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1. Vector-based active surfaces for segmentation of dynamic PET images

Author

Imagerie et cerveau ; INSERM - Université François Rabelais - Tours - CNRS, Service Hospitalier Frédéric Joliot (SHFJ) ; CEA, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) ; Université Paris-Sud - Paris 11 (UP11) - IN2P3 - Université Paris Diderot - Paris 7 (UP7) - CNRS, European Project : 278850, HEALTH, FP7-HEALTH-2011-two-stage, INMIND(2012), Jaouen, Vincent, Gonzalez, Paulo, Stute, Simon, GUILLOTEAU, Denis, Buvat, Irène, Tauber, Clovis, Imagerie et cerveau ; INSERM - Université François Rabelais - Tours - CNRS, Service Hospitalier Frédéric Joliot (SHFJ) ; CEA, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) ; Université Paris-Sud - Paris 11 (UP11) - IN2P3 - Université Paris Diderot - Paris 7 (UP7) - CNRS, European Project : 278850, HEALTH, FP7-HEALTH-2011-two-stage, INMIND(2012), Jaouen, Vincent, Gonzalez, Paulo, Stute, Simon, GUILLOTEAU, Denis, Buvat, Irène, and Tauber, Clovis

Abstract

International audience, Dynamic PET imaging enables the study of radiotracers concentration kinetics along time. However, PET images suffer from limited spatial resolution, low signal-to-noise ratio, and time dependent contrast between tissues, making segmentation of biological volumes difficult. Deformable models are of great interest due to their inherent boundary continuity, but their applications to PET images still remains challenging due to high sensitivity to noise. To address these limitations, we propose a method to perform 3-D+time dynamic PET image segmentation using parametric active surfaces based on a gradient of the vectorial image. This method takes advantage of both spatial and temporal consistency of the signal along the acquisition. We validate our method using GATE Monte Carlo simulations and compare it with single frame based active surface models. We show significant improvement of several figures of merit.

2. Comparison of different segmentation approaches without using gold standard. Application to the estimation of the left ventricle ejection fraction from cardiac cine MRI sequences.

Author

Laboratoire d'Imagerie Fonctionnelle (LIF) ; INSERM - IFR14 - IFR49 - Université Pierre et Marie Curie (UPMC) - Paris VI, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) ; CNRS - IN2P3 - Université Paris VII - Paris Diderot - Université Paris XI - Paris Sud, IMPACT ; Laboratoire Traitement du Signal et de l'Image (LTSI) ; INSERM - Université de Rennes 1 - INSERM - Université de Rennes 1 - CIC-IT Rennes ; INSERM - Hôpital Pontchaillou - INSERM - Hôpital Pontchaillou - Laboratoire Traitement du Signal et de l'Image (LTSI) ; INSERM - Université de Rennes 1 - INSERM, Centre de recherche en applications et traitement de l'image pour la santé (CREATIS) ; CNRS - INSERM - Hospices Civils de Lyon - Université Claude Bernard - Lyon I (UCBL) - Institut National des Sciences Appliquées [INSA], Laboratoire d'Informatique Gaspard-Monge (LIGM) ; CNRS - Université Paris-Est Marne-la-Vallée (UPEMLV) - École des Ponts ParisTech (ENPC) - Fédération de Recherche Bézout - ESIEE, Laboratoire Electronique, Informatique et Image (Le2i) ; CNRS - Arts et Métiers ParisTech - Université de Bourgogne, Image ; Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen (GREYC) ; CNRS - Université de Caen Basse-Normandie - Ecole Nationale Supérieure d'Ingénieurs de Caen - CNRS - Université de Caen Basse-Normandie - Ecole Nationale Supérieure d'Ingénieurs de Caen, Laboratoire des sciences et matériaux pour l'électronique et d'automatique (LASMEA) ; CNRS - Université Blaise Pascal - Clermont-Ferrand II, PRIAM ; ESME-Sudria, Image Science for Interventional Techniques (ISIT) ; CNRS - Université d'Auvergne - Clermont-Ferrand I - Clermont Université, The authors gratefully acknowledge the GdR2647 Stic-Santé for its support to the MedIEvalaction., Lebenberg, Jessica, Buvat, Irène, Garreau, Mireille, Casta, Christopher, Constantinidès, Constantin, Cousty, Jean, Cochet, Alexandre, Jehan-Besson, Stéphanie, Tilmant, Christophe, Lefort, Muriel, Roullot, Elodie, Najman, Laurent, Sarry, Laurent, Clarysse, Patrick, De Cesare, Alain, Lalande, Alain, Frouin, Frédérique, Laboratoire d'Imagerie Fonctionnelle (LIF) ; INSERM - IFR14 - IFR49 - Université Pierre et Marie Curie (UPMC) - Paris VI, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) ; CNRS - IN2P3 - Université Paris VII - Paris Diderot - Université Paris XI - Paris Sud, IMPACT ; Laboratoire Traitement du Signal et de l'Image (LTSI) ; INSERM - Université de Rennes 1 - INSERM - Université de Rennes 1 - CIC-IT Rennes ; INSERM - Hôpital Pontchaillou - INSERM - Hôpital Pontchaillou - Laboratoire Traitement du Signal et de l'Image (LTSI) ; INSERM - Université de Rennes 1 - INSERM, Centre de recherche en applications et traitement de l'image pour la santé (CREATIS) ; CNRS - INSERM - Hospices Civils de Lyon - Université Claude Bernard - Lyon I (UCBL) - Institut National des Sciences Appliquées [INSA], Laboratoire d'Informatique Gaspard-Monge (LIGM) ; CNRS - Université Paris-Est Marne-la-Vallée (UPEMLV) - École des Ponts ParisTech (ENPC) - Fédération de Recherche Bézout - ESIEE, Laboratoire Electronique, Informatique et Image (Le2i) ; CNRS - Arts et Métiers ParisTech - Université de Bourgogne, Image ; Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen (GREYC) ; CNRS - Université de Caen Basse-Normandie - Ecole Nationale Supérieure d'Ingénieurs de Caen - CNRS - Université de Caen Basse-Normandie - Ecole Nationale Supérieure d'Ingénieurs de Caen, Laboratoire des sciences et matériaux pour l'électronique et d'automatique (LASMEA) ; CNRS - Université Blaise Pascal - Clermont-Ferrand II, PRIAM ; ESME-Sudria, Image Science for Interventional Techniques (ISIT) ; CNRS - Université d'Auvergne - Clermont-Ferrand I - Clermont Université, The authors gratefully acknowledge the GdR2647 Stic-Santé for its support to the MedIEvalaction., Lebenberg, Jessica, Buvat, Irène, Garreau, Mireille, Casta, Christopher, Constantinidès, Constantin, Cousty, Jean, Cochet, Alexandre, Jehan-Besson, Stéphanie, Tilmant, Christophe, Lefort, Muriel, Roullot, Elodie, Najman, Laurent, Sarry, Laurent, Clarysse, Patrick, De Cesare, Alain, Lalande, Alain, and Frouin, Frédérique

Abstract

International audience, A statistical method is proposed to compare several estimates of a relevant clinical parameter when no gold standard is available. The method is illustrated by considering the left ventricle ejection fraction derived from cardiac magnetic resonance images and computed using seven approaches with different degrees of automation. The proposed method did not use any a priori regarding with the reliability of each method and its degree of automation. The results showed that the most accurate estimates of the ejection fraction were obtained using manual segmentations, followed by the semiautomatic methods, while the methods with the least user input yielded the least accurate ejection fraction estimates. These results were consistent with the expected performance of the estimation methods, suggesting that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available.

3. Electrophysiological brain mapping: Basics of recording evoked potentials induced by electrical stimulation and its physiological spreading in the human brain

Author

Hugues Duffau, Emmanuel Mandonnet, David Guiraud, François Bonnetblanc, Marion Vincent, Control of Artificial Movement and Intuitive Neuroprosthesis (CAMIN), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-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), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Control of Artificial Movement and Intuitive Neuroprosthesis ( CAMIN ), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier ( LIRMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Stimulation, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Brain mapping, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Humans, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Evoked Potentials, ComputingMilieux_MISCELLANEOUS, Brain Mapping, business.industry, Brain, Electroencephalography, Human brain, Electric Stimulation, Sensory Systems, Electrophysiology, 030104 developmental biology, medicine.anatomical_structure, Neurology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience

Published
2017

4. Neuronavigated Fiber Dissection with Pial Preservation: Laboratory Model to Simulate Opercular Approaches to Insular Tumors

Author

Juan Martino, Francesco Corrivetti, Hugues Duffau, Emmanuel Mandonnet, Sébastien Froelich, Schahrazed Bouazza, Damien Bresson, Silvio Sarubbo, Universidad de Cantabria, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Subpial dissection, medicine.medical_specialty, Neuronavigation, Insula, Uncinate fasciculus, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Dissection (medical), Insular cortex, Nerve Fibers, Myelinated, behavioral disciplines and activities, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Fasciculus, Humans, Medicine, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, Operculum (brain), Cerebral Cortex, biology, Brain Neoplasms, business.industry, Dissection, Anatomy, biology.organism_classification, medicine.disease, Fiber dissection, Surgery, medicine.anatomical_structure, nervous system, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030220 oncology & carcinogenesis, Pia Mater, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, psychological phenomena and processes, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

International audience; BACKGROUND:Advances in the oncologic and functional results of insular surgery have been reported recently. Such successes have been made possible by the advent of the transopercular approach under awake monitoring and by improved anatomic and functional knowledge of white matter pathways surrounding the insula. Nonetheless, given the rarity of insular tumors, it is difficult to get familiar with the complex 3-dimensional anatomy of the different neuronal and vascular structures encountered during a transopercular insular resection. We thus propose to develop a laboratory model allowing to train transopercular approaches of the insula.METHODS:Two hemispheres prepared with Klinger's technique were dissected under light microscope, preserving all pial membranes. The different steps of the dissection were video recorded.RESULTS:Preservation of pial membranes enabled us to simulate subpial resection, both during operculum removal and during insular cortex resection. The medial wall of the resection was defined by the inferior-fronto-occipital fasciculus, protecting from the lenticulostriate arteries.CONCLUSION:In this paper, we show that Klinger dissection with preservation of pial membranes provides a realistic model of insular surgery, allowing surgeons to learn and train on this highly specialized surgery.

Published
2017

5. Proposition de dépistage des gliomes diffus de bas grade dans la population de 20 à 40 ans

Author

Mandonnet, Emmanuel, Taillandier, Luc, Duffau, Hugues, Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)

Subjects
Adult, Incidental Findings, Young Adult, Brain Neoplasms, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Age Factors, Humans, Glioma, Prophylactic Surgical Procedures, Early Detection of Cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Diffuse low-grade gliomas (DLGG) are cerebral tumors occurring in young adults, with an inescapable progression to higher grade of malignancy, resulting in functional impairment and death. DLGG evolve in several phases: an asymptomatic period despite a slow radiological growth; a period in which inaugural symptoms occur, usually epilepsy with possible mild cognitive disorders; then a phase with malignant transformation generating disabling neurological deficits; and ultimately the terminal stage. Early maximal surgical resection significantly increases overall survival while preserving quality of life. Surgeries are conducted under local anesthesia in order to map neural networks crucial for brain functions, and with the goal to use neuroplasticity mechanisms by sparing cerebral connectivity. Adjuvant oncological treatments such as chemotherapy and/or radiotherapy are kept for partial resection or non-operable recurrences. Because of an increase of incidentally discovered DLGG, explained by a facilitated access to brain imaging, awake surgery has been proposed in asymptomatic patients, with the aim of maximizing the rate of total or even "supratotal" resection in smaller tumors. Outcomes have been optimized, both regarding oncological results thanks to minimization of malignant transformation, as well as regarding functional results, with neither neurological deficit nor epilepsy in this sub-group of incidental DLGG. Thus, it seems legitimate to set up a screening by cerebral MRI in the population from 20 to 40years, to propose adapted therapeutic strategies based upon an upfront radical surgery, and so to create the foundations of a prophylactic and personalized functional neuro-oncologie.

Published
2017

6. Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

Author

Claire Martin, Frédéric Pain, Suhan Senova, Stéphane Palfi, Antoine Chaillet, Chih-Chieh Chiang, Ilona Scisniak, Isabelle Doignon, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Warsaw (UW), National Tsing Hua University [Hsinchu] (NTHU), Intéractions cellulaires et physiopathologie hépathique (Orsay, Essonne) UMRS 1174 (ICPH ), Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), ANR-13-JS03-0006,SYNCHNEURO,Théorie de la commande pour la synchronisation neuronale: modélisation à partir de données l'optogénétique, et alteration boucle-fermée des oscillations cérébrales pathologiques(2013), Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris-Sud - Paris 11 ( UP11 ), PAIN, FREDERIC, Jeunes Chercheuses et Jeunes Chercheurs - Théorie de la commande pour la synchronisation neuronale: modélisation à partir de données l'optogénétique, et alteration boucle-fermée des oscillations cérébrales pathologiques - - SYNCHNEURO2013 - ANR-13-JS03-0006 - JC - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Hot Temperature, [SPI.OPTI] Engineering Sciences [physics]/Optics / Photonic, Light, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Irradiance, Biology, Optogenetics, Photostimulation, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Animals, Rats, Wistar, ComputingMilieux_MISCELLANEOUS, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Cerebral Cortex, Neurons, Multidisciplinary, High irradiance, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuromodulation (medicine), Electrophysiology, 030104 developmental biology, medicine.anatomical_structure, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Cerebral cortex, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, [ SPI.OPTI ] Engineering Sciences [physics]/Optics / Photonic, Erratum, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.

Published
2017
Full Text
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7. Miura transformations for discrete Painlevé equations coming from the affine E$_8$ Weyl group

Author

B. Grammaticos, A. Ramani, Ralph Willox, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Pure mathematics, Integrable system, [PHYS.MPHY]Physics [physics]/Mathematical Physics [math-ph], group theory, 01 natural sciences, symbols.namesake, affine Weyl groups, 02.30.Ik, 0103 physical sciences, Korteweg-de Vries equation, Canonical form, transforms, 0101 mathematics, Invariant (mathematics), 010306 general physics, Miura transformations, Mathematical Physics, Mathematics, Weyl group, 05.45.Yv, Nonlinear Sciences - Exactly Solvable and Integrable Systems, 010102 general mathematics, Statistical and Nonlinear Physics, Nonlinear Sciences::Exactly Solvable and Integrable Systems, symbols, [ PHYS.MPHY ] Physics [physics]/Mathematical Physics [math-ph], Affine transformation
Abstract

We derive integrable equations starting from autonomous mappings with a general form inspired by the additive systems associated to the affine Weyl group E$_8^{(1)}$. By deautonomisation we obtain two hitherto unknown systems, one of which turns out to be a linearisable one, and we show that both these systems arise from the deautonomisation of a non-QRT mapping. In order to unambiguously prove the integrability of these nonautonomous systems, we introduce a series of Miura transformations which allows us to prove that one of these systems is indeed a discrete Painlev\'e equation, related to the affine Weyl group E$_7^{(1)}$, and to cast it in canonical form. A similar sequence of Miura transformations allows us to effectively linearise the second system we obtain. An interesting off-shoot of our calculations is that the series of Miura transformations, when applied at the autonomous limit, allows one to transform a non-QRT invariant into a QRT one., Comment: 10 pages, no figures

Published
2017

8. Theoretical dosimetric evaluation of carbon and oxygen minibeam radiation therapy

Author

C. Peucelle, Wilfredo Gonzalez, Yolanda Prezado, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[PHYS]Physics [physics], Radiobiology, [ PHYS ] Physics [physics], Sobp, chemistry.chemical_element, Bragg peak, General Medicine, Molecular physics, Oxygen, Charged particle, Carbon, 030218 nuclear medicine & medical imaging, Ion, 03 medical and health sciences, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Oxygen enhancement ratio, Neutron, Protons, Radiometry, Monte Carlo Method
Abstract

International audience; PURPOSE:Charged particles have several advantages over x-ray radiations, both in terms of physics and radiobiology. The combination of these advantages with those of minibeam radiation therapy (MBRT) could help enhancing the therapeutic index for some cancers with poor prognosis. Among the different ions explored for therapy, carbon ions are considered to provide the optimum physical and biological characteristics. Oxygen could be advantageous due to a reduced oxygen enhancement ratio along with a still moderate biological entrance dose. The aforementioned reasons justified an in-depth evaluation of the dosimetric features of carbon and oxygen minibeam radiation therapy to establish the interest of further explorations of this avenue.MATERIALS AND METHODS:The GATE/Geant4 6.2 Monte Carlo simulation platform was employed to simulate arrays of rectangular carbon and oxygen minibeams (600 μm × 2 cm) at a water phantom entrance. They were assumed to be generated by means of a magnetic focusing. The irradiations were performed with a 2-cm-long spread-out Bragg peak (SOBP) centered at 7-cm-depth. Several center-to-center (c-t-c) distances were considered. Peak and valley doses, as well as peak-to-valley dose ratio (PVDR) and the relative contribution of nuclear fragments and electromagnetic processes were assessed. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions.RESULTS:Carbon and oxygen MBRT lead to very similar dose distributions. No significant advantage of oxygen over carbon ions was observed from physical point of view. Favorable dosimetric features were observed for both ions. Thanks to the reduced lateral scattering, the standard shape of the depth dose curves (in the peaks) is maintained even for submillimetric beam sizes. When a narrow c-t-c is considered (910-980 μm), a (quasi) homogenization of the dose can be obtained at the target, while a spatial fractionation of the dose is maintained in the proximal normal tissues with low PVDR. In contrast when a larger c-t-c is used (3500 μm) extremely high PVDR (≥ 50) are obtained in normal tissues, corresponding to very low valley doses. This suggests that carbon and oxygen MBRT might lead to a significant reduction of normal tissue complication probability. The main participant to the valley doses are secondary nuclear products at all depths. Among them the highest yield in normal tissues corresponds to the lightest fragments, neutrons and protons. Heavier fragments are dominant in the valleys only at the target position, which might favor tumor control.CONCLUSIONS:The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of carbon and oxygen ions for the treatment of radioresistant tumors, while preserving normal tissues. Only biological experiments could confirm the shifting of the normal tissue complication probability curves. The authors' results support the further exploration of this avenue.

Published
2017

9. Nanoprobe Synthesized by Magnetotactic Bacteria, Detecting Fluorescence Variations under Dissociation of Rhodamine B from Magnetosomes following Temperature, pH Changes, or the Application of Radiation

Author

Edouard Alphandéry, Alain Trautmann, Darine Abi Haidar, Florence Gazeau, Nadège Bercovici, François Guyot, Maxime Thoreau, Olivier Seksek, Imène Chebbi, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Nanobactérie SARL, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Institut de minéralogie, de physique des matériaux et de cosmochimie ( IMPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de recherche pour le développement [IRD] : UR206, Nanobacterie SARL, Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Materials science, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Magnetotactic bacteria, Magnetosome, Analytical chemistry, Nanoprobe, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, magnetosomes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, Rhodamine B, General Materials Science, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, magnetic hyperthermia, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, magnetotactic bacteria, 021001 nanoscience & nanotechnology, alternating magnetic field, Fluorescence, Photobleaching, nanomedicine, thermometer, 0104 chemical sciences, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Magnetic hyperthermia, chemistry, fluorescent probe, Biophysics, [SDV.IB]Life Sciences [q-bio]/Bioengineering, fluorescence, 0210 nano-technology
Abstract

International audience; We report a method of fabrication of fluorescent magnetosomes, designated as MCR400, in which 400 μM of rhodamine B are introduced in the growth medium of AMB-1 magnetotactic bacteria and fluorescent magnetosomes are then extracted from these bacteria. These fluorescent magnetosomes behave differently from most fluorescent nanoprobes, which often lead to fluorescence losses over time due to photobleaching. Indeed, when MCR400 are heated to 30–90 °C, brought to an acidic pH, or exposed to radiations, we observed that their fluorescence intensity increased. We attributed this behavior to the dissociation of rhodamine B from the magnetosomes. Interestingly, enhanced fluorescence was also observed in vitro when MCR400 were mixed with either primary macrophages or tumor cells (TC1-GFP or RG2-Cells) or in vivo when MCR400 were introduced in rat glioblastoma. We showed that MCR400 internalize in tumor and immune cells (macrophages) leading to enhanced fluorescence, suggesting that fluorescent magnetosomes could be used during cancer treatments such as magnetic hyperthermia to image cells of interest such as immune or tumor cells.

Published
2017

10. Setting the Balance between the Lexical and Sublexical Pathways of Dual-Route Models of Reading: Insight from Atypical Dyslexia in Surgical Glioma Patients

Author

Hugues Duffau, Emmanuel Mandonnet, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)

Subjects
Opinion, Computer science, media_common.quotation_subject, Speech recognition, connectionist dual-process, computer.software_genre, 050105 experimental psychology, surgery, 03 medical and health sciences, 0302 clinical medicine, Connectionism, reading, Reading (process), glioma, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Psychology, 0501 psychology and cognitive sciences, dual-route cascade, General Psychology, ComputingMilieux_MISCELLANEOUS, media_common, Computational model, Parsing, business.industry, 05 social sciences, fMRI, Dyslexia, Phonology, DUAL (cognitive architecture), medicine.disease, Pseudoword, computational models, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Natural language processing, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Reading is a complex skill that has been acquired only recently in the evolution of humans. This fascinating ability has motivated many neuropsychological models. In particular, it has been proposed that reading is sustained by two parallel and complementary systems (see for example Epelbaum et al., 2008 for a plausible anatomical implementation of this model): a lexico-semantic one and a phonological one (that further requires attentional resources for processing serially the different syllables of a given word). In parallel to advances in neuropsychological models of reading, computational models have been intensively studied. Such models attempt to go further than the usual “boxology”, by providing a simulation on a computer of the different cognitive processes that are involved in reading. One of the very first version in 1989 (Seidenberg and McClelland, 1989) was a connectionist approach, known as the “triangle model”, that already implemented the two routes (a semantic one and a phonological one). Since then, two categories have been competing in order to achieve the best fit between simulations and human datas in healthy and brain-damaged individuals: the dual-route cascade (DRC) (Coltheart et al., 2001) and the connectionist dual-process (CDP) (Zorzi et al., 1998) and its updated versions CDP+ (Perry et al., 2007), CDP++ (Perry et al., 2010), and CDP++-parser (Perry et al., 2013). Both kind of models share the same architecture regarding the lexical route, while differing in the sublexical route. In both cases, the balance between the lexical and sub-lexical route is a critical issue: whenever the lexical route is too strong, pseudowords will be read as a lexical neighbor, and whenever the sub-lexical route is too strong, error rates rise for irregular words (which are regularized by the sublexical route). As clearly explained in the paragraph “Searching parameter space” of Coltheart et al. (2001), the optimal balance is found in the DRC model by trial and error, testing the ability of the system to read a specific pair of irregular word and pseudoword (respectively “chef” and “starn”). Similarly, it is stated in Perry et al. (2007): “The first step was to determine the appropriate balance between lexical and sublexical phonology, which in turn largely depends on the speed at which the serial process of grapheme parsing occurs. These parameters need to be chosen together, because slower grapheme parsing speeds reduce the amount of sublexical phonology in the model, and faster speeds increase it. Performance on irregular words provides a particularly important benchmark for parameter setting.” Importantly, in both models, there is no explicit computational system that resets the balance between the two routes depending on the characteristics of each trial (regular, irregular, and pseudowords).

Published
2016

11. Optimization of the mechanical collimation for minibeam generation in proton minibeam radiation therapy

Author

C. Peucelle, Consuelo Guardiola, Yolanda Prezado, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
medicine.medical_specialty, Materials science, Proton, Collimated light, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, Optics, law, medicine, Proton Therapy, Neutron, Medical physics, Irradiation, Radiometry, Proton therapy, Mechanical Phenomena, [PHYS]Physics [physics], Range (particle radiation), [ PHYS ] Physics [physics], business.industry, Collimator, General Medicine, Full width at half maximum, 030220 oncology & carcinogenesis, business, Monte Carlo Method
Abstract

International audience; PURPOSE:The dose tolerances of normal tissues continue to be the main barrier in radiation therapy. To lower it, a novel concept based on a combination of proton therapy and the use of arrays of parallel and thin beams has been recently proposed: proton minibeam radiation therapy (pMBRT). It allies the inherent advantages of protons with the remarkable normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. Due to multiple Coulomb scattering, the tumor receives a homogeneous dose distribution, while normal tissues in the beam path benefit from the spatial fractionation of the dose. This promising technique has already been implemented at a clinical center (Proton therapy Center of Orsay) by means of a first prototype of a multislit collimator. The main goal of this work was to optimize the minibeam generation by means of a mechanical collimation.METHODS:Monte Carlo simulations (GATE V7.1) were used to evaluate the influence of the collimator material (brass, nickel, iron, tungsten), thickness, phantom-to-collimator distance (PCD), among other parameters, on the dose distributions. Maximization of the peak-to-valley dose ratios (PVDR) in normal tissues along with minimization of full width at half maximum, penumbras and neutron contamination were used as figures of merit. As a starting point for the optimization, the collimator employed in our previous works was used. It consisted in 400 μm × 2 cm slits with a center-to-center distance (c-t-c) of 3200 μm. As the main targets of pMBRT will be neurological cases, 100 MeV energy proton minibeams were considered. This energy range would allow treating tumors located at the center of the brain (the worst scenario).RESULTS:Tungsten and brass are the most advantageous materials among those considered. A tungsten collimator provides the highest PVDR and lowest penumbra. Although the neutron yield generated in the tungsten collimator is 3 times higher than that of the other materials, the biologic neutron doses at the patient position amount to less than 0.05% and 0.7% of the peak and valley doses, respectively. In addition, shorter PCD than the one currently used (7 cm) leads to thinner beams (enhancing the dose-volume effects), accompanied, however, by an increase of neutron dose at the phantom surface. Finally, no gain in dose distributions is obtained by using nonparallel slits.CONCLUSIONS:The collimator design and irradiation configuration have been optimized to minimize the angular spread, deliver the highest PVDR and the lowest valley possible in the normal tissues in pMBRT. We have also confirmed that even though the neutron yield generated in the multislit collimator is higher with respect to the one produced by the collimators used in conventional proton therapy, the increase of biological neutron dose in the patient will remain low (less than 1%).

Published
2016

12. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

Author

Johan, Pallud, Etienne, Audureau, Georges, Noel, Robert, Corns, Emmanuèle, Lechapt-Zalcman, Julien, Duntze, Vladislav, Pavlov, Jacques, Guyotat, Phong Dam, Hieu, Pierre-Jean, Le Reste, Thierry, Faillot, Claude-Fabien, Litre, Nicolas, Desse, Antoine, Petit, Evelyne, Emery, Jimmy, Voirin, Johann, Peltier, François, Caire, Jean-Rodolphe, Vignes, Jean-Luc, Barat, Olivier, Langlois, Edouard, Dezamis, Eduardo, Parraga, Marc, Zanello, Edmond, Nader, Michel, Lefranc, Luc, Bauchet, Bertrand, Devaux, Philippe, Menei, Philippe, Metellus, Anne, Vital, Centre Hospitalier Sainte-Anne, Université Paris Descartes - Paris 5 ( UPD5 ), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Universitaire de Caen, CHU Caen, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), CHU Pontchaillou [Rennes], Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurochirurgie, CHU Caen-Caen University Hospital, CHU Amiens-Picardie-Hôpital Nord - Amiens, Laboratoire de Neurochirurgie, Centre hospitalier Sainte-Anne (Paris), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), 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 ), CHU Angers, Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Leeds General Infirmary (LGI), Leeds Teaching Hospitals NHS Trust, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital pasteur [Colmar], CHU Strasbourg, CHU Amiens-Picardie, Service de Neurochirurgie [CHU Limoges], CHU Limoges, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Privé Clairval [Marseille], Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], 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), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Réseau d'Etude des Gliomes, REG, Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Università degli studi di Napoli Federico II, CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Neurochirurgie [CHU Angers], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Biomimétiques, and Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Survival, [SDV]Life Sciences [q-bio], Clinical Investigations, Kaplan-Meier Estimate, Disease-Free Survival, Cohort Studies, Young Adult, medicine, Humans, Progression-free survival, Young adult, Antineoplastic Agents, Alkylating, Aged, Aged, 80 and over, Carmustine, [ SDV ] Life Sciences [q-bio], Brain Neoplasms, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, carmustine wafers, Chemoradiotherapy, Middle Aged, 3. Good health, Surgery, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, Cohort, Propensity score matching, Female, Neurology (clinical), business, Glioblastoma, medicine.drug, Cohort study
Abstract

CERVOXY COLL; International audience; BACKGROUND: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. METHODS: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. RESULTS: The median progression-free survival was 12.0 months (95% CI: 10.7-12.6) in the implantation group and 10.0 months (9.0-10.0) in the standard group and the median overall survival was 20.4 months (19.0-22.7) and 18.0 months (17.0-19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63-0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60-0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80-1.13], P = .574; HR, 1.06 [0.87-1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44-0.76], P \textless .0001; HR, 0.54 [0.41-0.70], P \textless .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40-0.78], P \textless .0001; HR, 0.46 [95% CI: 0.33-0.64], P \textless .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. CONCLUSIONS: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit

Published
2015

13. In vivo quantification of localized neuronal activation and inhibition in the rat brain using a dedicated high temporal-resolution β + -sensitive microprobe

Author

Frédéric Pain, Françoise Vaufrey, Philippe Hantraye, Laurent Pinot, Laurent Besret, Marie-Claude Grégoire, Lydie Ploux, Gilles Bloch, Roland Mastrippolito, Philippe Laniece, Philippe Gervais, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ura 2210, Centre National de la Recherche Scientifique (CNRS), ura2210, Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, UMR 9199, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris-Sud - Paris 11 ( UP11 ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Procédés Alimentaires et Microbiologiques ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), 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 Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Microdialysis, Fluorescence-lifetime imaging microscopy, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Biology, Somatosensory system, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Fluorodeoxyglucose F18, In vivo, medicine, Animals, Radiometry, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Cerebral Cortex, Neurons, Multidisciplinary, medicine.diagnostic_test, Brain, Magnetic resonance imaging, Somatosensory Cortex, Rat brain, Corpus Striatum, Malonates, Rats, Succinate Dehydrogenase, medicine.anatomical_structure, Cerebral cortex, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Physical Sciences, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, [ SPI.OPTI ] Engineering Sciences [physics]/Optics / Photonic, Energy Metabolism, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Understanding brain disorders, the neural processes implicated in cognitive functions and their alterations in neurodegenerative pa-thologies, or testing new therapies for these diseases would benefit greatly from combined use of an increasing number of rodent models and neuroimaging methods specifically adapted to the rodent brain. Besides magnetic resonance (MR) imaging and functional MR, positron-emission tomography (PET) remains a unique methodology to study in vivo brain processes. However, current high spatial-resolution tomographs suffer from several technical limitations such as high cost, low sensitivity, and the need of restraining the animal during image acquisition. We have developed a-sensitive high temporal-resolution system that overcomes these problems and allows the in vivo quantification of cerebral biochemical processes in rodents. This-MICROPROBE is an in situ technique involving the insertion of a fine probe into brain tissue in a way very similar to that used for microdialysis and cell electrode recordings. In this respect, it provides information on molecular interactions and pathways, which is complementary to that produced by these technologies as well as other modalities such as MR or fluorescence imaging. This study describes two experiments that provide a proof of concept to substantiate the potential of this technique and demonstrate the feasibility of quantifying brain activation or metabolic depression in individual living rats with 2-[ 18 F]fluoro-2-deoxy-D-glucose and standard compartmental modeling techniques. Furthermore, it was possible to identify correctly the origin of variations in glucose consumption at the hexokinase level, which demonstrate the strength of the method and its adequacy for in vivo quantitative metabolic studies in small animals. A lterations in local cerebral metabolic rate of glucose (lCMR-glc) have been reported in several human brain conditions such as psychiatric disorders or neurodegenerative diseases. Understanding the cellular mechanisms involved in these diseases and the development of new therapeutic strategies will advance more rapidly through the use of animal models. The quantitation of metabolic rates in the rodent brain was achieved initially by using the 2-deoxy-D-[ 14 C]glucose autoradiographic method (1). Although efficient, this technique requires the sacrifice of several animals to obtain each time point and thus can provide only ex vivo, averaged kinetic constants calculated from values obtained from various animals. As an alternative, positron-emission tomography (PET), an imaging technology designed to use compounds labeled with positron-emitting radioisotopes to image and measure biochemical processes in vivo, has been adapted to use in small animals. The implementation of several high spatial-resolution PET scanners within the last several years (2–9) has enabled the adaptation of the 2-deoxy-D-[ 14 C]glucose method to in vivo imaging of small animals by using 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) as a tracer. However , such PET scanners require high counting statistics for image reconstruction that strongly reduce the possibility of performing high temporal-resolution measurements. PET cannot provide direct chemical analysis of reaction products in tissue and in many instances uses labeled compounds such as FDG to trace a reduced number of steps in a biochemical process such that kinetic analysis can be used to estimate the reaction rates. Such applications require high temporal-resolution PET measurements of tissue radioactivity over time and the time course of the radiolabeled tracer concentration in plasma. These data then can be analyzed in a compartmental model describing the transport and biochemical reactions that the radiotracer undergoes to yield a quantitative estimate of the local biochemical process. If for phar-macokinetic experiments using a single tracer injection a coarse temporal resolution is acceptable at the end of the experiment, the use of complex modeling approaches involving multiple-injection protocols requires a high temporal sampling of regional brain kinetics (sampling rate 30 s) that is not readily compatible with the performance of current small-animal PET scanners, especially at the end of the experiment when radioactive signals become low because of radioisotope decay and biological washout. The development of a new generation of small-animal PET scanners and dedicated software should overcome part of this limitation, but both remain at present under progress (10). As a complementary approach to PET imaging, we developed a radiosensitive implant-able microprobe to record locally radioactive concentrations with a high temporal resolution (1 s) compatible with the use of compart-mental modeling. This-MICROPROBE is an in situ technique involving the insertion of a fine probe into the brain tissue in a way very similar to that currently used for microdialysis or cell electrode recordings. In the present study, we used two successive experimental approaches in which patterns of neuronal activation and mitochondrial energy impairment are involved to provide a proof of concept to substantiate the-MICROPROBE's potential and demonstrate that it can be used to determine accurately the kinetic rates for each individual animal and therefore estimate interindi-vidual variation by using a three-compartmentfour-rate constant model (1, 11, 12). First, local metabolic decreases observed after local mitochondrial blockade were investigated in individual rat striata after unilateral intrastriatal injection of the mitochondrial complex II inhibitor, malonate. Second, the ability of the probe to measure modest increases (5–10%) in somatosensory cortex metabolic rates in response to physiological sensory stimulation was evaluated in the well established whisker-stimulation model (13, 14). In addition, the present studies show that in comparison with small-animal PET imaging, the-MICROPROBE allows absolute quantitative studies of local cerebral kinetics and, by using com-partmental modeling approaches, the determination of kinetic rate constants for any radiolabeled positron-emitting probe. Further-Abbreviations: lCMRglc, local cerebral metabolic rate of glucose; PET, positron-emission tomography; FDG, 2-[ 18 F]fluoro-2-deoxy-D-glucose.

Published
2002

14. Monitoring tumour response during chemo-radiotherapy: a parametric method using FDG-PET/CT images in patients with oesophageal cancer

Author

Frédéric Di Fiore, Caroline Rousseau, Ahmed Benyoucef, Bernard Dubray, Sébastien Hapdey, Isabelle Gardin, Irène Buvat, Romain Modzelewski, Pierre Michel, Stéphane Bardet, Odré Palie, Marc-Etienne Meyer, Pierre Vera, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), service de radiothérapie et de physique médicale, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Istituto di Astrofisica Spaziale e Fisica cosmica - Roma (IASF-Roma), Istituto Nazionale di Astrofisica (INAF), Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), CRLCC Henri Becquerel, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Equipe Quantification en Imagerie Fonctionnelle ( QuantIF-LITIS ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ) -Université Le Havre Normandie ( ULH ), Normandie Université ( NU ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris-Sud - Paris 11 ( UP11 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Istituto di Astrofisica Spaziale e Fisica cosmica - Roma ( IASF-Roma ), Istituto Nazionale di Astrofisica ( INAF ), and Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR )

Subjects
Positron emission tomography, Multivariate analysis, [SDV]Life Sciences [q-bio], Physical examination, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Text mining, [ INFO.INFO-TI ] Computer Science [cs]/Image Processing, Biopsy, medicine, Radiology, Nuclear Medicine and imaging, Parametric imaging, Cardiac imaging, Original Research, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, business.industry, Oesophageal cancer, Cancer, medicine.disease, Chemo-radiotherapy, 3. Good health, Fluoro-deoxy-d-glucose, 030220 oncology & carcinogenesis, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], medicine.symptom, business, Nuclear medicine
Abstract

Background The objective of this study is to investigate the feasibility and the additional interest of a parametric imaging (PI) method to monitor the early tumour metabolic response in a prospective series of oesophageal cancer patients who underwent positron emission tomography with fluoro-2-deoxy-d-glucose (FDG-PET/CT) before and during curative-intent chemo-radiotherapy. Methods Fifty-seven patients with squamous cell carcinoma (SCC) of the oesophagus prospectively underwent FDG-PET/CT before chemo-radiotherapy (CRT) (PET1) and at 21 ± 3 days after the beginning of CRT (PET2). The outcome was assessed at 3 months and 1 year after the completion of CRT (clinical examination, CT scan or FDG-PET/CT, biopsy). For each patient, PET1 and PET2 were registered using CT images. The 2 PET image sets were subtracted, so the voxels with significant changes in FDG uptake were identified. A model-based analysis of this graph was used to identify the tumour voxels in which significant changes occurred between the two scans and yielded indices characterising these changes (green and red clusters). Quantitative parameters were compared with clinical outcome at 3 months and at 1 year. Results The baseline tumour FDG uptake decreased significantly at PET2 (p

Published
2014

15. Segmentation of dynamic PET images with kinetic spectral clustering

Author

Sandrine Mouysset, Jean-Marc Girault, Irène Buvat, Simon Stute, Hiba Zbib, Sylvie Chalon, Clovis Tauber, Joseph Noailles, Jamal Charara, Algorithmes Parallèles et Optimisation (IRIT-APO), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement of Physics & Electronics (Hadath, Lebanon), National Council for Scientific Research = Conseil national de la recherche scientifique du Liban [Lebanon] (CNRS-L), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), (OATAO), Open Archive Toulouse Archive Ouverte, Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'Energie Atomique et aux énergies alternatives - CEA (FRANCE), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université de Paris Diderot - Paris 7 (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), Centre Hospitalier Régional Universitaire de Tours - CHU Tours (FRANCE), Université de Tours (FRANCE), Université Paris-Sud 11 (FRANCE), Imagerie et Modélisation en Neurobiologie et Cancérologie - IMNC (Orsay, France), and Institut National Polytechnique de Toulouse - INPT (FRANCE)

Subjects
Fluorine Radioisotopes, Correlation clustering, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Clustering, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Segmentation, 0302 clinical medicine, Dynamic imaging, Spectral clustering, [INFO.INFO-DC] Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], Image Processing, Computer-Assisted, Animals, Radiology, Nuclear Medicine and imaging, Computer vision, Positron emission images, Cluster analysis, Image resolution, Mathematics, Radiological and Ultrasound Technology, business.industry, Segmentation-based object categorization, Phantoms, Imaging, Pattern recognition, Real image, Rats, Calcul parallèle, distribué et partagé, Kinetics, PET, ComputingMethodologies_PATTERNRECOGNITION, Pyrimidines, Positron-Emission Tomography, Pyrazoles, Artificial intelligence, [INFO.INFO-DC]Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], Laplacian matrix, business, Monte Carlo Method, 030217 neurology & neurosurgery, Algorithms
Abstract

Segmentationis often required for the analysis ofdynamicpositron emission tomography (PET)images. However, noise and low spatial resolution make it a difficult task and several supervised and unsupervised methods have been proposed in the literature to perform thesegmentationbased on semi-automaticclusteringof the time activity curves of voxels. In this paper we propose a new method based onspectralclusteringthat does not require any prior information on the shape of clusters in the space in which they are identified. In our approach, the p-dimensional data, where p is the number of time frames, is first mapped into a high dimensional space and thenclusteringis performed in a low-dimensional space of the Laplacian matrix. An estimation of the bounds for the scale parameter involved in thespectralclusteringis derived. The method is assessed usingdynamicbrainPETimagessimulated with GATE and results on realimagesare presented. We demonstrate the usefulness of the method and its superior performance over three otherclusteringmethods from the literature. The proposed approach appears as a promising pre-processing tool before parametric map calculation or ROI-based quantification tasks.

Published
2013

16. Optimized spectral clustering for segmentation of dynamic PET images

Author

Jean-Marc Girault, Sandrine Mouysset, Laurent Galineau, Clovis Tauber, Irène Buvat, Hiba Zbib, Simon Stute, Sylvie Chalon, Jamal Charara, Lebanese University [Beirut] (LU), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Algorithmes Parallèles et Optimisation (IRIT-APO), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Université Toulouse III - Paul Sabatier (UT3), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'Energie Atomique et aux énergies alternatives - CEA (FRANCE), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Lebanese University - LU (LEBANON), Université de Paris Diderot - Paris 7 (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), Centre Hospitalier Régional Universitaire de Tours - CHU Tours (FRANCE), Université de Tours (FRANCE), Université Paris-Sud 11 (FRANCE), Imagerie et Cerveau (Tours, France), and Imagerie et Modélisation en Neurobiologie et Cancérologie - IMNC (Orsay, France)

Subjects
Image segmentation, Positron emission tomography, Clustering algorithms, Computer science, business.industry, Segmentation-based object categorization, Probabilistic logic, Pattern recognition, Indexes, Spectral clustering, Weighting, Calcul parallèle, distribué et partagé, Manuals, Segmentation, Computer vision, Artificial intelligence, [INFO.INFO-DC]Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], business, Cluster analysis, Kinetic theory, Noise, Global optimization
Abstract

he quantification of dynamic PET images requires the definition of regions of interest. The manual delineation is a time consuming and unreproducible process due to the poor resolution of PET images. Approaches were proposed in the literature to classify the kinetic profiles of voxels, however, they are generally either sensitive to initial conditions or favor convex shaped clusters. Recently we have proposed a kinetic spectral clustering (KSC) method for segmentation of dynamic PET images that has the advantage of handling clusters with arbitrary shape in the space in which they are identified. However, its use for clinical applications is still hindered by the manual setting of several parameters. In this paper, we propose an extension of KSC to make it automatic (ASC). A new unsupervised clustering criterion is tailored and a global optimization by a probabilistic metaheuristic algorithm is used to select the scale parameter and the weighting factors involved in the method. We validate our approach with GATE Monte Carlo simulations. Results obtained with ASC compare closely with those obtained with optimal manual parameterization of KSC, and outperform those obtained with two other approaches from the literature.

Published
2013

17. Imagerie Compton en protonthérapie : de la simulation GATE à la reconstruction d'images

Author

Hilaire, E., Robert, Cédric, Lojacono, X., Lartizien, C., Buvat, I., Maxim, Voichita, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 4 - Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-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 ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), and 2 - Images et Modèles

Subjects
[ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

18. Compton imaging in proton beam therapy: from GATE simulations to image reconstruction

Author

Hilaire, E., Robert, Cédric, Lojacono, X., Lartizien, C., Buvat, I., Maxim, Voichita, 4 - Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-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 ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), 2 - Images et Modèles, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, ComputingMilieux_MISCELLANEOUS, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging
Abstract

International audience

Published
2013

19. Comparison of different segmentation approaches without using gold standard. Application to the estimation of the left ventricle ejection fraction from cardiac cine MRI sequences

Author

Patrick Clarysse, Jessica Lebenberg, Christopher Casta, Alain Lalande, Frédérique Frouin, Alexandre Cochet, Stéphanie Jehan-Besson, Alain De Cesare, Laurent Najman, Constantin Constantinides, Jean Cousty, Christophe Tilmant, Muriel Lefort, Irène Buvat, Elodie Roullot, Mireille Garreau, Laurent Sarry, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Gaspard-Monge (LIGM), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Equipe Image - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences et matériaux pour l'électronique et d'automatique (LASMEA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), PRIAM, ESME-Sudria, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), The authors gratefully acknowledge the GdR2647 Stic-Santé for its support to the MedIEvalaction., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris-Sud - Paris 11 ( UP11 ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 1 - Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales ( MOTIVATE ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-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 ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Laboratoire d'Informatique Gaspard-Monge ( LIGM ), Université Paris-Est Marne-la-Vallée ( UPEM ) -École des Ponts ParisTech ( ENPC ) -ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen ( GREYC ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des sciences et matériaux pour l'électronique et d'automatique ( LASMEA ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Image Science for Interventional Techniques ( ISIT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université-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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Senhadji, Lotfi, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Ventricular Function, Left, [ INFO.INFO-TS ] Computer Science [cs]/Signal and Image Processing, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, 02 engineering and technology, MESH: Regression Analysis, Ventricular Function, Left, Article, MESH: Ventricular Function, Left, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, 03 medical and health sciences, MESH : Heart, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, MESH : Magnetic Resonance Imaging, MESH : Regression Analysis, 0202 electrical engineering, electronic engineering, information engineering, Humans, Medicine, Segmentation, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Reliability (statistics), [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Ejection fraction, MESH: Humans, business.industry, MESH : Humans, Heart, Regression analysis, Pattern recognition, Image segmentation, Gold standard (test), Magnetic Resonance Imaging, MESH: Heart, medicine.anatomical_structure, Ventricle, Regression Analysis, A priori and a posteriori, 020201 artificial intelligence & image processing, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Artificial intelligence, business, Nuclear medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

International audience; A statistical method is proposed to compare several estimates of a relevant clinical parameter when no gold standard is available. The method is illustrated by considering the left ventricle ejection fraction derived from cardiac magnetic resonance images and computed using seven approaches with different degrees of automation. The proposed method did not use any a priori regarding with the reliability of each method and its degree of automation. The results showed that the most accurate estimates of the ejection fraction were obtained using manual segmentations, followed by the semiautomatic methods, while the methods with the least user input yielded the least accurate ejection fraction estimates. These results were consistent with the expected performance of the estimation methods, suggesting that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available.

Published
2011

20. Méthodologie Pour Comparer Différentes Méthodes D'extraction De Biomarqueurs Sans Méthode De Référence. Application À La Segmentation Du Ventricule Gauche En Irm Cardiaque Pour Estimer La Fraction D'éjection

Author

Frédérique Frouin, Mireille Garreau, Irène Buvat, Christopher Casta, Constantin Constantinidès, Jean Cousty, Alexandre Cochet, Stéphanie Jehan-Besson, Christophe Tilmant, Murielle Lefort, Laurent Najman, Laurent Sarry, Clarysse, P., Cesare, A., Lalande, A., Laboratoire d'imagerie fonctionnelle [CHU Pitié-Salpétriêre] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle de Recherche en Ingénierie Appliquée à la Médecine (PRIAM), ESME Sudria [Paris], Laboratoire d'Informatique Gaspard-Monge (LIGM), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Equipe Image - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal (IP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS), Plateforme Tropicale d'Expérimentation sur l'Animal (PTEA), Institut National de la Recherche Agronomique (INRA), Université Auvergne ERIM EA 3295, Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Communication Parlée et traitement du Signal (LCPTS ), Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene [Alger] (USTHB), Laboratoire d'imagerie fonctionnelle [Paris] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Gaspard-Monge (ligm), Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen (GREYC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS), Université des Sciences et de la Technologie Houari Boumediene [Alger] (USTHB), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Le Corre, Morgane, Laboratoire d'imagerie fonctionnelle [Paris] ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), 1 - Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales ( MOTIVATE ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pôle de Recherche en Ingénierie Appliquée à la Médecine ( PRIAM ), Laboratoire d'Informatique Gaspard-Monge ( LIGM ), Université Paris-Est Marne-la-Vallée ( UPEM ) -École des Ponts ParisTech ( ENPC ) -ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique ( CNRS ), Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen ( GREYC ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pascal ( IP ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Sigma CLERMONT ( Sigma CLERMONT ) -Centre National de la Recherche Scientifique ( CNRS ), Plateforme Tropicale d'Expérimentation sur l'Animal ( PTEA ), Institut National de la Recherche Agronomique ( INRA ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire de Communication Parlée et traitement du Signal ( LCPTS ), Université des Sciences et de la Technologie Houari Boumediene [Alger] ( USTHB ), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, Modélisation statistique, Segmentation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Evaluation non supervisée, IRM cardiaque, Fraction d’éjection, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

International audience; Une méthodologie est proposée pour comparer plusieurs méthodes d’estimation d’un paramètre d’intérêt clinique sans connaître de gold standard. Elle est appliquée à un problème de comparaison de la fraction d’éjection du ventricule gauche en IRM cardiaque obtenue par sept approches de segmentation différentes et appliquée à 30 examens issus de la base de données constituée pour le challenge Miccai 2009 de segmentation du ventricule gauche. La comparaison des méthodes montre une supériorité du tracé manuel, un bon comportement des méthodes de segmentation semi-automatiques et un plus mauvais comportement des méthodes plus largement automatisées. La méthodologie de comparaison proposée qui ne fait aucun a priori sur les méthodes retrouve ainsi l’ordre attendu. Cette approche méthodologique est donc pertinente et doit permettre une classification non supervisée de différentes méthodes d’estimation de biomarqueurs.

Published
2011

21. Comparison of bootstrap resampling methods for 3-D PET imaging

Author

Irène Buvat, J.-B Aubin, Carole Lartizien, Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), 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)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] ( ICJ ), École Centrale de Lyon ( ECL ), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 ( UCBL ), 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 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Computer science, Monte Carlo method, Probability density function, Method of moments (statistics), Poisson distribution, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Resampling, Statistics, Image Interpretation, Computer-Assisted, Humans, Electrical and Electronic Engineering, Bootstrapping (statistics), Parametric statistics, [STAT.AP]Statistics [stat]/Applications [stat.AP], Radiological and Ultrasound Technology, Noise measurement, business.industry, Estimation theory, [ STAT.AP ] Statistics [stat]/Applications [stat.AP], Nonparametric statistics, Statistical parameter, Reproducibility of Results, Pattern recognition, Signal Processing, Computer-Assisted, Image Enhancement, Computer Science Applications, Sample size determination, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Sample Size, symbols, Analysis of variance, Artificial intelligence, business, Software, Algorithms
Abstract

International audience; Two groups of bootstrap methods have been proposed to estimate the statistical properties of positron emission tomography (PET) images by generating multiple statistically equivalent data sets from few data samples. The first group generates resampled data based on a parametric approach assuming that data from which resampling is performed follows a Poisson distribution while the second group consists of nonparametric approaches. These methods either require a unique original sample or a series of statistically equivalent data that can be list-mode files or sinograms. Previous reports regarding these bootstrap approaches suggest different results. This work compares the accuracy of three of these bootstrap methods for 3-D PET imaging based on simulated data. Two methods are based on a unique file, namely a list-mode based nonparametric (LMNP) method and a sinogram based parametric (SP) method. The third method is a sinogram-based nonparametric (SNP) method. Another original method (extended LMNP) was also investigated, which is an extension of the LMNP methods based on deriving a resampled list-mode file by drawings events from multiple original list-mode files. Our comparison is based on the analysis of the statistical moments estimated on the repeated and resampled data. This includes the probability density function and the moments of order 1 and 2. Results show that the two methods based on multiple original data (SNP and extended LMNP) are the only methods that correctly estimate the statistical parameters. Performances of the LMNP and SP methods are variable. Simulated data used in this study were characterized by a high noise level. Differences among the tested strategies might be reduced with clinical data sets with lower noise.

Published
2010

23. The PRAE Multidisciplinary Project

Author

D. Marchand, C. Vallerand, R. Delorme, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de l'Accélérateur Linéaire (LAL), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS]Physics [physics], Nuclear and High Energy Physics, 010308 nuclear & particles physics, Particle accelerator, 7. Clean energy, 01 natural sciences, Linear particle accelerator, law.invention, law, Multidisciplinary approach, 0103 physical sciences, Systems engineering, Subatomic particle, Instrumentation (computer programming), 010306 general physics
Abstract

International audience; The Platform for Research and Applications with Electrons (PRAE) facility [1] under construction in the Orsay campus of the Paris-Sud University is a multidisciplinary platform based on a high-performance new generation linear accelerator delivering a pulsed electron beam in the energy range 30–70 MeV, upgradable to 140 MeV. This project originates from the complementary expertise of several local scientific research communities involved in radiobiology, subatomic physics, instrumentation, and particle accelerator technologies to perform multidisciplinary studies of significant impact.

Published
2019

24. First theoretical determination of relative biological effectiveness of very high energy electrons

Author

Camille Etoh, Yolanda Prezado, Rachel Delorme, Thongchai A. M. Masilela, François Smekens, Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Institut Curie [Paris]

Subjects
Photon, Science, Physics::Medical Physics, Biophysics, Linear energy transfer, chemistry.chemical_element, Radiation Therapy, General Physics and Astronomy, Electron, 7. Clean energy, Article, 030218 nuclear medicine & medical imaging, Ion, 03 medical and health sciences, Neon, microdosimetric kinetic model, 0302 clinical medicine, Relative biological effectiveness, Radiology, Nuclear Medicine and imaging, Physics, [PHYS]Physics [physics], Range (particle radiation), Multidisciplinary, Radiotherapy, Computational science, GATE, Very high-energy electrons, General Medicine, microdosimetry, chemistry, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Medicine, Atomic physics, Biological physics, Energy (signal processing)
Abstract

International audience; Purpose: Very high energy electrons (VHEEs) present promising clinical advantages over conventional beams. They are able to target deep-seated tumors due to their increased range and improved penumbra compared to low energy electrons. VHEEs are also relatively insensitive to tissue heterogeneities, and are able to be electromagnetically scanned. These advantages facilitate their use in conjunction with spatial fractionation techniques or FLASH irradiations. However, the lack of radiobiological data concerning their biological efficacy is a limiting factor. This study aims to characterize different VHEE beams against clinically available beams by making use of Monte Carlo (MC) based numerical simulations to compare their macroand microdosimetric properties.Methods: All simulations were performed on GATE version 8.2. A solid water phantom was irradiated by the following beams: 5, 20, 100, and 300 MeV electrons, a 60Co source (1.25 MeV photons), 105 MeV protons, 194.2 MeV/nucleon 12C ions, and 262 MeV/nucleon 20Ne ions. The dose-averaged linear energy transfer (¯(L_d )) was evaluated as the macrodosimetric quantity of interest. On a microscopic scale, the lineal energy y was used in order to account for the stochasticity of irradiations. The dose-mean lineal energy ¯(y_d ) and the lineal energy distribution described as a function of its dose density, d(y), were calculated. A tissue equivalent proportional counter (TEPC) was implemented in GATE to record the lineal energy spectra. Finally, the modified microdosimetric kinetic model (MKM) was used to calculate the respective cell survival curves using biological parameters of HSG cell line and the lineal energy spectra as inputs.Results: From the macrodosimetric point of view, VHEEs present a potential improved biological efficacy over clinical photon/electron beams due to their increased ¯(L_d ). At a depth of 4 cm in water, the ratio of 300 MeV ¯(L_d ) values to other particles is 0.2, 1.9, 3.2, and 2.4 for protons, 100 MeV electrons, 20 MeV electrons, and photons respectively. The microdosimetric data, however, suggests no increased biological effectiveness of VHEEs over clinical electron beams, as seen in Figure 1 and Table 1. No significant differences were found between their lineal energy spectra nor their ¯(y_d ) depth profiles. Correspondingly, application of the MKM yielded similar cell survival curves, resulting in relative biological effectiveness (RBE10) values for VHEEs of approximately 1. Furthermore, RBE values of 1.2, 2.9 and 3.3 were obtained for proton, carbon-ion and neon-ion beams respectively, while ¯(L_d ) values above 200 keV/µm and lineal energies as high as 2000 keV/µm were obtained in the Bragg peak region for neon-ions.Conclusion: This study represents a first step towards a full evaluation of the biological efficacy of VHEE beams. The biologically relevant information obtained from these theoretical MC simulations could be used to complement further experiments which explore the radiobiological response to VHEE treatment.

Published
2021

25. Spatially Modulated Proton Minibeams Results in the Same Increase of Lifespan as a Uniform Target Dose Coverage in F98-Glioma-Bearing Rats

Author

Charlotte Lamirault, Marine Le Dudal, Delphine Crépin, Laurène Jourdain, Ludovic De Marzi, Elise Brisebard, Annalisa Patriarca, Grégory Jouvion, Rémi Dendale, Catherine Sebrié, Yolanda Prezado, Frederic Pouzoulet, David Hardy, Marjorie Juchaux, Dalila Labiod, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris]-Université Paris Cité (UPCité), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Protonthérapie d'Orsay, Université Paris-Sud - Paris 11 (UP11), Plateforme de Radiothérapie Expérimentale, Département de Recherche Translationnelle, Institut Curie [Paris]-Institut Curie [Paris], Université Paris-Saclay, Unité BioMaps (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité d'Embryologie, d'Histologie et d'Anatomie Pathologique, École nationale vétérinaire - Alfort (ENVA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Recombinaison, réparation et cancer: de la molécule au patient, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Université de Paris (UP), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), and LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS)

Subjects
Proton, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Biophysics, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, Glioma, Proton Therapy, Animals, Medicine, Radiology, Nuclear Medicine and imaging, Irradiation, Proton therapy, Radiation, Brain Neoplasms, business.industry, Radiotherapy Dosage, medicine.disease, Magnetic Resonance Imaging, Xenograft Model Antitumor Assays, Rats, 3. Good health, Target dose, Radiation therapy, 030220 oncology & carcinogenesis, Toxicity, Nuclear medicine, business
Abstract

International audience; Proton minibeam radiation therapy (pMBRT) is a new approach in proton radiotherapy, by which a significant increase in the therapeutic index has already been demonstrated in RG2 glioma-bearing rats. In the current study we investigated the response of other types of glioma (F98) and performed a comparative evaluation of tumor control effectiveness by pMBRT (with different levels of dose heterogeneity) versus conventional protons. The results of our study showed an equivalent increase in the lifespan for all evaluated groups (conventional proton irradiation and pMBRT) and no significant differences in the histopathological analysis of the tumors or remaining brain tissue. The reduced long-term toxicity observed with pMBRT in previous evaluations at the same dose suggests a possible use of pMBRT to treat glioma with less side effects while ensuring the same tumor control achieved with standard proton therapy.

Published
2020

26. JRJC 2019. Book of Proceedings

Author

Celine Armand, Halim Ashkar, Bowen Bai, Ophelie Bugnon, Reina Camacho Toro, Robin Albert Andre Caron, Etienne Chardonnet, David Cohen, Coelho, João A. B., Nicolas Dray, Jean-Grégoire Ducoin, Guillaume Falmagne, Aishik Ghosh, Andreas Goudelis, Diego Gruyer, Romain Gaior, Maxime Guilbaud, Chun-Lu Huang, Victor Hui, Anastasia Kotsokechagia, Loïc Labit, Adrien Laviron, Ariel Matalon, Ali Mjallal, Giorgos Papadopoulos, Letizia Parato, Carole Perigois, Lorenzo Périssé, Lennart Rustige, Sabrina Sacerdoti, Konstantin Shchablo, Julianna Stermer, Taibah, Reem Hani M., Guillaume Taillepied, Lucas Torterotot, Antonio Uras, Laura Zambelli, Pauline Ascher, Aoife Bharucha, François Brun, Nicolas Chanon, Emmanuel Chauveau, Rachel Delorme, Julien Masbou, Laure Massacrier, Dimitris Varouchas, Isabelle Cossin, Raphael Hulsken, Luis Pascual Dominguez, Mouchard, Q., Chloé Fougéres, Armel Kamenyero, Joel Quincray, Nishu Goyal, Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), CEA - Commissariat à l'Energie Atomique, Saclay, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique subatomique et des technologies associées (SUBATECH), 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 National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE (UMR_7585)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Commissariat à l'Energie Atomique, Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire de Physique Théorique (LPT), 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), Laboratoire Leprince-Ringuet (LLR), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de Physique de Clermont (LPC), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy-le-Vieux de Physique Théorique (LAPTH), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), CPT - E1 Physique des particules, Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Grand Accélérateur National d'Ions Lourds (GANIL), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Nantes - Faculté des Sciences et des Techniques, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), 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 de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)

Subjects
[PHYS.HTHE]Physics [physics]/High Energy Physics - Theory [hep-th], [PHYS.HPHE]Physics [physics]/High Energy Physics - Phenomenology [hep-ph], [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

27. A Fluorescent Nanoprobe to Detect Local Temperature Changes During Antitumoral Hyperthermia Therapy

Author

Cynthia El Hedjaj, Edouard Alphandéry, Imène Chebbi, Olivier Seksek, Nanobactérie SARL, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), and Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, medicine.medical_treatment, 010401 analytical chemistry, Biophysics, Nanoprobe, 010402 general chemistry, 01 natural sciences, Fluorescence, Hyperthermia therapy, 0104 chemical sciences, 3. Good health, Cancer research, medicine, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

28. Synchrotron-Based Infrared Microscopy Studies of the Radiosensitization Effects of Nanoparticles used in Radiotherapy

Author

Olivier Seksek, I. Martínez-Rovira, Ibraheem Yousef, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), and Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Materials science, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biophysics, Nanoparticle, Nanotechnology, Synchrotron, 3. Good health, law.invention, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Infrared microscopy, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2020

29. Modelling In Vitro Aggregation of Cancer Cells

Author

Christophe Deroulers, Marjorie Juchaux, Olivier Seksek, Léo Adenis, Mathilde Badoual, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, 03 medical and health sciences, Chemistry, [SDV]Life Sciences [q-bio], Cancer cell, Biophysics, Cancer research, 02 engineering and technology, 021001 nanoscience & nanotechnology, 0210 nano-technology, In vitro, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2020

30. WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial

Author

Felice Giangaspero, Chris Jones, Christophe Deroulers, Dominique Figarella-Branger, Marie-Cécile Le Deley, Thomas S. Jacques, Gwénaël Le Teuff, Tim Jaspan, Torsten Pietsch, J. Grill, Pascale Varlet, Felipe Andreiuolo, Christine Haberler, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], Datasets as Topic, MESH: Neoplasm Grading, Central Pathology Review, MESH: World Health Organization, MESH: Glioma, 0302 clinical medicine, MESH: Child, Multicenter Studies as Topic, MESH: Datasets as Topic, Child, Randomized Controlled Trials as Topic, MESH: Chemoradiotherapy, [PHYS]Physics [physics], biology, Brain Neoplasms, Chemoradiotherapy, Glioma, Prognosis, 3. Good health, Bevacizumab, Glioma grading, Child, Preschool, 030220 oncology & carcinogenesis, Ki-67, MESH: Brain Neoplasms, Female, MESH: Clinical Trials, Phase II as Topic, high-grade glioma, medicine.medical_specialty, Adolescent, Antineoplastic Agents, World Health Organization, World health, MESH: Prognosis, 03 medical and health sciences, Clinical Trials, Phase II as Topic, MESH: Bevacizumab, Internal medicine, grading criteria, pediatric, Temozolomide, medicine, Humans, Grading (tumors), MESH: Temozolomide, High-Grade Glioma, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Who grade, medicine.disease, MESH: Male, MESH: Randomized Controlled Trials as Topic, biology.protein, MESH: Multicenter Studies as Topic, MESH: Antineoplastic Agents, Neurology (clinical), Neoplasm Grading, business, Pediatric Neuro-Oncology, MESH: Female, 030217 neurology & neurosurgery
Abstract

Background The World Health Organization (WHO) adult glioma grading system is questionable in pediatric high-grade gliomas (pHGGs), which are biologically distinct from adult HGGs. We took advantage of the neuropathological review data obtained during one of the largest prospective randomized pHGG trials, namely HERBY (NCT01390948), to address this issue in children with newly diagnosed non-brainstem HGG. Methods HGG diagnosis was confirmed by pre-randomization, real-time central pathology review using WHO 2007 criteria, followed by a consensus review blinded to clinical factors and outcomes. We evaluated association between WHO 2007 grade and other clinical/radiological/biological characteristics and the prognostic value of WHO 2007 grade, midline location, and selected biomarkers (Ki-67 index/Olig2/CD34/EGFR/p53/H3F3A K27M mutation) on overall survival. Results Real-time central neuropathological review was feasible in a multicenter study, with a mean time of 2.4 days, and led to the rejection of HGG diagnosis in 20 of 163 cases (12.3%). The different grading criteria and resulting WHO grade were not significantly associated with overall survival in the entire population (n = 118) or in midline and non-midline subgroups. H3F3A K27M mutation was significantly associated with poor outcome. No significant prognostic value was observed for grade, even after regrading H3F3A K27M-mutated midline glioma as grade IV (WHO 2016). Midline location and a high Ki-67 index (≥20%) were associated with poor outcome (P = 0.004 and P = 0.04, respectively). A 10% increase in Ki-67 index was associated with a hazard ratio of 1.53 (95% CI: 1.27–1.83; P < 0.0001). Conclusion Our findings suggest that WHO grade III versus IV has no prognostic value in pediatric HGG.

Published
2020

31. Minibeam radiation therapy: a micro- and nano-dosimetry Monte Carlo study

Author

M. Dos Santos, R. Delorme, R. Salmon, Yolanda Prezado, Laboratoire de radiobiologie des expositions accidentelles (LRAcc), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, Photon, Proton, Monte Carlo method, GEANT4 48 49, Electron, Minibeam Radiation Therapy, 7. Clean energy, Molecular physics, Imaging phantom, 030218 nuclear medicine & medical imaging, Monte Carlo simulations, 03 medical and health sciences, 0302 clinical medicine, Dosimetry, Nanotechnology, Irradiation, Radiometry, ComputingMilieux_MISCELLANEOUS, Range (particle radiation), Radiotherapy, General Medicine, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], DNA damage, Monte Carlo Method
Abstract

Purpose: Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro- and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. Methods: Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4-DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi-scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we consid- ered the treatmen t of a brain tumor located at a depth of 75 mm. Results: Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double- strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained con- stant, irrespective of the depth and region (peak or valley). Conclusions: Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. The se results can aid understanding of the biological mechanisms of MBRT.

Published
2020

32. Minibeam radiation therapy at a conventional irradiator: Dose-calculation engine and first tumor-bearing animals irradiation

Author

Yolanda Prezado, R. Delorme, M. Le Dudal, M. Dos Santos, Wilfredo Gonzalez, Marjorie Juchaux, Grégory Jouvion, Consuelo Guardiola, Charlotte Lamirault, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Institut Pasteur [Paris] (IP)

Subjects
Male, Dose calculation, medicine.medical_treatment, Normal Distribution, Biophysics, General Physics and Astronomy, Electrons, Kaplan-Meier Estimate, Dose distribution, Tumor response, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Treatment plan, Mean Survival Time, medicine, Animals, Radiology, Nuclear Medicine and imaging, Irradiation, Radiometry, Ions, [PHYS]Physics [physics], Brain Neoplasms, business.industry, Radiotherapy Planning, Computer-Assisted, Reproducibility of Results, Radiotherapy Dosage, Glioma, Neoplasms, Experimental, General Medicine, Rats, Inbred F344, Rats, Radiation therapy, Disease Models, Animal, Treatment Outcome, 030220 oncology & carcinogenesis, Tomography, Protons, Nuclear medicine, business, Monte Carlo Method, Synchrotrons
Abstract

International audience; PURPOSE:Minibeam radiation therapy (MBRT) is a novel therapeutic strategy, whose exploration was hindered due to its restriction to large synchrotrons. Our recent implementation of MBRT in a wide-spread small animal irradiator offers the possibility of performing systematic radiobiological studies. The aim of this research was to develop a set of dosimetric tools to reliably guide biological experiments in the irradiator.METHODS:A Monte Carlo (Geant4)-based dose calculation engine was developed. It was then benchmarked against a series of dosimetric measurements performed with gafchromic films. Two voxelized rat phantoms (ROBY, computer tomography) were used to evaluate the treatment plan of F98 tumor-bearing rats. The response of a group of 7 animals receiving a unilateral irradiation of 58 Gy was compared to a group of non-irradiated controls.RESULTS:The good agreement between calculations and the experimental data allowed the validation of the dose-calculation engine. The latter was first used to compare the dose distributions in computer tomography images of a rat's head and in a digital model of a rat's head (ROBY), obtaining a good general agreement. Finally, with respect to the in vivo experiment, the increase of mean survival time of the treated group with respect to the controls was modest but statistically significant.CONCLUSIONS:The developed dosimetric tools were used to reliably guide the first MBRT treatments of intracranial glioma-bearing rats outside synchrotrons. The significant tumor response obtained with respect to the non-irradiated controls, despite the heterogenous dose coverage of the target, might indicate the participation of non-targeted effects.

Published
2020

33. Verification of a Monte Carlo dose calculation engine in proton minibeam radiotherapy in a passive scattering beamline for preclinical trials

Author

Consuelo Guardiola, Yolanda Prezado, Ludovic De Marzi, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Curie, and Institut Curie [Paris]

Subjects
Male, Organs at Risk, Materials science, Film Dosimetry, Dose calculation, Proton, medicine.medical_treatment, Monte Carlo method, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Proton Therapy, Animals, Scattering, Radiation, Radiology, Nuclear Medicine and imaging, Proton therapy special feature: Full Paper, Radiation Injuries, Proton therapy, ComputingMilieux_MISCELLANEOUS, Therapeutic strategy, [PHYS]Physics [physics], business.industry, Scattering, Phantoms, Imaging, Radiotherapy Dosage, General Medicine, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Rats, Inbred F344, Rats, Radiation therapy, Benchmarking, Beamline, ACM: I.: Computing Methodologies/I.6: SIMULATION AND MODELING, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Radiation Dose Hypofractionation, Nuclear medicine, business, Monte Carlo Method
Abstract

Objectives: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that combines the benefits of proton therapy with the remarkable normal tissue preservation observed with the use of submillimetric spatially fractionated beams. This promising technique has been implemented at the Institut Curie-Proton therapy centre (ICPO) using a first prototype of a multislit collimator. The purpose of this work was to develop a Monte Carlo-based dose calculation engine to reliably guide preclinical studies at ICPO. Methods: The whole “Y1”-passive beamline at the ICPO, including pMBRT implementation, was modelled using the Monte Carlo GATE v. 7.0 code. A clinically relevant proton energy (100 MeV) was used as starting point. Minibeam generation by means of the brass collimator used in the first experiments was modelled. A virtual source was modelled at the exit of the beamline nozzle and outcomes were compared with dosimetric measurements performed with EBT3 gafchromic films and a diamond detector in water. Dose distributions were recorded in a water phantom and in rat CT images (7-week-old male Fischer rats). Results: The dose calculation engine was benchmarked against experimental data and was then used to assess dose distributions in CT images of a rat, resulting from different irradiation configurations used in several experiments. It reduced computational time by an order of magnitude. This allows us to speed up simulations for in vivo trials, where we obtained peak-to-valley dose ratios of 1.20 ± 0.05 and 6.1 ± 0.2 for proton minibeam irradiations targeting the tumour and crossing the rat head. Tumour eradication was observed in the 67 and 22% of the animals treated respectively. Conclusion: A Monte Carlo dose calculation engine for pMBRT implementation with mechanical collimation has been developed. This tool can be used to guide and interpret the results of in vivo trials. Advances in knowledge: This is the first Monte Carlo dose engine for pMBRT that is being used to guide preclinical trials in a clinical proton therapy centre.

Published
2020

34. On the singularity structure of the discrete KdV equation

Author

Basil Grammaticos, Ralph Willox, Doyong Um, Alfred Ramani, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Statistics and Probability, [PHYS]Physics [physics], Property (philosophy), Reduction (recursion theory), Quadrilateral, Nonlinear Sciences - Exactly Solvable and Integrable Systems, 010308 nuclear & particles physics, Mathematical analysis, Structure (category theory), General Physics and Astronomy, FOS: Physical sciences, Statistical and Nonlinear Physics, Mathematical Physics (math-ph), 16. Peace & justice, 01 natural sciences, Singularity, Modeling and Simulation, 0103 physical sciences, Order (group theory), Gravitational singularity, Exactly Solvable and Integrable Systems (nlin.SI), 010306 general physics, Korteweg–de Vries equation, Mathematical Physics, Mathematics
Abstract

The discrete KdV (dKdV) equation, the pinnacle of discrete integrability, is often thought to possess the singularity confinement property because it confines on an elementary quadrilateral. Here we investigate the singularity structure of the dKdV equation through reductions of the equation, obtained for initial conditions on a staircase with height 1, and show that it is much more subtle than one might assume. We first study the singularities for the mappings obtained after reduction and contrast these with the singularities that arise in non-integrable generalizations of those mappings. We then show that the so-called `express method' for obtaining dynamical degrees for second order mappings can be succesfully applied to all the higher order mappings we derived. Finally, we use the information obtained on the singularity structure of the reductions to describe an important subset of singularity patterns for the dKdV equation and we present an example of a non-confining pattern and explain why its existence does not contradict the integrability of the dKdV equation., Comment: 20 pages, 10 figures [revised version with 6 references added]

Published
2020

35. Study of the intracellular nanoparticle-based radiosensitization mechanisms in F98 glioma cells treated with charged particle therapy through synchrotron-based infrared microspectroscopy

Author

Olivier Seksek, I. Martínez-Rovira, Ivana Dokic, Amir Abdollahi, Ibraheem Yousef, Stephan Brons, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Heidelberg Ion Beam Therapy Center - HIT, and Heidelberg University Clinic

Subjects
Radiation-Sensitizing Agents, Silver, Light, Protein Conformation, DNA damage, Metal Nanoparticles, Gadolinium, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Analytical Chemistry, law.invention, chemistry.chemical_compound, Protein structure, law, Cell Line, Tumor, Nucleic Acids, Electrochemistry, medicine, Animals, Environmental Chemistry, Cell damage, ComputingMilieux_MISCELLANEOUS, Spectroscopy, [PHYS]Physics [physics], Principal Component Analysis, Chemistry, Proteins, 021001 nanoscience & nanotechnology, medicine.disease, Lipids, Synchrotron, Charged particle, Rats, 0104 chemical sciences, Microspectrophotometry, Nucleic acid, Biophysics, Nucleic Acid Conformation, 0210 nano-technology, Synchrotrons, Intracellular, DNA
Abstract

International audience; The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently,the use of NP has been extended to charged particle therapy in order to improve the performance inradioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved inNP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-basedFourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NPinduced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped withAuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon andoxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectralregions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellularmodifications were detected, such as conformational changes in secondary protein structures, intensityvariations in the lipid CHx stretching bands, as well as complex DNA rearrangements following chargedparticle therapy irradiations. These spectral features seem to be correlated with the already shownenhancement both in the DNA damage response and in the reactive oxygen species (ROS) production bythe NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational featureswere NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided newinsights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches.

Published
2020

36. Uptake and excretion dynamics of gold nanoparticles in cancer cells and fibroblasts

Author

Darine Abi Haidar, Sandrine Lacombe, Stéphane Roux, Vladimir Ivosev, Gloria Jiménez Sánchez, Xiaomin Yang, Lenka Štefančíková, César R González Vargas, Erika Porcel, Rana Bazzi, Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), European Project: 608163,EC:FP7:PEOPLE,FP7-PEOPLE-2013-ITN,ARGENT(2014), and European Project: 624370,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IEF,NANOHAPY(2014)

Subjects
Radiation-Sensitizing Agents, Materials science, medicine.medical_treatment, media_common.quotation_subject, Cell, Metal Nanoparticles, Bioengineering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, HeLa, Prostate cancer, Cell Line, Tumor, medicine, Humans, General Materials Science, Electrical and Electronic Engineering, Internalization, Cell Proliferation, media_common, [PHYS]Physics [physics], biology, Mechanical Engineering, Cancer, General Chemistry, Fibroblasts, Pentetic Acid, 021001 nanoscience & nanotechnology, biology.organism_classification, medicine.disease, 3. Good health, 0104 chemical sciences, Radiation therapy, medicine.anatomical_structure, Mechanics of Materials, Colloidal gold, PC-3 Cells, Cancer cell, Cancer research, Gold, 0210 nano-technology, HeLa Cells
Abstract

International audience; Radiotherapy is one of the main treatments used to fight cancer. A major limitation of this modality is the lack of selectivity between cancerous and healthy tissues. One of the most promising strategies proposed in this last decade is the addition of nanoparticles with high-atomic number to enhance radiation effects in tumors. Gold nanoparticles (AuNPs) are considered as one of the best candidates because of their high radioenhancing property, simple synthesis and low toxicity. Ultra small AuNPs (core size of 2.4 nm and hydrodynamic diameter of 4.5 nm) covered with dithiolated diethylenetriaminepentaacetic acid (Au@DTDTPA) are of high interest because of their properties to bind MRI active or PET active compounds at their surface, to concentrate in some tumors and be eliminated via renal clearance thanks to their small size. These key figures make Au@DTDTPA the best candidate to develop image-guided radiotherapy. Surprisingly the capacity of the nanoparticles to penetrate cells, an important issue to predict radioenhancement, has not been established yet. Here, we report the uptake dynamics, internalization routes and excretion dynamics of Au@DTDTPA nanoparticles in various cancer cell lines including glioblastoma (U87-MG), chordoma (UM-Chor1), cervix (HeLa), prostate (PC3), and pancreatic (BxPC-3) cell lines as well as fibroblasts (Dermal fibroblasts). This study demonstrates a strong cell line dependence of the nanoparticle uptake and excretion dynamics. Different pathways of cell internalization evidenced here explain this dependence. As a major finding, the retention of Au@DTDTPA nanoparticles was found to be higher in cancer cells than in fibroblasts. This result strengthens the strategy of using nanoagents to improve tumor selectivity of radiation treatments. In particular Au@DTDTPA nanoparticles are good candidates to improve the treatment of radioresitant gliobastoma, pancreatic and prostate cancer in particular. In conclusion, the variability of cell-to-nanoparticle interaction is a new parameter to consider in the choice of nanoagents in a combined treatment.

Published
2020

37. Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas

Author

Prezado, Yolanda, Jouvion, Gregory, Patriarca, Annalisa, Nauraye, Catherine, Guardiola, Consuelo, Juchaux, Marjorie, Lamirault, Charlotte, Labiod, Dalila, Jourdain, Laurene, Sebrie, Catherine, Dendale, Remi, Gonzalez, Wilfredo, Pouzoulet, Frederic, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Curie, Université Paris-Sud - Paris 11 (UP11), Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11), and Institut Pasteur [Paris] (IP)

Subjects
[PHYS]Physics [physics], Male, lcsh:R, lcsh:Medicine, Radiotherapy Dosage, Glioma, Magnetic Resonance Imaging, Xenograft Model Antitumor Assays, Article, Rats, Disease Models, Animal, Therapeutic Index, Treatment Outcome, Proton Therapy, Animals, lcsh:Q, Neoplasm Grading, Radiometry, lcsh:Science
Abstract

International audience; Proton minibeam radiation therapy (pMBRT) is a novel strategy which has already shown a remarkable reduction in neurotoxicity as to compared with standard proton therapy. Here we report on the first evaluation of tumor control effectiveness in glioma bearing rats with highly spatially modulated proton beams. Whole brains (excluding the olfactory bulb) of Fischer 344 rats were irradiated. Four groups of animals were considered: a control group (RG2 tumor bearing rats), a second group of RG2 tumor-bearing rats and a third group of normal rats that received pMBRT (70 Gy peak dose in one fraction) with very heterogeneous dose distributions, and a control group of normal rats. The tumor-bearing and normal animals were followed-up for 6 months and one year, respectively. pMBRT leads to a significant tumor control and tumor eradication in 22% of the cases. No substantial brain damage which confirms the widening of the therapeutic window for high-grade gliomas offered by pMBRT. Additionally, the fact that large areas of the brain can be irradiated with pMBRT without significant side effects, would allow facing the infiltrative nature of gliomas.

Published
2018

38. Survey on current practice within the European Low-Grade Glioma Network: Where do we stand and what is the next step?

Author

Luc Taillandier, Fabien Almairac, Fabio Barone, Etienne Gayat, Maria Zetterling, Juan Martino, Thomas Santorius, Christian F. Freyschlag, Hugues Duffau, Caterina Madadaki, Geert-Jan Rutten, Emmanuel Mandonnet, Philip C. De Witt Hamer, Marie-Therese Forster, Amélie Darlix, Giannantonio Spena, Marie-Hélène Baron, Marie Blonski, Monika E. Hegi, Michel Wager, John Goodden, Silvio Sarubbo, Gord von Campe, Santiago Gil Robles, Lorenzo Bello, Denys Fontaine, Nicolas Foroglu, Johan Pallud, Miran Skrap, Catarina Pessanha Viegas, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Neurosurgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life

Subjects
[PHYS]Physics [physics], medicine.medical_specialty, Temozolomide, business.industry, medicine.medical_treatment, Medicine (miscellaneous), Original Articles, Evidence-based medicine, medicine.disease, Chemotherapy regimen, 3. Good health, Radiation therapy, 03 medical and health sciences, Regimen, 0302 clinical medicine, Current practice, 030220 oncology & carcinogenesis, Glioma, medicine, Physical therapy, Low-Grade Glioma, Medical physics, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

Published
2017

39. SRF Co-factors Control the Balance between Cell Proliferation and Contractility

Author

Aengus Stewart, Francesco Gualdrini, Nik Matthews, Richard Treisman, Stuart Horswell, Cyril Esnault, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), and University of Colorado [Boulder]

Subjects
0301 basic medicine, Serum Response Factor, Transcription, Genetic, Mice, Elk-1, Hi-C, Transcription (biology), Gene expression, Ras/MAPK signaling, Extracellular Signal-Regulated MAP Kinases, 3. Good health, Cell biology, Cytoskeletal Gene, embryonic structures, cardiovascular system, Tetradecanoylphorbol Acetate, SRF, transcription, Signal Transduction, animal structures, education, cell contraction, Ternary Complex Factors, Biology, immediate-early genes, Article, Cell Line, Contractility, 03 medical and health sciences, transcription factors, Serum response factor, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene, Transcription factor, Cell Proliferation, ets-Domain Protein Elk-1, Base Sequence, Cell growth, Gene Expression Profiling, Genetic Complementation Test, Cell Biology, Fibroblasts, Molecular biology, 030104 developmental biology, Gene Expression Regulation, Ternary Complex Factor, Trans-Activators
Abstract

Summary The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation. These also include a significant number of cytoskeletal gene targets for the Rho-regulated myocardin-related transcription factor (MRTF) SRF cofactor family. The TCFs act as general antagonists of MRTF-dependent SRF target gene expression, competing directly with the MRTFs for access to SRF. As a result, TCF-deficient MEFs exhibit hypercontractile and pro-invasive behavior. Thus, competition between TCFs and MRTFs for SRF determines the balance between antagonistic proliferative and contractile programs of gene expression., Graphical Abstract, Highlights • Integrated ChIP-seq Hi-C analysis identifies over 700 TCF-dependent SRF target genes • Over 60% of TPA-inducible gene transcription is TCF-dependent • TCF-dependent transcription potentiates cell proliferation • TCF/MRTF competition for SRF determines contractility and pro-invasive behavior, Two cofactor families, the TCFs and the MRTFs, compete for binding to SRF, a key regulator of the mitogen-responsive transcription. TCFs not only control proliferative gene expression programs but also regulate access of the MRTFs to SRF, thereby regulating cell contractility and pro-invasive behavior.

Published
2016

40. High-energy electrons and minibeams therapy: a micro and nano dosimetry Monte Carlo study

Author

Rachel Delorme, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Delorme, Rachel

Subjects
[PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

41. Développement d’un imageur gamma ambulatoire pour le contrôle de la dose en radiothérapie interne vectorisée

Author

Trigila, Carlotta, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Yves Charon, Université Paris Saclay (COmUE), and STAR, ABES

Subjects
Instrumentation nucléaire, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Simulation Monte Carlo, Gamma imaging, Imagerie gamma, Nuclear instrumentation, Dosimétrie, Targeted radionucleide therapy, Monte Carlo simulations, [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Dosimetry, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Thérapie par radio-nucléide
Abstract

Targeted radionuclide therapy is still a developing area among the different treatment modalities against cancer. However, its range of applications is rapidly expanding thanks to the emergence of new radiopharmaceuticals labeled with beta or alpha emitters (peptides, ²²³ Ra alpha-therapy, ²²¹ As alpha- immunotherapy, ...) (Ersahin 2011). In that context, the large heterogeneity of absorbed doses and the range of effects observed, both in terms of toxicity and response, demonstrate that individualized patient dosimetry is essential to optimize this therapy (Strigari 2011). In clinical practice, patient-specific dosimetry of tumors and organs-at-risk (liver, kidney, ...) is image-based and rely on the quantification of radio- pharmaceutical uptake as a function of time. These images can be obtained from either a pre-therapy tracer study or from a previous therapy procedure. The detection constraints imposed by the treatment protocols are very different from those associated with diagnostic imaging. (Flux 2011 Konijnenberg 2011). Thus, conventional gamma cameras are not suited for detecting high activity of gamma emitters with energy below 100 keV (²²³ Ra) or greater than 300 keV (¹³¹ I, ⁹⁰Y ). Moreover, high activities of the injected tracer typically require isolation of the patient, making the use of standard imaging devices difficult. Finally, the availability of these devices is incompatible with an accurate temporal sampling of the kinetics of the tracer, which is a key parameter for the quantification of the absorbed doses. The objective of my thesis was precisely to propose new instrumental and methodological approaches aiming to strengthen the control of the dose released to patients during molecular radiotherapy. This is achieved by reducing the uncertainties associated to activity quantification (and therefore to the absorbed dose calculation) through the use of a compact and highly optimized imaging system. Specifically, the work consisted in the development and optimization of a miniaturized, high-resolution mobile gamma camera specifically designed to improve the individual quantitative assessment of the heterogeneous distribution and biokinetics of the radiotracer before and after treatment administration. The study was focused on the treatment of benign and malign thyroid disease with ¹³¹ I. The first prototype of the mobile camera, with a field of view of 5x5 cm², consists of a high-energy parallel- hole collimator, optimized with Monte Carlo simulation and made with 3D printing, coupled to a 6 mm thick continuous CeBr3 scintillator readout by a recent and well-suited technology based on arrays of Silicon Pho- tomultiplier (SiPMs) detectors. Its intrinsic properties, in term of energy and spatial response, have been tested with collimated point source of ⁵⁷Co and ¹³³Ba. The first feasibility prototype has been then calibrated with a line and five cylindrical sources filled with ¹³¹ I. The system calibration leads to an overall spatial resolution of (3.14±0.03) mm at a distance of 5 cm and a sensitivity that decreases with distance and slightly changes with source size. An average sensitivity of (1.23±0.01) cps/MBq has been found at 5 cm. In order to test the quantification capability of the camera, the first preclinical planar studies involved the use of different 3D-printed thyroid phantoms filled with ¹³¹ I, with and without nodules. Although corresponding to a relatively ideal, but realistic, clinical situation (no superimposition of background activity), the optimized imaging features of the camera leads to very promising results, with activity recovery factors that deviate of around 2% from the unity., La thérapie interne par radionucléides est encore aujourd’hui un domaine peu exploité parmi les différentes modalités de traitement contre le cancer. Son spectre d’applications est toutefois en pleine évolution grâce notamment à l'apparition de nouveaux radiopharmaceutiques émetteurs beta ou alpha (peptides, alpha-thérapie ²²³ Ra, alpha-immunothérapie ²²¹ As,...) (Ersahin 2011). Dans ce contexte, la grande hétérogénéité des doses délivrées et des effets observés, à la fois en terme de toxicité et de réponse, démontrent qu'une dosimétrie personnalisée est essentielle pour optimiser le traitement (Strigari 2011). En pratique clinique, la dosimétrie de la tumeur et des organes à risque (foie, rein, ...) repose sur l’image de la biodistribution et de la cinétique précise du radiopharmaceutique chez chaque patient. Ces images peuvent être réalisées avec un traceur pré-thérapeutique pour planifier le traitement ou après celui-ci, afin de corréler directement les effets observés aux doses délivrées de manière à optimiser le protocole (activité maximum à injecter, intervalle entre les injections). Les contraintes de détection imposées par les protocoles de traitement sont très différentes de celles associées à un examen diagnostique (Flux 2011, Konijnenberg 2011). Les gamma-caméras conventionnelles ne sont ainsi pas adaptées à la détection de fortes activités de rayonnements gamma d'énergies inférieures à 100 keV (²²³ Ra) ou supérieures à 300 keV (¹³¹I, ⁹⁰Y). D’autre part, les fortes activités des traceurs injectés exigent généralement que le patient reste isolé, ce qui le rend donc plus difficilement accessible par les techniques d’imagerie standard. Enfin, la disponibilité de ces systèmes est incompatible avec un échantillonnage temporel précis de la cinétique du traceur, qui joue un rôle très important dans la quantification des doses absorbées. L'objectif de ma thèse était de proposer de nouvelles approches instrumentales visant à renforcer le contrôle de la dose délivrée aux patients lors d'un traitement de radiothérapie moléculaire. Ceci est réalisé en réduisant les incertitudes associées à la quantification de l'activité (et donc au calcul de la dose absorbée) grâce à l'utilisation d'un système d'imagerie compact et hautement optimisé. Il consistait à mettre au point et à optimiser une gamma-caméra mobile miniaturisée à haute résolution spécialement conçue pour améliorer l'évaluation quantitative individuelle de la distribution hétérogène et de la bio-cinétique du radiotraceur avant et après administration du traitement. L'étude était axée sur le traitement des maladies bénignes et malignes de la thyroïde à l'aide de l'¹³¹ I. Le premier prototype de la caméra, avec un champ de vue de 5x5 cm² , consiste en un collimateur à trous parallèles à haute énergie, réalisé en impression 3D et optimisé par simulations Monte Carlo, couplé à un scintillateur inorganique continu, lu par une technologie récente basée sur des matrices de photomultiplicateurs au silicium (SiPM). Ses propriétés intrinsèques, en termes d'énergie et de réponse spatiale, ont été testées avec des sources ponctuelles de ⁵⁷ Co et ¹³³ Ba. Le premier prototype de la caméra a été calibré avec de l'¹³¹ I. La calibration du système conduit à une résolution spatiale globale de (3.14±0.03) mm et à une sensibilité moyenne de (1.23±0.01) cps/MBq, le deux à 5 cm de distance. Nous avons effectué les premières études précliniques avec l'utilisation de différents fantômes thyroïdiens imprimés en 3D, avec et sans nodules, remplis de ¹³¹ I. Des résultats très prometteurs ont été atteints (valeurs de RC proches de l’unité), qui mettent en évidence ses performances adaptées à une quantification précise dans un contexte clinique assez réaliste.

Published
2019

42. La microscopie optique tridimensionnelle, de l'imagerie biomédicale à la caractérisation des objets du patrimoine

Author

Latour, Gaël, Robinet, Laurianne, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche sur la Conservation (CRC ), Muséum national d'Histoire naturelle (MNHN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X)

Subjects
[PHYS]Physics [physics], [SHS.MUSEO]Humanities and Social Sciences/Cultural heritage and museology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

43. Contrast-enhanced synchrotron radiation therapy: From bench to bedside

Author

Elleaume, Hélène, Adam, Jean-François, Bobyk, Laure, Delorme, R., Taupin, Florence, Ravanat, Jean-Luc, Nemoz, Christian, Renier, Michel, Estève, François, Balosso, Jacques, Rayonnement Synchrotron et Recherche Medicale (RSRM), European Synchrotron Radiation Facility (ESRF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biomedical Beamline (ID17), European Synchrotron Radiation Facility (ESRF), Centre Hospitalier Universitaire [Grenoble] (CHU), Rayet, Béatrice, Université Joseph Fourier - Grenoble 1 (UJF)-European Synchrotron Radiation Facility (ESRF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
[PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph]
Abstract

International audience; Background: Radiation therapy remains a fundamental tool for cancer treatment, but selective dose deposition within a targeted-tumor, while sparing surrounding structures, remains a challenge. This objective can be achieved by loading the tumor with high-Z elements prior delivery of radiation therapy. Synchrotron sources are ideal sources since they provide high-intensity and tunable monochromatic X-rays within the optimal energy-range.Aim: We evaluated the ability of various high-Z elements, either as molecular agents (iodine or gadolinium contrast agents) or in the form of nanoparticles (gold and gadolinium), to act as radiation dose-enhancers through theoretical and experimental studies.Methods: Clonogenic assays were used to quantify cell survival after irradiation in the presence of the dose-enhancers using monochromatic X-rays from a synchrotron or 1.25 MeV photons from a Cobalt-60 source. Preclinical studies were performed on rats bearing F98 glioma after administration of either iodine as contrast agent or AuNPs. In parallel, Monte Carlo simulations were performed to evaluate the dose, for comparisons. Finally, a pilot clinical study was performed using an iodinated contrast agent as the radiation-dose-enhancer. 14 Patients with brain metastases received one fraction of the overall radiotherapy treatment at the synchrotron, the additional fractions were delivered using a conventional Linac at the university hospital.Results/Conclusions Radiosensitization was demonstrated with all agents in combination with X-irradiation at low energies. The radiation dose-enhancements were found to be highly energy-dependent for all agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Iodine and Gd contrast agents or AuNPs act as dose-enhancers. Increase of the animal’s survival was observed after iodine systemic injection or intracerebral infusion of AuNPs. The phase I-II clinical studies demonstrated the feasibility of this technique. Our overall experience will be summarized, pointing out the advantages and difficulties of applying this method for the treatment of brain tumors.

Published
2019

44. Comparison of optically‐derived biomarkers in healthy and brain tumor tissue under one‐ and two‐photon excitation

Author

Mira Sibai, Pascale Varlet, Darine Abi Haidar, Bertrand Devaux, Hussein Mehidine, Emile Kaadou Moawad, Marjorie Juchaux, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
In situ, Fluorescence-lifetime imaging microscopy, Optical Phenomena, Brain tumor, General Physics and Astronomy, Multimodal Imaging, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Diffusion, 010309 optics, Meningioma, Two-photon excitation microscopy, 0103 physical sciences, Biomarkers, Tumor, medicine, Humans, General Materials Science, Neoplasm Metastasis, [PHYS]Physics [physics], Brain tumor resection, Photons, Brain Neoplasms, business.industry, 010401 analytical chemistry, General Engineering, Brain, General Chemistry, medicine.disease, 0104 chemical sciences, Neoplasm Grading, business, Biomedical engineering, Submicron scale, Brain metastasis
Abstract

International audience; The surgical outcome of brain tumor resection and needle biopsy is significantly correlated to the patient's prognosis. Brain tumor surgery is limited to resecting the solid portion of the tumor as current intraoperative imaging modalities are incapable of delineating infiltrative regions. For accurate delineation, in situ tissue interrogation at the submicron scale is warranted. Additionally, multimodal detection is required to remediate the genetically and molecularly heterogeneous nature of brain tumors, notably, that of gliomas, meningioma and brain metastasis. Multimodal detection, such as spectrally‐ and temporally‐resolved fluorescence under one‐ and two‐photon excitation, enables characterizing tissue based on several endogenous optical contrasts. In order to assign the optically‐derived parameters to different tissue types, construction of an optical database obtained from biopsied tissue is warranted. This report showcases the different quantitative and semi‐quantitative optical markers that may comprise the tissue discrimination database. These include: the optical index ratio, the optical redox ratio, the relative collagen density, spectrally‐resolved fluorescence lifetime parameters, two‐photon fluorescence imaging and second harmonic generation imaging.

Published
2019

45. An in vivo two photon fluorescence endomicroscopic probe based on a 2-axis electrothermal MEMS mirror

Author

C. Esnault, F. Bouvet, Hussein Mehidine, D. Abi Haidar, Min Li, L. Pinot, Huikai Xie, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS]Physics [physics], Microelectromechanical systems, 0303 health sciences, Modality (human–computer interaction), Computer science, Cellular level, Two photon fluorescence, Scan line, Deformable mirror, 03 medical and health sciences, 0302 clinical medicine, Linear Scan, Endomicroscopy, 030217 neurology & neurosurgery, 030304 developmental biology, Biomedical engineering
Abstract

International audience; Nowadays, the ability to diagnose brain tumors intraoperatively and to delineate their margins, as accurately as possible, is of primordial importance during surgery. However, the exact tumor boundaries and the infiltrated tumor cells outside its solid volume are difficult to be found by the surgeon due to the similar visual appearances especially at the margins, leading in many cases to poor surgical outcomes and a high risk of recurrences. To solve this issue, our group develop a two-photon multimodal endomicroscope to analyze the endogenous fluorescence of cerebral tissues in order to provide reliable informations intraoperatively on the tissues nature at cellular level. For that, and in order to implement the imaging modality in our endomicroscope, we launched a study based on an original miniaturized scanning system to be coupled with our endomicroscope. In this work, we characterize a scanning system prototype based on an electrothermally-actuated scanning micro-mirror. This type of scanning devices can provide a wide linear scan range at a low driving voltage and a high stable scanning speed along a straight scan line which help to acquire high-quality images

Published
2019

46. Optical Signatures Derived From Deep UV to NIR Excitation Discriminates Healthy Samples From Low and High Grades Glioma

Author

Darine Abi Haidar, Fanny Poulon, Audrey Chalumeau, Frédéric Jamme, Bertrand Devaux, Pascale Varlet, Hussein Mehidine, Matthieu Réfrégiers, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)

Subjects
Adult, 0301 basic medicine, Fluorescence-lifetime imaging microscopy, Optical measurements, lcsh:Medicine, Context (language use), Tumor solid, Article, Recurrence risk, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Glioma, Image Processing, Computer-Assisted, medicine, Humans, lcsh:Science, High-Grade Glioma, [PHYS]Physics [physics], Spectroscopy, Near-Infrared, Multidisciplinary, Brain Neoplasms, Chemistry, Optical Imaging, lcsh:R, Imaging and sensing, Near infrared excitation, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Spectrophotometry, Ultraviolet, Cancer imaging, lcsh:Q, Neoplasm Grading, 030217 neurology & neurosurgery
Abstract

Among all the tumors of the central nervous system (CNS), glioma are the most deadly and the most malignant. Surgical resection is the standard therapeutic method to treat this type of brain cancer. But the diffusive character of these tumors create many problems for surgeons during the operation. In fact, these tumors migrate outside the tumor solid zone and invade the surrounding healthy tissues. These infiltrative tissues have the same visual appearance as healthy tissues, making it very difficult for surgeons to distinguish the healthy ones from the diffused ones. The surgeon, therefore, cannot properly remove the tumor margins increasing the recurrence risk of the tumor. To resolve this problem, our team has developed a multimodal two-photon fibered endomicroscope, compatible with the surgeon trocar, to better delimitate tumor boundaries by relying on the endogenous fluorescence of brain tissues. In this context, and in order to characterize the optical signature of glioma tumors, this study offers multimodal and multi-scaled optical measurements from healthy tissues to high grade glioma. We can interrogate tissue from deep ultra-violet to near infrared excitation by working with spectroscopy, fluorescence lifetime imaging, two-photon fluorescene imaging and Second Harmonic Generation (SHG) imaging. Optically derived ratios such as the Tryptophan/Collagen ratio, the optical redox ratio and the long lifetime intensity fraction, discriminated diseased tissue from its normal counterparts when fitted by Gaussian ellipsoids and choosing a threshold for each. Additionally two-photon fluorescence and SHG images were shown to display similar histological features as Hematoxylin-Eosin stained images.

Published
2019

47. MAPSSIC, a communicating MAPS-based intracerebral positrons probe for deep brain imaging in awake and freely-moving rats

Author

L. Pinot, M. Bautista, L. Ammour, P. Laniece, Christian Morel, F. Gensolen, J. Baudot, L. Zimmer, M. Kachel, J. Heymes, F. Lefebvre, P. Gisquet, M. A. Verdier, S. Fieux, P. Pangaud, Centre de Physique des Particules de Marseille (CPPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université Paris-Sud - Paris 11 (UP11), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Positron emission tomography, Computer science, Nuclear imaging, QC1-999, Molecular imaging, Context (language use), 030218 nuclear medicine & medical imaging, CMOS Image sensors, 03 medical and health sciences, 0302 clinical medicine, Positron, Neuroimaging, Nuclear Imaging, medicine, Computer vision, Implants, Image sensor, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Active pixel sensors, Pixel, medicine.diagnostic_test, business.industry, Physics, Monte Carlo methods, 030220 oncology & carcinogenesis, Artificial intelligence, business, Animal behavior
Abstract

International audience; Radioisotope imaging is a powerful tool to understand the biological mechanisms in-vivo, especially in the brain of small animals, providing a significant model to study the human brain.In this context, we have developed and built a pixelated intracerebral positron probe to be embedded on awake and freely moving small animals, typically rats. This pixelated probe will represent a key instrument for neuroscientists to study neural mechanisms and correlate them to behavioral experiments.We describe in this paper the simulations carried out to design the intracerebral sensor, its architecture, and the detection of positrons in a volume with a couple of sensors assembled back-to-back. We also depict the architecture of the wireless acquisition system. Finally, we present the first measurements performed in real-time by this miniaturized probe with sealed radioactive sources and a 18F solution.Key words: Active pixel sensors / Animal behavior / CMOS Image sensors / Implants / Molecular imaging / Monte Carlo methods / Nuclear Imaging / Positron emission tomography

Published
2019

48. Theoretical study at the nanometer scale of photon, high-energy electron and proton minibeam radiation therapy

Author

Dos Santos, M., Rachel Delorme, Remi Salmon, Yolanda Prezado, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)

Subjects
[PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

49. Optics design and beam dynamics simulation for a VHEE radiobiology beam line at PRAE accelerator

Author

Faus-Golfe, Angeles, Bai, Bowen, Delorme, Rachel, Dosanjh, Manjit, Duchesne, Patricia, Favaudon, Vincent, Fouillade, Charles, Han, Yanliang, Poortmans, Philip, Pouzoulet, Frederic, Prezado, Yolanda, Vallerand, Cynthia, Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Institut Curie, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), and Institut Curie [Paris]

Subjects
electron, History, Radiobiology, [PHYS.PHYS.PHYS-ACC-PH]Physics [physics]/Physics [physics]/Accelerator Physics [physics.acc-ph], Electron, Radiation, Linear particle accelerator, Accelerator Physics, MC8: Applications of Accelerators, Technology Transfer and Industrial Relations, 030218 nuclear medicine & medical imaging, Education, law.invention, 03 medical and health sciences, 0302 clinical medicine, Optics, law, linac, Physics, business.industry, Particle accelerator, Accelerators and Storage Rings, optics, Computer Science Applications, radiation, gun, Beamline, 030220 oncology & carcinogenesis, Subatomic particle, business, Beam (structure)
Abstract

The Platform for Research and Applications with Electrons (PRAE) is a multidisciplinary R facility gathering subatomic physics, instrumentation, radiobiology and clinical research around a high-performance electron accelerator with beam energies up to 70 MeV. In this paper we report the complete optics design and performance evaluation of a Very High Energy Electron (VHEE) innovative radiobiology study, in particular by using Grid mini-beam and FLASH methodologies, which could represent a major breakthrough in Radiation Therapy (RT) treatment modality., Proceedings of the 10th Int. Particle Accelerator Conf., IPAC2019, Melbourne, Australia

Published
2019

50. MAPSSIC, a Novel CMOS Intracerebral Positrons Probe for Deep Brain Imaging in Awake and Freely Moving Rats: A Monte Carlo Study

Author

Ammour, L., Heymes, J., Bautista, M., Fieux, S., Gensolen, F., Kachel, M., Dubois, André, Lefebvre, Fabrice, Pain, F., Pangaud, P., Pinot, L., Baudot, J., Gisquet-Verrier, Pascale, Lanièce, Philippe, Morel, C., Zimmer, L., Verdier, M., Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département Recherches Subatomiques (DRS-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), laniece, philippe, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

International audience; Preclinical behavior neuroimaging gathers simultaneous assessment of behavior and functional brain imaging. It is a potential key breakthrough to improve the understanding of brain processes and assess the validity of preclinical studies in drug development. Achieving such a combination is difficult, anesthesia or restraints inherent to conventional nuclear imaging preclude its use for behavior studies. In that context, we have proposed an original strategy using submillimetric probes to directly measures positrons inside the rat brain. This paper gives the results of Monte Carlo simulations of a new generation of intracerebral positron probe based on a CMOS Monolithic Active Pixel Sensor. We present the results obtained for a probe into a large homogeneous volume of radioactive water (18 F) leading to a sensitivity of 0.88 cps · Bq −1 · mm 3 and a mean energy deposition by positrons of 15.1 keV. Simulation in simplified brain-shaped sources modeling a 11 C-raclopride experiment shows that the implanted volume modeling the left putamen contribute to 92.4 % of the signal from positrons. We also investigate the effects of the thickness of the sensitive layer, the energy threshold and pixel dimensions on the detection capacities of the sensor. We demonstrate that an increase in the sensitive thickness from 18 to 190 µm would lead to an increase of positrons sensitivity by a factor of 1.74, but to a decrease of the direct (positrons) to indirect (γ-rays and electrons) sensitivity ratio by a factor of 1.59. Finally we show that for a threshold lower than about 5 keV the effect of the pixel dimensions is negligible.

Published
2019

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