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Olivier Clément

Publications and source records attributed to Olivier Clément.

14 recordsLinked to original sources
PubMed2006

Placental perfusion and permeability: simultaneous assessment with dual-echo contrast-enhanced MR imaging in mice.

PURPOSE: To assess placental perfusion and permeability in mice with magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was conducted according to French law and National Institutes of Health recommendations for animal care. Twenty-two pregnant BALB/c mice were examined at 1.5 T with a single-section dual-echo fast spoiled gradient-echo sequence. Two injection protocols were used: monophasic injection (double the clinical dose of contrast agent) and biphasic injection (quadruple the clinical dose). Signal intensities (SIs) were measured in the maternal left ventricle, placenta, and fetus (n = 16). At these high gadolinium doses, a T2* effect correction was used. SIs were converted to gadolinium concentrations and were analyzed by using a three-compartment model. Quantitative microcirculation parameters were calculated. Results with the monophasic and biphasic protocols were compared, and final arterial concentrations determined with MR imaging were compared with those determined with atomic emission spectrophotometry by using the unpaired Student t test. RESULTS: Perfusion and permeability parameters for monophasic and biphasic injections were similar: Mean placental blood flow was 180 mL/min/100 g, mean permeability surface coefficient from maternal placental to fetal placental compartment was 10.3 x 10(-4) sec(-1) +/- 6.81 (standard deviation), mean permeability surface coefficient from fetal placental to maternal placental compartment was 4.65 x 10(-4) sec(-1) +/- 4.37, and mean fractional volume of the maternal vascular placental compartment was 36.5% +/- 0.9. Placental (146 vs 105 micromol/L, P < .004) and fetal (33.3 vs 19.1 micromol/L, P < .001) gadolinium concentrations were higher with the biphasic than with the monophasic protocol. Arterial gadolinium concentrations at MR imaging did not differ significantly from those at spectrophotometry for the monophasic (P = .254) or biphasic (P = .776) injection protocol. CONCLUSION: Placental perfusion and permeability can be measured in vivo by using high gadolinium doses and a dual-echo MR imaging sequence.

Animals↗
PubMed2006

Magnetic targeting of magnetoliposomes to solid tumors with MR imaging monitoring in mice: feasibility.

PURPOSE: To establish the feasibility of magnetoliposome tumor targeting with an extracorporeal magnet. MATERIALS AND METHODS: Animal experiments were performed in compliance with Institut National de la Santé Et de la Recherche Médicale animal protection guidelines and were approved by local government authorities. Magnetophoresis was used to measure the velocity of magnetoliposomes constituted of polyethylene glycol-lipids and anionic maghemite nanocrystals in a calibrated magnetic field in vitro. For in vivo studies, 38 male Swiss nude mice bearing a PC3 human prostate carcinoma tumor in each flank received an intravenous injection of magnetoliposomes (n = 27), saline (n = 9), or nonencapsulated superparamagnetic particles (n = 2) after a small magnet with a magnetic field of 0.3 T and a field gradient of 11 T/m was fixed to the skin above one tumor. The animals were examined at magnetic resonance (MR) imaging with eight different sequences, iron doses (13 mice), and magnet-application durations (12 mice). Their excised tumors were then stained with Perls Prussian blue and hematoxylin-eosin and were examined histologically. With use of the paired Student t test, signal intensity, tumor surface enhancement, and number of stained cells were compared between the control and magnet-exposed tumors to determine significant differences (P </= .01). RESULTS: The mean magnetoliposome velocity ranged from 10 to 40 mum/sec when the magnetic field equaled 0.13 T and the field gradient equaled 25 T/m. At T1-weighted three-dimensional spoiled gradient-echo MR imaging in vivo, the tumor exposed to the magnet showed strong negative enhancement, -52%, compared with the -7% enhancement of the other tumor. Maximal enhancement occurred after 3 hours of magnet application. After 24 hours of magnet application, intracapillary iron particle accumulation was observed in the targeted tumors only. CONCLUSION: Magnetic targeting of sterically stabilized magnetoliposomes after they are intravenously injected is feasible in vivo.

Animals↗
PubMed2006

In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach to cell-based anticancer therapy.

The aim of this study was to demonstrate the feasibility of in vivo cell tracking to monitor anticancer cell therapy by means of a high-resolution noninvasive MRI method. Ovalbumin-specific splenocytes (OT-1) labeled with anionic gamma-Fe2O3 superparamagnetic iron oxide (SPIO) nanoparticles were adoptively transferred into C57BL/6 mice with growing ovalbumin-expressing tumors. OT-1 cells were tracked in vivo by 7 T MRI 24, 48, and 72 hr after they were injected. The results showed significant negative enhancement of the spleen at 24 hr, and of the tumor at 48 and 72 hr, after labeled cell injection. This suggests that the lymphocytes initially homed toward the spleen and were then recruited by the tumor. The presence of labeled cells was confirmed in ex vivo by 9.4 T microimaging of tumors and magnetic sorting of spleen cells. These results confirm that MR tracking of lymphocytes is feasible in vivo. This high-resolution imaging method could be used to improve the monitoring of immune cell therapy.

Animals↗
PubMed2006

Phenotypic study of human gingival fibroblasts labeled with superparamagnetic anionic nanoparticles.

BACKGROUND: A specific labeler of the human gingival fibroblast (HGF) does not exist. Anionic maghemite nanoparticles allow labeling of a wide cell variety and their recognition in cellular, organotypical, and animal models. METHODS: We studied internalization effects of nanoparticles on an HGF phenotype in vitro, evaluating transcription and secretion of connective tissue remodeling molecules, i.e., matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines controlling their activation/inhibition, i.e., transforming growth factor-beta (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), and interleukins 1beta and 4 (IL-1beta and IL-4). After proliferation kinetics, cellular uptake was studied by Perls coloration and magnetophoresis on labeled culture. Dot blotting, Western blotting, and zymography were used to detect MMP-1, -2, and -3 and TIMP-1 and -2 secretions in culture supernatants, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of these molecules. Enzyme-linked immunosorbent assay (ELISA) tests were used to determine TGF-beta1, TNF-alpha, IL-1beta, and IL-4 levels. RESULTS: Our data indicated high (15.3+/-5.8 pg/cell) but heterogeneous distribution of nanoparticles in HGF. Twenty-four hours after labeling, MMP-1, -2, and -3 and TIMP-2 secretion increased (P<0.001) with RT-PCR confirmation at 12 hours, whereas TIMP-1 did not. IL-1beta increased at day 1 (D1) (P<0.001) and IL-4 at D3 (P<0.01), but not TGF-beta1 or TNF-alpha. CONCLUSIONS: After labeling with these maghemite nanoparticles, HGF increased secretion of IL-1beta at D1, probably inducing the increase of MMP-1, -2, and -3 and TIMP-2. The increase of IL-4 secretion began with the decreased synthesis of MMPs and TIMPs at D3. Despite this transitory inflammatory reaction at 3 days following internalization, maghemite nanoparticles did not affect HGF phenotype, thereby authorizing their use as labelers.

Adult↗
PubMed2005

Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging.

Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes.

Animals↗
PubMed2005

Placental perfusion MR imaging with contrast agents in a mouse model.

PURPOSE: To quantitatively analyze placental perfusion by using magnetic resonance (MR) imaging with contrast agents in a mouse model. MATERIALS AND METHODS: Study was conducted according to French law and in full compliance with National Institutes of Health recommendations for animal care. Thirty-six pregnant Balb/c mice at 16 days of gestation were injected intravenously with either a conventional or macromolecular gadolinium chelate, and 1.5-T single-section T1-weighted two-dimensional fast spoiled gradient-echo sequential MR imaging was then performed for 14 minutes. Images were analyzed qualitatively, and parametric map analysis was performed in the resultant 25 mice included in the study. Signal intensity was measured in maternal left ventricle (input function), placenta, and fetus on all images. After converting signal intensity into contrast agent tissue concentrations, a three-compartment model was developed with compartmental and numeric modeling software. Placental perfusion was calculated for conventional (n = 12) and macromolecular (n = 13) gadolinium chelates. Finally, placental and fetal gadolinium concentrations were assayed by means of atomic emission spectrophotometry (n = 15). Perfusion values and placental and fetal gadolinium concentrations for conventional and macromolecular chelates were compared by using an unpaired t test. RESULTS: Based on a constant transfer parameter, estimated placental perfusion did not differ between procedures with conventional and macromolecular gadolinium chelates (0.99 mL/min/g +/- 0.5 [standard deviation] and 1.28 mL/min/g +/- 0.6, respectively, P = .22). Likewise, mean placental gadolinium concentrations did not differ after injection of conventional and macromolecular chelates. In contrast, mean fetal gadolinium concentration was 9.83 micromol/L after conventional chelate injection and below detection limit after macromolecular chelate injection. CONCLUSION: Placental perfusion can be calculated by using dynamic contrast-enhanced MR imaging, as shown in this mouse model.

Animals↗
PubMed2005

New criteria for assessing fit quality in dynamic contrast-enhanced T1-weighted MRI for perfusion and permeability imaging.

Contrast-enhanced (CE) MRI provides in vivo physiological information that cannot be obtained by conventional imaging methods. This information is generally extracted by using models to represent the circulation of contrast agent in the body. However, the results depend on the quality of the fit obtained with the chosen model. Therefore, one must check the fit quality to avoid working on physiologically irrelevant parameters. In this study two dimensionless criteria-the fraction of modeling information (FMI) and the fraction of residual information (FRI)-are proposed to identify errors caused by poor fit. These are compared with more conventional criteria, namely the quadratic error and the correlation coefficient, both theoretically and with the use of simulated and real CE-MRI data. The results indicate the superiority of the new criteria. It is also shown that these new criteria can be used to detect oversimplified models.

Algorithms↗
PubMed2004

Imaging the lymphatic system: possibilities and clinical applications.

The lymphatic system is anatomically complex and difficult to image. Lymph ducts are responsible for the drainage of part of the body's interstitial fluid. Lymph nodes account for the enrichment of lymph fluid, and can be involved in a large variety of diseases, especially cancer. For a long time, lymphatic imaging was limited to the sole use of conventional lymphography involving invasive procedures and patient discomfort. New contrast agents and techniques in ultrasound, nuclear medicine, and MR imaging are now available for imaging of both the lymphatic vessels and the lymph nodes. The objective of this review is to discuss the different imaging modalities of the lymphatic system, with a special focus on the new possibilities of lymphatic imaging including enhanced MR lymphography, sentinel node and positron emission tomography imaging, and contrast-enhanced ultrasound.

Contrast Media↗
PubMed2004

In vivo cellular imaging of magnetically labeled hybridomas in the spleen with a 1.5-T clinical MRI system.

The feasibility of in vivo cellular imaging using a 1.5 T clinical magnet was studied in the mouse. Hybridoma cells were labeled with anionic gamma-Fe2O3 superparamagnetic iron oxide nanoparticles. These were internalized by the endocytose pathway. Both electron spin resonance and magnetophoresis as a measure of the labeled cells migration velocity under a magnetic field were used to quantify particle uptake. A fast (< 2 hr) and substantial (up to 5 pg of iron per cell) internalization of nanoparticles by hybridomas was found, with good agreement between the two methods used. Hybridomas labeled with 2.5 pg iron per cell were injected intraperitoneally to male Swiss nude mice. A decrease in the spleen signal, suggesting a "homing" of labeled hybridomas to this organ, was found 24 hr later by MRI performed at 1.5 T. Furthermore, in labeled cells recovered from the spleen by ex vivo magnetic sorting, a mean of 0.5 pg iron per cell was found, i.e., a value five times lower than that of the injected hybridomas. This finding is consistent with in vivo proliferation of these cells. In addition, the amount of labeled hybridomas present in the spleen was found to correlate with MRI signal intensity.

Animals↗
PubMed2002

Distribution of injected MRI contrast agents in mouse livers studied by confocal and SIMS microscopy.

OBJECTIVE: To localize magnetic resonance imaging (MRI) contrast agents injected intravenously into mouse livers. STUDY DESIGN: Parallel studies were performed on fluorescent europium and nonfluorescent, paramagnetic gadolinium and on a product combining nanoparticles of Fe and Texas Red to obtain combined information on the distribution of these molecules inside the liver. The distribution of different superparamagnetic iron oxides was also studied because the size of these new compounds is not always convenientfor microcirculation studies. RESULTS: Europium and Texas Red can be detected by confocal microscopy. Europium, iron and gadolinium can be detected by secondary ion mass spectrometry (SIMS) microscopy. Studies confirmed the complementarity of both microscopies. They also confirmed the possibility of using europium as a model of gadolinium to analyze thefate of MRI contrast agents. CONCLUSION: The methodology can be used on mice injected intravenously and analyzed by confocal and SIMS microscopy to localize MRI contrast agents inside cellular and tissue specimens of mice.

Animals↗