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Claire Corot

Publications and source records attributed to Claire Corot.

36 records · Page 2Linked to original sources

Prophylaxis of iodinated contrast media-induced nephropathy: a pharmacological point of view.

Iodinated contrast media are a frequent cause of acute renal failure, especially in patients whose renal function is already impaired. In addition to hydration, which remains the most commonly acknowledged means of protection, numerous pharmacological approaches for the prophylaxis of contrast nephropathy have been tested so far. They include diuretics, calcium channel blockers, adenosine receptor antagonists, N-acetylcysteine, low-dose dopamine and the dopamine D1 receptor agonist fenoldopam, endothelin receptor antagonists, and even captopril. The present review of the literature critically discusses the drugs used to prevent contrast nephropathy from a pharmacological point of view.

Acute Kidney Injury↗

Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging.

The long blood circulating time and the progressive macrophage uptake in inflammatory tissues of ultrasmall superparamagnetic iron oxide (USPIO) particles are 2 properties of major importance for magnetic resonance imaging (MRI) pathologic tissue characterization. This article reviews the proof of principle of applications such as imaging of carotid atherosclerotic plaque, stroke, brain tumor characterization, or multiple sclerosis. In the human carotid artery, USPIO accumulation in activated macrophages induced a focal drop in signal intensity compared with preinfusion MRI. The USPIO signal alterations observed in ischemic areas of stroke patients is probably related to the visualization of inflammatory macrophage recruitment into human brain infarction since animal experiments in such models demonstrated the internalization of USPIO into the macrophages localized in these areas. In brain tumors, USPIO particles which do not pass the ruptured blood-brain barrier at early times postinjection can be used to assess tumoral microvascular heterogeneity. Twenty-four hours after injection, when the cellular phase of USPIO takes place, the USPIO tumoral contrast enhancement was higher in high-grade than in low-grade tumors. Several experimental studies and a pilot multiple sclerosis clinical trial in 10 patients have shown that USPIO contrast agents can reveal the presence of inflammatory multiple sclerosis lesions. The enhancement with USPIO does not completely overlap with the gadolinium chelate enhancement. While the proof of concept that USPIO can visualize macrophage infiltrations has been confirmed in animals and patients in several applications (carotid atherosclerotic lesions, stroke, brain tumors and multiple sclerosis), larger prospective clinical studies are needed to demonstrate the clinical benefit of using USPIO as an MRI in vivo surrogate marker for brain inflammatory diseases.

Arteriosclerosis↗

Improved MR coronary angiography with use of a new rapid clearance blood pool contrast agent in pigs.

PURPOSE: To evaluate in an animal model the potential for clinical use of a new rapid clearance blood pool contrast agent to improve free-breathing and breath-hold magnetic resonance (MR) coronary angiography. MATERIALS AND METHODS: Free-breathing and breath-hold MR coronary angiography were performed in a pig model (n = 9) (a) without use of a contrast agent; (b) with P792 (Guerbet Research, Aulnay Sous Bois, France), a monodisperse monogadolinated macromolecular compound that acts as a blood pool contrast agent with rapid clearance properties; and (c) with an extravascular gadolinium-based contrast agent. This resulted in six imaging options, which were compared in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio, and vessel length measurements by using the Student t test. RESULTS: Use of P792 improved CNR and visible vessel length significantly with both MR respiratory motion correction approaches, as compared with nonenhanced MR imaging (P <.05). CNR was improved by 76% (from 5.0 to 8.6) with the free-breathing approach and by 34% (from 6.2 to 8.2) with the breath-hold approach. Visible vessel length was increased by 27% (from 79.7 to 99.2 mm) with the free-breathing approach and by 90% (from 48.2 to 86.5 mm) with the breath-hold approach. The P792-enhanced free-breathing approach allowed more distal visualization of the coronary arteries than did the P792-enhanced breath-hold approach (P <.05). Use of the extravascular contrast agent did not improve image quality significantly when compared with that of nonenhanced MR images. CONCLUSION: Use of P792 improves coronary artery MR imaging in conjunction with free-breathing and breath-hold approaches.

Animals↗

Assessment of normal, inflammatory, and tumor-bearing lymph nodes with contrast-enhanced interstitial magnetic resonance lymphography: preliminary results in rabbits.

PURPOSE: To assess different gadolinium (Gd)-based contrast agents for interstitial magnetic resonance (MR) lymphography in normal, inflammatory, and tumor-bearing lymph nodes in rabbits. MATERIALS AND METHODS: Three paramagnetic contrast agents were assessed: a standard extracellular 0.5 M Gd-chelate, gadoterate meglumine (Gd-DOTA), and two macromolecular agents, P792 and P760 (all Guerbet, Aulnay-sous-Bois, France). A volume of 0.5 mL of each agent were injected subcutaneously into the dorsal footpads of six rabbits (three groups, 18 rabbits). Imaging was performed prior to as well as two weeks following induction of either reactive (complete Freund adjuvant) or tumorous (VX2 tumor) lymph nodes. T1-weighted three-dimensional gradient-echo and maximum intensity projection (MIP) images were obtained up to 120 minutes as well as 24 hours after administration of the different compounds. Signal-to-noise ratios (SNRs) of enhancing lymph nodes were calculated. The different compounds were compared regarding nodal enhancement over time, depiction of regional nodes, and lymphatic vessels. Furthermore, enhancement patterns were compared between normal, inflammatory, and metastasized nodes. RESULTS: Inguinal and iliac lymph nodes and lymph vessels revealed enhancement following interstitial injection of all evaluated compounds. For all agents, inflammatory lymph nodes revealed no significantly different SNRs compared to normal nodes (P > 0.2), whereas tumorous nodes showed signal voids and significantly lower SNRs (P < 0.05). Compared to P760 and P792, depiction of tumor-bearing nodes with Gd-DOTA was less reliable. CONCLUSION: Interstitial MR lymphography with P760 and P792 allows differentiation of tumor-bearing lymph nodes from reactive inflammatory and normal nodes based on a contrast uptake pattern assessed qualitatively as well as quantitatively.

Animals↗

Three-dimensional navigator coronary MRA with the aid of a blood pool agent in pigs: improved image quality with inclusion of the contrast agent first-pass.

PURPOSE: To evaluate the effect of including the first-pass of a blood pool agent (BPA) on the image quality of three-dimensional navigator coronary MRA. MATERIALS AND METHODS: A pig model was used to perform: 1) T1 simulation of the BPA, based on actual blood samples, and 2) BPA-enhanced three-dimensional navigator coronary MRA, with or without inclusion of the first-pass of the BPA. The acquisitions with inclusion of the first-pass were timed with the use of a test bolus. The acquisitions without first-pass were started one minute after bolus injection (steady-state). A gradient echo acquisition technique with centric k-space sampling was applied. Comparison of both acquisitions was based on determination of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and vessel length. RESULTS: T1 simulation shows a distinct T1 reduction during first-pass (to a level below 50 msec), increasing to 190 msec during steady-state. Images obtained with first-pass inclusion showed improved CNR (8.6 +/- 1.7 vs. 4.5 +/- 1.8), SNR (11.9 +/- 1.6 vs. 7.4 +/- 2.0), and vessel length (99.2 +/- 10.9 mm vs. 60.5 +/- 21.8 mm) as compared to the acquisitions during steady-state only (all: P< 0.05). CONCLUSION: The image quality of three-dimensional navigator coronary MRA combined with a gadolinium BPA in pigs is improved when starting the image acquisition during first-pass of the bolus.

Animals↗

In vivo comparative antithrombotic effects of ioxaglate and iohexol and interaction with the platelet antiaggregant clopidogrel.

RATIONALE AND OBJECTIVES: Experiments were designed to (1) compare the effects of iodinated contrast media (CM) on a rat model of arterial thrombosis, (2) evaluate which element of the ioxaglate solution supports its antithrombotic activity, and (3) investigate the interaction of ionic and non-ionic CM with the antiplatelet agent clopidogrel. MATERIALS AND METHODS: Carotid thrombosis was induced in rats by extravascular application of a filter paper soaked in FeCl3 (35% vol/wt), proximal to an ultrasonic flow probe. (1) The antithrombotic potential of low-osmolar ionic (ioxaglate Na/meglumine) or nonionic contrast media (iohexol and iodixanol) (all 1600 mg iodine/kg, IV) was assessed by measuring the time to occlusion (TTO) of the carotid artery and the thrombus weight (TW). (2) Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), sodium ioxaglate (600 mOsm/kg) and sodium and meglumine ioxaglate (commercial solution) were tested under similar conditions. (3) Interaction with clopidogrel was tested by injecting lower dose of CM (960 mg iodine/kg) 2 hours after clopidogrel (2 mg/kg per os). RESULTS: (1) Ioxaglate prolonged TTO when compared with saline (30.0 +/- 1.1 minute vs. 19.6 +/- 2.4 minutes, P< 0.001), whereas iohexol had no effect (21.3 +/- 1.3 minutes). Ioxaglate's effect was associated with a reduction in TW with ioxaglate versus saline (2.6 +/- 0.4 mg and 4.7 +/- 0.7 mg, respectively, P< 0.05) whereas TW remained unchanged in the iohexol group (4.2 +/- 0.4 mg). The nonionic dimer iodixanol induced a direct vasoconstrictor effect on the carotid artery and was consequently excluded from the study. (2) Neither iso-osmolar nor hyperosmolar solutions of meglumine had any effect on TTO whereas both sodium and meglumine salts of ioxaglic acid prolonged TTO, suggesting that the antithrombotic effect of ioxaglate is mediated by the ioxaglic acid moiety alone as neither meglumine, osmolality or sodium played a significant role. (3) A synergistic effect on TTO was found when ioxaglate was associated with clopidogrel whereas no such effect was observed with iohexol. CONCLUSIONS: These data show a greater in vivo antithrombotic potential for the ionic contrast medium ioxaglate than for the non-ionic contrast medium iohexol and, for the first time, a synergistic effect between a contrast medium and a platelet antiaggregant drug in vivo.

Animals↗

Comparison of different types of blood pool agents (P792, MS325, USPIO) in a rabbit MR angiography-like protocol.

RATIONALE AND OBJECTIVES: The objective of this study is to determine the influence of the pharmacokinetic behaviors of different classes of blood pool agents (BPA) on a rabbit experimental model that mimics a magnetic resonance angiographic protocol. BPA were as follows: P792, a macromolecular agent (RCBPA), USPIO, an ultrasmall superparamagnetic iron oxide particle agent (SCBPA), and MS-325, a small gadolinium chelate that expresses intravascular behavior by reversible albumin binding. METHODS: The 2 main phases of early distribution following contrast agent injection, that is, the bolus phase and the steady-state phase, are investigated by measuring Gd or Fe blood concentrations in the first 5 minutes postinjection. T1 relaxation times and r1 relaxivity were calculated at each time point of blood sampling. Furthermore, in the case of MS-325, the concentrations of the free and bound forms were calculated, according to the measured concentrations and the apparent r1 relaxivities. RESULTS: Injected under similar conditions, the 3 BPA have, during the bolus phase, a comparable profile to Gd-DOTA. Signal enhancement was maximum during this short bolus phase, as were the T1 relaxation times under 30 ms for all agents. At 1 minute postinjection, P792 (r1 = 39 seconds(-1) x mmol/L(-1), 20 MHz) demonstrated the same pharmacokinetic behavior as USPIO (r1 = 33 seconds(-1) x mmol/L(-1), 20 MHz): C1 minute/C0 values were 91 +/- 6% and 92 +/- 12%, respectively. Immediately after the injection at clinical dose, 74% of MS-325 was in free form, resulting in an apparent r1 relaxivity of only 13 seconds(-1) x mmol/L(-1) (20 MHz); 1 minute postinjection, the C1 minute/C0 value of 61 +/- 4% was the lowest as compared with P792 and USPIO and the bound form represented 75% of the MS-325 molecules. CONCLUSIONS: The BPA P792 and USPIO have favorable properties that result from their intravascular retention and their lack of extravasation, allowing optimal contrast between the vessel and the adjacent tissue for several minutes postinjection. Combining a rapid body clearance and a marked T1 effect, P792 presents optimal blood pool characteristics for angiographic applications. During the bolus phase, MS-325 is mainly in free form, which presents the disadvantage of increasing the tissue signal background, due to extravasation of the free form.

Animals↗

MR angiography with a new rapid-clearance blood pool agent: Initial experience in rabbits.

The purpose of this study was to assess a new Gd-based macromolecular intravascular contrast agent (P792, Vistarem(R); Laboratoire Guerbet, Aulnay sous Bois, France) for MR angiography (MRA). P792 is a macrocyclic gadolinium compound based on a gadoterate meglumine structure substituted by hydrophilic arms. In vitro imaging of phantoms containing varying concentrations of P792 and gadoterate meglumine (Gd-DOTA) was performed. In rabbits (N = 5), arterial concentrations for P792 and Gd-DOTA were determined, and in vivo 3D MRA was performed. For gadolinium concentrations ranging from 200 to 3000 micromol/l, in vitro imaging showed higher SNR values for P792 compared to Gd-DOTA. Determination of arterial Gd concentration showed comparable bolus phase curves for P792 and Gd-DOTA. With P792, higher concentrations were obtained due to a restricted diffusion into the interstitial space. P792 allowed acquisition of high-quality MR angiograms. Image quality was rated as superior for P792 in the post-bolus phase images. In conclusion, P792 appears to be well suited for high-quality first-pass and equilibrium-phase MRA. The intravascular properties lead to an excellent signal in the vasculature, with limited background enhancement. Since the agent is rapidly renally excreted, it should be well suited for perfusion and permeability imaging.

Animals↗

Standardized MR protocol for the evaluation of MRA sequences and/or contrast agents effects in high-degree arterial stenosis analysis.

PURPOSE: To investigate the relative role of high resolution (spatial or temporal) magnetic resonance angiography (MRA) sequence and of contrast agent properties in the evaluation of high-degree arterial stenosis. METHODS: We qualitatively and quantitatively studied both 50 and 95% (300 microm diameter) stenosis of a 6 mm arterial phantom with two contrast agents (CA), Gd-DOTA (r(1)=2.9 mM(-1) s(-1)) versus P760 (r(1)=25 mM(-1) s(-1)) at several CA concentrations, including arterial peak concentration after injection of either a single or double dose of CA, using either a high temporal (booster) or high spatial (HR) resolution 3D MRA sequences. Experimental data were then compared to theoretical data. RESULTS: With the 3D HR sequence, both visual and quantitative analysis were significantly better compared to the 3D booster sequence, at each phantom diameter. Quantitative analysis was significantly improved by injection of a double versus a single dose of each CA (Gd-DOTA or P760), primarily in high degree stenosis. CONCLUSION: Combined MRA spatial resolution and high CA efficiency are mandatory to correctly evaluate high degree stenosis.

Arterial Occlusive Diseases↗

Dynamic computed tomography with low- and high-molecular-mass contrast agents to assess microvascular permeability modifications in a model of liver fibrosis.

Interstitial collagen formation and transformation of the fenestrated hepatic sinusoids into continuous capillaries are major ultrastructural changes that occur in liver cirrhosis and fibrosis. These modifications lead to progressive restriction of blood-liver exchanges. The purpose of our study was to evaluate the permeability changes in a model of hepatic fibrosis by using dynamic computed tomography (CT) enhanced with contrast agents of different molecular masses. Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass contrast agent (iobitridol) and an experimental high-molecular-mass agent (P840) in normal control rabbits and in rabbits with hepatic fibrosis. Hepatic, aortic and portal venous time-density curves were fitted with a dual-input one-compartmental model to calculate the hepatic mean transit time and distribution volume of the contrast agents. In the rabbits with liver fibrosis, the mean transit time of the high-molecular-mass agent was shorter than that of the low-molecular-mass agent (10.0+/-1.8 s and 12.0+/-1.2 s respectively; P<0.05). The distribution volume accessible to the high-molecular-mass agent was also smaller (22.2+/-4.8% compared with 32.0+/-6.7%; P<0.01). In the normal rabbits, the mean transit times of the high- and low-molecular-mass agents did not differ significantly, and nor did their distribution volumes. Our results demonstrate decreased sinusoidal permeability for the high-molecular-mass agent P840 in a model of hepatic fibrosis. Non-invasive assessment of permeability changes in liver fibrosis can be performed with dynamic CT and contrast agents of different molecular masses.

Animals↗

Effects of two dimeric iodinated contrast media on renal medullary blood perfusion and oxygenation in dogs.

RATIONALE AND OBJECTIVES: To compare the effects of two iodinated contrast media, iodixanol and ioxaglate, on outer medullary blood flow (MBF) and oxygen tension (MPO(2)) in the dog kidney. METHODS: Iodixanol and ioxaglate were injected selectively into the renal artery (320 mgI/kg) of anesthetized Beagle dogs. MBF and MPO(2) were measured with a laser-Doppler probe and an oxygen-sensing microelectrode implanted in the outer medulla. Urine samples were collected for viscosity and osmolality measurements. RESULTS: Both contrast media produced a moderate decrease in MBF and MPO(2). The hypoperfusion and hypoxia lasted significantly longer with iodixanol than with ioxaglate. Theophylline, an adenosine receptor antagonist, partially prevented iodixanol-induced hypoxia. Urine viscosity was dramatically increased by iodixanol but not by ioxaglate. Urine osmolality did not differ significantly between groups. CONCLUSION: Iodixanol produced a more sustained medullary hypoxia than ioxaglate when injected selectively into the dog renal artery. This may lead to hypoxic cellular damage and subsequent impairment of kidney functions.

Animals↗