Bich-Thuy Doan | PSL - Academia.edu (original) (raw)

Papers by Bich-Thuy Doan

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM)

Journal de Radiologie, 2004

Objectifs Les nanoparticules superparamagnetiques anioniques sont particulierement adaptees pour ... more Objectifs Les nanoparticules superparamagnetiques anioniques sont particulierement adaptees pour l’imagerie cellulaire in vivo. Le but de cette etude etait le suivi in vivo en IRM de l’infiltration lymphocytaire dans des tumeurs implantees chez la souris, et de comparer les images 7 T in vivo a celles ex vivo a 9,4 T. Materiels et methodes Le modele tumoral utilise etait une lignee de lymphome EL-4. Des lymphocytes T ont ete utilises comme modele cellulaire. Les lymphocytes T etaient marques magnetiquement (1,5 pg fer par cellule), puis injectes en intraveineux (5×106 par voie retro-orbitale) dans des souris C57BL/6, porteuses de tumeurs. Les animaux etaient images a differents temps post-injection sur une IRM 7 T, avec des sequences d’echo de gradient. Les tumeurs etaient analysees ex vivo en IRM 9,4 T. Resultats A 7 T, les resultats ont montre des zones en hyposignal au niveau de la tumeur a J3, suggerant la presence de cellules marquees. En IRM 9,4 T ex vivo, les images a J3 montraient des zones en hyposignal bien distinctes, en comparaison avec des tumeurs sans rehaussement negatif. Conclusion Cette approche montre la faisabilite du suivi in vivo de cellules marquees en IRM, apres injection intraveineuse des cellules, avec une bonne correlation entre les etudes in vivo et ex vivo.

Journal of magnetic resonance. Series B, 1995

This report describes the first 1H-1H phased spectrum obtained in vivo from the hind-leg muscles ... more This report describes the first 1H-1H phased spectrum obtained in vivo from the hind-leg muscles of an intact mouse. TOCSY correlations can follow the complete spin system and give a more detailed graph of each molecule than can COSY. TOCSY is also better suited than COSY for studying long fatty-acid chains. All the peaks are in phase in a TOCSY experiment and the intensities of the cross-correlation peaks are less sensitive to low digitalization in the t1 domain than are those of COSY. The improvement in sensitivity was estimated by measuring the volumes of the cross-correlation peaks in COSY and TOCSY spectra.

Pharmaceutical Research, 2015

Purpose The objective was to develop, characterize and assess the potentiality of W 1 /O/W 2 self... more Purpose The objective was to develop, characterize and assess the potentiality of W 1 /O/W 2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). Methods For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Results Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. Conclusion New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these selfformation formulations.

New J. Chem., 2014

ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and h... more ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and highly resolved images. The search for efficient contrast agents to increase the signal to background ratio led us to evaluate paramagnetic spherulites as potential Magnetic Resonance Imaging (MRI) contrast agents. Spherulites are supramolecular assemblies, made of lipidic concentric multilayers, able to encapsulate with high efficiency soluble macromolecules. Despite their highly interesting structure, spherulites have never been proposed as imaging agents. We proposed here three approaches to render spherulites paramagnetic: encapsulating a soluble contrastophore, inserting a lipidic contrastophore derivative or grafting a soluble contrastophore at the surface of the spherulites. Following similar strategies, liposomes were prepared for comparison. The conservation of the spherulite structure, throughout these three strategies, was shown by cryoelectron microscopy and small angle light scattering. The effect of the paramagnetic spherulites was studied by magnetic resonance imaging at different magnetic fields. The results showed that insertion of a contrastophore lipidic derivative into spherulite bilayers and grafting a contrastophore at the surface of the spherulites were the two strategies which led to the highest MRI contrast improvement.

International Journal of Molecular Imaging, 2013

Background and Objectives. To determine the most appropriate technique for tumour followup in exp... more Background and Objectives. To determine the most appropriate technique for tumour followup in experimental therapeutics, we compared ultrasound (US) and magnetic resonance imaging (MRI) to characterize ectopic and orthotopic colon carcinoma models. Methods. CT26 tumours were implanted subcutaneously (s.c.) in Balb/c mice for the ectopic model or into the caecum for the orthotopic model. Tumours were evaluated by histology, spectrofluorescence, MRI, and US. Results. Histology of CT26 tumour showed homogeneously dispersed cancer cells and blood vessels. The visualization of the vascular network using labelled albumin showed that CT26 tumours were highly vascularized and disorganized. MRI allowed high-resolution and accurate 3D tumour measurements and provided additional anatomical and functional information. Noninvasive US imaging allowed good delineation of tumours despite an hypoechogenic signal. Monitoring of tumour growth with US could be accomplished as early as 5 days after impl...

Advanced Functional Materials, 2014

Recent breakthroughs in the rational development of multifunctional nanocarriers have highlighten... more Recent breakthroughs in the rational development of multifunctional nanocarriers have highlightened the advantage of combining the complementary forces of several imaging modalities into one single nanotool fully dedicated to the biomedical field and diagnosis applications. A novel multimodal optical‐magnetic resonance imaging nanoprobe is introduced. Designed on the basis of a spinel zinc gallate structure doped with trivalent chromium and gadolinium, this nanocrystal bears the ability to serve as both a highly sensitive persistent luminescence nanoprobe for optical imaging, and a negative contrast agent for highly resolved magnetic resonance imaging (MRI). Additional proof is given that surface coverage can be modified in order to obtain stealth nanoparticles highly suitable for real‐time in vivo application in mice, showing delayed reticulo‐endothelial uptake and longer circulation time after systemic injection.

European Journal of Biochemistry, 1998

Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure. Under aerobic cond... more Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure. Under aerobic conditions, NO is transformed into its higher oxides (N 2O4, NO2, NO/NO2 or N2O3) and oxoperoxonitrate (currently named peroxynitrite) by coupling with superoxide. Previous studies have shown that these reactive nitrogen species should be involved in vivo in the transformation of cysteine and tyrosine into the corresponding nitrosothiol and 3-nitrotyrosine. In the present study, attention has been focused on the relative reactivities of HNO 2 , peroxynitrite, and NO in the presence of dioxygen, towards the arginine and tyrosine residues of the peptide angiotensin II. Nitration of the tyrosine residue is clearly the main reaction with peroxynitrite. By contrast, besides 20% of nitration of the tyrosine residue, NO in the presence of dioxygen leads to nitrosation reactions with the arginine residue similar to those observed with HNO 2 at pH 5, possibly through the intermediate N 2 O 3 reactive species. Angiotensin II is converted for the most part to peptides having lost either a terminal amine function or the whole guanido group, leading respectively to citrulline-containing angiotensin II or to a diene derivative. Identification established mainly by tandem mass spectrometry of peptidic by-products allows us to propose a cascade of nitrosations of all the amine functions of the arginine residue. Further in vivo studies show that transformations of the arginine residue in angiotensin II do not alter its vasoconstrictive properties, whereas nitration of the tyrosine residue totally inhibits them.

PLoS ONE, 2008

Background: TNF-related lymphotoxin a (LTa) is essential for the development of Plasmodium berghe... more Background: TNF-related lymphotoxin a (LTa) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTa-signaling essential for ECM development through LTb-R, receptor of LTa1b2 heterotrimer. Methodology/Principal Findings: LTbR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTab deficient mice. Resistance of LTab or LTbR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin + CD8 + T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTbR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM. Conclusions/Significance: LTbR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTbR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.

NMR in Biomedicine, 2002

Hepatic encephalopathy may occur following acute hepatic failure (AHF), which results in the rele... more Hepatic encephalopathy may occur following acute hepatic failure (AHF), which results in the release of toxic compounds from the injured liver. These compounds, which induce cerebral edema, are not well characterized, yet. The aim of this study was to evaluate the potential interest of NMR spectroscopy in the follow-up of different plasma compounds in pigs with ischemia-induced fulminant hepatic failure treated or not with a bioartificial liver (BAL), which has been previously shown to improve the neurological status of the animals. Qualitative analysis of pig plasma was achieved by one-dimensional-1 H CPMG, two-dimensional homonuclear 1 H-1 H TOCSY CPMG and heteronuclear 1 H-13 C HSQC sequences. Semi-quantitative analysis of selected plasma metabolites along the disease evolution was carried out on pigs with ischemia-induced AHF treated with the BAL containing alginate beads with or without hepatocytes. A quantitative longitudinal follow-up was performed on characteristic metabolites via a one-dimensional CPMG sequence, including choline, glutamine, N-acetylglucosamine (NAG), pyruvate and trimethylamine-N-oxide (TMAO). The concentrations of choline and TMAO increased from the beginning to the end in animals treated with the BAL containing alginate beads without hepatocytes. Treatment of pigs with BAL containing hepatocytes resulted in an improvement of survival, the plasma concentrations of choline and TMAO being decreased in three out of five animals. Thus, NMR spectroscopy is a useful approach for the identification of toxic compounds which are involved in hepatic encephalopathy associated with AHF. These compounds can be cleared by a BAL resulting in the improvement of survival and neurological parameters of the animals.

NeuroToxicology, 2008

Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting... more Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

Magnetic Resonance Materials in Physics, Biology and Medicine, 2004

Localized in vivo NMR spectroscopy, chemical shift imaging or multi-voxel spectroscopy are potent... more Localized in vivo NMR spectroscopy, chemical shift imaging or multi-voxel spectroscopy are potentially useful tools in small animals that are complementary to MRI, adding biochemical information to the mainly anatomical data provided by imaging of water protons. However the contribution of such methods remains hampered by the low spectral resolution of the in vivo 1D spectra. Two-dimensional methods widely developed for in vitro studies have been proposed as suitable approaches to overcome these limitations in resolution. The different homonuclear and heteronuclear sequences adapted to in vivo studies are reviewed. Their specific contributions to the spectral resolution of spectroscopic data and their limitations for in vivo investigations are discussed. The applications to experimental models of pathological processes or pharmacological treatment in mainly brain and muscle are presented. According to their combined sensitivity, acquisition duration and spatial resolution, the heteronuclear 2D experiments, which are mainly used for 1H detected-13C spectroscopy after administration of 13C-labeled compounds, appear to be less efficient than 1H detected-13C 1D methods at high field. However, the applications of 2D proton homonuclear methods show that they remain the best tools for in vivo studies when an improved resolution is required.

Magnetic Resonance in Medicine, 2006

The aim of this study was to demonstrate the feasibility of in vivo cell tracking to monitor anti... more The aim of this study was to demonstrate the feasibility of in vivo cell tracking to monitor anticancer cell therapy by means of a high-resolution noninvasive MRI method. Ovalbumin-specific splenocytes (OT-1) labeled with anionic ␥-Fe 2 O 3 superparamagnetic iron oxide (SPIO) nanoparticles were adoptively transferred into C57BL/6 mice with growing ovalbumin-expressing tumors. OT-1 cells were tracked in vivo by 7 T MRI 24, 48, and 72 hr after they were injected. The results showed significant negative enhancement of the spleen at 24 hr, and of the tumor at 48 and 72 hr, after labeled cell injection. This suggests that the lymphocytes initially homed toward the spleen and were then recruited by the tumor. The presence of labeled cells was confirmed in ex vivo by 9.4 T microimaging of tumors and magnetic sorting of spleen cells. These results confirm that MR tracking of lymphocytes is feasible in vivo. This high-resolution imaging method could be used to improve the monitoring of immune cell therapy. Magn Reson Med 56:498 -508, 2006.

Journal of Physical Organic Chemistry, 2006

Isabelle Correia,1* Nello Ronzani,1 Nicole Platzer,2 Bich-Thuy Doan2 and Jean-Claude Beloeil2 1St... more Isabelle Correia,1* Nello Ronzani,1 Nicole Platzer,2 Bich-Thuy Doan2 and Jean-Claude Beloeil2 1Structure et Fonction de Molécules Bioactives (UMR 7613), UPMC Paris 6, BP 45, 4 Place Jussieu, 75252 Paris Cedex 05, France 2Laboratoire de RMN Biologique, ICSN, CNRS, ...

Journal of Physical Organic Chemistry, 2002

Previous molecular modeling studies, in our laboratory, have shown that some esters of type RCOO(... more Previous molecular modeling studies, in our laboratory, have shown that some esters of type RCOO(CH2) nC5H5N+Cl− are potentially active against Alzheimer's disease. We have also demonstrated that acridine, which has strong anticholinesterase activity appears to be a suitable R substituent. The main obstacle to the possible pharmaceutical application of these compounds is their limited solubility in water, which is due to the poor aqueous solubility of acridine itself (0.26 mM). Inclusion complexation with cyclodextrins may overcome this problem. Solubility diagrams and NMR spectroscopy were used to study the inclusion of acridine (Acr) within β‐cyclodextrin (βCD) and heptakis(2,6‐di‐O‐methyl)cyclomaltoheptose (DMβCD). A 1:1 complex was formed for the Acr–βCD system and both 1:1 and 2:1 complexes for the Acr–DMβCD system (apparent Ka 215 ± 20 and 1150 ± 100 M −1, respectively). Data from 1H NMR studies corrected the assignment of the acridine H1, H8 and H4, H5 protons in D2O, whi...

Journal of Magnetic Resonance, 2009

H-( 13 C) localized MRS POCE-STEAM POCE-PRESS Hadamard encoding Cerebral energy metabolism [U-13 ... more H-( 13 C) localized MRS POCE-STEAM POCE-PRESS Hadamard encoding Cerebral energy metabolism [U-13 C] glucose injection a b s t r a c t 13 C spectroscopy combined with the injection of 13 C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13 C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references.

Contrast Media & Molecular Imaging, 2008

Gd 3 L is a trinuclear Gd 3R complex of intermediate size, designed for contrast agent applicatio... more Gd 3 L is a trinuclear Gd 3R complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H 12 L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine-N,N,N 00 ,N 00 -tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd 3 L has remarkable proton relaxivities at high magnetic field (r 1 ¼ 10.2 vs 3.0 mM S1 s S1 for GdDOTA at 9.4 T, 37-C, in H 2 O). Here we report an in vivo MRI feasibility study, complemented with dynamic g scintigraphic imaging and biodistribution experiments using the 153 Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd 3 L and the commercial contrast agent gadolinium(III)-1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd 3 L was well tolerated by the animals at the dose of 8 mmol Gd kg S1 body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd 3 L injection than after GdDOTA injection at an identical dose. The relaxation rates, DR 1 , were calculated from the IR TrueFISP data. During the excretory phase, the DR 1 for various tissues was similar for Gd 3 L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 mmol Gd kg S1 body weight). These results point to an approximately three times higher in vivo relaxivity (per (www.interscience.wiley.com) 78 Gd) for Gd 3 L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd 3 L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd 3 L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic g scintigraphic studies and the biodistribution experiments performed in Wistar rats with 153 Sm-enriched * Sm 3 L are also indicative of a fast elimination via the kidneys.

Cellular Microbiology, 2006

In vivo imaging of small animals is a rapidly developing field. However, the potential of global ... more In vivo imaging of small animals is a rapidly developing field. However, the potential of global imaging of infectious processes in animal models remains poorly explored. We used magnetic resonance imaging (MRI) to follow the development and regression of inflammatory lesions caused by infection by Klebsiella pneumoniae in mouse lungs. A virulent strain caused an intense inflammation within 2 days in the whole lungs, while an avirulent strain did not show significant changes. Mice infected with the virulent strain and subsequently treated with antibiotics presented a severe inflammation localized mainly in the left lung that disappeared after a week. The lesions observed by MRI correlated with the damage seen by histological analysis and a 3D representation of the tissue allowed better visualization of the development and healing of inflammatory lesions. MRI thus represents a powerful technique to study in vivo the interactions between a pathogen and its host in real time.