PubMed Health⌕ Search

Biomedical subjects

C A Cuénod

Publications and source records attributed to C A Cuénod.

18 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↗
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↗
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↗
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↗
PubMed1998

Liver imaging with ferumoxides (Feridex): fundamentals, controversies, and practical aspects.

Superparamagnetic nanoparticles (Feridex) have been recently made available to the radiological community as a contrast agent for MR imaging of the liver. This article reviews the principal physicochemical characteristics of this new compound, with an emphasis on the explanation of the contrast obtained (either positive or negative enhancement) that depends on the local concentration and the sequence used. The clinical use of Feridex is detailed, both for lesion detection and characterization. Finally, some guidelines for image optimization are given.

Contrast Media↗
PubMed1998

Anatomy of spontaneous splenorenal and gastrorenal venous anastomoses. Review of the literature.

Portal hypertension is characterised by the development of a collateral portocaval circulation. Among these venous reroutings, some are situated posteriorly in the left subphrenic compartment. These are the spontaneous splenorenal and gastrorenal anastomoses. Their incidence is estimated at around 16%. On the one hand, there are the direct shunts, which anastomose the spelling v. to the left renal v., of an anecdotal nature, and on the other the spontaneous indirect splenorenal shunts, characterised by the presence of a complete neurovascular pedicle traversing the gastrophrenic ligament. This relates to the gastric collateral v., which is connected to the left renal v. via the inferior v. of the left crus of the diaphragm and the middle capsular v., hence the name "gastro-phreno-capsulo-renal shunt". At an advanced stage of portal hypertension these splenorenal shunts may acquire a major caliber and behave like actual surgical shunts.

Collateral Circulation↗
PubMed1996

Capillary leakage of a macromolecular MRI agent, carboxymethyldextran-Gd-DTPA, in the liver: pharmacokinetics and imaging implications.

Capillary leakage of a macromolecular contrast agent, Carboxymethyl Dextran-Gd-DTPA (CMD-Gd-DTPA) was characterized in a highly permeable system, the liver, to assess its potential as a blood pool marker. Its elimination kinetics in hepatic lymph were compared in nephrectomized rabbits with that of a tracer of extra cellular fluid space, Gd-DOTA. Four parameters were defined: volume of distribution, normalized initial leakage rate (ILRn), maximum ratio of lymph and plasma concentrations (max Cl/Cp), and the time to obtain this maximum ratio. The effect of this leakage was studied on MR images by comparing liver contrast enhancement after injection and after almost total removal of the contrast agent from the blood by exchange transfusion. Capillary leakage of CMD-Gd-DTPA was detected in lymph. Compared to Gd-DOTA, it was slower (ILRn = 0.36 10(-5) l min-1 for CMD-Gd-DTPA and ILRn = 2.6 10(-5) l min-1 for Gd-DOTA), less abundant (max Cl/Cp was 80% for CMD-Gd-DTPA and 100% for Gd-DOTA). Liver enhancement remained stable, which indicated that the leakage did not modify the enhancement induced by the intravascular fraction of the contrast agent. These results obtained in a highly permeable capillary model indicate that this agent can be used as a selective blood pool enhancer.

Animals↗
PubMed1996

Acute vertebral collapse due to osteoporosis or malignancy: appearance on unenhanced and gadolinium-enhanced MR images.

PURPOSE: To distinguish malignant from osteoporotic acute vertebral collapses. MATERIALS AND METHODS: Sixty-three osteoporotic and 30 malignant vertebral collapses were studied in 51 patients (aged 33-88 years) with T1-weighted magnetic resonance (MR) images (n=93), gadolinium-enhanced T1-weighted images (n=72), and T2-weighted images (n=53). RESULTS: Four findings were suggestive of osteoporosis: retropulsion of a bone fragment (10 osteoporotic cases vs 0 malignant cases), preservation of normal signal intensity on T1-weighted images (43 vs four), return to normal signal intensity after gadolinium injection (42 vs four) with horizontal bandlike patterns, and isointense vertebrae on T2-weighted images (28 vs two). Six findings were suggestive of malignancy: convex posterior cortex (21 malignant cases vs four osteoporotic cases), epidural mass (24 vs 0), diffuse low signal intensity within the vertebral body on T1-weighted images (23 vs 12) and in the pedicles (24 vs four), high or inhomogeneous signal intensity after gadolinium injection (17 vs 0) and on T2-weighted images (17 vs 0). CONCLUSION: Gadolinium-enhanced and unenhanced MR images are useful in the differentiation of vertebral collapses.

Acute Disease↗
PubMed1995

Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31 magnetic resonance spectroscopy.

OBJECTIVE: To determine whether changes in phosphomonoester and phosphodiester levels could be detected in vivo with phosphorus magnetic resonance spectroscopy in the early stage of Alzheimer's disease (AD). DESIGN: Survey-type of case-control study using neuropsychological testing as criterion standard with blinded data analysis. SETTING: Patients were from a neurology clinic in Paris, France. The controls were from the community. Magnetic resonance measurements were performed in the prefrontal region of the brain with a clinical 1.5-T scanner. Blinded data analysis. PARTICIPANTS: Twenty-four patients with mild AD and 15 age-matched healthy volunteers. Subjects were separated into two groups, both composed of patients with AD and healthy volunteers. Two successive acquisition protocols were used in the two groups. RESULTS: A significant increase in the phosphomonoester-total phosphorus ratio was found in patients with AD compared with controls. In this series, use of a ratio above 11% as a threshold to test our sample yielded an 83.3% sensitivity and a 73.3% specificity test for AD. Other metabolite ratios (inorganic phosphate, phosphodiesters, phosphocreatine, and nucleotide phosphates to total phosphorus) were not significantly different between patients and controls. No metabolite ratio correlated with the neuropsychological status as assessed by the Mini-Mental State Examination. CONCLUSION: Changes in phospholipid metabolism can be detected in vivo in the early stage of AD. Discrepancies in the literature may be due to differences in technical setting or in subject population types.

Aged↗
PubMed1993

Activation of human primary visual cortex during visual recall: a magnetic resonance imaging study.

The degree to which the process involved in visual perception and visual imagery share a common neuroanatomical substrate is unclear. Physiological evidence for localization of visual imagery early in the visual pathways would have important bearing on current theories of visual processing. A magnetic resonance imaging technique sensitive to regional changes in blood oxygenation was used to obtain functional activation maps in the human visual cortex. During recall of a visual stimulus, focal increases in signal related to changes in blood flow were detected in V1 and V2 cortex in five of seven subjects. These experiments show that the same areas of the early visual cortex that are excited by visual stimulation are also activated during mental representation of the same stimulus. Some of the processes used in topographically mapped cortical areas during visual perception may also be utilized during visual recall.

Adult↗
PubMed1993

Amygdala atrophy in Alzheimer's disease. An in vivo magnetic resonance imaging study.

OBJECTIVES: To study the ability of magnetic resonance imaging to measure the volume of the amygdala and detect amygdala atrophy in patients with early Alzheimer's disease. DESIGN: Prospective case-control study and "blind" measurements. SETTING: Subjects were ambulatory outpatients selected from an institutional practice in Paris, France. PATIENTS: We studied 11 patients with probable Alzheimer's disease according to National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) inclusion and exclusion criteria, as well as six age-matched control subjects. INTERVENTION: None. MAIN OUTCOME MEASURE: A 1.5-T magnetic resonance imager was used to acquire the images. Two neuroradiologists independently and blindly measured the volume of the right and left amygdalas on high-resolution contiguous slices. In addition, other cerebral structures, ie, the sylvian fissures, temporal lobes, lateral and third ventricles, corpus callosum, and hippocampal formation, were measured on a single slice. RESULTS: The values obtained by the two observers correlated highly (r = .90), and interrater variability was 13%. The Alzheimer's disease group showed significant (33%, P < .0001) atrophy of the amygdala when compared with the control group. The other structures showed less variation. CONCLUSION: Significant amygdala atrophy can be detected in vivo in patients with early Alzheimer's disease by means of standard magnetic resonance imaging. This technique may be useful in the early diagnosis of Alzheimer's disease.

Aged↗