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Nathalie Siauve

Publications and source records attributed to Nathalie Siauve.

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

Evaluation of antiangiogenic treatment effects on tumors' microcirculation by Bayesian physiological pharmacokinetic modeling and magnetic resonance imaging.

A physiological pharmacokinetic (PBPK) model was used to estimate tumor microcirculation in nude mice with a grafted tumor. The kinetics of a rapid clearance blood pool agent, Vistarem, were investigated by dynamic MRI after bolus administration. Signal enhancements were recorded in arterial blood and in tumor tissue. To analyze these data, we developed a whole-body mathematical model of the agent's biodistribution using physiological parameters. The model included six compartments: arterial and venous plasma, tumor (split into capillaries and interstitium), and the rest of the body (also split into capillaries and interstitium). As an application, changes in tumor microcirculation parameters were evaluated in mice receiving either an antiangiogenic treatment (ZD4190) or a placebo. The analysis was performed in a Bayesian framework, and the model was fitted to experimental data using Markov Chain Monte Carlo techniques. Results showed a significant difference in tumor microcirculation between the two groups of mice when the microcirculation parameters are considered together. This whole-body physiological model enables to analyze jointly data in tumor tissue and in arterial blood. This leads to accurate estimates of microcirculation parameters and the evaluation of their uncertainty.

Animals↗
PubMed2005

Comprehensive model for simultaneous MRI determination of perfusion and permeability using a blood-pool agent in rats rhabdomyosarcoma.

To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/alpha 13 ms/1.2 ms/60 degrees ) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume Vdistribution, volume transfer constant Ktrans, rate constant of influx kpe, and initial extraction (fraction) E. Tumor perfusion was F=43+/-29 ml.min-1.100 g-1. The permeability study allowed the measurement of kpe=0.37+/-0.12 min-1 and Ktrans=0.01+/-0.0031 min-1. The blood volume could be assimilated to the distribution volume (Vdistribution=2.9+/-1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34+/-1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization.

Algorithms↗
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

Cystathionine beta synthase deficiency affects mouse endochondral ossification.

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations, notably characteristic skeletal abnormalities. To investigate this aspect of hyperhomocysteinemia, we analyzed the skeleton of CBS-deficient mice, a murine model of severe hyperhomocysteinemia. Radiography, Alcian Blue/Alizarin Red S-stained whole skeletal preparations, and histological comparisons were used to determine the extent, pattern, and distribution of skeletal abnormalities in CBS-deficient mice. Disruption of the murine CBS gene leads to skeletal abnormalities, notably kyphoscoliosis, with temporal shortening of long bones due to impaired cartilage differentiation, albeit to differing degrees.

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↗
PubMed2005

Accuracy of magnetic resonance imaging in rectal cancer depends on location of the tumor.

PURPOSE: This study was designed to evaluate prospectively magnetic resonance imaging for the prediction of the circumferential resection margin in rectal cancer to identify in which patient magnetic resonance imaging could accurately assess the circumferential resection margin before surgery and in which patients it could not. METHODS: During a 17-month period, a preoperative magnetic resonance imaging for the assessment of circumferential resection margin was obtained prospectively in 38 patients with mid or low rectal cancer. The agreement of magnetic resonance imaging and pathologic examination for assessment of circumferential resection margin was analyzed. RESULTS: Overall, magnetic resonance imaging agreed with histologic examination of the circumferential resection margin assessment in 28 patients (73 percent; kappa = 0.47). In all cases of disagreement between magnetic resonance imaging and pathology, magnetic resonance imaging overestimated the circumferential resection margin involvement. For the 11 patients with mid rectal cancer, circumferential resection margin was well predicted by magnetic resonance imaging in all cases (kappa = 1). For 27 patients with low rectal tumor, overall agreement between magnetic resonance imaging and histologic assessment was 63 percent (kappa = 0.35). Agreement was 22 percent (kappa = 0.03) for the 9 patients with low anterior and 83 percent (kappa = 0.67) for the 18 patients with low posterior rectal tumor. Univariate analysis revealed that only low and anterior rectal tumor was risk factor of overestimation of the circumferential resection margin by magnetic resonance imaging. CONCLUSIONS: Although magnetic resonance imaging remains the best imaging tool for the preoperative assessment of the circumferential resection margin in patients with rectal cancer, it can overestimate the circumferential resection margin involvement in low and anterior tumor with the risk of overtreating the patients.

Adult↗
PubMed2004

Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent.

Macromolecular contrast-enhanced functional CT was performed to characterize early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with chemically induced primary liver tumors ranging pathologically from hyperplasia to HCC and 15 control rats were investigated. Two dynamic CT scans using an experimental macromolecular contrast agent were performed on a single slice 11 and 18 weeks after tumor induction followed by pathological examination. A deconvolution mathematical model was applied, yielding the hepatic perfusion index (HPI), mean transit time (MTT), liver distribution volume (LDV) and arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC. On the first scans, HCC at an early pathological stage had a low FP (-30%, P=0.002) but a normal arterial-portal balance. On the scan contemporary to pathology, HCC perfusion parameters showed an inversion of the arterial-portal balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (-69%, P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even though only one (7%) was visible to the eye. Perfusion-CT allowed early detection of HCC. This technique could contribute in the detection and characterization of liver lesions in clinical studies.

Animals↗
PubMed2004

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes.

PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors. MATERIALS AND METHODS: Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test. RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 [SD], 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2). CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.

Animals↗
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↗