging, were demonstrated in rats using intravenous injections of microbubble suspensions. Suitable signal and spatial resolution were achieved. The potential of this technique for lung perfusion assessment was assessed using an experimental animal embolism model. Lung perfusion defects and recovery towards a normal perfusion state were visualized. This study was completed with the demonstration of a new ventilation-perfusion lung exploration method based entirely on HP 3He.
Animals↗
Detection of experimental hepatic tumors using long circulating superparamagnetic particles.
RATIONALE AND OBJECTIVES: To evaluate the potential of an iron oxide-based MR contrast agent for the detection and delineation of experimental liver tumors during the early vascular phase of the compound. METHODS: Superparamagnetic blood pool agent (SBPA) was administered intravenously to rabbits bearing VX2 tumors. Images were acquired before the injection, immediately after, and 1 or 3 weeks later. The variations of signal intensity were measured in the tumors and in several tissues for various T1-weighted spin-echo, T2-weighted fast spin-echo, and T2-weighted gradient-recalled-echo sequences. RESULTS: Fourteen and 12 of the 16 tumors were detected immediately after SBPA injection using, respectively, the T2-weighted fast spin-echo and T2-weighted gradient-recalled-echo sequences. A significant decrease in signal intensity was observed in well-perfused organs, and blood signal was abolished even at the lowest injected dose and using a T1-weighted sequence. In the late phase, the loss in signal intensity of the liver was even more pronounced. CONCLUSION: The dominant T2 effect of SBPA induces an increase in the tumor-to-liver and tumor-to-blood contrast during the vascular phase, improving the detection of the tumors and allowing the distinction between small lesions and vessels through plane. This effect on the liver signal persists for several days because of the incorporation of SBPA in the reticuloendothelial system.
Animals↗
Effects of trifluralin on Trypanosoma cruzi in vitro and in vivo.
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Animals↗
Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats.
This study examines the anti-ulcerogenic activity of a chloroform extract of Tanacetum vulgare and purified parthenolide, the major sesquiterpene lactone found in the extract. Gastric ulcers induced by oral administration of absolute ethanol to rats were reduced dose-dependently by oral pretreatment of animals with the chloroform extract (2.5-80 mg kg(-1)) or parthenolide (5-40 mg kg(-1)). When administered 30 min before challenge with the alcohol the protection ranged between 34 and 100% for the extract and 27 and 100% for parthenolide. When the products were administered orally 24 h before treatment with ethanol, 40 mg kg(-1) of the extract and of the lactone reduced the mean ulcer index from 4.8+/-0.3 for control animals to 1.4+/-0.2 and 0.5+/-0.1, respectively. The products also prevented alcohol-induced reduction of the number of sulphydryl groups within the gastric mucosa (50.6+/-2.3 microg (mgprotein)(-1) for normal animals compared with 17.7+/-3.0 microg (mg protein)(-1) for alcohol-treated animals). Administration of the extract (80 mg kg(-1)) or parthenolide (40 mg kg(-1)) 24 h before ethanol treatment restored the numbers of mucosal -SH groups to values near those found for normal animals. These results suggest that the products assayed, in particular parthenolide, might find therapeutic application, although further work is required to establish their profit/risk ratio.
Animals↗
Long circulating superparamagnetic particles with high T2 relaxivity.
Novel superparamagnetic particles coated with a phospholipid and a surfactant were characterized and evaluated in vivo. These particles (SBPA) were shown to exhibit r2 relaxivities in the range of 350-450 mM-1.s-1, r1 values of 8-12 mM-1.s-1 and sizes of 50-80 nm. Preliminary results of pharmacokinetics were obtained in rats following the administration of 59Fe-labelled preparations. The particles were shown to remain for hours in the blood stream before being cleared mainly by the liver. Most of 59Fe was eliminated from the body and recovered in the feces within a week. These biodistribution and elimination properties deserve more detailed studies and suggest the potential use of this product as a blood pool contrast agent.
Animals↗
Effects of lovastatin on the fatty acid desaturation in a human lung mucoepidermoid carcinoma grown in nude mice.
The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.
Animals↗
Enhancement of computed tomography liver contrast using iomeprol-containing liposomes and detection of small liver tumors in rats.
RATIONALE AND OBJECTIVES: We evaluated iomeprol-containing liposomes (Lipiom), a new contrast medium for computed tomography (CT) liver scanning, in an animal model of chemically induced hepatocellular carcinomas and other liver tumors in rats. METHODS: Liver tumors were induced by administration of carcinogens to rats, either 0.55% (w/w) 1'-hydroxysafrole in the diet or induction by 3'-methyl-4-diethylaminoazobenzene followed by promotion with carbon tetrachloride. CT scanning was performed 1-3 hr after intravenous injection of iomeprol-containing liposomes. RESULTS: After injection of iomeprol-containing liposomes at a dose of 70 mg of liposome-entrapped iodine per kilogram of body weight, the normal liver parenchyma showed a contrast enhancement, in Hounsfield units, of more than 60% over the control value before bolus. Liver tumors with no or few Kupffer cells were not enhanced and appeared as dark areas within the normal parenchyma. Tumors and pretumoral lesions devoid of Kupffer cells, as small as 3 mm in diameter, could be distinguished using this non-invasive method. CONCLUSION: CT liver scanning after injection of iomeprol-containing liposomes appears to be promising method for detecting liver tumors and focal liver lesions.
Animals↗
[Effect of dietary supplementation with gamma-linolenic acid on the growth of a human lung carcinoma implanted in nude mice].
We have studied the effect of a gamma-linolenic acid (18:3 n-6, GLA)-supplemented diet on the growth of a human lung mucoepidermoid carcinoma (HLMC) implanted in athymic mice and on its uptake of human low density lipoproteins labeled with 99mTc (99mTc-LDL). Mice bearing the HLMC were divided into two experimental groups. One of them was administered a control diet (C diet) and the other one was given a diet supplemented with 25 mg GLA/g pellet (GLA diet) for three weeks (Table 1). A tumor growth inhibition with the GLA diet was evident at the second week of treatment, and a marked inhibition (56%) was reached at the end of the third week (Fig. 1). The GLA diet produced some changes in the total fatty acid composition of tumor, plasma and liver of host mice: GLA and arachidonic acid (20:4 n-6, AA) induced significant increases, whereas oleic (18:1 n-9, OA) and linoleic acids (18:2 n-6, LA) were decreased (Table 2). Tumors of those animals fed both diets were labeled by 99mTc-LDL, and no difference was observed in the ratio of tumor/liver and tumor/kidney uptake of host animal (Table 3). Results obtained using this experimental model suggest that the inhibitory effect of GLA on tumor growth is not related to the LDL tumor uptake.
Analysis of Variance↗
Separation of ApoA- and ApoB-containing lipoproteins of human plasma by affinity chromatography on concanavalin A.
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Adult↗
Changes in the plasma free fatty acid composition during VLDL lipolysis induced by heparin: their effect on platelet phosphatidylcholine biosynthesis.
The contribution of the acyl specificity of post heparin lipolytic enzymes to changes in the plasma free fatty acid (FFA) pattern during very low density lipoproteins (VLDL) lipolysis, was studied. The effect of these changes in the 3H-choline incorporation into platelet phosphatidylcholine (PC) during incubation, was also investigated. "In vitro" experiments with post heparin plasma and isolated VLDL showed an increase of 61.1 in the percentage of linoleic acid (C 18:2) concomitant with a decrease of 57.1% in the relative concentration of stearic acid (C 18:0) during VLDL triacylglycerol lipolysis. Similarly, a decrease of 39.2% in the plasma concentration of C 18:0 and an increase of 29.4% in the C 18:2 and 9.6% in the oleic acid (C 18:1) concentration were observed after intravenous injection of low doses of heparin. The plasma FFA compositional changes that occur during "in vitro" VLDL lipolysis accelerate not only the incorporation of labeled choline but also the incorporation of C 18:2 into platelet PC. It is suggested that the above observed changes on platelet response are due to the increase in the C 18:2 concentration during incubation.
Adult↗
Effect of protein depletion on the VLDL triacylglycerol secretion and apoprotein synthesis by the perfused liver from pregnant rats.
The effect of protein depletion in the pregnant rat on the polyunsaturated fatty acid incorporation into very low density lipoproteins (VLDL) has been investigated. The apoprotein pattern of these particles was determined. In in vivo experiments the amounts of serum and liver triacylglycerol were determined. VLDL were isolated and their apo C concentration calculated. In in vitro experiments the radioactivity of [3H]leucine incorporated into VLDL apoproteins was measured. The results show that protein depletion during pregnancy promotes a drastic increase in serum and liver triacylglycerol. The VLDL isolated from these animals show an increase in the triacylglycerol/protein ratio and a decrease in their content of apo C. Meanwhile, a significant reduction in the [3H]leucine incorporation into apo C peptides by the perfused liver of protein depleted rats was detected. On the other hand, protein deprivation did not affect labeled linoleic and arachidonic acid incorporation into triacylglycerol of the newly secreted VLDL. Taking these results together, let us deduce that a defective VLDL is secreted by the liver of the protein depleted pregnant rats. The abnormal composition of these particles may influence its normal metabolism through their effects on lipoprotein lipase and this fact could affect the normal supply of polyunsaturated fatty acids to the fetus.
Animals↗
[Trypanosoma cruzi: influence of human plasma on the morphogenesis of blood trypomastigotes in a cell-free culture media].
Morphogenesis of blood stream trypomastigotes in the cell free culture medium F69 at 37 degrees C for 10 days showed qualitative differences either with or without human plasma. Without human plasma, blood stream trypomastigotes performed only one cycle before disappearing and the culture kept growing as amastigotes and epimastigotes until the end of the experiment. In contrast, human plasma induced multiple cycles of transformation. The sequence was blood stream trypomastigotes, regressive parasites, amastigotes, progressive parasite and again trypomastigotes. Human plasma preserved the trypomastigote stage, produced a blockade of the epimastigote stage and inhibited the division of amastigotes. In this experimental model, human plasma modified the biological cycle of T. cruzi by inducing or inhibiting different stages.
Animals↗