82 results on '"Boudewijn, van der Sanden"'
Search Results
2. 3D two-photon polymerization of smart cell gelatin – collagen matrixes with incorporated ruthenium complexes for the monitoring of local oxygen tensions
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Olivier Stephan, Didier Wion, Laetitia Gredy, Boudewijn van der Sanden, Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
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food.ingredient ,0206 medical engineering ,Biomedical Engineering ,chemistry.chemical_element ,02 engineering and technology ,Biochemistry ,Gelatin ,Ruthenium ,Polymerization ,Biomaterials ,Extracellular matrix ,3D cell culture ,food ,Molecular Biology ,Mitosis ,ComputingMilieux_MISCELLANEOUS ,Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Oxygen ,Cell culture ,Cancer cell ,Biophysics ,Collagen ,0210 nano-technology ,[PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft] ,Biotechnology - Abstract
The extra cellular matrix plays a major role in the biomechanical properties of tissues that impact cell behavior and fate. It is therefore crucial to mimic these complex cell-matrix interactions in 3D cell cultures. Here, two-photon polymerization is applied to produce gelatin methacryloyl (GelMA) - collagen matrixes that further enable local pO2matrix measurement, when ruthenium complexes are used as photo-activators. The fluorescence intensity of these complexes has a direct and inverse relationship with the local pO2matrix. The 3D structures reached their maximum size in cell culture conditions after 3H with a swelling factor of ~1.5. Their shape and the ruthenium fluorescence intensity of the alveoli walls stayed constant for at least 2 weeks in the absence of cells. They were used in time series to monitor the local pO2matrix adjacent to cancer cells during their division, migration and the formation of a tumor tissue mass. At the presence of these cell activities that consume O2, a significant ~3-fold increase of the ruthenium fluorescence intensity in the alveoli walls was observed. This study demonstrates that online monitoring of the local pO2matrix is possible. The ruthenium complexes provide the bio-optical sensors that are useful for further analysis of cancer and healthy cell energy metabolism in a 3D matrix that better mimics in vivo conditions and migration paths. Unraveling the cancer cell metabolic adaptations in a changing micro-environment will help the development of new therapeutic opportunities. STATEMENT OF SIGNIFICANCE: In 3D cell cultures, monitoring pericellular pO2 is as critical as controlling pH. This facility is currently missing. Here, we take advantage of the direct and inverse relationship between pO2 and the fluorescence intensity of ruthenium complexes to generate stable gelatin-collagen matrixes able to continuously monitoring the pO2 at the pericellular level. The ruthenium complexes, which are photo-activators in the two-photon polymerization of these matrixes, became covalently bind to the collagen fibers. Indeed, local O2 consumption by cancer cells during migration, mitosis and tumor mass formation caused a 3-fold increase of the ruthenium fluorescence. In the future, incorporating ruthenium complexes with other bio-optical sensors will create new drug screening platforms that monitor cell culture parameters at the pericellular level.
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- 2021
3. Applications of Magnetic Resonance in Model Systems: Tumor Biology and Physiology
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Robert J. Gillies, Zaver M. Bhujwalla, Jeffrey Evelhoch, Michael Garwood, Michal Neema, Simon P. Robinson, Christopher H. Sotak, and Boudewijn Van Der Sanden
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Magnetic Resonance Imaging (MRI) ,Magnetic Resonance Spectroscopy (MRS) ,Tumor Perfusion ,Tumor Oxygenation ,Tumor pH ,Tumor Metabolism ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
A solid tumor presents a unique challenge as a system in which the dynamics of the relationship between vascularization, the physiological environment and metabolism are continually changing with growth and following treatment. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies have demonstrated quantifiable linkages between the physiological environment, angiogenesis, vascularization and metabolism of tumors. The dynamics between these parameters continually change with tumor aggressiveness, tumor growth and during therapy and each of these can be monitored longitudinally, quantitatively and non-invasively with MRI and MRS. An important aspect of MRI and MRS studies is that techniques and findings are easily translated between systems. Hence, pre-clinical studies using cultured cells or experimental animals have a high connectivity to potential clinical utility. In the following review, leaders in the field of MR studies of basic tumor physiology using pre-clinical models have contributed individual sections according to their expertise and outlook. The following review is a cogent and timely overview of the current capabilities and state-of-the-art of MRI and MRS as applied to experimental cancers. A companion review deals with the application of MR methods to anticancer therapy.
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- 2000
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4. Vascular bifurcation mapping with photoacoustic microscopy
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Boudewijn van der Sanden, Olivier Hugon, Mehdi Inglebert, Eric Lacot, Olivier Jacquin, Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPhy-OPTIMA, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
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0303 health sciences ,[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] ,Materials science ,Early detection ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,Article ,010309 optics ,03 medical and health sciences ,Photoacoustic microscopy ,0103 physical sciences ,Medical imaging ,sense organs ,Bifurcation ,030304 developmental biology ,Biotechnology ,Biomedical engineering - Abstract
The early detection of microvascular changes in cancer diagnosis is needed in the clinic. A change in the vascular bifurcation density is a biomarker for the sprouting activity. Here, Optical-Resolution PhotoAcoustic Microscopy is used for quantitative vascular bifurcation mapping in 2D after the creation of Virtual Tubes out of Bifurcations. In stacks of OR-PAM images of the hemoglobin distribution, bifurcations become tubes and are selected by the 3D tubeness filter. These fast analyses will be compared to a classical approach and are easier to implement for functional analysis of the vascular bifurcation density in healthy and diseased tissues.
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- 2020
5. Specific in vivo staining of astrocytes in the whole brain after intravenous injection of sulforhodamine dyes.
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Florence Appaix, Sabine Girod, Sylvie Boisseau, Johannes Römer, Jean-Claude Vial, Mireille Albrieux, Mathieu Maurin, Antoine Depaulis, Isabelle Guillemain, and Boudewijn van der Sanden
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Medicine ,Science - Abstract
Fluorescent staining of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy studies. Current methods involved either transgenic mice or local intracerebral injection of sulforhodamine 101. Transgenic rat models rarely exist, and in mice, a backcross with GFAP transgenic mice may be difficult. Local injections of fluorescent dyes are invasive. Here, we propose a non-invasive, specific and ubiquitous method to stain astrocytes in vivo. This method is based on iv injection of sulforhodamine dyes and is applicable on rats and mice from postnatal age to adulthood. The astrocytes staining obtained after iv injection was maintained for nearly half a day and showed no adverse reaction on astrocytic calcium signals or electroencephalographic recordings in vivo. The high contrast of the staining facilitates the image processing and allows to quantify 3D morphological parameters of the astrocytes and to characterize their network. Our method may become a reference for in vivo staining of the whole astrocytes population in animal models of neurological disorders.
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- 2012
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6. Coumarin-containing thermoresponsive hyaluronic acid-based nanogels as delivery systems for anticancer chemotherapy
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Francielle P. Garcia, Bruno G. De Geest, Talitha Fernandes Stefanello, Celso Vataru Nakamura, Patrice Woisel, Benoit Couturaud, Anna Szarpak-Jankowska, David Fournier, Boudewijn van der Sanden, Rachel Auzély-Velty, and Benoit Louage
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Materials science ,media_common.quotation_subject ,Mice, Nude ,Antineoplastic Agents ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,Anticancer chemotherapy ,01 natural sciences ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Coumarins ,Chlorocebus aethiops ,Hyaluronic acid ,Animals ,Humans ,General Materials Science ,Hyaluronic Acid ,Internalization ,Vero Cells ,media_common ,biology ,CD44 ,Hydrogels ,021001 nanoscience & nanotechnology ,Coumarin ,Xenograft Model Antitumor Assays ,0104 chemical sciences ,chemistry ,Cancer cell ,Self-healing hydrogels ,Drug delivery ,biology.protein ,Nanoparticles ,Female ,0210 nano-technology ,HeLa Cells - Abstract
Multi-stimuli responsive nanogels based on biocompatible hydrophilic polymers have emerged as promising drug delivery systems to improve anticancer therapy with hydrophobic drugs, through increase of circulating-time in the bloodstream, tumor-targeting and reduction of systemic toxicity. This paper reports on the synthesis, characterization and biological perspectives of light- and thermoresponsive hyaluronic acid (HA)-based nanogels containing coumarin as the photocleavable group. Newly synthesized nanogels exhibited interesting features: formation by a temperature-triggered self-assembly process, successful incorporation of poorly water-soluble molecules, light-responsiveness as demonstrated by a significant shift in the critical aggregation temperature after light irradiation, efficient internalization by cancer cells overexpressing the CD44 receptor of HA, ability to circulate for a prolonged period of time in the bloodstream after intravenous injection in mice and considerable detection in tumor tissues. Our findings indicate that coumarin-containing HA-based nanogels may be promising delivery systems for anticancer chemotherapy.
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- 2017
7. Multi-wavelength photo-acoustic microscopy in the frequency domain for simultaneous excitation and detection of dyes
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Olivier Hugon, Boudewijn van der Sanden, Mehdi Inglebert, Chaouqi Misbah, Eric Lacot, Olivier Jacquin, OPTIMA, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPhy-OPTIMA, LIPHY-DYFCOM, and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
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Materials science ,Microscope ,Optical power ,01 natural sciences ,Article ,law.invention ,010309 optics ,03 medical and health sciences ,chemistry.chemical_compound ,law ,0103 physical sciences ,Microscopy ,Medical imaging ,Irradiation ,030304 developmental biology ,Diode ,[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] ,0303 health sciences ,business.industry ,Atomic and Molecular Physics, and Optics ,eye diseases ,chemistry ,Frequency domain ,Optoelectronics ,business ,Methylene blue ,Biotechnology - Abstract
International audience; An optical-resolution photoacoustic microscope with modulated CW laser diodes allowing multi-channel imaging is presented that can be used for both imaging biological tissues and for targeted photo-dynamic therapy (PDT) varying the optical power and exposure time. The effects of this therapy are immediately monitored in order to optimize the time of irradiation. After the description of the experimental setup, in vitro and in vivo applications are presented on a synthetic sample and on the mouse ear using hemoglobin as endogenous and methylene blue as exogenous dye for imaging and PDT, respectively.
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- 2019
8. Photo-Acoustic Tomography (PAT) based on Laser Optical Feedback Imaging (LOFI) of surface displacements
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Olivier Hugon, Boudewijn van der Sanden, Eric Lacot, Olivier Jacquin, Bathilde Riviere, Vadim Girardeau, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), LIPhy-OPTIMA, Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPhy-OLA, Lacot, Eric, OPTique et IMAgeries [Grenoble] (OPTIMA-LIPhy), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
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[PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics] ,[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] ,Materials science ,business.industry ,Laser ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,Imaging phantom ,Surface energy ,law.invention ,010309 optics ,Amplitude ,Optics ,law ,0103 physical sciences ,Medical imaging ,Tomography ,Irradiation ,Electrical and Electronic Engineering ,business ,Engineering (miscellaneous) ,Laser Doppler vibrometer - Abstract
We present how a laser optical feedback imaging (LOFI) setup can be used for the optical detection of ultrasound in photo-acoustic tomography (PAT). A PAT image is reconstructed by an inversion algorithm using surface displacement measurements made at several locations with our LOFI setup and following the optical irradiation with a pulsed Nd:YAG laser of a sample with absorbing inclusions. The width of the reconstructed inclusions and the signal-to-noise ratio (SNR) of the reconstructed images are first studied on the numerical model of a sample with three absorbing inclusions (i.e., with three acoustic punctual sources). Finally, an experimental PAT image of a phantom composed of two polyamide tubes with an internal diameter of 800 μm filled with red ink and submerged at -3.5 mm depth in a tank filled with water is reconstructed. Experimentally, the water surface displacement measurements have been made with our LOFI vibrometer, which provides an amplitude sensitivity of 1 nm (for a single-shot measurement) in a detection bandwidth of roughly 1 MHz adapted to the detection of the polyamide tubes. Under our experimental conditions, the surface energy densities of the LOFI focalized beam for the detection and of the pulsed Nd:YAG laser used for the irradiation, are compatible with the maximum permissive exposure for future biomedical measurements. The SNR and the resolution of the reconstructed PAT images are in good agreement with the theoretical predictions.
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- 2019
9. Design of Hyaluronic Acid Hydrogels to Promote Neurite Outgrowth in Three Dimensions
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Flavien Caraguel, Anna Szarpak-Jankowska, Dominte Tarus, Rachel Auzély-Velty, Boudewijn van der Sanden, Lauriane Hamard, and Didier Wion
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0301 basic medicine ,Materials science ,Neurite ,Neuronal Outgrowth ,Nanotechnology ,macromolecular substances ,02 engineering and technology ,Hippocampal formation ,Extracellular matrix ,03 medical and health sciences ,chemistry.chemical_compound ,Hyaluronic acid ,Neurites ,General Materials Science ,Hyaluronic Acid ,Progenitor cell ,Regeneration (biology) ,technology, industry, and agriculture ,Hydrogels ,021001 nanoscience & nanotechnology ,Neural stem cell ,Extracellular Matrix ,030104 developmental biology ,chemistry ,Self-healing hydrogels ,Biophysics ,0210 nano-technology - Abstract
A hyaluronic acid (HA)-based extracellular matrix (ECM) platform with independently tunable stiffness and density of cell-adhesive peptide (RGD, arginine-glycine-aspartic acid) that mimics key biochemical and mechanical features of brain matrix has been designed. We demonstrated here its utility in elucidating ECM regulation of neural progenitor cell behavior and neurite outgrowth. The analysis of neurite outgrowth in 3-D by two-photon microscopy showed several important results in the development of these hydrogels. First, the ability of neurites to extend deeply into these soft HA-based matrices even in the absence of cell-adhesive ligand further confirms the potential of HA hydrogels for central nervous system (CNS) regeneration. Second, the behavior of hippocampal neural progenitor cells differed markedly between the hydrogels with a storage modulus of 400 Pa and those with a modulus of 800 Pa. We observed an increased outgrowth and density of neurites in the softest hydrogels (G' = 400 Pa). Interestingly, cells seeded on the surface of the hydrogels functionalized with the RGD ligand experienced an optimum in neurite outgrowth as a function of ligand density. Surprinsingly, neurites preferentially progressed inside the gels in a vertical direction, suggesting that outgrowth is directed by the hydrogel structure. This work may provide design principles for the development of hydrogels to facilitate neuronal regeneration in the adult brain.
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- 2016
10. Microscopic DTI accurately identifies early glioma cell migration: correlation with multimodal imaging in a new glioma stem cell model
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Michele El-Atifi, Boudewijn van der Sanden, François Berger, Karin Pernet-Gallay, Hana Lahrech, Florence Appaix, Ulysse Gimenez, Adriana-T. Perles-Barbacaru, and Arnaud Millet
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Pathology ,medicine.medical_specialty ,Chemistry ,Brain tumor ,Cell migration ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Glioma ,Fractional anisotropy ,medicine ,Molecular Medicine ,Radiology, Nuclear Medicine and imaging ,Stem cell ,030217 neurology & neurosurgery ,Spectroscopy ,Ex vivo ,Diffusion MRI - Abstract
Monitoring glioma cell infiltration in the brain is critical for diagnosis and therapy. Using a new glioma Glio6 mouse model derived from human stem cells we show how diffusion tensor imaging (DTI) may predict glioma cell migration/invasion. In vivo multiparametric MRI was performed at one, two and three months of Glio6 glioma growth (Glio6 (n = 6), sham (n = 3)). This longitudinal study reveals the existence of a time window to study glioma cell/migration/invasion selectively. Indeed, at two months only Glio6 cell invasion was detected, while tumor mass formation, edema, blood-brain barrier leakage and tumor angiogenesis were detected later, at three months. To robustly confirm the potential of DTI for detecting glioma cell migration/invasion, a microscopic 3D-DTI (80 μm isotropic spatial resolution) technique was developed and applied to fixed mouse brains (Glio6 (n = 6), sham (n = 3)). DTI changes were predominant in the corpus callosum (CC), a known path of cell migration. Fractional anisotropy (FA) and perpendicular diffusivity (D⊥ ) changes derived from ex vivo microscopic 3D-DTI were significant at two months of tumor growth. In the caudate putamen an FA increase of +38% (p < 0.001) was observed, while in the CC a - 28% decrease in FA (p < 0.005) and a + 95% increase in D⊥ (p < 0.005) were observed. In the CC, DTI changes and fluorescent Glio6 cell density obtained by two-photon microscopy in the same brains were correlated (p < 0.001, r = 0.69), validating FA and D⊥ as early quantitative biomarkers to detect glioma cell migration/invasion. The origin of DTI changes was assessed by electron microscopy of the same tract, showing axon bundle disorganization. During the first two months, Glio6 cells display a migratory phenotype without being associated with the constitution of a brain tumor mass. This offers a unique opportunity to apply microscopic 3D-DTI and to validate DTI parameters FA and D⊥ as biomarkers for glioma cell invasion.
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- 2016
11. Photostable far-red emitting pluronic silicate nanoparticles: perfect blood pool fluorophores for biphotonic in vivo imaging of the leaky tumour vasculature
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Zheng Zheng, Yann Bretonnière, Boudewijn van der Sanden, Chantal Andraud, Yuan-Yuan Liao, Flavien Caraguel, Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
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[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Chemistry ,General Chemical Engineering ,Analytical chemistry ,Nanoparticle ,Vascular permeability ,[CHIM.MATE]Chemical Sciences/Material chemistry ,02 engineering and technology ,General Chemistry ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,Poloxamer ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,Two-photon excitation microscopy ,In vivo ,Biophysics ,Absorption (chemistry) ,0210 nano-technology ,Preclinical imaging - Abstract
International audience; For correct analysis of anti-angiogenic therapies, we need new fluorescent probes that do not diffuse across the leaky tumour vascular endothelium before any treatment. The latter makes estimations of the functional blood volume and changes in vascular permeability uncertain after treatment. Therefore, we present here a new non diffusible fluorescent probe for two photon microscopy, which is composed of a hydrophobic push–pull dye (1) encapsulated in the apolar core of Pluronic F127–silica nanoparticles (1@F127–SiO2, d = 22 nm). In apolar media, (1) has intense emission in the red (Φf = 39% at 650 nm) and two-photon absorption properties in the NIR. The NP probe was successfully tested in vivo on mice bearing tumours without diffusion across the tumour vascular endothelium. The two photon excitation wavelength at 1000 nm is optimum for deep tissue excitation.
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- 2016
12. General and Scalable Approach to Bright, Stable, and Functional AIE Fluorogen Colloidal Nanocrystals for in Vivo Imaging
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Chantal Andraud, Zheng Zheng, Stéphane Chambert, Christophe O. Soulage, Elsa Hoibian, Maxime Rémond, Yann Bretonnière, Xibo Yan, Julien Bernard, Boudewijn van der Sanden, François Ganachaud, Ingénierie des Matériaux Polymères (IMP), 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), 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 des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Chimie Organique et Bioorganique (COB), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-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)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR project PREPROPOSAL ANR-15-CE09-0021, French program 'Investissement d'Avenir', grant 'Infrastructure d'avenir en Biologie Sante' ANR11-INBS-0006, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-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)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), 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 de Chimie du CNRS (INC)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)
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Materials science ,aggregation-induced emission ,Polymers ,Nanotechnology ,02 engineering and technology ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,010402 general chemistry ,01 natural sciences ,Organic molecules ,organic nanocrystals ,nanoprecipitation ,Colloid ,In vivo ,General Materials Science ,Aggregation-induced emission ,ComputingMilieux_MISCELLANEOUS ,Fluorescent Dyes ,Fluorescent nanoparticles ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,[CHIM.CATA]Chemical Sciences/Catalysis ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Science research ,Nanocrystal ,Ouzo domain ,Nanoparticles ,in vivo imaging ,0210 nano-technology ,Preclinical imaging - Abstract
International audience; Fluorescent nanoparticles built from aggregation-induced emission-active organic molecules (AIE-FONs) have emerged as powerful tools in life science research for in vivo bioimaging of organs, biosensing, and therapy. However, the practical use of such biotracers has been hindered owing to the difficulty of designing bright nanoparticles with controlled dimensions (typically below 200 nm), narrow size dispersity and long shelf stability. In this article, we present a very simple yet effective approach to produce monodisperse sub-200 nm AIE fluorescent organic solid dispersions with excellent redispersibility and colloidal stability in aqueous medium by combination of nanoprecipitation and freeze-drying procedures. By selecting polymer additives that simultaneously act as stabilizers, promoters of amorphous-crystalline transition, and functionalization/cross-linking platforms, we demonstrate a straightforward access to stable nanocrystalline FONs that exhibit significantly higher brightness than their amorphous precursors and constitute efficient probes for in vivo imaging of the normal and tumor vasculature. FONs design principles reported here are universal, applicable to a range of fluorophores with different chemical structures and crystallization abilities, and are suitable for high-throughput production and manufacturing of functional imaging probes.
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- 2018
13. Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages
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Boudewijn van der Sanden, Florence Appaix, Talitha Fernandes Stefanello, Celso Vataru Nakamura, Rachel Auzély-Velty, Lauriane Hamard, Anna Szarpak-Jankowska, Bruno G. De Geest, and Benoit Louage
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Materials science ,Proton Magnetic Resonance Spectroscopy ,Biomedical Engineering ,Nanogels ,Spleen ,Biochemistry ,Fluorescence ,Cell Line ,Polyethylene Glycols ,Biomaterials ,Mice ,chemistry.chemical_compound ,In vivo ,Hyaluronic acid ,medicine ,Animals ,Polyethyleneimine ,Hyaluronic Acid ,Particle Size ,Molecular Biology ,Drug Carriers ,Photons ,Macrophages ,Temperature ,General Medicine ,Endocytosis ,In vitro ,medicine.anatomical_structure ,chemistry ,Drug delivery ,Drug carrier ,Hydrophobic and Hydrophilic Interactions ,Ethylene glycol ,Intracellular ,Biotechnology - Abstract
Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases.
- Published
- 2014
14. Keto-polymethines: a versatile class of dyes with outstanding spectroscopic properties for in cellulo and in vivo two-photon microscopy imaging
- Author
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San-Hui Chi, Boudewijn van der Sanden, Olivier Maury, Denis Jacquemin, Chantal Andraud, Joseph W. Perry, Alexei Grichine, Cyrille Monnereau, Alain Duperray, Boris Le Guennic, Jérôme Cuny, Simon Pascal, Florence Appaix, Sandrine Denis-Quanquin, Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPHY-DYFCOM, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), INSERM U823, équipe 8 (Immunologie Analytique des Pathologies Chroniques), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Modélisation, Agrégats, Dynamique (LCPQ) (MAD), Laboratoire de Chimie et Physique Quantiques (LCPQ), Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), School of Chemistry and Biochemistry, and Center for Organic Electronics and Photonics, Georgia Institute of Technology [Atlanta], D. J. acknowledges the ERC for financial support in the framework of a Starting Grant (Marches – 278845). J. W. P. and S.-H. C. acknowledge the support from the DARPA ZOE Program (W31P4Q-09-1-0012), and the AFOSR MURI (FA9550-10-1-0558)., Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), DYnamique des Fluides COmplexes et Morphogénèse [Grenoble] (DYFCOM-LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Elefantis, Nicolas, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
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Chemistry ,Stereochemistry ,Hydrogen bond ,Quantum yield ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,Molecular engineering ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,[CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry ,Molecular dynamics ,Membrane ,Two-photon excitation microscopy ,Molecule ,0210 nano-technology - Abstract
International audience; The synthesis of keto-heptamethine derivatives has been expanded to various new symmetrical and asymmetrical structures, including an unprecedented di-anionic keto-polymethine. The spectroscopic behavior of these new dyes has been systematically and thoroughly investigated, revealing that the formation of hydrogen bond interactions with protic solvents is responsible for a dramatic enhancement of the fluorescence quantum yield in the far-red spectral region. The existence of these strong hydrogen-bond interactions was further confirmed by molecular dynamics simulations. These bis-dipolar polymethines exhibit large two-photon absorption (TPA) cross-sections (σ2 in GM) in the near-infrared, making them ideal candidates for NIR-to-NIR two-photon microscopy imaging applications. We demonstrate that the molecular engineering of the hydrophilic/hydrophobic balance enables targeting of different cellular components, such as cytoplasm or cell membranes. Addition of appropriate substituents provides the molecule with high-water-solubility, affording efficient two-photon probes for angiography.
- Published
- 2017
15. Rapid-Steady-State-T1signal modeling during contrast agent extravasation: Toward tumor blood volume quantification without requiring the arterial input function
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François Berger, Boudewijn van der Sanden, Hana Lahrech, Adriana T. Perles-Barbacaru, and Michel Sarraf
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Pathology ,medicine.medical_specialty ,Steady state (electronics) ,business.industry ,Angiogenesis ,media_common.quotation_subject ,Vascular permeability ,Blood volume ,Extravasation ,030218 nuclear medicine & medical imaging ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Blood Volume Fraction ,Medicine ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Arterial input function ,business ,030217 neurology & neurosurgery ,media_common ,Biomedical engineering - Abstract
Purpose This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1)-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination. Methods For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase. We applied the mathematical model in a pilot-study on a RG2-glioma model to compare extravasation of two Gd-based CAs. The BVf quantification using the mathematical model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated using a ΔR2*-steady-state MRI method with an USPIO and by immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye in the same rats. Results BVf in tumor and in healthy brain tissues (0.034 ± 0.005 and 0.026 ± 0.004, respectively) derived from the dynamic RSST1 signal were confirmed by ΔR2*-steady-state MRI (0.036 ± 0.003 and 0.027 ± 0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036 ± 0.003 and 0.025 ± 0.004 respectively, rS = 0.87). Conclusion Straightforward tumor BVf quantification without AIF determination is demonstrated in presence of CA leakage. The method will facilitate angiogenesis assessment in longitudinal neuro-oncologic studies in particular when monitoring the response to antiangiogenic therapies. Magn Reson Med 73:1005–1014, 2015. © 2014 Wiley Periodicals, Inc.
- Published
- 2014
16. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo
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Valentin-Adrian Maraloiu, Florence Appaix, Alexis Broisat, Dominique Le Guellec, Valentin Serban Teodorescu, Catherine Ghezzi, Boudewijn van der Sanden, and Marie Genevieve Blanchin
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0303 health sciences ,03 medical and health sciences ,02 engineering and technology ,021001 nanoscience & nanotechnology ,0210 nano-technology ,030304 developmental biology - Published
- 2016
17. Translation of the ecological trap concept to glioma therapy: the cancer cell trap concept
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Didier Wion, Jean-Paul Issartel, Boudewijn van der Sanden, François Berger, Laurent Selek, and Florence Appaix
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Cancer Research ,Cancer therapy ,Biology ,Article ,Trap (computing) ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Local population ,030304 developmental biology ,0303 health sciences ,Ecology ,fungi ,food and beverages ,General Medicine ,medicine.disease ,Data science ,Oncology ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,Ecological trap - Abstract
Viewing tumors as ecosystems offers the opportunity to consider how ecological concepts can be translated to novel therapeutic perspectives. The ecological trap concept emerged approximately half a century ago when it was observed that animals can prefer an environment of low quality for survival over other available environments of higher quality. The presence of such a trap can drive a local population to extinction. The cancer cell trap concept is the translation of the ecological trap into glioma therapy. It exploits and diverts the invasive potential of glioma cells by guiding their migration towards specific locations where a local therapy can be delivered efficiently. This illustrates how an ecological concept can change therapeutic obstacles into therapeutic tools.
- Published
- 2013
18. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice
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Clément Ricard, Jean Claude Vial, Christoph Segebarth, Boudewijn van der Sanden, Manuel Fernandez, Herwig Requardt, Didier Wion, Issartel, Jean-Paul, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), Inserm U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), INSERM, ESRF, Université Joseph Fourier, and Ministère Français de la Recherche et de l'Education
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Nuclear and High Energy Physics ,synchrotron photoactivation therapy ,Mice, Nude ,cisplatin ,Antineoplastic Agents ,Hindlimb ,macromolecular substances ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Glioma ,glioma ,medicine ,Tumor Cells, Cultured ,Combined Modality Therapy ,Animals ,Irradiation ,two-photon microscopy ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Instrumentation ,Hemibody Irradiation ,030304 developmental biology ,Cisplatin ,0303 health sciences ,Radiation ,Dose-Response Relationship, Drug ,Chemistry ,Brain Neoplasms ,Cancer ,Dose-Response Relationship, Radiation ,medicine.disease ,equipment and supplies ,Research Papers ,3. Good health ,Rats ,Disease Models, Animal ,030220 oncology & carcinogenesis ,biological sciences ,Cancer research ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,synergistic effects ,Perfusion ,Synchrotrons ,Glioblastoma ,medicine.drug - Abstract
Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion., Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.
- Published
- 2013
19. Keto-polymethines: a versatile class of dyes with outstanding spectroscopic properties for
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Simon, Pascal, Sandrine, Denis-Quanquin, Florence, Appaix, Alain, Duperray, Alexei, Grichine, Boris, Le Guennic, Denis, Jacquemin, Jérôme, Cuny, San-Hui, Chi, Joseph W, Perry, Boudewijn, van der Sanden, Cyrille, Monnereau, Chantal, Andraud, and Olivier, Maury
- Subjects
Chemistry ,lipids (amino acids, peptides, and proteins) - Abstract
The keto-heptamethine family has been expanded to various symmetrical and asymmetrical structures., The synthesis of keto-heptamethine derivatives has been expanded to various new symmetrical and asymmetrical structures, including an unprecedented di-anionic keto-polymethine. The spectroscopic behavior of these new dyes has been systematically and thoroughly investigated, revealing that the formation of hydrogen bond interactions with protic solvents is responsible for a dramatic enhancement of the fluorescence quantum yield in the far-red spectral region. The existence of these strong hydrogen-bond interactions was further confirmed by molecular dynamics simulations. These bis-dipolar polymethines exhibit large two-photon absorption (TPA) cross-sections (σ 2 in GM) in the near-infrared, making them ideal candidates for NIR-to-NIR two-photon microscopy imaging applications. We demonstrate that the molecular engineering of the hydrophilic/hydrophobic balance enables targeting of different cellular components, such as cytoplasm or cell membranes. Addition of appropriate substituents provides the molecule with high-water-solubility, affording efficient two-photon probes for angiography.
- Published
- 2016
20. The brain tissue response to surgical injury and its possible contribution to glioma recurrence
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David Ratel, Lauriane Hamard, Laurent Selek, Didier Wion, Boudewijn van der Sanden, François Berger, Institut National de la Santé et de la Recherche Médicale (INSERM), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and wion, didier
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Cancer Research ,Pathology ,medicine.medical_specialty ,Microenvironment ,Angiogenesis ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Wound healing ,Inflammation ,Neurosurgical Procedures ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Glioma ,medicine ,Humans ,Dormancy ,Paradigm shift ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Brain Neoplasms ,business.industry ,Regeneration (biology) ,Brain ,Immunotherapy ,medicine.disease ,3. Good health ,[SDV] Life Sciences [q-bio] ,Neurology ,Oncology ,030220 oncology & carcinogenesis ,Resection margin ,Cancer research ,Surgery ,Neurology (clinical) ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Surgery is the first line therapy for glioma. However, glioma recurs in 90 % of the patients in the resection margin. The impact of surgical brain injury (SBI) on glioma recurrence is largely overlooked. Herein, we review some of the mechanisms involved in tissue repair that may impact glioma recurrence at the resection margin. Many processes or molecules involved in tissue repair after brain injury are also critical for glioma growth. They include a wide array of secreted growth factors, cytokines and transcription factors including NFКB and STAT3 which in turn activate proliferative and anti-apoptotic genes and processes such as angiogenesis and inflammation. Because some residual glioma cells always remain in the tumor resection margin, there are now compelling arguments to suggest that some aspects of the brain tissue response to SBI can also participate to glioma recurrence at the resection margin. Brain tissue response to SBI recruits angiogenesis and inflammation that precede and then follow tumor recurrence at the resection margin. The healingresponse to SBI is double edged, as inflammation is involved in regeneration and healing, and has both pro- and anti-tumorigenic functions. A promising therapeutic approach is to normalize and re-educate the molecular and cellular responses at the resection margin to promote anti- tumorigenic processes involved in healing while inhibiting pro-tumorigenic activities. Manipulation of the inflamma- tory response to SBI to prevent local recurrence could also enhance the efficacy of other therapies such as immunotherapy. However, our current knowledge is far from sufficient to achieve this goal. Acknowledging, understanding and manipulating the double-edged role played by SBI in glioma recurrence is surely challenging, but it cannot be longer delayed.
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- 2016
21. Glioma Recurrence following Surgery: Peritumoral or Perilesional?
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Didier Wion, Boudewijn van der Sanden, François Berger, and David Ratel
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Opinion ,surgery injury ,recurrence ,business.industry ,medicine.disease ,microenvironment ,lcsh:RC346-429 ,Surgery ,03 medical and health sciences ,030104 developmental biology ,Text mining ,Neurology ,paradigm shift ,inflammation ,Glioma ,glioma ,medicine ,Neurology (clinical) ,business ,lcsh:Neurology. Diseases of the nervous system ,Neuroscience - Published
- 2016
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22. Fluorescent Tobacco mosaic virus-derived bio-nanoparticles for intravital two-photon imaging
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Boudewijn van der Sanden, Annette Niehl, Sonia Boscá, Florence Appaix, Jean-François Nicoud, Frédéric Bolze, Manfred Heinlein, Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Conception et application de molécules bioactives (CAMB), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Systèmes Fonctionnels, Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
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0301 basic medicine ,Plant virus ,02 engineering and technology ,Plant Science ,Biology ,lcsh:Plant culture ,Blood–brain barrier ,03 medical and health sciences ,Two-photon excitation microscopy ,Tobacco mosaic virus ,medicine ,Fluorescence microscope ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,[SDV.BV] Life Sciences [q-bio]/Vegetal Biology ,lcsh:SB1-1110 ,two-photon microscopy ,Original Research ,viral nanoparticles ,021001 nanoscience & nanotechnology ,Virology ,Fluorescence ,030104 developmental biology ,medicine.anatomical_structure ,Biophysics ,intravital imaging ,Nanocarriers ,0210 nano-technology ,Preclinical imaging - Abstract
Multi-photon intravital imaging has become a powerful tool to investigate the healthy and diseased brain vasculature in living animals. Although agents for multi-photon fluorescence microscopy of the microvasculature are available, issues related to stability, bioavailability, toxicity, cost or chemical adaptability remain to be solved. In particular, there is a need for highly fluorescent dyes linked to particles that do not cross the blood brain barrier (BBB) in brain diseases like tumor or stroke to estimate the functional blood supply. Plant virus particles possess a number of distinct advantages over other particles, the most important being the multi-valency of chemically addressable sites on the particle surface. This multi-valency, together with biological compatibility and inert nature, makes plant viruses ideal carriers for in vivo imaging agents. Here, we show that the well-known Tobacco mosaic virus is a suitable nanocarrier for two-photon dyes and for intravital imaging of the mouse brain vasculature.
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- 2016
23. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo
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Valentin S. Teodorescu, Dominique Le Guellec, Florence Appaix, M.G. Blanchin, Boudewijn van der Sanden, Alexis Broisat, Valentin-Adrian Maraloiu, Catherine Ghezzi, Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
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0301 basic medicine ,Biodistribution ,Pathology ,medicine.medical_specialty ,Materials science ,Metabolic Clearance Rate ,MRI contrast agent ,Biomedical Engineering ,Iron oxide ,Contrast Media ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,[SPI]Engineering Sciences [physics] ,Microscopy, Electron, Transmission ,Two-photon excitation microscopy ,In vivo ,Materials Testing ,medicine ,Animals ,[CHIM]Chemical Sciences ,Tissue Distribution ,General Materials Science ,Magnetite Nanoparticles ,High-resolution transmission electron microscopy ,ComputingMilieux_MISCELLANEOUS ,[PHYS]Physics [physics] ,biology ,Dextrans ,021001 nanoscience & nanotechnology ,Plaque, Atherosclerotic ,Mice, Inbred C57BL ,Ferritin ,Metabolism ,Microscopy, Fluorescence, Multiphoton ,030104 developmental biology ,chemistry ,biology.protein ,Molecular Medicine ,0210 nano-technology ,Ex vivo ,Subcellular Fractions ,Biomedical engineering - Abstract
The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.
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- 2016
24. The role of fluctuations and stress on the effective viscosity of cell aggregates
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Boudewijn van der Sanden, Philippe Marmottant, Jean-Claude Vial, François Graner, Jean-Paul Rieu, Abbas Mgharbel, Benjamin Audren, Athanasius F. M. Marée, Hélène Delanoë-Ayari, Jos Käfer, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, ANTE-INSERM U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Theoretical Biology/Bioinformatics, Utrecht University [Utrecht], Génétique du Développement et Cancer, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Issartel, Jean-Paul, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
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MESH: Emulsions ,Compressive Strength ,Constitutive equation ,MESH: Cell Cycle ,[SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph] ,01 natural sciences ,[SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph] ,Surface tension ,Mice ,MESH: Cell Aggregation ,Stress relaxation ,MESH: Animals ,[PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph] ,MESH: Biomechanics ,MESH: Cell Size ,Cell Aggregation ,MESH: Cells ,0303 health sciences ,MESH: Stress, Mechanical ,Multidisciplinary ,Viscosity ,Cell Cycle ,Mechanics ,Cell aggregation ,Biomechanical Phenomena ,Compressive strength ,Physical Sciences ,Emulsions ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,MESH: Cell Line, Tumor ,Materials science ,Cells ,MESH: Viscosity ,Nanotechnology ,03 medical and health sciences ,Cell Line, Tumor ,surface tension ,0103 physical sciences ,cellular Potts model ,Animals ,[PHYS.MECA.MEFL] Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph] ,Elasticity (economics) ,010306 general physics ,MESH: Mice ,Cell Size ,030304 developmental biology ,[SDV.IB] Life Sciences [q-bio]/Bioengineering ,statistical model ,Cellular Potts model ,MESH: Compressive Strength ,Apparent viscosity ,Elasticity ,MESH: Elasticity ,Stress, Mechanical - Abstract
Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregate's shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time t c ). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find t c of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.
- Published
- 2009
25. Microscopic DTI accurately identifies early glioma cell migration: correlation with multimodal imaging in a new glioma stem cell model
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Ulysse, Gimenez, Adriana-T, Perles-Barbacaru, Arnaud, Millet, Florence, Appaix, Michele, El-Atifi, Karin, Pernet-Gallay, Boudewijn, van der Sanden, François, Berger, and Hana, Lahrech
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Brain Neoplasms ,Statistics as Topic ,Mice, Nude ,Reproducibility of Results ,Glioma ,Multimodal Imaging ,Sensitivity and Specificity ,Corpus Callosum ,Mice ,Diffusion Tensor Imaging ,Imaging, Three-Dimensional ,Microscopy, Fluorescence, Multiphoton ,Cell Movement ,Cell Tracking ,Cell Line, Tumor ,Neoplastic Stem Cells ,Animals ,Female ,Neoplasm Invasiveness ,Longitudinal Studies - Abstract
Monitoring glioma cell infiltration in the brain is critical for diagnosis and therapy. Using a new glioma Glio6 mouse model derived from human stem cells we show how diffusion tensor imaging (DTI) may predict glioma cell migration/invasion. In vivo multiparametric MRI was performed at one, two and three months of Glio6 glioma growth (Glio6 (n = 6), sham (n = 3)). This longitudinal study reveals the existence of a time window to study glioma cell/migration/invasion selectively. Indeed, at two months only Glio6 cell invasion was detected, while tumor mass formation, edema, blood-brain barrier leakage and tumor angiogenesis were detected later, at three months. To robustly confirm the potential of DTI for detecting glioma cell migration/invasion, a microscopic 3D-DTI (80 μm isotropic spatial resolution) technique was developed and applied to fixed mouse brains (Glio6 (n = 6), sham (n = 3)). DTI changes were predominant in the corpus callosum (CC), a known path of cell migration. Fractional anisotropy (FA) and perpendicular diffusivity (D
- Published
- 2015
26. Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward tumor blood volume quantification without requiring the arterial input function
- Author
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Michel, Sarraf, Adriana Teodora, Perles-Barbacaru, Marie France, Nissou, Boudewijn, van der Sanden, François, Berger, Hana, Lahrech, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Blood Volume ,Blood Volume Determination ,Neovascularization, Pathologic ,Brain Neoplasms ,Contrast Media ,Magnetic Resonance Imaging ,Models, Biological ,Rats, Inbred F344 ,Rats ,Heterocyclic Compounds ,Cell Line, Tumor ,Image Interpretation, Computer-Assisted ,Organometallic Compounds ,Animals ,Computer Simulation ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Extravasation of Diagnostic and Therapeutic Materials - Abstract
International audience; PURPOSE: This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination. METHODS: For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase. We applied the mathematical model in a pilot-study on a RG2-glioma model to compare extravasation of two Gd-based CAs. The BVf quantification using the mathematical model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated using a ΔR2 *-steady-state MRI method with an USPIO and by immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye in the same rats. RESULTS: BVf in tumor and in healthy brain tissues (0.034 ± 0.005 and 0.026 ± 0.004, respectively) derived from the dynamic RSST1 signal were confirmed by ΔR2 *-steady-state MRI (0.036 ± 0.003 and 0.027 ± 0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036 ± 0.003 and 0.025 ± 0.004 respectively, rS = 0.87). CONCLUSION: Straightforward tumor BVf quantification without AIF determination is demonstrated in presence of CA leakage. The method will facilitate angiogenesis assessment in longitudinal neuro-oncologic studies in particular when monitoring the response to antiangiogenic therapies.
- Published
- 2015
27. Cancer research in need of a scientific revolution: Using 'paradigm shift' as a method of investigation
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François Berger, Meriwether Burruss, Boudewijn van der Sanden, Didier Wion, Florence Appaix, wion, didier, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Math, École normale supérieure - Lyon (ENS Lyon), [GIN] Grenoble Institut des Neurosciences (GIN), and École normale supérieure de Lyon (ENS de Lyon)
- Subjects
cancer stem cell ,General method ,Biomedical Research ,extracellular matrix ,[SDV]Life Sciences [q-bio] ,Disease ,Biology ,overdiagnosis ,Reification (Marxism) ,General Biochemistry, Genetics and Molecular Biology ,Neoplasms ,Humans ,cancer ,Overdiagnosis ,Infectious Disease Medicine ,therapy ,Cancer prevention ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,overtreatment ,General Medicine ,Kuhn ,microenvironment ,Scientific revolution ,3. Good health ,[SDV] Life Sciences [q-bio] ,Paradigm shift ,Cancer research ,General Agricultural and Biological Sciences ,Koch's postulate ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of 'paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the 'paradigm shift' method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the 'paradigm shift' method to produce perspective reversals consistent with current experimental evidence. The 'paradigm shift' method enlightens the existence of a tumour physiologic-prophylactic-pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The 'paradigm shift' method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy
- Published
- 2015
28. Long-Term in Vivo Clearance of Gadolinium-Based AGuIX Nanoparticles and Their Biocompatibility after Systemic Injection
- Author
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Blandine Laurent, Olivier Tillement, Lucie Sancey, Eloise Thomas, Arthur Marais, Pascal Perriat, Jean-Philippe Klein, Gérard Panczer, Rodolphe Antoine, François Lux, Charles Truillet, Shady Kotb, Michèle Cottier, Vincent Motto-Ros, Philippe Dugourd, Florence Appaix, Boudewijn van der Sanden, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées (LINA-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), 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)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), and Rayet, Béatrice
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Models, Molecular ,Materials science ,Kidney Cortex ,Biocompatibility ,MRI contrast agent ,Electrospray ionization ,Gadolinium ,Molecular Conformation ,General Physics and Astronomy ,Nanoparticle ,chemistry.chemical_element ,Contrast Media ,Metal Nanoparticles ,Biocompatible Materials ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Injections ,Mice ,Nuclear magnetic resonance ,Two-photon excitation microscopy ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,In vivo ,Animals ,Humans ,General Materials Science ,Laser-induced breakdown spectroscopy ,X-Rays ,General Engineering ,technology, industry, and agriculture ,Biological Transport ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,3. Good health ,Kinetics ,chemistry ,Biophysics ,Safety ,0210 nano-technology - Abstract
International audience; We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.
- Published
- 2015
29. Glioma resection and tumor recurrence: back to Semmelweis
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Boudewijn van der Sanden, David Ratel, Didier Wion, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), wion, didier, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Cancer Research ,medicine.medical_specialty ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,[SDV]Life Sciences [q-bio] ,medicine.disease ,Resection ,Tumor recurrence ,[SDV] Life Sciences [q-bio] ,03 medical and health sciences ,0302 clinical medicine ,Neoplasm Recurrence ,Text mining ,Oncology ,030220 oncology & carcinogenesis ,Glioma ,medicine ,Neurology (clinical) ,Radiology ,business ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery - Abstract
International audience; No abstract
- Published
- 2016
30. Assessment of the neovascular permeability in glioma xenografts by dynamicT1MRI with Gadomer-17
- Author
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H. Peters, Gilke Pee, Arend Heerschap, Boudewijn van der Sanden, Albert J. van der Kogel, Marleen Verhoye, Greetje Vanhoutte, P.F.J.W. Rijken, and Annemie Van der Linden
- Subjects
Pathology ,medicine.medical_specialty ,Human glioma ,medicine.diagnostic_test ,Gadolinium ,chemistry.chemical_element ,Magnetic resonance imaging ,Vascular permeability ,medicine.disease ,Vascular architecture ,Neovascularization ,Nuclear magnetic resonance ,chemistry ,Permeability (electromagnetism) ,Glioma ,medicine ,Radiology, Nuclear Medicine and imaging ,medicine.symptom - Abstract
The uptake of Gadomer-17, as probed by fast dynamic T(1) measurements, was used to assess the vascular permeability surface-area product per leakage volume of tissue (k(Tofts)) of human glioma xenografts implanted in mice. With this approach we could discriminate between two types of glioma xenograft lines with a known difference in the perfused vascular architecture and degree of hypoxia. The T(1) data were analyzed according to the Tofts-Kermode compartment model. The fast-growing E102 tumor demonstrated a homogeneous distribution of the vascular permeability surface area across the tumor (mean k(Tofts) value = 0.18 +/- 0.05 min(-1)). The slowly growing E106 tumor showed a more heterogeneous pattern. Three perfused tumor areas with differences in vascular permeability surface area could be distinguished: a well-perfused periphery with high k(Tofts) values (0.24 +/- 0.04 min(-1)), perfused capillaries inside the tumor with low k(Tofts) values (0.108 +/- 0.026 min(-1)), and perfused capillaries adjacent to necrotic regions with high k(Tofts) values (0.29 +/- 0.10 min(-1)). On a different series of tumors, the hypoxic fractions were measured, and these were significantly higher in E106 tumors (0.14 +/- 0.05) compared to tumors of the E102 line (0.03 +/- 0.02).
- Published
- 2002
31. Improved subtraction by adiabatic FAIR perfusion imaging
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Boudewijn van der Sanden, Klaas Nicolay, Michael Garwood, and Janneke Schepers
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Physics ,Offset (computer science) ,Sinc function ,Echo-Planar Imaging ,Phantoms, Imaging ,business.industry ,Subtraction ,Brain ,Image subtraction ,Perfusion scanning ,Site-directed spin labeling ,Image Enhancement ,Sensitivity and Specificity ,Rats ,Optics ,Nuclear magnetic resonance ,Regional Blood Flow ,Subtraction Technique ,Image Processing, Computer-Assisted ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,business ,Adiabatic process ,Excitation - Abstract
For pulsed arterial spin labeling techniques (e.g., FAIR), mismatches between the imaging and inversion slice profile result in a nonperfusion-related offset. Several methods have been proposed to reduce subtraction errors in FAIR imaging. Here an acquisition method for FAIR experiments based on adiabatic principles is proposed. It is shown that with adiabatic pulses the same pulse can be used for labeling and echo refocusing, thereby reducing the mismatch between imaging and labeling slice. A twofold reduction in subtraction errors compared to 5-lobe sinc excitation was shown both experimentally and by simulation.
- Published
- 2002
32. Visualisation 3D de la vascularisation cérébrale par microscopie à deux photons
- Author
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Florence Appaix, Boudewijn van der Sanden, and Cyrille Monnereau
- Abstract
Les techniques d'imagerie vasculaire cerebrale IRM ou scanner constituent des outils incontournables aussi bien en diagnostic clinique qu'en recherche biomedicale. Si ces techniques restent non invasives, leur resolution au mieux millimetrique represente une limite dans l'observation des processus mis en jeu au niveau cellulaire. De fait, la microscopie de fluorescence a deux photons, de resolution micrometrique, s'impose comme un dispositif complementaire majeur dans la recherche en neurobiologie et en oncologie. Cet article propose un descriptif de la technique mise en jeu dans ce type d'imagerie, du dispositif experimental utilise pour l'acquisition des donnees sur animal vivant, jusqu'a un etat de l'art de la conception d'agents de contraste fluorescents pour l'utilisation in vivo.
- Published
- 2014
33. Brain mesenchymal stem cells: The other stem cells of the brain?
- Author
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François Berger, Marie-France Nissou, Boudewijn van der Sanden, Matthieu Dreyfus, Didier Wion, Florence Appaix, and Jean-Paul Issartel
- Subjects
Pathology ,medicine.medical_specialty ,Histology ,business.industry ,Mesenchymal stem cell ,Cell Biology ,Regenerative medicine ,Neural stem cell ,Cell biology ,medicine.anatomical_structure ,Cancer stem cell ,Cell Plasticity ,Genetics ,medicine ,Pericyte ,Bone marrow ,Topic Highlight ,Stem cell ,business ,Molecular Biology ,Genetics (clinical) - Abstract
Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.
- Published
- 2014
34. Two-voxel localization sequence for in vivo two-dimensional homonuclear correlation spectroscopy
- Author
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Boudewijn van der Sanden, Jean-Claude Beloeil, Klaas Nicolay, Florence Delmas, Brigitte Gillet, and University of Groningen
- Subjects
multivoxel localization ,Nuclear and High Energy Physics ,Magnetic Resonance Spectroscopy ,Biophysics ,Hadamard encoding ,RAT-BRAIN ,PROTON ,computer.software_genre ,METABOLITES ,LACTATE ,Biochemistry ,Aminobutyric acid ,Homonuclear molecule ,Brain Ischemia ,Nuclear magnetic resonance ,Reference Values ,In vivo ,Voxel ,rat brain ,Image Processing, Computer-Assisted ,Animals ,Lactic Acid ,Threonine ,Dominance, Cerebral ,IN-VIVO ,Alanine ,Phantoms, Imaging ,Chemistry ,Brain ,RADIOFREQUENCY PULSES ,two-dimensional correlation H-1 MRS ,Image Enhancement ,Condensed Matter Physics ,Magnetic Resonance Imaging ,Rats ,RF PULSES ,Glutamine ,PHOSPHORUS ,NMR-SPECTROSCOPY ,cerebral metabolites ,Brain Damage, Chronic ,Energy Metabolism ,1D-HADAMARD ,computer ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
The combination of localized 2D 1H MR correlation spectroscopy and Hadamard encoding allows the simultaneous acquisition of multiple volumes of interest without an increase in the experimental duration, compared to single-voxel acquisition. In the present study, 2D correlation spectra were acquired simultaneously within 20 to 40 min in two voxels located in each hemisphere of the rat brain. An intervoxel distance of 20% of the voxel size was sufficient to limit spatial contamination. The following cerebral metabolites gave detectable crosspeaks: N-acetylaspartate, the glutamate/glutamine pool, aspartate, phosphoethanolamine, glucose, glutathione, taurine, myo-inositols, lactate, threonine, ¿-aminobutyric acid, and alanine. Most of the metabolites were measured without contamination of other resonances. two-dimensional correlation 1H MRS
- Published
- 2001
35. Noninvasive assessment of the functional neovasculature in 9L-glioma growing in rat brain by dynamic 1H magnetic resonance imaging of gadolinium uptake
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Boudewijn van der Sanden, Albert J. van der Kogel, H. Peters, W.M.M.J. Bovée, Arend Heerschap, P.F.J.W. Rijken, and Tom H. Rozijn
- Subjects
Gadolinium DTPA ,Pathology ,medicine.medical_specialty ,Gadolinium ,Contrast Media ,chemistry.chemical_element ,computer.software_genre ,030218 nuclear medicine & medical imaging ,Neovascularization ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Voxel ,Glioma ,Biomedische Magnetische Resonantie ,medicine ,Fluorescence microscope ,Animals ,Distribution (pharmacology) ,Experimental radiotherapy and neuro-oncology ,Neovascularization, Pathologic ,medicine.diagnostic_test ,Brain Neoplasms ,Chemistry ,Magnetic resonance imaging ,medicine.disease ,Experimentele radiotherapie en neuro-oncologie ,Immunohistochemistry ,Magnetic Resonance Imaging ,Rats, Inbred F344 ,Rats ,Biomedical Magnetic Resonance ,Neurology ,cardiovascular system ,Neurology (clinical) ,Protons ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,computer ,030217 neurology & neurosurgery - Abstract
Pathophysiologic parameters of the functional neovasculature and the blood-brain barrier of 9L-glioma in rat brain were measured noninvasively by dynamic 1H magnetic resonance imaging studies of gadolinium (Gd)-DTPA uptake. Changes of apparent [Gd-DTPA] uptake in time (CT[t]) were analyzed in a slice through the center of 10 9L-gliomas using fast T1 measurements. The distribution of the contrast agent was spatially correlated with the distribution of perfused microvessels as determined by immunohistochemical analysis. This method permits a distinction between perfused and nonperfused microvessels with a disrupted blood-brain barrier. In transverse slices of the whole tumor, a spatial correlation was observed between CT maps and the two-dimensional distribution of perfused microvessels. In the next step, Gd-DTPA uptake rates were spatially related to the perfused microvessel density (Np) or vascular surface area (Sp). In tumor voxels with perfused microvessels, a linear correlation was found between Gd-DTPA uptake rate constants (k values) and Np or Sp. No correlation was observed between k values and the total microvessel density. These are the first data that show a relation between Gd-DTPA uptake rates and parameters of the functional neovasculature in 9L-glioma growing in rat brain. Now that Gd-DTPA uptake studies can be related to parameters of the functional neovasculature, they may be used more efficiently as a prognostic tool before or during therapy.
- Published
- 2000
36. Determination of in vivo rat muscle GdâDTPA relaxivity at 6.3 T
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Boudewijn Van der Sanden
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Radiological and Ultrasound Technology ,Biophysics ,Radiology, Nuclear Medicine and imaging - Published
- 1999
37. Fast dynamic gadolinium-enhanced MR imaging of urinary bladder and prostate cancer
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Boudewijn van der Sanden, Arend Heerschap, Marc R. W. Engelbrecht, Gerrit J. Jager, J. Alfred Witjes, Jean de LaRosette, Henkjan J. Huisman, and Jelle O. Barentsz
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medicine.medical_specialty ,Chemotherapy ,Urinary bladder ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Granulation tissue ,Magnetic resonance imaging ,medicine.disease ,Prostate cancer ,Vascularity ,medicine.anatomical_structure ,Seminal vesicle ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,medicine.symptom ,business ,Grading (tumors) - Abstract
Among the noninvasive imaging modalities, contrast enhanced magnetic resonance (MR) imaging is the most powerful tool with which to visualize vascularity. Common pathology only shows microvessel density, whereas dynamic MR imaging is sensitive to the total endothelial surface area of perfused vessels. Therefore, dynamic MR imaging may be of additional value in tumor staging and in evaluating therapies that affect the perfused microvessel density or surface area, such as chemo-, radiation, or anti-angiogenic therapy. In urinary bladder cancer, this technique results in improved local and nodal staging, in improved separation of transurethral granulation tissue and edema from malignant tumor, and in improved evaluation of the effect of chemotherapy. In prostate cancer, dynamic MR imaging may be of help in problematic cases. This technique can assist in determining seminal vesicle infiltration, in depicting of minimal capsular penetration, and in recognizing tumors within the transitional zone. Also, based on very rapid enhancement, very poorly differentiated tumors can be recognized. Evaluation of the effects of therapy is another promising area, however a lot of research remain to be done. This article reviews some basics of fast enhancement techniques, provides practical information, and shows recent developments, in using these fast techniques for staging and grading of bladder and prostate cancer, and for evaluating the effect of therapy.
- Published
- 1999
38. Effect of carbogen breathing on the physiological profile of human glioma xenografts
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Louis Hoofd, Albert J. van der Kogel, Willy N.J.M. Colier, Arend Heerschap, Boudewijn van der Sanden, Klaas Nicolay, Annette van der Toorn, and Arjan W. Simonetti
- Subjects
Pathology ,medicine.medical_specialty ,Chemistry ,Hemodynamics ,Oxygenation ,Tumor Oxygenation ,Oxygen tension ,Endocrinology ,Carbogen ,Internal medicine ,Breathing ,medicine ,Radiology, Nuclear Medicine and imaging ,Carbogen Breathing ,Perfusion - Abstract
The aim of this study was to evaluate the effect of carbogen breathing on the physiological profile of human glioma xenografts. Near infrared spectroscopy was used to investigate changes in oxy- and deoxyhemoglobin concentrations in tumor blood. Oxygen tension changes in tumor tissue were evaluated by (19)F-MR relaxometry, using perfluoro-15-crown-5-ether, and modifications of tumor blood perfusion (TBP) were analyzed by fast dynamic (1)H-MR imaging of Gd-DTPA uptake. Finally, changes of the bioenergetic status and pH of tumor cells were analyzed by (31)P-MRS. After 5 to 8 min of carbogen breathing, the average oxygen tension increase in tumor tissue was 4.6 +/- 1.3 mm Hg, which is in agreement with an increase of the oxyhemoglobin concentration in tumor blood (Delta[O(2)Hb] = 9. 2 +/- 3 microM). However, simultaneously the TBP was reduced, the bioenergetic status was diminished, and pH was decreased. As 100% O(2) breathing alone did not result in a detectable increase of oxyhemoglobin in tumor blood, the increase of the tumor oxygenation by carbogen appears to be mediated by its CO(2) content. This component may cause a nutrient-limited decrease of oxidative energy metabolism, indirectly via a steal-effect and/or by inhibition of the glycolytic rate resulting from tissue acidification. Magn Reson Med 42:490-499, 1999.
- Published
- 1999
39. Engineering of hyaluronic acid-based nanogels with tunable thermosensitivity and stability
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Talitha, Stefanello, primary, Marl�ne, Rippe, additional, Benoit, Couturaud, additional, David, Fournier, additional, Anna, Szarpak-Jankowska, additional, Bruno, De Geest, additional, Boudewijn, Van Der Sanden, additional, Patrice, Woisel, additional, and Rachel, Auzely-Velty, additional
- Published
- 2016
- Full Text
- View/download PDF
40. Hypoxia-induced expression of VE-cadherin and Filamin B in gliomacell cultures and pseudopalisade structures
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Audrey Guttin, Catherine Godfraind, Emmanuel Garcion, Didier Wion, Marie-France Nissou, Jean-Paul Issartel, Boudewijn van der Sanden, Michèle El Atifi, Caroline Salon, François Berger, Nanomédecine et Cerveau, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pathologie, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Clinique Saint-Luc, Service de Pathologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Inserm U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, and Ligue Nationale contre le Cancer (National, Rhône-Alpes, Isère et Puy de Dôme)
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Cancer Research ,Pathology ,Filamin ,Immunoenzyme Techniques ,0302 clinical medicine ,VE-cadherin ,Cell Movement ,Tumor Cells, Cultured ,Hypoxia ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,Brain Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Glioma ,Cadherins ,Filamin B ,Endothelial stem cell ,Neurology ,Oncology ,pseudopalisade ,030220 oncology & carcinogenesis ,medicine.medical_specialty ,Filamins ,Blotting, Western ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Real-Time Polymerase Chain Reaction ,Article ,03 medical and health sciences ,Necrosis ,Antigens, CD ,Neurosphere ,medicine ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,030304 developmental biology ,Cell Proliferation ,Cadherin ,Cell growth ,Gene Expression Profiling ,medicine.disease ,Cell culture ,Cancer cell ,Cancer research ,Neurology (clinical) ,Endothelium, Vascular ,endothelial to mesenchymal transition ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Most of our knowledge regarding glioma cell biology comes from cell culture experiments. For many years the standards for glioma cell culture were the use of cell lines cultured in the presence of serum and 20 % O2. However, in vivo, normoxia in many brain areas is in close to 3 % O2. Hence, in cell culture, the experimental value referred as the norm is hyperoxic compared to any brain physiological value. Likewise, cells in vivo are not usually exposed to serum, and low-passaged glioma neurosphere cultures maintained in serum-free medium is emerging as a new standard. A consequence of changing the experimental normoxic standard from 20 % O2 to the more brain physiological value of 3 % O2, is that a 3 % O2 normoxic reference point enabled a more rigorous characterization of the level of regulation of genes by hypoxia. Among the glioma hypoxia-regulated genes characterized using this approach we found VE-cadherin that is required for blood vessel formation, and filamin B a gene involved in endothelial cell motility. Both VE-cadherin and filamin B were found expressed in pseudopalisades, a glioblastoma pathognomonic structure made of hypoxic migrating cancer cells. These results provide additional clues on the role played by hypoxia in the acquisition of endothelial traits by glioma cells and on the functional links existing between pseudopalisades, hypoxia, and tumor progression.
- Published
- 2013
41. How stereological analysis of vascular morphology can quantify the blood volume fraction as a marker for tumor vasculature: comparison with magnetic resonance imaging.: Blood volume quantification by stereology and MRI
- Author
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Adriana T. Perles-Barbacaru, Régine Farion, Hana Lahrech, Boudewijn van der Sanden, Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and The study was funded by PhD and post doc stipends from the French Cancer Research Association (ARC, Association pour la Recherche sur le Cancer) and the French National Cancer Institute(INCa, Institut National du Cancer).
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Models, Anatomic ,Pathology ,MESH: Blood Volume ,Angiogenesis ,Gadolinium ,Contrast Media ,Stereology ,MESH: Microscopy, Fluorescence ,MESH: Models, Anatomic ,030218 nuclear medicine & medical imaging ,MESH: Magnetic Resonance Imaging ,MESH: Glioma ,0302 clinical medicine ,Heterocyclic Compounds ,Image Processing, Computer-Assisted ,Medicine ,MESH: Animals ,MESH: Brain Mapping ,Brain Mapping ,Blood Volume ,Blood Volume Determination ,Neovascularization, Pathologic ,medicine.diagnostic_test ,Brain Neoplasms ,Glioma ,Magnetic Resonance Imaging ,MESH: Image Processing, Computer-Assisted ,vascular volume fraction ,MESH: Microvessels ,Neurology ,Blood Volume Fraction ,MESH: Brain Neoplasms ,Original Article ,RSST1-MRI ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,MESH: Cell Line, Tumor ,MESH: Rats ,MESH: Heterocyclic Compounds ,MESH: Blood Volume Determination ,chemistry.chemical_element ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,Tumor vasculature ,03 medical and health sciences ,vessel diameter ,Cell Line, Tumor ,MESH: Contrast Media ,Organometallic Compounds ,Animals ,Rats, Wistar ,business.industry ,Magnetic resonance imaging ,MESH: Organometallic Compounds ,MESH: Rats, Wistar ,Rats ,Microscopy, Fluorescence ,Vascular morphology ,chemistry ,blood volume fraction ,Microvessels ,stereology ,Neurology (clinical) ,business ,MESH: Neovascularization, Pathologic ,Neoplasm Transplantation ,030217 neurology & neurosurgery ,MESH: Neoplasm Transplantation ,GADOTERATE MEGLUMINE - Abstract
To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid-steady-state- T1 (RSST1) magnetic resonance imaging (MRI) method was used for microvascular blood volume fraction (BVf) quantification with a novel contrast agent gadolinium per (3,6 anhydro) α-cyclodextrin (Gd-ACX). In brain tissue contralateral to the tumor, equal BVfs were obtained with Gd-ACX and the clinically approved gadoterate meglumine (Gd-DOTA). Contrary to Gd-DOTA, which leaks out of the tumor vasculature, Gd-ACX was shown to remain vascular in the tumor tissue allowing quantification of the tumor BVf. We sought to confirm the obtained tumor BVf using an independent method: instead of using a ‘standard’ two-dimensional histologic method, we study here how vascular morphometry combined with a stereological technique can be used for three-dimensional assessment of the vascular volume fraction ( VV). The VV is calculated from the vascular diameter and length density. First, the technique is evaluated on simulated data and the healthy rat brain vasculature and is then applied to the same C6 tumor vasculature previously quantified by RSST1-MRI with Gd-ACX. The mean perfused VV and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI.
- Published
- 2012
42. On the importance of the submicrovascular network in a computational model of tumour growth
- Author
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Lauriane Hamard, Boudewijn van der Sanden, Anne-Cécile Lesart, Angélique Stéphanou, François Estève, Issartel, Jean-Paul, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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), Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, Dynamiques Cellulaire, Tissulaire & Microscopie fonctionnelle (TIMC-IMAG-DyCTiM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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), CNRS (PEPS-INS2I 2010-2011) Rhˆone-Alpes Institute for Complex Systems (RNCS and IXXI respectively)French National Network, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies (TIMC-IMAG-DyCTiM), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
- Subjects
Vascular Endothelial Growth Factor A ,MESH: Tumor Burden ,MESH: Models, Cardiovascular ,Time Factors ,Computer science ,MESH: Cell Hypoxia ,Tumor burden ,hybrid model ,Apoptosis ,Biochemistry ,MESH: Glioma ,Mice ,angiogenesis ,0302 clinical medicine ,MESH: Animals ,Skin ,0303 health sciences ,Neovascularization, Pathologic ,Models, Cardiovascular ,Glioma ,Cell Hypoxia ,Tumor Burden ,MESH: Reproducibility of Results ,computational model ,030220 oncology & carcinogenesis ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cardiology and Cardiovascular Medicine ,Hybrid model ,Algorithm ,MESH: Oxygen ,Dorsum ,Scale (ratio) ,Mice, Nude ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Regular grid ,03 medical and health sciences ,Necrosis ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,MESH: Skin ,MESH: Computer Simulation ,MESH: Cell Proliferation ,MESH: Mice, Nude ,Animals ,Computer Simulation ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,dorsal skinfold chamber ,MESH: Mice ,030304 developmental biology ,Mice nude ,Cell Proliferation ,Solid tumour ,MESH: Necrosis ,MESH: Capillaries ,MESH: Apoptosis ,MESH: Vascular Endothelial Growth Factor A ,tumour growth ,MESH: Time Factors ,Reproducibility of Results ,Cell Biology ,Capillaries ,Oxygen ,Microvascular Network ,microvascular network ,multiscale model ,MESH: Neovascularization, Pathologic - Abstract
International audience; A computational model is potentially a powerful tool to apprehend complex phenomena like solid tumour growth and to predict the outcome of therapies. To that end, the confrontation of the model with experiments is essential to validate this tool. In this study, we develop a computational model specifically dedicated to the interpretation of tumour growth as observed in a mouse model with a dorsal skinfold chamber. Observation of the skin vasculature at the dorsal window scale shows a sparse network of a few main vessels of several hundreds micrometers in diameter. However observation at a smaller scale reveals the presence of a dense and regular interconnected network of capillaries about ten times smaller. We conveniently designate this structure as the submicrovascular network (SMVN).(1) The question that we wish to answer concerns the necessity of explicitly taking into account the SMVN in the computational model to describe the tumour evolution observed in the dorsal chamber. For that, simulations of tumour growth realised with and without the SMVN are compared and lead to two distinct scenarios. Parameters that are known to strongly influence the tumour evolution are then tested in the two cases to determine to which extent those parameters can be used to compensate the observed differences between these scenarios. Explicit modelling of the smallest vessels appears mandatory although not necessarily under the form of a regular grid. A compromise between the two investigated cases can thus be reached.
- Published
- 2012
43. Specific in vivo staining of astrocytes in the whole brain after intravenous injection of sulforhodamine dyes
- Author
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Boudewijn van der Sanden, Johannes Römer, Mireille Albrieux, Florence Appaix, Antoine Depaulis, Mathieu Maurin, Isabelle Guillemain, Sylvie Boisseau, Sabine Girod, Jean-Claude Vial, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Inserm U836, équipe 7, Nanomédecine et cerveau, FFRE Contrat de projets Etat-région (CPER), and Issartel, Jean-Paul
- Subjects
Pathology ,Anatomy and Physiology ,Mouse ,lcsh:Medicine ,MESH: Rats, Sprague-Dawley ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Molecular Cell Biology ,MESH: Animals ,Histochemistry ,lcsh:Science ,Neurons ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,Brain ,Electroencephalography ,Neurochemistry ,Animal Models ,MESH: Staining and Labeling ,Injections, Intravenous ,Cytochemistry ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cellular Types ,Intravital microscopy ,Research Article ,Genetically modified mouse ,medicine.medical_specialty ,MESH: Rats ,Neural Networks ,Transgene ,Population ,Biology ,MESH: Rhodamines ,MESH: Calcium Signaling ,Stain ,Neurological System ,03 medical and health sciences ,MESH: Brain ,Model Organisms ,In vivo ,MESH: Mice, Inbred C57BL ,MESH: Electroencephalography ,medicine ,Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Calcium Signaling ,education ,MESH: Mice ,030304 developmental biology ,Staining and Labeling ,Rhodamines ,lcsh:R ,Sulforhodamine 101 ,MESH: Injections, Intravenous ,Staining ,Rats ,MESH: Astrocytes ,Mice, Inbred C57BL ,Neuroanatomy ,chemistry ,Astrocytes ,Cellular Neuroscience ,Rat ,lcsh:Q ,030217 neurology & neurosurgery ,Neuroscience - Abstract
International audience; Fluorescent staining of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy studies. Current methods involved either transgenic mice or local intracerebral injection of sulforhodamine 101. Transgenic rat models rarely exist, and in mice, a backcross with GFAP transgenic mice may be difficult. Local injections of fluorescent dyes are invasive. Here, we propose a non-invasive, specific and ubiquitous method to stain astrocytes in vivo. This method is based on iv injection of sulforhodamine dyes and is applicable on rats and mice from postnatal age to adulthood. The astrocytes staining obtained after iv injection was maintained for nearly half a day and showed no adverse reaction on astrocytic calcium signals or electroencephalographic recordings in vivo. The high contrast of the staining facilitates the image processing and allows to quantify 3D morphological parameters of the astrocytes and to characterize their network. Our method may become a reference for in vivo staining of the whole astrocytes population in animal models of neurological disorders.
- Published
- 2011
44. Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles
- Author
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Boudewijn van der Sanden, Seth R. Marder, Mathieu Maurin, Jean-Claude Vial, Olivier Stephan, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), School of Chemistry and Biochemistry, and Center for Organic Electronics and Photonics, Georgia Institute of Technology [Atlanta], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by a grant from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche., and Issartel, Jean-Paul
- Subjects
MESH: Photons ,Optical Phenomena ,02 engineering and technology ,Pluronic nanomicelles ,01 natural sciences ,Micelle ,chemistry.chemical_compound ,Mice ,Two-photon excitation microscopy ,Blood plasma ,MESH: Microscopy, Confocal ,MESH: Animals ,MESH: Dextrans ,Micelles ,Microscopy, Confocal ,Blood Volume Determination ,Chemistry ,MESH: Micelles ,Brain ,Dextrans ,021001 nanoscience & nanotechnology ,MESH: Fluorescent Dyes ,Atomic and Molecular Physics, and Optics ,Extravasation ,Electronic, Optical and Magnetic Materials ,Dextran ,MESH: Neoplasms, Experimental ,MESH: Styrenes ,Intravital two-photon microscopy ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,0210 nano-technology ,MESH: Optical Phenomena ,Preclinical imaging ,Diagnostic Imaging ,MESH: Cell Line, Tumor ,MESH: Blood Volume Determination ,Biomedical Engineering ,Mice, Nude ,Nanotechnology ,Poloxamer ,MESH: Rhodamines ,Article ,Styrenes ,Biomaterials ,MESH: Brain ,MESH: Nanostructures ,In vivo ,Cell Line, Tumor ,MESH: Mice, Nude ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Mice ,Fluorescent Dyes ,Photons ,MESH: Humans ,010405 organic chemistry ,Rhodamines ,MESH: Diagnostic Imaging ,Neoplasms, Experimental ,cerebral and tumor microvasculature ,MESH: Blood Vessels ,MESH: Poloxamer ,0104 chemical sciences ,Nanostructures ,Biophysics ,Blood Vessels - Abstract
International audience; Our purpose is to test if Pluronic® fluorescent nanomicelles can be used for in vivo two-photon imaging of both the normal and the tumor vasculature. The nanomicelles were obtained after encapsulating a hydrophobic two-photon dye: di-stryl benzene derivative, in Pluronic block copolymers. Their performance with respect to imaging depth, blood plasma staining, and diffusion across the tumor vascular endothelium is compared to a classic blood pool dye Rhodamin B dextran (70 kDa) using two-photon microscopy. Pluronic nanomicelles show, like Rhodamin B dextran, a homogeneous blood plasma staining for at least 1 h after intravenous injection. Their two-photon imaging depth is similar in normal mouse brain, using 10 times less injected mass. In contrast with Rhodamin B dextran, no extravasation is observed in leaky tumor vessels due to their large size: 20-100 nm. In conclusion, Pluronic nanomicelles can be used as a blood pool dye, even in leaky tumor vessels. The use of Pluronic block copolymers is a valuable approach for encapsulating two-photon fluorescent dyes that are hydrophobic and not suitable for intravenous injection.
- Published
- 2011
45. Optimizing stem cell culture
- Author
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Boudewijn van der Sanden, Mehdi Dhobb, François Berger, Didier Wion, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Contre le Cancer, and Issartel, Jean-Paul
- Subjects
MESH: Stem Cell Niche ,CELL CULTURE ,Cell Culture Techniques ,MESH: Stem Cells ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Stem cell culture ,Biochemistry ,Article ,OXYGEN ,law.invention ,03 medical and health sciences ,MESH: Bioreactors ,Bioreactors ,0302 clinical medicine ,law ,Animals ,Humans ,Nanotechnology ,Nanotopography ,MESH: Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Stem Cell Niche ,Molecular Biology ,MESH: Nanotechnology ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,030304 developmental biology ,0303 health sciences ,MESH: Cell Culture Techniques ,MESH: Humans ,Recombinant Cytokines ,Stem Cells ,Petri dish ,Cell Biology ,STEM CELL ,NANOTOPOGRAPHY ,Cell biology ,Cell metabolism ,Cell culture ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Stem cell ,Stem cell biology ,030217 neurology & neurosurgery - Abstract
International audience; Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness, and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh's plane.
- Published
- 2010
46. Tolerance of arteries to microplanar X-ray beams.: Microplanar X-ray beam irradiation of arteries
- Author
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Boudewijn van der Sanden, E.A. Siegbahn, Elke Bräuer-Krisch, Clément Ricard, Jean-Claude Vial, Jean A. Laissue, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, ANTE-INSERM U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), Department of Oncology and Pathology, Karolinska Institutet [Stockholm], Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Oncology - Pathology - Anatomy, Institute of Pathology-University of Bern, and Clement Ricard received a grant of the French Ministry of Education and Research
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Cancer Research ,MESH: Radiotherapy ,medicine.medical_treatment ,Radiation Tolerance ,Muscle, Smooth, Vascular ,030218 nuclear medicine & medical imaging ,Mice ,0302 clinical medicine ,Occlusion ,Medicine ,MESH: Animals ,Mice, Inbred BALB C ,Microscopy ,Radiation ,Microbeam radiation ,MESH: Radiation Tolerance ,MESH: Hindlimb ,Arteries ,MESH: Muscle, Smooth, Vascular ,Hindlimb ,Muscular Atrophy ,Radiation Injuries, Experimental ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Circulatory system ,MESH: Fibrosis ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Tunica Media ,Blood vessel ,Artery ,MESH: Radiation Dosage ,MESH: Microscopy ,MESH: Mice, Inbred BALB C ,Radiation Dosage ,Radiosurgery ,03 medical and health sciences ,Animals ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Two-photon microscopy ,MESH: Arteries ,MESH: Mice ,Radiotherapy ,business.industry ,MESH: Muscular Atrophy ,Radiation effect ,Fibrosis ,Radiation therapy ,Artery smooth muscle cells ,MESH: Tunica Media ,MESH: Radiation Injuries, Experimental ,business ,Nuclear medicine - Abstract
International audience; PURPOSE: The purpose is to evaluate effects of a new radiotherapy protocol, microbeam radiation therapy, on the artery wall. In previous studies on animal models, it was shown that capillaries recover well from hectogray doses of X-rays delivered in arrays of narrow (< or = 50 microm) beams with a minimum spacing of 200 microm. Here, short- and long-term effects of comparable microplanar beam configurations on the saphenous artery of the mouse hind leg were analyzed in situ by use of nonlinear optics and compared with histopathologic findings. METHODS AND MATERIALS: The left hind leg of normal mice including the saphenous artery was irradiated by an array of 26 microbeams of synchrotron X-rays (50 microm wide, spaced 400 microm on center) with peak entrance doses of 312 Gy and 2,000 Gy. RESULTS: The artery remained patent, but narrow arterial smooth muscle cell layer segments that were in the microplanar beam paths became atrophic and fibrotic in a dose-dependent pattern. The wide tunica media segments between those paths hypertrophied, as observed in situ by two-photon microscopy and histopathologically. CONCLUSIONS: Clinical risks of long-delayed disruption or occlusion of nontargeted arteries from microbeam radiation therapy will prove less than corresponding risks from broad-beam radiosurgery, especially if peak doses are kept below 3 hectograys.
- Published
- 2010
47. Existence of tumor-derived endothelial cells suggests an additional role for endothelial-to-mesenchymal transition in tumor progression
- Author
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Laurent Selek, Didier Wion, François Berger, Boudewijn van der Sanden, Mehdi Dhobb, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Issartel, Jean-Paul
- Subjects
0303 health sciences ,Cancer Research ,Pathology ,medicine.medical_specialty ,Transition (genetics) ,Mesenchymal stem cell ,Tumor cells ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Tumor-Derived ,Biology ,Endothelial stem cell ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Tumor progression ,030220 oncology & carcinogenesis ,medicine ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience
- Published
- 2010
48. Short-term effects of synchrotron irradiation on vasculature and tissue in healthy mouse brain
- Author
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Jean-Claude Vial, Boudewijn van der Sanden, Laurette Somveille, Lucie Dupin, Régine Farion, Christoph Segebarth, Clément Ricard, Hélène Elleaume, Manuel Fernandez, Herwig Requardt, Jérôme Gastaldo, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie Fonctionnelle et Metabolique, European Synchrotron Radiation Facility (ESRF), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Serduc, Raphael, and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
- Subjects
Collagen Type IV ,Nuclear and High Energy Physics ,Pathology ,medicine.medical_specialty ,Mice, Nude ,synchrotron radiotherapy ,Blood–brain barrier ,Basement Membrane ,law.invention ,03 medical and health sciences ,Mice ,0302 clinical medicine ,law ,Glial Fibrillary Acidic Protein ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,blood-brain-barrier permeability ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Irradiation ,Instrumentation ,Cisplatin ,Radiation ,Chemistry ,Brain ,Radiotherapy Dosage ,equipment and supplies ,Fluorescence ,Immunohistochemistry ,Extravasation ,Synchrotron ,3. Good health ,medicine.anatomical_structure ,gliosis ,Gliosis ,Permeability (electromagnetism) ,Blood-Brain Barrier ,healthy brain tissue and irradiation ,030220 oncology & carcinogenesis ,multiphoton microscopy ,Female ,medicine.symptom ,030217 neurology & neurosurgery ,Synchrotrons ,medicine.drug - Abstract
International audience; The purpose of this study is to measure the effects of a tomographic synchrotron irradiation on healthy mouse brain. The cerebral cortexes of healthy nude mice were irradiated with a monochromatic synchrotron beam of 79 keV at a dose of 15 Gy in accordance with a protocol of photoactivation of cisplatin previously tested in our laboratory. Forty-eight hours, one week and one month after irradiation, the blood brain barrier (BBB) permeability was measured in the irradiated area with intravital multiphoton microscopy using fluorescent dyes with molecular weights of 4 and 70 kDa. Vascular parameters and gliosis were also assessed using quantitative immunohistochemistry. No extravasation of the fluorescent dyes was observed in the irradiated area at any measurement time (48 h, 1 week, 1 month). It appears that the BBB remains impermeable to molecules with a molecular weight of 4 kDa and above. The vascular density and vascular surface were unaffected by irradiation and no gliosis was induced. These findings suggest that a 15 Gy/79 keV synchrotron irradiation does not induce important damage on brain vasculature and tissue on the short term following irradiation.
- Published
- 2009
49. Fluorescent Pluronic nanodots for in vivo two-photon imaging
- Author
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Laeticia Vurth, Boudewijn van der Sanden, Patrice L. Baldeck, Mathieu Maurin, Olivier Stéphan, Seth R. Marder, Jean-Claude Vial, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Chemistry and Biochemistry, and Center for Organic Electronics and Photonics, Georgia Institute of Technology [Atlanta], and Serduc, Raphael
- Subjects
Diagnostic Imaging ,Hydrodynamic radius ,Materials science ,Analytical chemistry ,Nanoparticle ,Bioengineering ,02 engineering and technology ,Poloxamer ,010402 general chemistry ,Kidney ,01 natural sciences ,Mice ,Two-photon excitation microscopy ,Animals ,Surface Tension ,General Materials Science ,Electrical and Electronic Engineering ,Particle Size ,Fluorescent Dyes ,Mice, Inbred BALB C ,Rhodamines ,Mechanical Engineering ,Absorption cross section ,Brain ,Reproducibility of Results ,Dextrans ,General Chemistry ,021001 nanoscience & nanotechnology ,Fluorescence ,0104 chemical sciences ,3. Good health ,Liver ,Mechanics of Materials ,Nanoparticles ,Nanodot ,0210 nano-technology ,Luminescence ,Visible spectrum - Abstract
International audience; We report the synthesis of new nanosized fluorescent probes based on bio-compatible polyethylene-polypropylene glycol (Pluronic) materials. In aqueous solution, mini-emulsification of Pluronic with a high fluorescent di-stryl benzene-modified derivative, exhibiting a two-photon absorption cross section as high as 2500 Goeppert-Mayer units at 800 nm, leads to nanoparticles exhibiting a hydrodynamic radius below 100 nm. We have demonstrated that these new probes with luminescence located in the spectral region of interest for bio-imaging (the yellow part of the visible spectrum) allow deep (500 microm) bio-imaging of the mice brain vasculature. The dose injected during our experiments is ten times lower when compared to the classical commercial rhodamine-B isothicyanate-Dextran system but gives similar results to homogeneous blood plasma staining. The mean fluorescent signal intensity stayed constant during more than 1 h.
- Published
- 2009
50. An ethylene-glycol decorated ruthenium(ii) complex for two-photon photodynamic therapy
- Author
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Adeline Bonne, Gilles Lemercier, Boudewijn van der Sanden, Simion Astilean, Mickaël Four, Patrice L. Baldeck, Sanda Boca, Serduc, Raphael, Nanobiophotonics Laboratory, Babes-Bolyai University [Cluj-Napoca] (UBB), Laboratoire de Chimie - UMR5182 (LC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie Fonctionnelle et Metabolique, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Grenoble Institut des Neurosciences (GIN), Faculty of Physics, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC)
- Subjects
Ethylene Glycol ,medicine.medical_treatment ,chemistry.chemical_element ,Photodynamic therapy ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Catalysis ,Ruthenium ,chemistry.chemical_compound ,Two-photon excitation microscopy ,Materials Chemistry ,medicine ,Organometallic Compounds ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Photons ,Photosensitizing Agents ,Molecular Structure ,010405 organic chemistry ,Metals and Alloys ,Water ,General Chemistry ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry ,Photochemotherapy ,Solubility ,Ceramics and Composites ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Ethylene glycol - Abstract
International audience; A novel water-soluble Ru(ii) complex has been prepared, which represents a promising new class of selective two-photon sensitizers for use in photodynamic therapy within a confined space.
- Published
- 2009
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