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Biomedical subjects

O Clément

Publications and source records attributed to O Clément.

At least 19 recordsLinked to original sources
PubMed2006

[Treatment response evaluation by functional imaging].

Imaging in cancer plays a capital role to guide the clinician in his choice of therapies. We will discuss the new techniques available to predict and evaluate treatment response in oncology. The method of reference to evaluate treatment response is based on the measure of lesion size. Functional imaging doesn't evaluate size, but rather a physiological or molecular feature, which is probably modified earlier in response to treatment. Dynamic contrast-enhanced functional imaging of microcirculation follows the biodistribution of a contrast agent and analyses tumour vascularization. Diffusion-weighted Magnetic Resonance Imaging differentiates free and restrained water molecules in tissues, reflecting tumor cellularity. Nuclear Magnetic Resonance spectroscopy is an application of MRI that yields information on the metabolic content of a tissue. It detects relative quantities of various molecules which differ in tumour compared to normal tissue. Positon-emission tomography using (18)FDG is a nuclear medicine technique which gives information on tissue metabolism. Captation of FDG is proportional to the proliferative activity and the number of viable cells in a tumour. Human studies concerning these techniques are still quite preliminary, and the medical community must determine their potential in clinical practice to evaluate treatment response in oncology.

Contrast Media↗
PubMed2005

In vivo dynamic MRI measurement of the noradrenaline-induced reduction in placental blood flow in mice.

PURPOSE: We developed a new model for in vivo placental perfusion measurements based on dynamic MRI in mice. As noradrenaline has been implicated in the pathogenesis of preeclampsia, we examined whether it reduced placental perfusion in mice, and whether such a reduction could be detected with our MRI model. MATERIALS AND METHODS: Mice at 16 days of gestation were injected intramuscularly with saline or noradrenaline solution. A conventional gadolinium chelate was then injected IV, and a single-slice T1-weighed 2D Fast SPGR sequence was acquired for 200 s. Signal intensity was measured on all the images and converted into contrast agent tissue concentrations in the maternal left ventricle (input function) and placentas. A one-compartment model was developed using compartmental and numerical modeling software. Mean blood flow (F) was calculated from a transfer constant. RESULTS: Twenty-six mice were studied, yielding a total of 55 MRI measurements of placental perfusion (29 in the control group and 26 in the noradrenaline group). Mean placental blood flow (F) was significantly lower in the noradrenaline group (0.72+/-0.84 ml/min/g of placenta) than in the control group (1.26+/-0.54 ml/min/g of placenta). CONCLUSION: Noradrenaline reduces placental perfusion in mice. Our MRI dynamic model might be useful for detecting and investigating abnormal placental blood flow, thereby avoiding the need for invasive procedures and animal sacrifice.

Animals↗
PubMed2005

Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles.

This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution.

Adenocarcinoma↗
PubMed2005

[Iatrogenic complications from contrast materials].

Iodinated or gadolinium-based contrast agents are usually well tolerated, but some adverse events can happen due to a direct toxicity of the injected molecule (contrast-induced nephropathy, abnormal thyroid function), or to an indirect effect like in true allergic reactions. Radiologists must be familiar with the possibility of adverse events from contrast agents or injection procedures, and should be able to treat the patient. Also, they should take all necessary actions to minimize the occurrence of possible reactions in the presence of risk factors.

Contrast Media↗
PubMed2005

[Placental functional assessment using MRI: mice today, humans tomorrow?].

Placental insufficiency, a process due to either poor placental perfusion or permeability, may lead to progressive deterioration in placental function and materno-fetal morbidity. Advances in MR contrast media pharmacokinetic studies of transit through tissues and dynamic MRI allow to characterize organs microcirculation in vivo. Placental function assessment might be achieved using analysis of dynamic contrast enhanced MRI of tracers. A murine model of placental assessment has been constructed. Herein, principles, results and limitations of such techniques are discussed as well as their potential interest and weaknesses in humans.

Animals↗
PubMed2003

Analysis of the distribution of MRI contrast agents in the livers of small animals by means of complementary microscopies.

BACKGROUND: Magnetic resonance imaging (MRI) contrast agents contain magnetic molecules such as iron (Fe) or gadolinium (Gd) that are injected in vivo into rats or mice to study their distribution inside the liver. Fluorescent europium (Eu) can be used as a model of Gd to obtain comparable information of this distribution of corresponding contrast agents. In a similar approach, Fe can be attached to Texas Red and used as a model of ferumoxides and be detected by fluorescence. METHODS: To combine and compare the advantages of different microscopic imaging modes, characterization studies were carried out by means of a confocal laser scanning microscope (CLSM), a secondary ion mass spectrometric (SIMS) microscope, and an electron energy loss spectrometric (EELS) microscope. In the case of CLSM, the locations of fluorescent signals inside preparations were determined by factor analysis of biomedical image sequences (FAMIS) and selection of image sequences at emission. RESULTS: By CLSM and FAMIS, we distinguished chelated Eu and Texas Red attached to Fe. By SIMS microscopy, we distinguished Eu and Gd of chlorides and chelates and Fe of a ferumoxide. By EELS microscopy, we distinguished Eu and Gd of chlorides. CONCLUSIONS: Analysis of compounds inside correlative specimens by means of CLSM, SIMS, and EELS microscopes provided complementary results.

Animals↗
PubMed2001

Hepatocyte targeting with Gd-EOB-DTPA: potential application for gene therapy.

RATIONALE AND OBJECTIVES: To evaluate the suitability of the liver-specific MRI contrast agent Gd-EOB-DTPA as a nonviral vector for gene therapy of hepatocellular carcinoma. METHODS: Specific uptake of Gd-EOB-DTPA was quantified by relaxometry in rat cultured hepatocytes and the hepatoma cells HepG2 and Huh7. Nonviral vectors for gene transfer were synthesized by coupling Gd-EOB-DTPA to polyethyleneimine or polylysine as DNA condensing agents, and their efficiency was studied using beta-galactosidase (lacZ) as the reporter gene. RESULTS: Gd-EOB-DTPA was specifically taken up by rat cultured hepatocytes (4.32 vs. 1.08 mmol/L in nonhepatocyte control cells) but not by the hepatoma cells; this uptake was concentration-dependently inhibited by Bromsulphtalein. Polycation linkages were achieved with yields of 0.9 Gd-EOB-DTPA molecule per polyethyleneimine molecule and 10 Gd-EOB-DTPA molecules per polylysine molecule. Incubating the cells with plasmids containing lacZ reporter gene and polyethyleneimine-Gd-EOB-DTPA resulted in a few blue (transfected) cells, whereas no blue cells were observed on incubation with polylysine-Gd-EOB-DTPA. CONCLUSIONS: Gd-EOB-DTPA is taken up by normal hepatocytes but not by HepG2 and Huh7 cells, probably because of the lack of the organic anion transporter in these hepatoma cells. The Gd-EOB-DTPA polycation conjugates, such as polyethyleneimine-Gd-EOB-DTPA, could serve as transfer vectors of interest for gene targeting imagery at the early stage of hepatocarcinogenesis. However, the transfer efficiency of such conjugates is low and requires improvement.

Animals↗
PubMed2001

Early changes in liver perfusion caused by occult metastases in rats: detection with quantitative CT.

PURPOSE: To determine whether computed tomography (CT) can depict liver hemodynamic changes caused by occult hepatic micrometastases in rat. MATERIALS AND METHODS: Liver micrometastases (mean diameter, 500 micrometer +/- 300) were produced in seven BD IX rats by injecting 10(7) DHDK12 PROb colorectal carcinoma cells into the spleen. Macrometastases (mean diameter, 7 mm +/- 3) were produced in four other rats. Five normal rats were studied as controls. CT images were obtained every 300 msec for 30 seconds during the injection of 1 mL per kilogram of body weight of contrast medium. The time-attenuation curves of the aorta, portal vein, and liver were used to calculate liver perfusion with a deconvolution model designed for the dual blood supply. RESULTS: Micrometastases in an apparently normal liver caused a 34% decrease in portal blood flow and a 25% increase in the mean transit time for the blood to pass through the liver. These findings suggest increased resistance in the sinusoidal capillaries. Similar but greater changes were found in the macrometastases. CONCLUSION: Occult liver micrometastases in rats generate changes in liver perfusion that can be detected with CT.

Animals↗
PubMed2001

Confocal analysis of phosphatidylserine externalization with the use of biotinylated annexin V revealed with streptavidin-FITC, -europium, -phycoerythrin or -Texas Red in oxysterol-treated apoptotic cells.

OBJECTIVE: To analyze externalization of phosphatidylserine via annexin V on apoptotic cells by laser scanning confocal microscopy and factor analysis of biomedical image sequences (FAMIS). STUDY DESIGN: Streptavidin-fluorescein isothiocyanate (FITC), -europium (Eu), -phycoerythrin (PE) and -Texas Red (TR) were chosen to reveal the binding of biotinylated annexin V on apoptotic U937 human leukemic cells and ECV-304 human endothelial cells induced under treatment with 7-ketocholesterol or 7 beta-hydroxycholesterol. Excitation of each fluorochrome was obtained by selection of specific lines (351 + 364 nm, 488 nm) of the argon laser of a confocal microscope. Temporal and spectral series were performed to characterize each fluorochrome. FAMIS was applied to these series to estimate images corresponding to stains. RESULTS: Each fluorochrome was clearly distinguished, and images showed localization of phosphatidylserine, which was improved by image analysis. CONCLUSION: On apoptotic cells it is possible to analyze differences in the improved visualization of phosphatidylserine in series processed by FAMIS with the use of biotinylated annexin V revealed with streptavidin-FITC, -Eu, -PE or -TR.

Annexin A5↗
PubMed2001

Confocal image characterization of human papillomavirus DNA sequences revealed with Eu in HeLa cell nuclei stained with Hoechst 33342.

OBJECTIVE: To visualize and localize specific viral DNA sequences revealed with Eu by fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM) and factor analysis of biomedical image sequences (FAMIS). STUDY DESIGN: Human papillomavirus DNA (HPV-DNA) was identified in HeLa cells with biotinylated DNA probes recognizing HPV-DNA types 16/18. DNA-DNA hybrids were revealed by a three-step immunohistochemical amplification procedure involving an antibiotin mouse monoclonal antibody, a biotinylated goat antimouse polyclonal antibody and streptavidin-Eu. Cell nuclei were counterstained with Hoechst 33342. Image sequences were obtained using a CLSM that made possible ultraviolet excitation. The location of fluorescent signals inside cellular preparations was determined by FAMIS and selection of filters at emission. Image sequences were summarized into a reduced number of images, or factor images, and curves, or factors. Factors estimate spectral or temporal patterns and depth emission profiles. Factor images correspond to spatial distributions of the different factors. RESULTS: We distinguished between Eu corresponding to HPV-DNA hybridization signals and nuclear staining by taking into account differences in their spectral and temporal patterns and (using their decay rates). CONCLUSION: FAMIS, together with CLSM and Eu, made possible the detection and characterization of viral papillomavirus DNA sequences in HeLa cells.

Base Sequence↗
PubMed2000

Confocal multilaser focusing and single-laser characterization of ultraviolet excitable stains of cellular preparations.

BACKGROUND: The aims of this study were (1) to realign cellular preparations when spots and structures are excited by different lasers of a confocal laser scanning microscope (multilaser studies); (2) to avoid the use of realigment methods by selecting fluorochromes that can be excited by only one laser (single-laser experiments). METHODS: In multilaser studies, we used propidium iodide fluorescent beads, as well as tetramethyl rhodamine isothiocyanate (TRITC), fluorescein isothiocyanate (FITC), and 4'-6 diamidino-2-phenylindole (DAPI)-stained human cancer lines. They were excited using HeNe, argon, and ultraviolet (UV) argon laser lines of a confocal laser scanning microscope. Single-laser experiments using UV excitation only were performed using europium as a model for magnetic resonance paramagnetic contrast agents. Nuclei of human cancer lines and tissue were counterstained by DAPI and cytoplasms were labeled with ELF-97 substrates. Factor analysis of medical images (FAMIS) and correlation methods were used to realign shifted images, focus images, and characterize each fluorochrome when necessary. RESULTS: In multilaser studies, superimposition of factor images corrected Z shifts and correlation methods provided X, Y correction values. In single-laser experiments, each fluorochrome was clearly distinguished in the group of fluorochromes. Estimated images in both studies showed colocalizations of structures. CONCLUSIONS: It is possible to characterize differences in the focus and alignment of fluorescent probes and to correct them. It is also possible to study colocalization of UV excitable fluorochromes (DAPI, ELF-97, europium) in cellular and tissular preparations via multilaser or single-laser experiments.

Europium↗
PubMed2000

Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes.

Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene followed by the administration of ganciclovir (GCV) into hepatocellular carcinoma (HCC)-derived cell lines either in vitro or transplanted into nude mice has been shown to provide a potential strategy for HSV-tk-based gene therapy of HCC. We report herein an analysis of the antitumoral efficacy of two recombinant adenoviruses (Ads), Ad.CMVtk and Ad.AFPtk, in a relevant model of multifocal hepatic lesions induced in rats by a potent alkylating chemical carcinogen, diethylnitrosamine. Two routes of administration of the Ad were studied: intratumoral and intrahepatic artery injections. Both recombinant Ads, Ad.CMVtk and Ad.AFPtk, express the HSV-tk gene under the control of the early enhancer/promoter cytomegalovirus and alpha-fetoprotein regulatory gene sequences, respectively. The antitumor response was assessed by magnetic resonance imaging and by autopsy and histological analysis following postmortem. Tumor growth cessation was demonstrated by magnetic resonance imaging in large tumor nodules of size 5-8 mm treated by intratumoral administration of 2x10(9) pfu Ad.CMVtk plus i.p. treatment with GCV. We also show an antitumor efficacy in small tumor nodules of size <3 mm treated with 2x10(9) pfu Ad.CMVtk plus GCV by the intrahepatic artery route, albeit associated with an adverse toxicity. In vivo targeting of the HSV-tk gene to diethylnitrosamine-induced HCC cells with the recombinant Ad.AFPtk suppresses the hepatic toxicity in the nontumoral liver. The lower antitumor response would argue for the use of multiple injections of such adenoviral constructs. These observations may lead to potential approaches for designing gene therapy destined for early treatment of dysplastic nodules or advanced HCC in cirrhosis.

Adenoviridae↗
PubMed2000

Distribution of iron oxide nanoparticles in rat lymph nodes studied using electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI).

Superparamagnetic iron nanoparticles have been developed as contrast agents for magnetic resonance lymphography. The kinetics of uptake of these particles has not yet been accurately determined. We have therefore monitored the distribution of individual iron particles (ferumoxtran, AMI-227, Sinerem) in rat lymph nodes 1.5, 3, 6, 12, and 24 hours after i.v. injection (two rats per time point). The ultrastructural distribution of the iron was determined by energy-filtered transmission electron microscopy (EFTEM). This method allows the identification of elements using element-specific energy-loss electrons. Iron was identified by the Fe-L(2,3) edge (EELS), and iron maps were obtained using iron-specific electrons for imaging (ESI). The background was calculated by simplex optimization (EELS) and by the two-window method (ESI). Ferumoxtran particles were regularly observed at the periphery of the lymph nodes but not in their centers. Isolated iron particles were seen extracellularly within lymph vessels and, 3 hours after injection, as small dots in phagocytic cells. Numerous dense clusters appeared within the cells at later times (6 and 12 hours after injection). These results suggest that the contrast agent moves rapidly across the capillary wall to the lymph and is then taken up by phagocytic cells. J. Magn. Reson. Imaging 2000;12:505-509.

Animals↗
PubMed2000

MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection.

The objective of the study was to quantify the kinetics of the superparamagnetic nanoparticle ferumoxtran (AMI 227, Sinerem(R), Combidex(R)) in the efferent lymph of the subdiaphragmatic lymph nodes and in various node groups of the rat to elucidate the uptake mechanism. The thoracic lymph duct was catheterized in 24 rats after an IV injection of 40 micromol Fe/kg ferumoxtran. Three rats were studied at several time points between 1.5 and 24 hours. At each time point, 0.3 ml of lymph were collected over 45 minutes. Lymph nodes were differentiated into five groups. The iron concentration in the samples and in plasma was measured by relaxometry at 0.47 T and atomic absorption spectrometry. Cytology was performed on the lymph. High concentrations of nanoparticles were found in the thoracic lymph soon after injection (90 minutes). No particle was found in the lymph cells, indicating that ferumoxtran was extracellular in the lymph fluid. The maximum concentration was reached later in all node groups, at 12 hours, and then plateaued. The transcapillary pathway and subsequent lymph drainage of the particles seem to play a major role in the delivery to the lymph nodes.

Animals↗