PubMed Health⌕ Search

Biomedical subjects

Philippe Robert

Publications and source records attributed to Philippe Robert.

At least 19 recordsLinked to original sources

Discrimination of myocardial acute and chronic (scar) infarctions on delayed contrast enhanced magnetic resonance imaging with intravascular magnetic resonance contrast media.

OBJECTIVES: The purpose of this study was to examine the potential of intravascular gadolinium (Gd)-chelates in discriminating acute from chronic myocardial infarctions (MIs). BACKGROUND: A potential limitation of delayed contrast enhanced magnetic resonance imaging with standard extracellular Gd-chelates is its inability to distinguish acute from chronic MIs. METHODS: Eight pigs with MIs were studied at 3 days and 8 weeks. Inversion recovery gradient echo (IR-GRE), T(1)-turbo spin echo (TSE), and T(2)-TSE images were acquired before and after administration of intravascular and extracellular Gd-chelates. Triphenyltetrazolium chloride (TTC) was used to delineate infarctions at postmortem. Masson's trichrome and Biotinylated Bandeiria simplicifolia Isolectin B4 stains were used to characterize scarred myocardium. Analysis of variance was used to compare signal intensity (SI) ratios and determine differences in infarct extent. RESULTS: The intravascular agent produced differential enhancement of acute infarctions at 3 days (SI ratio 5.8 +/- 1.3) but not at 8 weeks (1.6 +/- 0.4, p < 0.01). The extracellular agent provided differential enhancement of both acute (SI ratio 7.7 +/- 1.4) and chronic (7.5 +/- 0.9) infarctions. The extents of enhanced regions in acute infarctions were not different after intravascular (16.0 +/- 1.3%) or extracellular (17.1 +/- 1.7%) agents; at 8 weeks the extent of extracellular enhanced and TTC regions were smaller (13.2 +/- 1.4% and 12.0 +/- 1.5%, respectively). Masson's trichrome stain demonstrated dense scar tissue, signaling the complete healing of infarction. The vascular stain showed that scar tissue contained fewer microvessels oriented in a haphazard array. CONCLUSIONS: The combination of intravascular and extracellular Gd-chelates discriminates acute from chronic infarctions on delayed images. This double contrast agent approach can be used to determine the age and extent of infarctions.

Animals↗

Recent advances in iron oxide nanocrystal technology for medical imaging.

Superparamagnetic iron oxide particles (SPIO and USPIO) have a variety of applications in molecular and cellular imaging. Most of the recent research has concerned cellular imaging with imaging of in vivo macrophage activity. According to the iron oxide nanoparticle composition and size which influence their biodistribution, several clinical applications are possible: detection liver metastases, metastatic lymph nodes, inflammatory and/or degenerative diseases. USPIO are investigated as blood pool agents with T1 weighted sequence for angiography, tumour permeability and tumour blood volume or steady-state cerebral blood volume and vessel size index measurements using T2 weighted sequences. Stem cell migration and immune cell trafficking, as well as targeted iron oxide nanoparticles for molecular imaging studies, are at the stage of proof of concept, mainly in animal models.

Animals↗

Multi-slice DCE-MRI data using P760 distinguishes between metastatic and non-metastatic rodent prostate tumors.

An intermediate molecular weight contrast agent P760 was used to investigate the ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and metastatic AT3.1 prostate tumors originally derived from the Dunning prostate cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE-MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently developed empirical mathematical model. The P760 multi-slice DCE-MRI data in combination with the empirical mathematical model successfully distinguished between metastatic and non-metastatic rodent prostate tumors. Specifically, fitting the data with the empirical model showed that metastatic tumors had significantly faster contrast media uptake (p<0.001) and slower washout rates (p<0.01) than non-metastatic tumors.

Algorithms↗

Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide.

PURPOSE: To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. MATERIALS AND METHODS: Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed. RESULTS: MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. CONCLUSION: Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mumol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.

Animals↗

[Behavioural and psychological symptoms in dementia in Alzheimer's disease].

Behavioral and psychological symptoms in dementia (BPSD) are, beside cognitive disorders, major features of Alzheimer's disease and related disorders. Their diagnosis is important to enhance our knowledge of the pathophysiology of dementia and of their functional consequences on patient and caregivers. Pharmacological and non-pharmacological management of dementia depend on a large extent on the presence of BPSD.

Aged↗

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↗

Organic matter characteristics of food processing industry wastewaters affecting their C and N mineralization in soil incubation.

This study aimed at determining food processing wastewater composition factors that regulate their carbon and nitrogen mineralization when added to soil. Twenty three different wastewaters from various food processing industries were characterized by C and N concentrations, liquid and solid physical separation and acid solubility. They were also incubated in a calcareous soil during six months at 28 degrees C. The C and N concentrations were low but covered a wide range. Carbon and nitrogen were variously distributed in the liquid and solid fractions and much C was present in the acid-soluble fraction in which C to N ratios were low. The C and N mineralization measured during soil incubation covered a wide range of decomposition pathways. Carbon mineralization was linked significantly (p=0.05) with the C to N ratio of the acid soluble fraction and C present in the liquid fraction. N mineralization was significantly correlated (p=0.05) with the organic C to organic N ratio and the C to N ratio of the acid soluble fraction. Multiple factor analysis and clustering also enabled defining clusters which partially overlap the various origins of the wastewaters.

Carbon↗

Impulsivity but not venturesomeness is related to morningness.

The Composite Scale of Morningness (CSM) is a psychometrically sound instrument available in several languages, including French, aimed at arranging individuals along a continuum from high "eveningness" to high "morningness." On the other hand, impulsivity is involved in many personality disorders and is thought to be orthogonal to venturesomeness, which can be seen as a component of the broader construct of sensation seeking. We hypothesized that evening-type subjects would be more impulsive than morning-types. Self-administered questionnaires were distributed to students, and only complete forms were analyzed (194 males and 358 females). A four-way analysis of covariance showed significant effects of age, gender and impulsivity, but not venturesomeness, on morningness in the sense of a higher degree of eveningness in more impulsive subjects. In addition, the correlation coefficients in both genders were similar to those reported in smaller samples. Our findings deserve further interest because, regardless of gender, they suggest a possible physiopathological approach to impulsivity that may be accessible by circadian interventions such as midday bright light exposure or pharmacological treatments.

Adolescent↗

Optimization of a blood pool contrast agent injection protocol for MR angiography.

PURPOSE: To design an ideal first-pass profile for MR angiography (MRA) by optimizing a multiphasic injection protocol based on two experimental animal models. MATERIALS AND METHODS: An equivalent contrast-enhanced (CE) MRA injection protocol was developed with controlled injection modalities (injection rate, volume, and dose) in rabbits and pigs. P792, a blood pool contrast agent, was injected in 17 male New Zealand rabbits and five farm pigs with variable injection schemes (mono- and multiphasic). From the gadolinium (Gd) blood concentration data, a simulation of an MR acquisition was performed to evaluate the impact of such an injection protocol on MR arterial signal and to select the best injection protocol. RESULTS: An empirical relationship between the arterial peak concentration and the injection parameters was found in the rabbits and pigs, allowing precise prediction of the first-pass profile. Of the four injection scheme strategies tested (standard bolus and bi-, tri-, and multiphasic injection protocols), the multiphasic "ramp" injection protocol provided the most optimal contrast agent pharmacokinetics with a durable plateau of concentration. CONCLUSION: Ramp injection protocol provides an optimized first-pass profile for CE-MRA.

Animals↗

Magnetic susceptibility matching at the air-tissue interface in rat lung by using a superparamagnetic intravascular contrast agent: influence on transverse relaxation time of hyperpolarized helium-3.

Transverse relaxation of hyperpolarized helium-3 magnetization in respiratory airways highly depends on local magnetic field gradients induced by the magnetic susceptibility difference between gas and pulmonary tissue. Fast transverse relaxation is known to be an important feature that yields information about lung microstructure and function, but it is also an essential limitation in designing efficient strategies for lung imaging. Using intravascular injections of a superparamagnetic contrast agent in rats, it was possible to increase the overall susceptibility of the perfused lung tissues and hence to match it with the gas susceptibility. The transverse decay time constant of inhaled hyperpolarized helium-3 was measured in multiple-spin-echo experiments at 1.5 T as a function of the superparamagnetic contrast agent concentration in the animal blood. The time constant was increased by a factor of 3 when an optimal concentration was reached as predicted for susceptibility matching by combining intrinsic susceptibilities of tissue, blood, and gas.

Administration, Inhalation↗

Contrast-enhanced dynamic MRI protocol with improved spatial and time resolution for in vivo microimaging of the mouse with a 1.5-T body scanner and a superconducting surface coil.

Magnetic resonance imaging (MRI) is well suited for small animal model investigations to study various human pathologies. However, the assessment of microscopic information requires a high-spatial resolution (HSR) leading to a critical problem of signal-to-noise ratio limitations in standard whole-body imager. As contrast mechanisms are field dependent, working at high field do not allow to derive MRI criteria that may apply to clinical settings done in standard whole-body systems. In this work, a contrast-enhanced dynamic MRI protocol with improved spatial and time resolution was used to perform in vivo tumor model imaging on the mouse at 1.5 T. The needed sensitivity is provided by the use of a 12-mm superconducting surface coil operating at 77 K. High quality in vivo images were obtained and revealed well-defined internal structures of the tumor. A 3-D HSR sequence with voxels of 59x59x300 microm3 encoded within 6.9 min and a 2-D sequence with subsecond acquisition time and isotropic in-plane resolution of 234 microm were used to analyze the contrast enhancement kinetics in tumoral structures at long and short time scales. This work is a first step to better characterize and differentiate the dynamic behavior of tumoral heterogeneities.

Animals↗

Frequency-shift based detection of BMS contrast agents using SSFP: potential for MRA.

A novel mechanism of MRI contrast enhancement, based on the detection by a balanced steady-state free precession (SSFP) sequence of the proton resonance frequency shift induced by bulk magnetic susceptibility (BMS) contrast agents, was investigated. The potential for this contrast mechanism to image blood vessels was explored. The relaxation time and the frequency shift effects of gadolinium- and dysprosium-DOTA on SSFP signal was first simulated and evaluated on a water phantom at 1.5 T. In vitro, a 5-mM concentration in contrast agent induced a 20-Hz frequency shift, leading to a signal increase of 92% for Dy-DOTA, and a 10-Hz frequency shift, leading to a signal increase of 58% for Gd-DOTA at the reference frequency, taking into account the nonlinear SSFP signal response on frequency offset. The concept was then evaluated in vivo on anesthetized rabbits. Low doses of dysprosium-DOTA were injected in their vascular system, and imaging was performed at the level of neck vessels. Following a bolus injection, mean signal changes of 31%, 20% and 14% were observed in the carotid arteries, the vertebral veins and the jugular veins, respectively. The bolus peak times in arteries and veins were consistent with the rabbit vascular circulation. This frequency-shift based contrast mechanism presents interesting potential for contrast-enhanced MR angiography (CE-MRA) compared to usual relaxation-based contrast, but further investigations on reproducibility will be necessary.

Animals↗

Renal functional contrast-enhanced magnetic resonance imaging: evaluation of a new rapid-clearance blood pool agent (p792) in sprague-dawley rats.

OBJECTIVES: The objective of the present study was to compare P792, a new rapid clearance blood pool agent characterized by negligible interstitial diffusion but unrestricted glomerular filtration, with Gd-DOTA in both qualitative and quantitative aspects of renal functional magnetic resonance imaging. MATERIALS AND METHODS: Dynamic imaging was performed with a fast T1-weighted gradient-echo sequence on a 1.5-T magnet in 25 Sprague-Dawley rats, after injection of 13 micromol Gd/kg-1 of P792 (n = 10), 100 (n = 10), or 50 micromol Gd/kg-1 of Gd-DOTA (n = 5). Signal-time curves from 6 regions of interest (ROIs), including renal parenchyma and contents, were analyzed. RESULTS: Qualitative analysis depicted a typical pattern of temporal enhancement as previously described with extracellular gadolinium chelates, including early and brief enhancement of the aorta, renal vessels and cortex, quickly followed by enhancement of the medulla and then renal pelvis. However, a decrease in signal intensity was noted in the inner medulla and the renal pelvis approximately 90 seconds after bolus injection, being more marked when using the full dose of Gd-DOTA. Curve analysis showed a similar vascular phase within each parenchymal ROI, confirmed by similar upslopes, which ranged from 0.015 +/- 0.007 to 0.019 +/- 0.005. Following this initial phase, T1-enhancement appeared greater and longer within the medulla and renal pelvis, and subsequently in the whole kidney ROI with P792 (time to maximal enhancement (sec)/ enhancement rate: 85.5 +/- 15.9/3.1 +/- 0.4) as compared with Gd-DOTA full (53.0 +/- 18.9/ 2.7 +/- 0.3) or half dosage (65.2 +/- 20.1/ 2.2 +/- 0.2). The subsequent decrease in signal intensity, characterized by a downslope during the minute following maximal enhancement, was faster with Gd-DOTA (0.006 +/- 0.002) as compared either to P792 or half dosage Gd-DOTA (0.003 +/- 0.001). CONCLUSIONS: Due to its physicochemical and pharmacokinetic properties, P792 allows the use of a reduced dosage of gadolinium, resulting in less T2* effect without compromising T1 enhancement. Thus, P792 appears suitable for renal functional MR imaging.

Animals↗

How to compare the efficiency of albumin-bound and nonalbumin-bound contrast agents in vivo: the concept of dynamic relaxivity.

RATIONALE AND OBJECTIVES: The objective of this study was to compare, in a rabbit experimental model that mimics a magnetic resonance (MR) angiographic protocol, the efficiency of the following types of compound on the MR signal: (1) a nonalbumin-bound blood pool contrast agent: P792; (2) a weak albumin-bound extracellular contrast agent: Gd-BOPTA; and (3) a strong albumin-bound blood pool contrast agent: MS325. METHODS: The 2 main phases of early distribution after contrast agent injection, ie, the bolus phase (0-15 seconds postinjection) and the postbolus phase (1-5 minutes postinjection) were investigated by measuring Gd blood concentrations in the first 5 minutes postinjection. In the case of MS325 and Gd-BOPTA, the percentage of the free and bound forms were calculated throughout the pharmacokinetic profile. The dynamic relaxivity at 60 MHz in plasma of each contrast agent was determined in the 2 phases after contrast agent injection, ie, the bolus phase and the postbolus phase. RESULTS: Injected under similar conditions, the 3 contrast agents had a comparable profile during the bolus phase (0-15 seconds postinjection). At 1 minute postinjection, only 38% of Gd-BOPTA remained in the blood, whereas 85% of P792 was still present in the blood. MS-325 had an intermediate position with 61% remaining in the blood. During the postbolus phase, the various compounds demonstrated similar behavior: the plasma concentration of P792 was higher than that of MS325 and Gd-BOPTA, ie, Ci/C0 (P792)>Ci/C0 (MS325)>Ci/C0 (Gd-BOPTA). At the peak of the bolus, 75% of MS325 and 93% of Gd-BOPTA was present in free form. This proportion decreased progressively during the postbolus phase, because 5 minutes postinjection, 23% of the free form remained for MS325 and 82% for Gd BOPTA. A significant decrease in dynamic r1 relaxivity was observed at 60 MHz for the products that bind to albumin (Gd-BOPTA and MS325) during the bolus phase. The dynamic relaxivity for MS325 at the bolus phase was 8.6 mMs and 5.2 mMs for Gd-BOPTA. At the postbolus phase, the dynamic relaxivity increased (17.3 mMs for MS325 and 6.7 mMs for Gd-BOPTA). The dynamic relaxivity of P792, which does not bind to albumin, was constantly equal to 26 mMs at each time point of the pharmacokinetic profile (bolus and postbolus phase). CONCLUSIONS: The physicochemical measurements of relaxivity in plasma are made in vitro at a fixed concentration of gadolinium and the value of relaxivity is not necessarily an accurate reflection of the efficiency of the contrast agent in vivo, especially for contrast agents that bind to albumin. Indeed, in vivo, the proportion of free and bound forms of albumin-binding contrast agents varies according to the pharmacokinetic profile, and the relaxivities of albumin-bound and free contrast agents are different. Consequently, the concept of dynamic relaxivity was introduced to compare the efficiency of MS325, Gd-BOPTA, and P792 in vivo. The variation of the dynamic relaxivity of MS325 and Gd-BOPTA between the bolus and postbolus phase is significant (101% for MS325 and 29% for Gd-BOPTA) as a result of the variation in the quantity of bound and free forms during the pharmacokinetic profile. The blood pool agent P792 has different properties, which result from its intravascular retention and its lack of albumin binding. Indeed, contrary to Gd-BOPTA and MS325, the dynamic relaxivity of P792 is higher at the bolus phase (26 mMs) and does not vary during the pharmacokinetic profile. The impact of these different dynamic relaxivities should be integrated in the analysis of the performance of the different classes of contrast agents in clinical MRA protocols.

Animals↗

JLK inhibitors: isocoumarin compounds as putative probes to selectively target the gamma-secretase pathway.

Alzheimer's disease is characterized by the extracellular deposition of the amyloid beta-peptide that derives from its precursor betaAPP by sequential actions of beta- and gamma- secretases, respectively. Recent studies aimed at identifying these enzymes have been reported as it is thougth that their inhibition should hopefully lead to reduce Abeta load in the AD brains. beta-secretase seems to be due to BACE1, a novel membrane-bound aspartyl protease. gamma-secretase identification is still a matter of controversy. Invalidation of presenilin genes was reported to impair both gamma-secretase-mediated Abeta production and Notch cleavage leading to NICD production. This observation together with another biochemical and pharmacological evidences led to suggest that presenilins could be the genuine long-searched gamma-secretase that would be responsible for both APP and Notch cleavages. We have designed novel non peptidic potential inhibitors of gamma-secretase (referred to as JLK inhibitors) and examined their ability to prevent Abeta40 and Abeta42 secretions as well as NICD production. Three out of a series of these agents drastically lower the recoveries of both Abeta40 and Abeta42 produced by betaAPP-expressing cell lines and concomitantly protect intracellular C99 and C83 recoveries. These inhibitors also prevent Abeta40/42 productions by C99-expressing cells. Interestingly, these inhibitors were totally unable to affect the DeltaENotch cleavage leading to NICD generation. Here, we also further characterize the pharmacological properties and specificity of these JLK inhibitors.

Amyloid Precursor Protein Secretases↗

Contrast-enhanced dark lumen PET/CT and MR colonography in a rodent polyp model: initial results with histopathologic correlation.

OBJECTIVE: The objective of this study was to assess the feasibility of PET/CT for the detection of colorectal masses in a rodent polyp model in an intraindividual comparison with dark-lumen MR colonography. CONCLUSION: Detection of small tumors with PET/CT and MR colonography is possible in a rodent model. The technique thus warrants further evaluation in animal studies as well as in patients with suspected colorectal disease.

Animals↗

New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.

Animals↗

Assessment of myocardial infarction in pigs using a rapid clearance blood pool contrast medium.

Delayed enhancement MRI using extracellular contrast media allows reliable detection of myocardial infarction. If blood pool contrast media like P792 (Vistarem, Guerbet, France), in addition to improving coronary MR angiography, can be shown to also produce delayed enhancement in myocardial infarction they could improve the prerequisites for a comprehensive cardiac MR examination. In this study reperfused myocardial infarction in five minipigs was imaged with an inversion-recovery fast low-angle shot sequence using P792 (0.013 mmol Gd/kg) and the extracellular contrast medium Gd-DOTA (Dotarem, 0.1 mmol Gd/kg, Guerbet). The infarction size determined on MRI using P792 (7.55 +/- 2.31 cm(2)) highly correlated both with histomorphometry (7.81 +/- 2.18 cm(2), r = 0.991, P < 0.002) and with MRI using Gd-DOTA (7.85 +/- 2.35 cm(2), r = 0.978, P < 0.005). Bland-Altman analysis showed that the limit of agreement of MRI using P792 compared to histomorphometry was 3.3 +/- 7.6% of the infarction size. The contrast-to-noise ratio between infarcted and remote myocardium was not significantly different between Gd-DOTA (5.9 +/- 2.4) and P792 (4.4 +/- 1.1, P = 0.5). The blood pool contrast medium P792 allows reliable assessment of viability with good contrast and accuracy.

Animals↗