22 results on '"Laboratoire Guerbet / Guerbet Research"'
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2. Learning to Jointly Segment the Liver, Lesions and Vessels from Partially Annotated Datasets
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Ali, Omar, Bone, Alexandre, Rohe, Marc-Michel, Vibert, Eric, Vignon-Clementel, Irene, Laboratoire Guerbet / Guerbet Research, Hôpital Paul Brousse, Université Paris-Saclay, SImulations en Médecine, BIOtechnologie et ToXicologie de systèmes multicellulaires (SIMBIOTX ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Physiopathogénèse et Traitement des Maladies du Foie, Hôpital Paul Brousse-Université Paris-Saclay, and AP-HP. Université Paris Saclay
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partially labeled data ,weighted loss function ,multi-task learning ,Semantic segmentation ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience; The segmentation of the liver, lesions, and vessels from pre-opera-tive CT scans is of major importance in hepatic surgery planning. However, large databases with reference segmentations for these regions of interest remain unavailable, a challenge often encountered in medical image segmentation. In this work, we propose the FuSeloss, a novel loss function for multi-task learning on datasets with partial annotations. By employing the nnU-Net’s 3D self-configur-ing pipeline to calibrate and train a deep network for the joint segmentation of the liver, lesions, and vessels, we show how the FuSeloss allows to learn from the differently annotated IRCAD and LiTS datasets, improving the overall baseline segmentation performance. With the FuSe loss, the dice scores reached up to 95.9%, 70.6% and 60.0% for the liver, lesions, and vessels respectively.
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- 2022
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3. From dose reduction to contrast maximization: can deep learning amplify the impact of contrast media on brain MR image quality? A reader study
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Bône, Alexandre, Ammari, Samy, Menu, Yves, Balleyguier, Corinne, Moulton, Eric, Chouzenoux, Emilie, Volk, Andreas, Garcia, Gabriel C.T.E., Nicolas, François, Robert, Philippe, Rohé, Marc-Michel, Lassau, Nathalie, Laboratoire Guerbet, LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), OPtimisation Imagerie et Santé (OPIS), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay, Chouzenoux, Emilie, and Laboratoire Guerbet / Guerbet Research
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brain neoplasms ,Diagnostic imaging ,multiparametric MRI ,deep learning ,image enhancement ,contrast media ,lesion detection ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,[SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience; ObjectivesThe aim of this study is to evaluate a deep learning method designed to increase the contrast-to-noise ratio in contrast-enhanced gradient echo T1-weighted brain MRI acquisitions. The processed images are quantitatively evaluated in terms of lesion detection performance.Materials and methodsA total of 250 multiparametric brain MRIs, acquired between November 2019 and March 2021 at Gustave Roussy Cancer Campus (Villejuif, France), were considered for inclusion in this retrospective monocentric study. Independent training (107 cases, age 55y±14, 58 women) and test (79 cases, age 59y±14, 41 women) samples were defined. Patients had glioma, brain metastasis, meningioma, or no enhancing lesion. Gradient echo and turbo spin echo with variable flip angles postcontrast T1 sequences were acquired in all cases. For the cases that formed the training sample, “low-dose” postcontrast gradient echo T1 images using 0.025mmol/kg injections of contrast agent were also acquired. A deep neural network was trained to synthetically enhance the low-dose T1 acquisitions, taking standard-dose T1 MRI as reference. Once trained, the contrast enhancement network was used to process the test gradient echo T1 images. A read was then performed by two experienced neuroradiologists to evaluate the original and processed T1 MRI sequences in terms of contrast enhancement and lesion detection performance, taking the turbo spin echo sequences as reference.ResultsThe processed images were superior to the original gradient echo and reference turbo spin echo T1 sequences in terms of contrast-to-noise ratio (44.5 versus 9.1 and 16.8, p.99). The same effect was observed when considering all lesions larger than 5mm: sensitivity increased from 70% to 85% (p
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- 2022
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4. Versatile Macrocyclic Platform for the Complexation of [(nat)Y/(90)Y]Yttrium and Lanthanide Ions
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Charlene Harriswangler, Laura Caneda-Martínez, Olivier Rousseaux, David Esteban-Gómez, Olivier Fougère, Rosa Pujales-Paradela, Laura Valencia, M. Isabel Fernández, Nicolas Lepareur, Carlos Platas-Iglesias, Universidade da Coruña, Laboratoire Guerbet / Guerbet Research, Universidade de Vigo, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), C.P.-I., and D.E.-G. thank Ministerio de Ciencia e Innovación (Grant PID2019-108352RJ-I00) and Xunta de Galicia (Grant ED431B 2020/52) for generous financial support. The authors are indebted to Centro de Supercomputación of Galicia (CESGA) for providing the computer facilities. C.H. thanks Ministerio de Ciencia e Innovación (Grant PRE2020-092888) and Xunta de Galicia (Grant ED481A 2021/070) for funding her PhD contracts. N.L. acknowledges Labex IRON (grant no. ANR-11-LABX-0018) and Guerbet for financial support. L.V. is indebted to CACTI (Universidade de Vigo) for X-ray measurements. Funding for open access provided by Universidade da Coruña/CISUG., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Laboratoire Guerbet, Jonchère, Laurent, and Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID
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[SDV] Life Sciences [q-bio] ,Inorganic Chemistry ,[SDV]Life Sciences [q-bio] ,Physical and Theoretical Chemistry - Abstract
International audience; We report a macrocyclic ligand (H) based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing three acetate pendant arms and a benzyl group attached to the fourth nitrogen atom of the macrocycle. The X-ray structures of the Y and Tb complexes reveal nine coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and three oxygen atoms of the carboxylate pendants. A combination of NMR spectroscopic studies (H, C, and Y) and DFT calculations indicated that the structure of the Y complex in the solid state is maintained in an aqueous solution. The detailed study of the emission spectra of the Eu and Tb complexes revealed Ln-centered emission with quantum yields of 7.0 and 60%, respectively. Emission lifetime measurements indicate that the ligand offers good protection of the metal ions from surrounding water molecules, preventing the coordination of water molecules. The Y complex is remarkably inert with respect to complex dissociation, with a lifetime of 1.7 h in 1 M HCl. On the other hand, complex formation is fast (∼1 min at pH 5.4, 2 × 10 M). Studies using the Y-nuclide confirmed fast radiolabeling since [Y]Y is nearly quantitatively formed (radiochemical yield (RCY) > 95) in a short time over a broad range of pH values from ca. 2.4 to 9.0. Challenging experiments in the presence of excess ethylenediaminetetraacetic acid (EDTA) and in human serum revealed good stability of the [Y]Y complex. All of these experiments combined suggest the potential application of H derivatives as Y-based radiopharmaceuticals.
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- 2022
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5. Tuning the lipophilic nature of pyclen-based 90Y3+ radiopharmaceuticals for β-radiotherapy
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Mariane Le Fur, Raphaël Tripier, Maryline Beyler, Olivier Fougère, Nicolas Lepareur, Olivier Rousseaux, Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire Guerbet, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CRLCC Eugène Marquis (CRLCC), Laboratoire Guerbet / Guerbet Research, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and GINOP-2.3.2-15-2016-00008, European Regional Development Fund
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[SDV]Life Sciences [q-bio] ,Biophysics ,Nanoparticle ,010402 general chemistry ,Ligands ,01 natural sciences ,Biochemistry ,digestive system ,Brain cancer ,Biomaterials ,chemistry.chemical_compound ,picolinate ,Ethiodized Oil ,lipophilicity ,Chelation ,Yttrium Radioisotopes ,90Y radiolabeling ,Picolinic Acids ,Alkyl ,Carbon chain ,chemistry.chemical_classification ,biodegradable nanoparticles ,Radiotherapy ,010405 organic chemistry ,Ligand ,internal radiotherapy ,Metals and Alloys ,pyclen ,Lipiodol® ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,chemistry ,Chemistry (miscellaneous) ,Lipophilicity ,Malic acid ,Radiopharmaceuticals ,Azabicyclo Compounds - Abstract
Pyclen-dipicolinate chelates proved to be very efficient chelators for the radiolabeling with β–-emitters such as 90Y. In this study, a pyclen-dipicolinate ligand functionalized with additional C12 alkyl chains was synthesized. The radiolabeling with 90Y proved that the addition of saturated carbon chains does not affect the efficiency of the radiolabeling, whereas a notable increase in lipophilicity of the resulting 90Y radiocomplex was observed. As a result, the compound could be extracted in Lipiodol® and encapsulated in biodegrable pegylated poly(malic acid) nanoparticles demonstrating the potential of lipophilic pyclen-dipicolinate derivatives as platforms for the design of radiopharmaceuticals for the treatment of liver or brain cancers by internal radiotherapy.
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- 2021
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6. Can deep learning replace gadolinium in neuro-oncology?
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Ammari, Samy, Bône, Alexandre, Balleyguier, Corinne, Moulton, Eric, Chouzenoux, Émilie, Volk, Andreas, Menu, Yves, Bidault, François, Nicolas, François, Robert, Philippe, Rohé, Marc-Michel, Lassau, Nathalie, LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Guerbet Research, France, OPtimisation Imagerie et Santé (OPIS), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay, Chouzenoux, Emilie, and Laboratoire Guerbet / Guerbet Research
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[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,[SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience; Objectives: This study proposes and evaluates a deep learning method that predicts surrogate images for contrast-enhanced T1 from multiparametric magnetic resonance imaging (MRI) acquired using only a quarter of the standard 0.1 mmol/kg dose of gadolinium-based contrast agent. In particular, the predicted images are quantitatively evaluated in terms of lesion detection performance.Materials and methods : This monocentric retrospective study leveraged 200 multiparametric brain MRIs acquired between November 2019 and February 2020 at Gustave Roussy Cancer Campus (Villejuif, France). A total of 145 patients were included: 107 formed the training sample (age 55y±14, 58 women) and 38 the separate test sample (age 62±12, 22 women). Patients had glioma, brain metastases, meningioma, or no enhancing lesion. T1, T2-Flair, DWI, low-dose and standard-dose postcontrast T1 sequences were acquired. A deep network was trained to process the precontrast and low-dose sequences in order to predict “virtual” surrogate images for contrast-enhanced T1. Once trained, the deep learning method was evaluated on the test sample. The discrepancies between the predicted virtual images and the standard-dose MRIs were qualitatively and quantitatively evaluated using both automated voxel-wisemetrics and a reader study, where two radiologists graded image qualities and marked all visible enhancing lesions.Results : The automated analysis of the test brain MRIs computed a structural similarity index of 87.1% (±4.8) between the predicted virtual sequences and the reference contrast-enhanced T1 MRIs, a peak signalto-noise ratio of 31.6dB (±2.0), and an area under the curve of 96.4% (±3.1). At Youden’s operating point, the voxel-wise sensitivity and specificity were 96.4% and 94.8% respectively. The reader study found that virtual images were preferred to standard-dose MRI in terms of image quality (p=.008). A total of 91 reference lesions were identified in the 38 test T1 sequences enhanced with full dose of contrast agent. On average across readers, the brain lesion sensitivity of the virtual images was 83% for lesions larger than 10mm (n=42), and the associated false detection rate was 0.08 lesion/patient. The corresponding positive predictive value of detected lesions was 92%, and the F1-score 88%. Lesion detection performance however dropped when smaller lesions were included: average sensitivity was 67% for lesions larger than 5mm (n=74), and 56% with all lesions included regardless of their size. The false detection rate remained below 0.50 lesion/patient in all cases, and the positive predictive value above 73%. The composite F1 score was 63% at worst.Conclusion : The proposed deep learning method for virtual contrast-enhanced T1 brain MRI prediction showed very high quantitative performance when evaluated with standard voxel-wise metrics. The reader study demonstrated that for lesions larger than 10mm, good detection performance could be maintained despite a 4-fold division in contrast agent usage, unveiling a promising avenue for reducing the gadolinium exposure of returning patients. Small lesions proved however difficult to handle for the deep network, showing that full-dose injections remain essential for accurate first-line diagnosis in neuro-oncology.
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- 2021
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7. Contrast-Enhanced Brain MRI Synthesis With Deep Learning: Key Input Modalities and Asymptotic Performance
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Philippe Robert, Samy Ammari, Francois Nicolas, Alexandre Bône, Nathalie Lassau, Jean-Philippe Lamarque, Corinne Balleyguier, Mickael Elhaik, Marc-Michel Rohe, Emilie Chouzenoux, Laboratoire Guerbet / Guerbet Research, Institut Gustave Roussy (IGR), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), OPtimisation Imagerie et Santé (OPIS), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay, Guerbet Research, France, Bône, Alexandre, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, and BioMaps (UMR1281), Université Paris-Saclay, CNRS, INSERM, CEA, Orsay, France
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[INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI] ,Computer science ,media_common.quotation_subject ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] ,030218 nuclear medicine & medical imaging ,Imaging modalities ,03 medical and health sciences ,gadolinium-based contrast agents (GBCA) ,0302 clinical medicine ,[STAT.ML]Statistics [stat]/Machine Learning [stat.ML] ,Brain mri ,medicine ,Contrast (vision) ,Brain magnetic resonance imaging ,virtual enhancement ,media_common ,Modalities ,medicine.diagnostic_test ,business.industry ,Deep learning ,Magnetic resonance imaging ,Pattern recognition ,[STAT.ML] Statistics [stat]/Machine Learning [stat.ML] ,Brain MRI ,Key (cryptography) ,Artificial intelligence ,business ,low-dose imaging ,030217 neurology & neurosurgery - Abstract
International audience; Contrast-enhanced medical images offer vital insights for the accurate diagnosis, characterization and treatment of tumors, and are routinely used worldwide. Acquiring such images requires to inject the patient intravenously with a gadolinium-based contrast agent (GBCA). Although GBCAs are considered safe, recent concerns about their accumulation in the body tilted the medical consensus towards a more parsimonious usage. Focusing on the case of brain magnetic resonance imaging, this paper proposes a deep learning method that synthesizes virtual contrast-enhanced T1 images as if they had been acquired after the injection of a standard 0.100 mmol/kg dose of GBCA, taking as inputs complementary imaging modalities obtained either after a reduced injection at 0.025 mmol/kg or without any GBCA involved. The method achieves a competitive structural similarity index of 94.2%. Its asymptotic performance is estimated, and the most important input modalities are identified.
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- 2021
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8. Long-Term Evaluation of Gadolinium Retention in Rat Brain After Single Injection of a Clinically Relevant Dose of Gadolinium-Based Contrast Agents
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Ryszard Lobinski, Cécile Factor, Pierre-Olivier Comby, Izabela Strzeminska, Philippe Robert, Claire Corot, Joanna Szpunar, Anne-Laure Grindel, Laboratoire Guerbet / Guerbet Research, Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Guerbet, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Guerbet Research
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Gadolinium DTPA ,gadolinium retention ,Gadolinium ,medicine.medical_treatment ,Contrast Media ,gadoterate ,030218 nuclear medicine & medical imaging ,Rats, Sprague-Dawley ,0302 clinical medicine ,Saline ,Inductively coupled plasma mass spectrometry ,55: 138-143) ,Washout ,Brain ,gadobenate ,General Medicine ,[CHIM.MATE]Chemical Sciences/Material chemistry ,3. Good health ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Injections, Intravenous ,Models, Animal ,Chromatography, Gel ,Female ,gadodiamide ,gadoterate (Invest Radiol 2020 ,medicine.drug ,cerebellum ,chemistry.chemical_element ,03 medical and health sciences ,Meglumine ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Mole ,medicine ,Organometallic Compounds ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Chelation ,gadolinium species ,business.industry ,Gadodiamide ,Original Articles ,Rat brain ,Rats ,[CHIM.POLY]Chemical Sciences/Polymers ,chemistry ,gadolinium-based contrast agent ,Nuclear medicine ,business ,030217 neurology & neurosurgery - Abstract
International audience; The aim of this study was to investigate the presence and chemical forms of residual gadolinium (Gd) in rat brain after a single dose of Gd-based contrast agent. METHODS: Four groups of healthy rats (2 sacrifice time-points, n = 10/group, 80 rats in total) were randomized to receive a single intravenous injection of 1 of the 3 Gd-based contrast agents (GBCAs) (gadoterate meglumine, gadobenate dimeglumine, or gadodiamide) or the same volume of 0.9% saline solution. The injected concentration was 0.6 mmol/kg, corresponding to a concentration of 0.1 mmol/kg in humans after body surface normalization between rats and humans (according to the US Food and Drug Administration recommendations). Animals were sacrificed at 2 washout times: 1 (M1) and 5 (M5) months after the injection. Total Gd concentrations were determined in cerebellum by inductively coupled plasma mass spectrometry. Gadolinium speciation was analyzed by size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry after extraction from cerebellum. RESULTS: A single injection of a clinically relevant dose of GBCA resulted in the detectable presence of Gd in the cerebellum 1 and 5 months after injection. The cerebellar total Gd concentrations after administration of the least stable GBCA (gadodiamide) were significantly higher at both time-points (M1: 0.280 ± 0.060 nmol/g; M5: 0.193 ± 0.023 nmol/g) than those observed for macrocyclic gadoterate (M1: 0.019 ± 0.004 nmol/g, M5: 0.004 ± 0.002 nmol/g; P < 0.0001). Gadolinium concentrations after injection of gadobenate were significantly lower at both time-points (M1: 0.093 ± 0.020 nmol/g; M5: 0.067 ± 0.013 nmol/g; P < 0.05) than the Gd concentration measured after injection of gadodiamide. At the 5-month time-point, the Gd concentration in the gadoterate group was also significantly lower than the Gd concentration in the gadobenate group (P < 0.05). Gadolinium speciation analysis of the water-soluble fraction showed that, after injection of the macrocyclic gadoterate, Gd was still detected only in its intact, chelated form 5 months after injection. In contrast, after a single dose of linear GBCAs (gadobenate and gadodiamide), 2 different forms were detected: intact GBCA and Gd bound to soluble macromolecules (above 80 kDa). Elimination of the intact GBCA form was also observed between the first and fifth month, whereas the amount of Gd present in the macromolecular fraction remained constant 5 months after injection. CONCLUSIONS: A single injection of a clinically relevant dose of GBCA is sufficient to investigate long-term Gd retention in the cerebellar parenchyma. Administration of linear GBCAs (gadodiamide and gadobenate) resulted in higher residual Gd concentrations than administration of the macrocyclic gadoterate. Speciation analysis of the water-soluble fraction of cerebellum confirmed washout of intact GBCA over time. The quantity of Gd bound to macromolecules, observed only with linear GBCAs, remained constant 5 months after injection and is likely to represent a permanent deposition.
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- 2020
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9. Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted Radiotherapy: From Yttrium(III) Complexation to 90Y Radiolabeling
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Nicolas Lepareur, Olivier Rousseaux, Olivier Fougère, Carlos Platas-Iglesias, Maryline Beyler, Mariane Le Fur, Raphaël Tripier, Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Laboratoire Guerbet / Guerbet Research, Departamento de Química Fundamental, Universidade da Coruña, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Guerbet research group, and Guerbet
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Serum ,Magnetic Resonance Spectroscopy ,Inorganic chemistry ,Organophosphonates ,Chemistry Techniques, Synthetic ,Triclinic crystal system ,Crystallography, X-Ray ,010402 general chemistry ,01 natural sciences ,Dissociation (chemistry) ,Inorganic Chemistry ,chemistry.chemical_compound ,Drug Stability ,Spectrophotometry ,medicine ,Humans ,Yttrium ,Yttrium Radioisotopes ,[CHIM.COOR]Chemical Sciences/Coordination chemistry ,Physical and Theoretical Chemistry ,Chelating Agents ,Chloroform ,Aqueous solution ,Radiotherapy ,medicine.diagnostic_test ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,010405 organic chemistry ,Chemistry ,Nuclear magnetic resonance spectroscopy ,Phosphonate ,0104 chemical sciences ,3. Good health ,Isotope Labeling ,Proton NMR ,Thermodynamics ,Spectrophotometry, Ultraviolet ,Radiopharmaceuticals ,Azabicyclo Compounds ,Nuclear chemistry - Abstract
International audience; The Y3+ complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as its Ho3+ and Lu3+ analogues. X-ray diffraction analyses revealed isomorphous dimeric M2(PCTMB)2·9H2O (M = Y, Ho, Lu) structures that crystallize in the centrosymmetric P1 triclinic space group. 1H NMR and UV studies in aqueous solutions indicated that Y3+ complexation is fast, being quantitative in 167 min at pH 3.8 and in 13 min at pH 5.5 (25 °C, acetate buffer, I = 0.150 M, [Y3+] = [PCTMB] = 0.2 mM). 1H NMR DOSY and photon correlation spectroscopy experiments evidenced the formation of aggregates in chloroform with a bimodal distribution that changes slightly with concentration (11-24 and 240-258 nm). The behavior of the acid-assisted dissociation of the complex of Y3+ with PCTMB was studied under pseudo-first-order conditions, and the half-life of the [Y(PCTMB)] complex in 0.5 M HCl at 25 °C was found to be 37 min, a value that decreases to 2.6 min in 5 M HCl. The Y3+ complex of PCTMB is thermodynamically very stable, with a stability constant of log KY-PCTMB = 19.49 and pY = 16.7 measured by potentiometry. 90Y complexation studies revealed fast radiolabeling kinetics; optimal radiolabeling conditions were obtained for 90Y in acetate medium, PCTMB at 10-4 to 10-2 M in acetate buffer pH = 4.75, 15 min at 45-60 °C. In vitro stability studies in human serum showed that [90Y(PCTMB)] is quite stable, with about 90% of the activity still in the form of the radiotracer at 24 h and 80% from 48 h to 72 h. A comparison with other ligands such as PCTA, DOTA, and DTPA already used for in vivo application shows that [90Y(PCTMB)] is an interesting lipophilic and neutral analogue of these reference chelates for therapeutic applications in aqueous and nonaqueous media. © 2016 American Chemical Society.
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- 2016
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10. Stable and Inert Yttrium(III) Complexes with Pyclen-Based Ligands Bearing Pendant Picolinate Arms: Toward New Pharmaceuticals for β-Radiotherapy
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Enikő Molnár, Olivier Fougère, Carlos Platas-Iglesias, David Esteban-Gómez, Mariane Le Fur, Nicolas Lepareur, Gyula Tircsó, Raphaël Tripier, Olivier Rousseaux, Maryline Beyler, Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), University of Debrecen Egyetem [Debrecen], Laboratoire Guerbet / Guerbet Research, Departamento de Química Fundamental, Universidade da Coruña, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-LABX-0018, Agence Nationale de la Recherche, GINOP-2.3.2-15-2016-00008, European Regional Development Fund, Magyar Tudományos Akadémia, Association Nationale de la Recherche et de la Technologie, Centre National de la Recherche Scientifique, NKP-17-3, Emberi Eroforrások Minisztériuma, Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche, K-120224, Nemzeti Kutat?si, Fejleszt?si ?s Innov?ci?s Hivatal, ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Guerbet Group, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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Metal ions in aqueous solution ,chemistry.chemical_element ,90YL4 ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,and 89Y NMR study ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,Ligands ,010402 general chemistry ,01 natural sciences ,Dissociation (chemistry) ,Inorganic Chemistry ,chemistry.chemical_compound ,picolinate ,Coordination Complexes ,Polymer chemistry ,DOTA ,Molecule ,[CHIM]Chemical Sciences ,Yttrium ,Chelation ,[CHIM.COOR]Chemical Sciences/Coordination chemistry ,Physical and Theoretical Chemistry ,Picolinic Acids ,13C ,Molecular Structure ,010405 organic chemistry ,Ligand ,Beta Particles ,0104 chemical sciences ,chemistry ,Cyclam ,Chemical stability ,multinuclear 1H ,Radiopharmaceuticals - Abstract
International audience; We report the synthesis of two azaligands based on the pyclen macrocyclic platform containing two picolinate and one acetate pendant arms. The two ligands differ in the relative positions of the pendant functions, which are arranged either in a symmetrical (L3) or nonsymmetrical (L4) fashion. The complexation properties of the ligands toward natY3+ and 90Y3+ were investigated to assess their potential as chelating units for radiopharmaceutical applications. The X-ray structures of the YL3 and YL4 complexes show nonadentate binding of the ligand to the metal ions. A multinuclear 1H, 13C, and 89Y NMR study shows that the complexes present a structure in solution similar to that observed in the solid state. The two complexes present very high thermodynamic stability constants (log KYL = 23.36(2) and 23.07(2) for YL3 and YL4, respectively). The complexes also show a remarkable inertness with respect to their proton-assisted dissociation, especially YL4. 90Y radiolabeling was proved to be efficient under mild conditions. The 90YL3 and 90YL4 radiochelates were found to be more stable than 90Y(DOTA).
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- 2018
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11. The role of the capping bond effect on pyclen natY3+/90Y3+ chelates: full control of the regiospecific N-functionalization makes the difference
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Mariane Le Fur, Nicolas Lepareur, Olivier Rousseaux, Enikő Molnár, Olivier Fougère, Gyula Tircsó, Carlos Platas-Iglesias, Raphaël Tripier, David Esteban-Gómez, Maryline Beyler, Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), University of Debrecen, Guerbet Group, Universidad de A Coruña, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Guerbet group, Association Nationale de la Recherche et de la Technologie, Hungarian Scientific Research Fund [NKFIH K-120224], Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences, EU, European Regional Development Fund [GINOP-2.3.2-15-2016-00008], Labex IRON [ANR-11-LABX-0018], Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), University of Debrecen Egyetem [Debrecen], Laboratoire Guerbet / Guerbet Research, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011)
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Pyclen ligands ,Stereochemistry ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,DFT calculations ,010402 general chemistry ,Thermodynamic stability ,01 natural sciences ,Catalysis ,Metal ,Természettudományok ,Polymer chemistry ,Materials Chemistry ,Chelation ,Kémiai tudományok ,Yttrium complexes ,Radiotherapy ,010405 organic chemistry ,Ligand ,Chemistry ,Metals and Alloys ,General Chemistry ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,visual_art ,Ceramics and Composites ,visual_art.visual_art_medium ,Surface modification ,Chemical stability ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
[Abstract] Thanks to a smart regiospecific N-functionalization, a pyclen based ligand bearing one picolinate and two acetate arms organized in a dissymmetric manner was synthesized for Y3+ complexation, and compared to its symmetric analogue. The nature of the capping bonds around the metal coordination environment has a dramatic effect on the properties of the chelate, the natY3+ and 90Y3+ dissymmetric derivatives presenting enhanced thermodynamic stability and kinetic inertness. Hungarian Scientific Research Fund; NKFIH K-120224
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- 2017
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12. Molecular Magnetic Resonance and Ultrasound Imaging of Tumor Angiogenesis
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Poirier-Quinot, Marie, Leguerney, Ingrid, De Rochefort, Ludovic, Pitre-Champagnat, Stéphanie, Violas, Xavier, Robin, Sandra, Dubuisson, Rose-Marie, Ginefri, Jean-Christophe, Robert, Philippe, Darrasse, Luc, Lassau, Nathalie, Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), Laboratoire Guerbet, Spatio-Temporal Activity Recognition Systems (STARS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), and Laboratoire Guerbet / Guerbet Research
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USPIO nanoemulsion ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Ανβ3- Targeted contrast agent ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Bimodal molecular imaging DCE-US/MRI ,US microbubbles - Abstract
International audience; Seeking out and identifying imaging biomarkers for early cancer diagnosis and the evaluation of patient response to therapy requires an improvement in the specificity of imaging techniques. This study explores in vivo neo-angiogenesis assessment using molecular mechanisms through target molecular Magnetic Resonance (MR) and Ultrasound (US). In this context, our study examines and compares the use of both imaging technics, targeting the same integrin in a mouse xeno graft tumor model. Following xeno transplantation of human renal cell carcinoma (Human A498), thirteen nude mice were injected with ανβ3-targeted and non-targeted Contrast Agents (CA) for MR and US use, respectively. CA binding to the targeted receptor was measured through Dynamic Susceptibility Contrast MR imaging and Differential Targeted Enhancement (DTE) US imaging. The specificities and co location of both targeted CAs were studied throughout the tumor, in both hypo- and hyper-vascularized areas. One hour post injection, a significant difference was observed between the signals of targeted and non-targeted MR CA (p = 0.03). The DTE-US targeted CA was significantly enhanced compared to non-targeted CA (p = 0.002). In the hypo- and hyper-vascularized regions of interest, a strong correlation was observable between both modalities, with values of r10min = 0.86 (p = 0.0003), r30min = 0.85 (p = 0.0004) and r60min = 0.87 (p = 0.0001). This study highlights the specificity of each targeted CA. A high correlation was noted between MR and US molecular imaging for angiogenesis assessment. These two molecular imaging modalities may be used interchangeably to monitor patient response to anti-angiogenic treatment.
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- 2017
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13. Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma
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Philippe Robert, Nathalie Lassau, Ludovic de Rochefort, Ingrid Leguerney, Paule Opolon, Alexandre Ingels, Stéphanie Pitre-Champagnat, Sandra Robin, Marie Poirier-Quinot, Rose-Marie Dubuisson, Xavier Violas, Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11), Unite de recherche en résonance magnétique médicale (U2R2M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Guerbet Research, Guerbet, Institut Gustave Roussy (IGR), Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Spatio-Temporal Activity Recognition Systems (STARS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), and Laboratoire Guerbet / Guerbet Research
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Male ,Pathology ,medicine.medical_specialty ,Indoles ,lcsh:Medical technology ,Bevacizumab ,Article Subject ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Antineoplastic Agents ,030218 nuclear medicine & medical imaging ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Cell Line, Tumor ,Immunochemistry ,Sunitinib ,Carcinoma ,Animals ,Humans ,Medicine ,Pyrroles ,Radiology, Nuclear Medicine and imaging ,Everolimus ,Molecular Targeted Therapy ,Carcinoma, Renal Cell ,Saline ,ComputingMilieux_MISCELLANEOUS ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Molecular Imaging ,3. Good health ,Treatment Outcome ,lcsh:R855-855.5 ,030220 oncology & carcinogenesis ,Heterografts ,business ,Research Article ,medicine.drug - Abstract
Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targetingαvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variationsΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecularαvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87,p=0.0003) and AUC (R=0.81,p=0.0013). The percentage of vessel tissue area was significantly reduced (p<0.01) in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US orαvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.
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- 2017
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14. Early detection of colonic dysplasia by magnetic resonance molecular imaging with a contrast agent raised against the colon cancer marker MUC5AC: MRI Contrast Agent Targeting MUC5AC
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Sébastien Ballet, Yannick Rossez, Catherine Robbe-Masselot, Walter Gonzalez, Pierre Gosset, Sophie Laurent, Robert N. Muller, Carmen Burtea, Olivier Rousseaux, Renaud Léonard, Jean-Claude Michalski, Luce Vander Elst, Timothée Dugué, Isabelle Raynal, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Mons (UMons), Université catholique de Lille (UCL), Laboratoire Guerbet, Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Laboratoire Guerbet / Guerbet Research
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Pathology ,medicine.medical_specialty ,Phage display ,Colorectal cancer ,Contrast Media ,colorectal cancer ,Mucin 2 ,Mouse model of colorectal and intestinal cancer ,Mucin 5AC ,digestive system ,Sensitivity and Specificity ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,mucin ,In vivo ,Peptide Library ,Medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Early Detection of Cancer ,Mucin-2 ,Tumor ,business.industry ,Mucin ,Cancer ,respiratory system ,medicine.disease ,MUC5AC ,Magnetic Resonance Imaging ,3. Good health ,Molecular Imaging ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Heterografts ,030211 gastroenterology & hepatology ,business ,Colorectal Neoplasms ,Biomarkers ,Aberrant crypt foci ,MRI - Abstract
Human gastric mucin MUC5AC is secreted in the colonic mucus of cancer patients and is a specific marker of precancerous lesions called aberrant crypt foci. Using MUC5AC as a specific marker can improve sensitivity in the detection of early colorectal cancer. Here we demonstrated that the accumulation of MUC5AC in xenograft and mouse stomach can be detected by magnetic resonance imaging (MRI). We used ultrasmall particles of iron oxide (USPIOs) conjugated with disulfide constrained heptapeptide that were identified using a screening phage display. To accomplish this, we employed positive selection of the phage display library on MUC5AC purified from fresh human colonic adenomas in combination with negative selection of the phage library on purified human MUC2, which is predominantly found in normal colorectal tissues. This conjugate was tested on human colorectal cancer cell lines that were either able or unable to secrete MUC5AC, both in vitro and in vivo. MUC5AC-USPIO contrast agent and USPIOs alone were not detected in cell lines unable to secrete MUC5AC. A combination of MRI and microscopy studies was performed to detect a specific accumulation of the contrast agent in vivo. Thus, the MUC5AC contrast agent enabled non-invasive detection of precancerous lesions and colorectal cancer, highlighting its potential use in diagnostics, in the early detection of colorectal cancer recurrences after treatment and in mechanistic studies implicating MUC5AC. Copyright © 2016 John Wiley & Sons, Ltd.
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- 2016
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15. In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T
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Flament, Julien, Geffroy, Françoise, Medina, Christelle, Robic, Caroline, Mayer, Jean-François, Mériaux, Sébastien, Valette, Julien, Robert, Philippe, Port, Marc, Le Bihan, Denis, Lethimonnier, Franck, Boumezbeur, Fawzi, Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Guerbet / Guerbet Research, Liquides Ioniques et Interfaces Chargées (LI2C), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université de Fribourg = University of Fribourg (UNIFR), Service Hospitalier Frédéric Joliot (SHFJ), Networks, Algorithms and Probabilities (RAP), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire Guerbet, Université de Fribourg, and Albert-Ludwigs-Universität Freiburg
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Mice ,Neovascularization, Pathologic ,Brain Neoplasms ,Cell Line, Tumor ,[SDV]Life Sciences [q-bio] ,Liposomes ,Animals ,Contrast Media ,Mice, Nude ,Magnetite Nanoparticles ,Magnetic Resonance Imaging ,Neoplasm Transplantation - Abstract
International audience; LipoCEST are liposome-encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)-complexes was conjugated to RGD tripeptide (RGD-lipoCEST), to target integrin α(ν)β(3) receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer-MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD-lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD-lipoCEST with α(ν)β(3) receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST.
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- 2013
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16. Dynamic study of blood-brain barrier closure after its disruption using ultrasound: a quantitative analysis
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Benoit Larrat, Benjamin Marty, Denis Le Bihan, Maxime Van Landeghem, Caroline Robic, Sébastien Mériaux, Marc Port, Mickael Tanter, Mathieu Pernot, Philippe Robert, Franck Lethimonnier, Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physico-Chimie des Polymères et des Milieux Dispersés (PPMD), Laboratoire Guerbet / Guerbet Research, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Projet Iseult, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Guerbet Research, Guerbet, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
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Male ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Rat model ,Contrast Media ,Blood–brain barrier ,Models, Biological ,030218 nuclear medicine & medical imaging ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Drug Delivery Systems ,Molecular size ,medicine ,Animals ,BBB disruption ,medicine.diagnostic_test ,business.industry ,Chemistry ,ultrasound ,Ultrasound ,Endothelial Cells ,Magnetic resonance imaging ,Mr contrast ,Anatomy ,T1 mapping ,Magnetic Resonance Imaging ,MR contrast agent ,Rats ,medicine.anatomical_structure ,Sound ,Neurology ,Blood-Brain Barrier ,Microbubbles ,cardiovascular system ,Original Article ,nanoparticles ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Quantitative analysis (chemistry) ,030217 neurology & neurosurgery ,Biomedical engineering ,MRI - Abstract
Delivery of therapeutic or diagnostic agents to the brain is majorly hindered by the blood–brain barrier (BBB). Recently, many studies have demonstrated local and transient disruption of the BBB using low power ultrasound sonication combined with intravascular microbubbles. However, BBB opening and closure mechanisms are poorly understood, especially the maximum gap that may be safely generated between endothelial cells and the duration of opening of the BBB. Here, we studied BBB opening and closure under magnetic resonance (MR) guidance in a rat model. First, MR contrast agents (CA) of different hydrodynamic diameters (1 to 65 nm) were employed to estimate the largest molecular size permissible across the cerebral tissues. Second, to estimate the duration of the BBB opening, the CA were injected at various times post-BBB disruption (12 minutes to 24 hours). A T1 mapping strategy was developed to assess CA concentration at the ultrasound (US) focal point. Based on our experimental data and BBB closure modeling, a calibration curve was obtained to compute the half closure time as a function of CA hydrodynamic diameter. These findings and the model provide an invaluable basis for optimal design and delivery of nanoparticles to the brain.
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- 2012
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17. Synthesis and evaluation of a tri-tyrosine decorated dextran MR contrast agent for vulnerable plaque detection
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Luc Picton, Frédéric Chaubet, Anne Beilvert, Didier Letourneur, Emmanuelle Canet-Soulas, Olivier Rousseaux, Roger Vassy, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Laboratoire de physicochimie biomoléculaire et cellulaire (LPBC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Guerbet Group, Polymères Biopolymères Surfaces (PBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
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Contrast Media ,Nanotechnology ,030204 cardiovascular system & hematology ,Conjugated system ,medicine.disease_cause ,Catalysis ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,In vivo ,Materials Chemistry ,medicine ,Animals ,[CHIM]Chemical Sciences ,Tyrosine ,ComputingMilieux_MISCELLANEOUS ,Chemistry ,Mr contrast agent ,Metals and Alloys ,Dextrans ,General Chemistry ,Vulnerable plaque ,Magnetic Resonance Imaging ,Plaque, Atherosclerotic ,3. Good health ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Dextran ,[CHIM.POLY]Chemical Sciences/Polymers ,Biochemistry ,Ceramics and Composites ,Lipid core - Abstract
This communication reports the synthesis, characterization and in vivo evaluation in mice of a new tri-tyrosine conjugated MR contrast agent, which may help to identify vulnerable plaques in atherosclerosis by targeting the lipid core.
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- 2011
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18. Long term in vivo biotransformation of iron oxide nanoparticles
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Alain Luciani, Sophie Lotersztajn, Nidhi Vats, Florence Gazeau, Claire Wilhelm, Guillaume Wang, Vanessa Deveaux, Francois Gendron, Dan Elgrabli, Nathalie Luciani, Sophie Chat, Cécile Factor, Christine Péchoux, Damien Alloyeau, Michael Levy, Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Matériaux et Phénomènes Quantiques (MPQ (UMR_7162)), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Imagerie Médicale, Groupe Henri Mondor Albert Chenevier, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Guerbet, Génomique et Physiologie de la Lactation (UR 1196), and Institut National de la Recherche Agronomique (INRA)
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Male ,Materials science ,Biophysics ,Iron oxide ,Bioengineering ,Nanotechnology ,Context (language use) ,BIODEGRADATION ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Ferric Compounds ,Biomaterials ,chemistry.chemical_compound ,Mice ,Biotransformation ,Microscopy, Electron, Transmission ,NANOTOXICITY ,NANOPARTICLES ,Animals ,NANOMAGNETISM ,biology ,Electron Spin Resonance Spectroscopy ,IRON OXIDE ,CONTRAST AGENT ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Ferritin ,chemistry ,Mechanics of Materials ,Nanotoxicology ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,[SDE]Environmental Sciences ,Ceramics and Composites ,biology.protein ,Nanomedicine ,0210 nano-technology ,Iron oxide nanoparticles ,Superparamagnetism - Abstract
International audience; The long term outcome of nanoparticles in the organism is one of the most important concerns raised by the development of nanotechnology and nanomedicine. Little is known on the way taken by cells to process and degrade nanoparticles over time. In this context, iron oxide superparamagnetic nanoparticles benefit from a privileged status, because they show a very good tolerance profile, allowing their clinical use for MRI diagnosis. It is generally assumed that the specialized metabolism which regulates iron in the organism can also handle iron oxide nanoparticles. However the biotransformation of iron oxide nanoparticles is still not elucidated. Here we propose a multiscale approach to study the fate of nanomagnets in the organism. Ferromagnetic resonance and SQUID magnetization measurements are used to quantify iron oxide nanoparticles and follow the evolution of their magnetic properties. A nanoscale structural analysis by electron microscopy complements the magnetic follow-up of nanoparticles injected to mice. We evidence the biotransformation of superparamagnetic maghemite nanoparticles into poorly-magnetic iron species probably stored into ferritin proteins over a period of three months. A putative mechanism is proposed for the biotransformation of iron-oxide nanoparticles
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- 2011
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19. A new paradigm for high-sensitivity 19F magnetic resonance imaging of perfluorooctylbromide
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Caroline Robic, Eric Giacomini, Sébastien Mériaux, Nicolas Tsapis, Denis Le Bihan, Fawzi Boumezbeur, Marc Port, Céline Giraudeau, Benjamin Marty, Julien Valette, Julien Flament, Elias Fattal, Franck Lethimonnier, Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service Hospitalier Frédéric Joliot (SHFJ), Liquides Ioniques et Interfaces Chargées (LI2C), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet, Institut Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Laboratoire Guerbet / Guerbet Research
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Contrast Media ,02 engineering and technology ,J-coupling ,Sensitivity and Specificity ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine ,Radiology, Nuclear Medicine and imaging ,Fluorine mri ,[PHYS]Physics [physics] ,Fluorocarbons ,medicine.diagnostic_test ,Chemistry ,Phantoms, Imaging ,Magnetic resonance imaging ,Fluorine ,021001 nanoscience & nanotechnology ,Image Enhancement ,Magnetic Resonance Imaging ,Hydrocarbons, Brominated ,Repetition Time ,Spin echo ,0210 nano-technology ,Chemical shift imaging ,Gradient echo - Abstract
International audience; In the present work, the NMR properties of perfluorooctylbromide are revisited to derive a high-sensitivity fluorine MRI strategy. It is shown that the harmful effects of J-coupling can be eliminated by carefully choosing the bandwidth of the 180 degrees pulses in a spin-echo sequence. The T(2) of the CF(3) resonance of the molecule is measured using a multispin-echo sequence and shown to dramatically depend on the interpulse delay. Following these observations, an optimized multispin-echo imaging sequence is derived and compared with short TE/pulse repetition time gradient echo and chemical shift imaging sequences. The unparalleled sensitivity yielded by the multispin-echo sequence is promising for future applications, in particular for targeted contrast agents such as perfluorooctylbromide nanoparticles.
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- 2010
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20. Optimization of a blood pool contrast agent injection protocol for MR angiography
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Denis Le Bihan, Philippe Robert, Claire Corot, Robin Santus, Xavier Violas, Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Human Brain Research Center [Kyoto] (HBRC), Kyoto University, Service Hospitalier Frédéric Joliot (SHFJ), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Guerbet Recherche, Guerbet, Guerbet Research, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Kyoto University [Kyoto]
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Male ,medicine.medical_specialty ,MESH: Heterocyclic Compounds ,Blood pool ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Swine ,Gadolinium ,chemistry.chemical_element ,MESH: Rabbits ,Contrast Media ,Injection rate ,MESH: Magnetic Resonance Angiography ,030218 nuclear medicine & medical imaging ,Peak concentration ,Injections ,03 medical and health sciences ,0302 clinical medicine ,Bolus (medicine) ,Pharmacokinetics ,Heterocyclic Compounds ,MESH: Contrast Media ,Organometallic Compounds ,Medicine ,MESH: Injections ,Animals ,Radiology, Nuclear Medicine and imaging ,MESH: Animals ,MESH: Swine ,business.industry ,Mr angiography ,Experimental Animal Models ,MESH: Organometallic Compounds ,MESH: Male ,chemistry ,Radiology ,Rabbits ,Nuclear medicine ,business ,030217 neurology & neurosurgery ,Magnetic Resonance Angiography - Abstract
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. J. Magn. Reson. Imaging 2005;21:611–619. © 2005 Wiley-Liss, Inc.
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- 2005
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21. Frequency-shift based detection of BMS contrast agents using SSFP: potential for MRA
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Françoise Vaufrey, Jessica Dubois, Denis Le Bihan, Philippe Robert, Franck Lethimonnier, Département de radiothérapie, CRLCC Val d'Aurelle - Paul Lamarque, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Guerbet Recherche, Guerbet, Guerbet Research, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, IFR de Neuroimagerie Fonctionnelle (IFR 49), Human Brain Research Center [Kyoto] (HBRC), Kyoto University [Kyoto], Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Guerbet, Laboratoire Guerbet / Guerbet Research, and Le Bihan, Denis
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MESH: Heterocyclic Compounds ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Gadolinium ,media_common.quotation_subject ,Biomedical Engineering ,Biophysics ,Contrast Media ,chemistry.chemical_element ,MESH: Rabbits ,MESH: Magnetic Resonance Angiography ,Signal ,Magnetic resonance angiography ,Imaging phantom ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,MESH: Computer Simulation ,Heterocyclic Compounds ,MESH: Contrast Media ,Organometallic Compounds ,medicine ,Animals ,Contrast (vision) ,Frequency offset ,Computer Simulation ,Radiology, Nuclear Medicine and imaging ,MESH: Animals ,media_common ,medicine.diagnostic_test ,Phantoms, Imaging ,MESH: Organometallic Compounds ,Steady-state free precession imaging ,Image Enhancement ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,MESH: Phantoms, Imaging ,chemistry ,Feasibility Studies ,Rabbits ,Bolus (digestion) ,MESH: Image Enhancement ,MESH: Feasibility Studies ,MESH: Neck ,Magnetic Resonance Angiography ,Neck ,030217 neurology & neurosurgery - Abstract
International audience; 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.
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- 2005
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22. Value of MRA sequences and contrast agents for the evaluation of high-degree stenosis : a phantom study
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Marchand, B., Douek, P., Robert, P., Corot, Claire, Roux, J.P., Adeleine, P., Hernández Hoyos, M., Crémillieux, Y., Orkisz, Maciej, Canet-Soulas, Emmanuelle, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Guerbet Research, Guerbet, Service Informatique et développements, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Grupo IMAGINE, Universidad de los Andes [Bogota] (UNIANDES), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de los Andes [Bogota], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Orkisz, Maciej, Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[INFO.INFO-IM] Computer Science [cs]/Medical Imaging ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,ComputingMilieux_MISCELLANEOUS ,[SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience
- Published
- 2001
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