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1. Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice

Author

J. Darcourt, Julien Guglielmi, Charles-Vivien Olivieri, Fanny Burel-Vandenbos, Matthieu Gérard, Virginie Flachon, Damien Ambrosetti, Laurent Suissa, Luc Pellerin, Philippe Franken, Thierry Pourcher, Jean-Marie Guigonis, Sabine Lindenthal, Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Epigénomique des mammifères (REMOD), Département Biologie des Génomes (DBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université de Lausanne (UNIL), Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), CEA ('Programme de Toxicologie nucleaire'), ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Université de Lausanne = University of Lausanne (UNIL), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Monocarboxylic Acid Transporters, medicine.medical_specialty, Aging, kidney, Ketone, Urinary system, brain, [SDV]Life Sciences [q-bio], Degeneration (medical), Ketone Bodies, SLC5A8, White matter, 03 medical and health sciences, 0302 clinical medicine, Brain White Matter, Leukoencephalopathies, Internal medicine, medicine, Animals, 030304 developmental biology, chemistry.chemical_classification, Tomography, Emission-Computed, Single-Photon, 0303 health sciences, Kidney, 3-Hydroxybutyric Acid, Chemistry, Transporter, Original Articles, ketone body, white matter, Mice, Mutant Strains, Mice, Inbred C57BL, medicine.anatomical_structure, Endocrinology, Glucose, Neurology, Ketone bodies, Neurology (clinical), Cardiology and Cardiovascular Medicine, 030217 neurology & neurosurgery
Abstract

SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.

Published
2019
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2. Distribution and Dynamics of 99mTc-Pertechnetate Uptake in the Thyroid and Other Organs Assessed by Single-Photon Emission Computed Tomography in Living Mice

Author

Philippe Franken, Michel Defrise, Jacques Darcourt, Thierry Pourcher, Malick Koulibaly, Christian Vanhove, and Julien Guglielmi

Subjects
Male, Sodium-iodide symporter, RADIOVIROTHERAPY, Technology and Engineering, TISSUES, Pertechnetate, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Thyroid Gland, Sodium Iodide, THERAPY, Salivary Glands, Mice, chemistry.chemical_compound, Endocrinology, MAMMARY-GLAND, Image Processing, Computer-Assisted, medicine, Animals, Tissue Distribution, Whole Body Imaging, IN-VIVO, GENE-EXPRESSION, Sodium Pertechnetate Tc 99m, Sodium:iodide symporter activity, Tomography, Emission-Computed, Single-Photon, PINHOLE SPECT, medicine.diagnostic_test, SODIUM-IODIDE SYMPORTER, ACQUISITION, business.industry, Chemistry, Stomach, Thyroid, Mice, Inbred C57BL, medicine.anatomical_structure, RESOLUTION, Gastric Mucosa, Thyroglobulin, Radiopharmaceuticals, Thyroid function, Nuclear medicine, business, Neck, Emission computed tomography
Abstract

Background: Tc-99m pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using Tc-99m pertechnetate or 123 iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. Methods: SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of Tc-99m pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. Results: This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that Tc-99m pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in Tc-99m pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. Conclusions: We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of Tc-99m pertechnetate accumulation in individual organs and revealed differences in uptake kinetics.

Published
2010
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3. Evaluation of tetrafunctional block copolymers as synthetic vectors for lung gene transfer

Author

Robert Marsault, Pauline Peuziat, Catherine Hervouet, Philippe Franken, Julie Warnez-Soulie, Thierry Pourcher, Jacques Darcourt, Thomas Haudebourg, Julien Guglielmi, Bruno Pitard, Peggy Richard-Fiardo, Georges Vassaux, Béatrice Cambien, Thibault Colombani, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunite anti-tumorale et chimiotactisme. Adenocarcinomes et métastases, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis - Faculté des Sciences (UNS UFR Sciences), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Chloramphenicol O-Acetyltransferase, Polymers, Transgene, Genetic enhancement, [SDV]Life Sciences [q-bio], Biophysics, Molecular imaging, Bioengineering, Biology, Gene delivery, Tetrafunctional block copolymers, Transfection, Cystic fibrosis, Biomaterials, Gene therapy, Gene expression, medicine, Animals, Humans, Transgenes, Lung, Inflammation, Tomography, Emission-Computed, Single-Photon, Mice, Inbred BALB C, Reporter gene, Symporters, Gene Transfer Techniques, medicine.disease, Immunohistochemistry, Molecular biology, Nonviral vector, 3. Good health, medicine.anatomical_structure, Mechanics of Materials, Ceramics and Composites, Female, Lungs, Tomography, X-Ray Computed
Abstract

International audience; In the present study, we evaluated, in mice, the efficacy of the tetrafunctional block copolymer 704 as a nonviral gene delivery vector to the lungs. SPECT/CT molecular imaging of gene expression, biochemical assays, and immunohistochemistry were used. Our dataset shows that the formulation 704 resulted in higher levels of reporter gene expression than the GL67A formulation currently being used in a clinical trial in cystic fibrosis patients. The inflammatory response associated with this gene transfer was lower than that induced by the GL67A formulation, and the 704 formulation was amenable to repeated administrations. The cell types transfected by the 704 formulation were type I and type II pneumocytes, and transgene expression could not be detected in macrophages. These results emphasize the relevance of the 704 formulation as a nonviral gene delivery vector for lung gene therapy. Further studies will be required to validate this vector in larger animals, in which the lungs are more similar to human lungs.

Published
2015
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4. Image-based motion detection in 4D images and application to respiratory motion suppression

Author

Julien Guglielmi, M. Breuilly, Grégoire Malandain, Philippe Franken, J. Darcourt, N. Ayache, Thierry Pourcher, Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Morphologie et Images (MORPHEME), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Département de Médecine Nucléaire [Nice] (CHU-Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Signal, Images et Systèmes (Laboratoire I3S - SIS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
Image fusion, Tomographic reconstruction, medicine.diagnostic_test, Computer science, business.industry, 3D reconstruction, Motion detection, Iterative reconstruction, Single-photon emission computed tomography, Signal, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 030220 oncology & carcinogenesis, medicine, Computer vision, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Image restoration
Abstract

International audience; Respiratory motion may blur the tomographic reconstruction of PET or SPECT images, which subsequently impairs quantitative measurements, e.g. in the upper abdomen area. Respiratory phase-based gated reconstruction addresses this problem for CT images, but deteriorates the signal-to-noise ratio and other intensity-based quality measures for ET images. This article describes an image-based motion detection method for dynamic images, which works for both 4D-CT and 4D-SPECT images. This method allowed us to identify the motionless phases from the image-based motion signal. Interestingly, we found that the peak of motion according to the pressure signal, recorded during the acquisition and considered as a reference, is temporally shifted compared to the motion-phases identified by the proposed method. Moreover, these observations permit to reconstruct a breath hold like 3D SPECT image improving the quality of the 3D reconstruction compared to both 4D reconstruction and standard 3D reconstruction.

Published
2013
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5. Amplitude-based data selection for optimal retrospective reconstruction in micro-SPECT

Author

J. Darcourt, Robert Marsault, Grégoire Malandain, Philippe Franken, Julien Guglielmi, Marine Breuilly, Thierry Pourcher, Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Morphologie et Images (MORPHEME), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Département de Médecine Nucléaire [Nice] (CHU-Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Signal, Images et Systèmes (Laboratoire I3S - SIS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
Computer science, Standardized uptake value, Iterative reconstruction, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Mice, 0302 clinical medicine, Imaging, Three-Dimensional, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, medicine, Animals, Radiology, Nuclear Medicine and imaging, Computer vision, Peritoneal Neoplasms, Retrospective Studies, Tomography, Emission-Computed, Single-Photon, Tomographic reconstruction, Radiological and Ultrasound Technology, medicine.diagnostic_test, Noise (signal processing), business.industry, Respiration, 3D reconstruction, Intensity (physics), Rats, Positron emission tomography, 030220 oncology & carcinogenesis, Female, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Emission computed tomography
Abstract

Respiratory motion can blur the tomographic reconstruction of positron emission tomography or single-photon emission computed tomography (SPECT) images, which subsequently impair quantitative measurements, e.g. in the upper abdomen area. Respiratory signal phase-based gated reconstruction addresses this problem, but deteriorates the signal-to-noise ratio (SNR) and other intensity-based quality measures. This paper proposes a 3D reconstruction method dedicated to micro-SPECT imaging of mice. From a 4D acquisition, the phase images exhibiting motion are identified and the associated list-mode data are discarded, which enables the reconstruction of a 3D image without respiratory artefacts. The proposed method allows a motion-free reconstruction exhibiting both satisfactory count statistics and accuracy of measures. With respect to standard 3D reconstruction (non-gated 3D reconstruction) without breathing motion correction, an increase of 14.6% of the mean standardized uptake value has been observed, while, with respect to a gated 4D reconstruction, up to 60% less noise and an increase of up to 124% of the SNR have been demonstrated.

Published
2013
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6. Normalisation to blood activity is required for the accurate quantification of Na/I symporter ectopic expression by SPECT/CT in individual subjects

Author

Jacques Darcourt, Fanny Graslin, Julien Guglielmi, Audrey Lamit, Sabine Lindenthal, Thierry Pourcher, Philippe Franken, Béatrice Cambien, Peggy Richard-Fiardo, Georges Vassaux, and Robert Marsault

Subjects
Pathology, medicine.medical_specialty, Pertechnetate, Colorectal cancer, Genetic enhancement, Science, Cancer Treatment, Context (language use), Real-Time Polymerase Chain Reaction, Adenoviridae, chemistry.chemical_compound, Mice, Model Organisms, Genes, Reporter, Biopsy, medicine, Animals, Humans, Longitudinal Studies, Biology, health care economics and organizations, Sodium Pertechnetate Tc 99m, Tomography, Emission-Computed, Single-Photon, Mice, Inbred BALB C, Multidisciplinary, medicine.diagnostic_test, Symporters, business.industry, Gene Transfer Techniques, Animal Models, medicine.disease, Immunohistochemistry, Kinetics, chemistry, Liver, Oncology, Symporter, RNA, Medicine, Ectopic expression, Radiopharmaceuticals, Nuclear Medicine, business, Radiology, HT29 Cells, Research Article
Abstract

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used (99m)Tc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy.

Published
2011

7. Single Photon Emission Computed Tomography

Author

Philippe Franken, Irène Buvat, and Jacques Darcourt and

Subjects
Physics, Tomographic reconstruction, Optics, medicine.diagnostic_test, business.industry, medicine, Single-photon emission computed tomography, business
Published
2010
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8. In vivo model of drug-induced valvular heart disease in rats: pergolide-induced valvular heart disease demonstrated with echocardiography and correlation with pathology

Author

Steven Droogmans, Vicky Caveliers, Bernard Cosyns, Philippe Franken, Danny Schoors, Tony Lahoutte, Caroline Weytjens, Guy Van Camp, Miriam Pipeleers-Marichal, Christian Garbar, Axel Bossuyt, Cardio-vascular diseases, Medical Imaging and Physical Sciences, and Pathological Anatomy

Subjects
serotonin 5-HT2B receptor, Male, medicine.medical_specialty, Pathology, Heart Valve Diseases, Regurgitation (circulation), Placebo, valve disease, Internal medicine, valvulopathy, medicine, Carcinoid Heart Disease, Animals, Rats, Wistar, Pergolide, Mitral regurgitation, business.industry, small animals, cardiac hypertrophy, valvular heart disease, Fibroblasts, medicine.disease, Rats, Disease Models, Animal, Echocardiography, Circulatory system, Dopamine Agonists, Cardiology, parkinsons disease, pathology, fenfluramine, Serotonin, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

The aim of this study was the comparison of the tumour uptake and the long-term retention of [I-123]-2-I-L-phenylalanine and [I-123]-2-I-D-phenylalanine with those of [I-123]-2-I-L-tyrosine and [I-123]-2-I-D-tyrosine in RIM rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in RIM tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting.[I-123]-2-iodo-L-phenylalanine, [I-123]-2-iodo-D-phenylalaine, [I-123] -2-I-L-tyrosine showed a considerable turnout uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L- and D-[I-123]-2-I-tyrosine were cleared for a large part from the tumours and the body. [I-123]-2-I-L-Phe and [I-123]-2-I-D-Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour-to-background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the RIM-bearing Wag/Rij rat model only [I-123]-2-1-L-phenylalanine and [I-123]-2-I-D-phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers.

Published
2007

9. Increased tumor uptake of 3-(123)I-Iodo-L-alpha-methyltyrosine after preloading with amino acids: an in vivo animal imaging study

Author

Tony Lahoutte, Vicky Caveliers, Philippe Franken, Axel Bossuyt, John Mertens, Hendrik Everaert, Nuclear Medicine, Medical Imaging and Physical Sciences, and Cyclotron

Subjects
Iodine Radioisotopes, Male, SPECT, Animals, Methyltyrosines, Neoplasms, Experimental, Amino Acids, Radiopharmaceuticals, Radionuclide Imaging, Technetium Tc 99m Aggregated Albumin, Rats
Abstract

3-(123)I-Iodo-L-alpha-methyltyrosine (3-IMT) is an amino acid analog used for tumor imaging. Specific accumulation is mediated mainly by the system L amino acid transport system. System L activity is known to increase when cells are loaded with amino acids. The aim of our study was to measure the effects of amino acid preload on (123)I-3-IMT tumor uptake and image contrast in a rat tumor model using in vivo dynamic imaging. METHODS: Rhabdomyosarcoma (R1M) tumor-bearing rats underwent 2 dynamic (123)I-3-IMT studies on separate days: 1 baseline study and 1 after intraperitoneal injection (0.25 mmol/kg) of a single amino acid (arginine, proline, glutamate, asparagine, tryptophan, or phenylalanine) administered 30 min before intravenous injection of 18.5 MBq (123)I-3-IMT. A (99m)Tc-labeled human serum albumin study was performed on each rat for the calculation of the blood-pool activity inside the tumor. Time-activity curves were generated for tumor, contralateral background region, kidney, heart, and total body.Tumor uptake was corrected for blood-pool and background activity. Image contrast was calculated as the ratio between tumor and background activity. The rate (K(1)) of tracer entering the tumor was obtained using Patlak analysis. A displacement study was performed on a separate group of rats, in which a high dose of phenylalanine was administered 40 min after (123)I-3-IMT injection. RESULTS: (123)I-3-IMT accumulation in tumor reached a plateau 10 min after injection. Tumor uptake on the baseline scans correlated well with tumor size (r = 0.92). After preloading, tumor uptake and contrast increased in all conditions: arginine, +26% and +26%; proline, +15% and +13%; glutamate, +14% and +9%; asparagine, +19% and +15%; tryptophan, +36% and 11%; phenylalanine, +22% and + 13%. K(1) values also increased. Administration of an afterload with phenylalanine induced a significant displacement of (123)I-3-IMT tumor accumulation. CONCLUSION: Prior amino acid administration increases (123)I-3-IMT tumor accumulation and image contrast. This effect can be explained by the increased antiporter activity of the amino acid transport system L in preloaded conditions. Our results indicate that the fasted state might not be the optimal metabolic condition to study tumor accumulation of L-transported tracers such as (123)I-3-IMT. Amino acid administration before (123)I-3-IMT injection could improve tumor uptake and image contrast.

Published
2002

10. 99mTcO4−-, Auger-Mediated Thyroid Stunning: Dosimetric Requirements and Associated Molecular Events

Author

Thierry Pourcher, Jacques Darcourt, Philippe Franken, Lydie Crescence, Audrey Lamit, Béatrice Cambien, Julien Guglielmi, Manuel Bardiès, Bernard Mari, Thibault Mauxion, Peggy Richard-Fiardo, and Georges Vassaux

Subjects
Programmed cell death, Pathology, medicine.medical_specialty, Multidisciplinary, Chemistry, Thyroid, Stunning, Context (language use), In vitro, medicine.anatomical_structure, In vivo, Absorbed dose, Symporter, Biophysics, medicine
Abstract

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4−) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4− required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4−–mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.

Published
2014
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11. Amylase, hemoglobine, and low molecular weight proteins

Author

Philippe Franken, Dany Brohée, Bernard Kennes, and Ludovic Rondelez

Subjects
Amylases -- metabolism -- urine, Hepatology, biology, Kidney Tubules -- metabolism, business.industry, Gastroenterology, Creatinine -- urine, Hemoglobinuria, Hemoglobinuria -- metabolism, Sciences bio-médicales et agricoles, Molecular Weight, Hemoglobins, Proteinuria, Text mining, Kidney Tubules, Biochemistry, Creatinine, Amylases, biology.protein, Medicine, Humans, Amylase, Proteinuria -- metabolism, business, Hemoglobins -- metabolism
Abstract

info:eu-repo/semantics/published

Published
1980

12. High-output right ventricular failure secondary to hepatic arteriovenous microfistulae. Selective arterial embolization treatment

Author

Brasseur P, Julien Struyven, Philippe Franken, Dany Brohée, Marc Fievez, Michel Baudoux, and Charles Henuzet

Subjects
medicine.medical_specialty, medicine.medical_treatment, Hypertension, Pulmonary, Hepatic Veins, Hepatic Artery, Ascites, Hypertension, Portal, Ascites -- etiology, Internal Medicine, medicine, Humans, Heart Failure -- etiology, Embolization, Telangiectasia, Heart Failure, business.industry, Arterial Embolization, Arteriovenous Fistula -- complications -- pathology -- therapy, Vascular lesion, Sciences bio-médicales et agricoles, Middle Aged, medicine.disease, Pulmonary hypertension, Embolization, Therapeutic, Surgery, medicine.anatomical_structure, Liver, Arteriovenous Fistula, Hypertension, Pulmonary -- etiology, Right ventricular failure, Female, medicine.symptom, business, Hypertension, Portal -- etiology, Liver -- pathology, Artery
Abstract

A patient with diffuse hepatic arteriovenous microfistulae suffered from secondary high-output right ventricular failure, pulmonary hypertension, and ascites, all of which could be managed by selective embolization of the hepatic artery. The vascular lesion of the liver seems to be essential, although hemorrhagic hereditary telangiectasia ,perhaps aggravated by administration of oral contraceptives, may be considered contributory factors in this case., info:eu-repo/semantics/published

Published
1984

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