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N Siauve

Publications and source records attributed to N Siauve.

At least 19 recordsLinked to original sources
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

[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↗
PubMed2004

Optimization of the sources in local hyperthermia using a combined finite element-genetic algorithm method.

This article describes an optimization process specially designed for local and regional hyperthermia in order to achieve the desired specific absorption rate in the patient. It is based on a genetic algorithm coupled to a finite element formulation. The optimization method is applied to real human organs meshes assembled from computerized tomography scans. A 3D finite element formulation is used to calculate the electromagnetic field in the patient, achieved by radiofrequency or microwave sources. Space discretization is performed using incomplete first order edge elements. The sparse complex symmetric matrix equation is solved using a conjugate gradient solver with potential projection pre-conditionning. The formulation is validated by comparison of calculated specific absorption rate distributions in a phantom to temperature measurements. A genetic algorithm is used to optimize the specific absorption rate distribution to predict the phases and amplitudes of the sources leading to the best focalization. The objective function is defined as the specific absorption rate ratio in the tumour and healthy tissues. Several constraints, regarding the specific absorption rate in tumour and the total power in the patient, may be prescribed. Results obtained with two types of applicators (waveguides and annular phased array) are presented and show the faculties of the developed optimization process.

Absorption↗
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↗
PubMed2003

Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.

We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.

Angiogenesis Inhibitors↗
PubMed2003

[MR imaging of ano-perineal suppurations].

A good digital examination is usually sufficient for the diagnosis and the treatment planning of anal fistulae. Cross-sectional imaging techniques, however, can accurately identify deep abscesses and characterize complex fistulae. MRI is well suited for this examination, with almost no motion artifact, excellent contrast between muscles and fatty spaces, and multiplanar acquisition. A fistula starts from an internal opening in the digestive tube and can end in an abscess cavity or open at the skin at an external opening. The cryptoglandular anal fistulae (fistula-in-ano) are non-specific in origin and are usually simple, whereas specific fistulae are due to many diseases such as Crohn's disease, tuberculosis, trauma, radiation, colloid carcinoma, hidradenitis suppurative, actinomycosis or lymphoma and are often complex. MRI appears useful in the cases with recurrent fistulae, Crohn's disease, when the secondary orifice is atypically placed, during a multistep treatment for complex fistulae, or when an anal stenosis forbids a clinical or ultrasound examination. A good knowledge of the perineum anatomy is required for analysing the fistula tracts. The muscle planes separate fatty spaces which have an important role in the spread of the disease: sub-mucosal space, marginal space, intersphincteric space, postanal space of Courtney, supralevator space, and the two ischioanal spaces on both sides of the anal canal. The anal canal is surrounded by the ring-like internal sphincter, which continues the internal muscularis propria of the rectum, and the external sphincter, which is intermingled with the puborectalis muscle. We perform our MRI examination with an external phased array coil, and we place a cannula to identify the anal canal. The T2W sequences give the more interesting information, but the sequences with fat-suppression and gadolinium chelate injection are also very useful. The MRI examination allows the analysis of: 1) the location of the fistula tracts according to Park's classification, 2) the location of the internal opening, 3) the locations of the external opening(s), 4) the location of deep abscesses, 5) the long distance extensions, 6) the state of the ano-rectal wall and the perirectal spaces, 6) the damages of the anal sphincter.

Abscess↗
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↗
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↗
PubMed2000

Metastatic jejunal VIPoma: beneficial effect of combination therapy with interferon-alpha and 5-fluorouracil.

The VIPoma syndrome is rare. It is usually caused by a neuroendocrine tumor located in the pancreas. Somatostatin analogs and interferon-a can be helpful in the symptomatic control of the disease, but the efficacy of chemotherapy in metastatic disease is limited. We report the case of a 32-yr-old patient who had a primary intestinal VIPoma with peritoneal carcinomatosis and hepatic metastases. Somatostatin analogs and conventional chemotherapy regimens were not effective on VIPoma syndrome and tumor progression. The combination of 5- fluorouracil and interferon-alpha was associated with a major clinical improvement and tumor regression. Further investigations should evaluate the place of such a combination as a first line treatment for patients with metastatic neuroendocrine tumors.

Adult↗
PubMed1999

The rete mirabile of the eel: a useful model for the study of transcapillary passage of MR contrast agents.

Our purpose was to study the capillary leakage of MR contrast media using a pure capillary model, the rete mirabile of the eel. The rete is a countercurrent-exchange organ composed of an arterial and a venous capillary system that can be catheterized and perfused. Substances are introduced at the arterial input by a constant infusion, and their steady-state concentrations are measured at the arterial and venous outputs. The capillary leakage of four MR contrast agents--Gd-DOTA(MW = 561 D), carboxymethyldextran-Gd-DTPA (MW = 38,900 D), albumin-Gd-DTPA (MW = 92,000 D), AMI-227 (400,000 D<MW<900,000 D)--was characterized by reference to radioactive tracers (3HHO, 22Na, 14C-sucrose, 125I-albumin) by two parameters. These parameters were the concentration ratio of the venous output over the arterial input [C(VOUT)(%)] and the permeability coefficient (P). The transcapillary pathway mechanisms for carboxymethyldextran-Gd-DTPA and albumin-Gd-DTPA were studied by electron microscopy. P values for Gd-DOTA (9.4+/-3.6 x 10(-7) cm/s) and albumin-Gd-DTPA (11.8+/-5.5 x 10(-7) cm/s) were close to P values for 14C-sucrose, while P values for carboxymethyldextran-Gd-DTPA (6.4+/-4.9 x 10(-7) cm/sec) were similar to P values for 125I-albumin. The lowest permeability was observed with AMI-227 (2.7+/-2 x 10(-7) cm/sec). Vesicular transport was demonstrated for carboxymethyldextran-Gd-DTPA and albumin-Gd-DTPA. The transcapillary passage of several MR contrast agents can be characterized with the rete mirabile model. Molecular weight is the major factor influencing transport.

Air Sacs↗
PubMed1999

Mechanisms of action of liver contrast agents: impact for clinical use.

New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticulo-endothelial system. After intravenous injection, all these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease.

Contrast Media↗
PubMed1998

Contrast agents in magnetic resonance imaging of the liver: present and future.

New contrast agents are being developed by drug companies to better image the liver magnetic resonance imaging (MRI). They can be divided into hepatobiliary agents (Gd-EOB-DTPA, Gd-BOPTA, Mangafodipir) and nanoparticulate agents directed to the reticulo-endothelial system (ferumoxides, SHU 555A). After intravenous injection, all these agents concentrate in the liver and induce profound signal changes. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a description of the principal pharmacokinetic characteristics of the compounds, this review paper summarizes the utility of the agents in the detection and characterization of focal liver diseases.

Contrast Media↗