Papers by Jean-sébastien Raynaud
Contrast Media & Molecular Imaging, Nov 21, 2012
Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and str... more Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nanoparticular contrast agent P03011, an USPIO (ultrasmall superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or nontargeted USPIO P03007 were injected 5 h after ischemia (100 mmol iron kg À1 ; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage.
Journal of Vascular Research, 2007
Background: Magnetic resonance imaging (MRI) enhanced with ultrasmall superparamagnetic particles... more Background: Magnetic resonance imaging (MRI) enhanced with ultrasmall superparamagnetic particles of iron oxide (USPIO) has previously been evaluated in hyperlipidemic rabbits. The aim of this study was therefore to compare USPIO in ruptured and non-ruptured arteries in an atherosclerotic rabbit model. Methods: Atherosclerotic-like lesions were induced by the combination of endothelial abrasion and high-cholesterol diet in iliac rabbit arteries (n = 16). Rupture of atherosclerotic lesions was realized by oversized balloon angioplasty in one iliac artery, whereas the contralateral artery was used as control. USPIO (ferumoxtran-10: 1 mmol Fe/kg) was administered immediately (n = 10) or 28 days (n = 6) after injury. MRI and histological analysis were performed 7 and 35 days after injury and in control arteries. Results: In vivo MRI analysis showed extended susceptibility artifact with transluminal signal loss in all ruptured arteries 7 days after injury. In contrast, hyposignal was reduced 35 days following injury (i.e. after healing), and absent in non-ruptured arteries. Similarly, histological analysis of iron uptake was significantly increased 7 days after injury compared to healed-ruptured and control arteries. Conclusions: Accumulation ofUSPIO is significantly increased in ruptured as compared to non-ruptured arteries in the atherosclerotic rabbit model.
Journal of Magnetic Resonance Imaging, Apr 10, 2015
Journal of magnetic resonance imaging : JMRI, Jan 10, 2015
To investigate the feasibility of detecting a living cell monolayer labeled with gadoterate (Gd-D... more To investigate the feasibility of detecting a living cell monolayer labeled with gadoterate (Gd-DOTA) in a microfluidic environment, by micromagnetic resonance imaging (MRI) in a 2.35T small-animal system. The development of new targeted contrast agents (CAs) requires proof-of-concept studies in order to establish the detectability of the CA and to predict the role of biodistribution in its uptake mechanisms. A promising approach is to carefully mimic the in vivo pharmacokinetic context with reduced experimental complexity compared to in vivo situations. A dedicated experimental system was built by combining a microfluidic slide and a radiofrequency probe based on a 6 mm diameter multiturn transmission-line resonator. Adherent KB cells were incubated with different concentrations of Gd. MRI data were acquired at 2.35T with a 3D gradient echo and a resolution of 12.4 μm perpendicular to the cell layer. The longitudinal relaxation rate, R1 , was measured as a function of the amount of...
Magnetic Nanoparticles - Particle Science, Imaging Technology, and Clinical Applications - Proceedings of the First International Workshop on Magnetic Particle Imaging, 2010
... MARC PORT, CLAIRE COROT, ISABELLE RAYNAL, CAROLINE ROBIC, PHILIPPE ROBERT, JEAN MARC IDÉE, GA... more ... MARC PORT, CLAIRE COROT, ISABELLE RAYNAL, CAROLINE ROBIC, PHILIPPE ROBERT, JEAN MARC IDÉE, GAELLE LOUIN, JEAN ... of Physics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA Institut für Elektrische Messtechnik und ...
Radiology, 2009
To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide... more To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque. The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis. With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93). Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system. http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.
Microsystem Technologies, 2006
In Magnetic Resonance Imaging (MRI), to achieve sufficient Signal to Noise Ratio (SNR), the elect... more In Magnetic Resonance Imaging (MRI), to achieve sufficient Signal to Noise Ratio (SNR), the electrical performance of the RF coil is critical. We developed a device (microcoil) based on the original concept of monolithic resonator. This paper presents the used fabrication process based on micromoulding. The dielectric substrates are flexible thin films of polymer, which allow the microcoil to be form fitted to none-plane surface. Electrical characterizations of the RF coils are first performed and results are compared to the attempted values. Proton MRI of a saline phantom using a flexible RF coil of 15 mm in diameter is performed. When the coil is conformed to the phantom surface, a SNR gain up to 2 is achieved as compared to identical but planar RF coil. Finally, the flexible coil is used in vivo to perform MRI with high spatial resolution on a mouse using a small animal dedicated scanner operating at in a 2.35 T.
Annales Pharmaceutiques Françaises, 2012
Due to numerous technical developments, in vivo imaging is suitable for pharmacokinetic and metab... more Due to numerous technical developments, in vivo imaging is suitable for pharmacokinetic and metabolism studies of new chemical entities as well as for evaluating their pharmacological or biological effects. MRI, nuclear medicine, X-Ray, ultrasound and optical imaging are available for both clinical and experimental imaging with even higher performance. For all these imaging modalities, diagnostic agents are useful to improve contrast and specificity. Specific targeting of biological events is addressed by molecular imaging. From a pharmacodynamic perspective, radiolabeling of a new chemical entity allows in vivo visualization quantitative measure of its biodistribution, its elimination and its specific molecular binding. Non-invasive imaging methods are useful for longitudinal investigations of biological changes. Based on nanotechnologies, specificity of drug delivery can be monitored by imaging. New developments in hybrid imaging technologies as well as multimodal contrast agents reinforce in vivo experimental and clinical proof of mechanism of new chemical entities.
Physical Review Letters, 2002
Magnetic-resonance-imaging rheometrical experiments show that concentrated suspensions or emulsio... more Magnetic-resonance-imaging rheometrical experiments show that concentrated suspensions or emulsions cannot flow steadily at a uniform rate smaller than a critical value (ᠨ g c). As a result, a "liquid" region (sheared rapidly, i.e., at a rate larger than ᠨ g c) and a "solid" region (static) coexist. The behavior of the fluid in the liquid region follows a simple power-law model, while the extent of the solid region increases with the degree of jamming of the material.
Journal of Rheology, 2002
... described in the following, these fluids tend to exhibit some long-time, irreversible aging t... more ... described in the following, these fluids tend to exhibit some long-time, irreversible aging that we ... the localization of the deformation in a cone and plate geometry for laponite suspensions as ... Magnin, J. Chang, JM Piau, and B. Cabane, Flow of colloidal aqueous silica dispersions ...
Magnetic Resonance in Medicine, 2001
T1‐based determination of perfusion was performed with the high temporal and spatial resolution t... more T1‐based determination of perfusion was performed with the high temporal and spatial resolution that monitoring of exercise physiology requires. As no data were available on the validation of this approach in human muscles, T1‐based NMRI of perfusion was compared to standard strain‐gauge venous occlusion plethysmography performed simultaneously within a 4 T magnet. Two different situations were investigated in 21 healthy young volunteers: 1) a 5‐min ischemia of the leg, or 2) a 2–3 min ischemic exercise consisting of a plantar flexion on an amagnetic ergometer. Leg perfusion was monitored over 5–15 min of the recovery phase, after the air‐cuff arterial occlusion had been released. The interesting features of the sequence were the use of a saturation‐recovery module for the introduction of a T1 modulation and of single‐shot spin echo for imaging. Spatial resolution was 1.7 × 2.0 mm and temporal resolution was 2 s. For data analysis, ROIs were traced on different muscles and perfusion...
European Journal of Ultrasound, 1998
NeuroImage, 2012
Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging o... more Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuroinflammation.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2008
Objective— Despite great advances in our knowledge, atherosclerosis continues to kill more people... more Objective— Despite great advances in our knowledge, atherosclerosis continues to kill more people than any other disease in the Western world. This is because our means of identifying truly vulnerable patients is limited. Prediction of atherosclerotic plaque rupture may be addressed by MRI of activated matrix metalloproteinases (MMPs), a family of enzymes that have been implicated in the vulnerability of plaques prone to rupture. This study evaluated the ability of the novel gadolinium-based MRI contrast agent P947 to target MMPs in atherosclerotic plaques. Methods and Results— The affinity of P947 toward activated MMPs was demonstrated in vitro. The affinity and specificity of P947 toward matrix metalloproteinase (MMP)-rich plaques was evaluated both in vivo using ApoE −/− mice and ex vivo in hyperlipidemic rabbits. Gadolinium content quantification and MRI showed a preferential accumulation of P947 in atherosclerotic lesions compared with the nontargeted reference compound, Gd-DOT...
Angiogenesis inducing agents, such as Sildenafil, can be used to treat stroke. In this study, USP... more Angiogenesis inducing agents, such as Sildenafil, can be used to treat stroke. In this study, USPIO-enhanced MRI was used to visualize collateral vessels in the penumbral area of lesions of rats subjected to transient middle cerebral artery occlusion (tMCAO), and the evaluate efficacy of the Sildenafil treatment. Here, P904, a USPIO agent, was used as a T1 reducing agent at a low dose for MR angiography and as a T2* reducing agent at a moderate dose for visualization of very small vessels on gradient echo susceptibility-weighted imaging (SWI). SWI scans without/with USPIO injection were performed for the following cases: tMCAO without any treatment (n=5), tMCAO with Sildenafil treatment (n=6), and sham tMCAO (n=1) at four different time points (i.e., baseline, 24 h, two weeks and four weeks after tMCAO). The presence of newly developed vessels in the periphery of the ischemic core was only observed in those animals showing severe ischemic brain damage and at the same time received S...
Les mesures simultanees de la perfusion par imagerie rmn, de la desoxymyoglobine par spectroscopi... more Les mesures simultanees de la perfusion par imagerie rmn, de la desoxymyoglobine par spectroscopie proton, et du rapport pi/pcr par spectroscopie phosphore presentent un interet majeur dans l'etude complexe de l'oxygenation au niveau du muscle. Elles apportent des informations sur l'apport, la captation et la consommation de l'oxygene, permettant ainsi de mesurer l'extraction maximale. Cependant, ce protocole d'analyse de l'oxygenation musculaire effectue sur temoins et patients necessite une mesure de la perfusion atraumatique a haute resolution temporelle et spatiale. Aucune sequence rmn validee chez l'homme ne presente ces caracteristiques dans la litterature. Depuis 1992, le signal de l'eau arterielle est utilise pour estimer de facon atraumatique la perfusion par rmn. Nous avons choisi d'y apporter une approche originale nommee satir (saturation-inversion recuperation), derivee de la technique fair (inversion-recuperation alternativement ...
INTRODUCTION The development of targeted contrast agents (CA) is of great interest to increase th... more INTRODUCTION The development of targeted contrast agents (CA) is of great interest to increase the specificity of MRI and allow early diagnosis and therapy follow-up of diseases. However, the efficiency of this approach is still limited due both to the low sensitivity of MRI and to the complexity of the binding and contrast mechanisms. In a previous work [1], a novel approach based on a dedicated micro-MRI set-up was proposed to investigate these issues with a cell monolayer model in a controlled microfluidic environment. Using this approach under physiological-like conditions, we demonstrate here the dynamic uptake of a RGD-targeted Gd-loaded emulsion by a HUVEC cell monolayer expressing the ανβ3 integrin, which is a promising target for molecular imaging due to its high level of expression during tumor angiogenesis. MATERIAL AND METHODS Cells: HUVEC cells were used due to their high level of expression of ανβ3 integrins. 280 000 of these cells were injected in the microfluidic cha...
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Papers by Jean-sébastien Raynaud