In vivo measurement of human brain elasticity using a light aspiration device

The brain deformation that occurs during neurosurgery is a serious issue impacting the patient "safety" as well as the invasiveness of the brain surgery. Model-driven compensation is a realistic and efficient solution to solve this problem. However, a vital issue is the lack of reliable and easily obtainable patient-specific mechanical characteristics of the brain which, according to clinicians' experience, can vary considerably. We designed an aspiration device that is able to meet the very rigorous sterilization and handling process imposed during surgery, and especially neurosurgery. The device, which has no electronic component, is simple, light and can be considered as an ancillary instrument. The deformation of the aspirated tissue is imaged via a mirror using an external camera. This paper describes the experimental setup as well as its use during a specific neurosurgery. The experimental data was used to calibrate a continuous model. We show that we were able to extract an in vivo constitutive law of the brain elasticity: thus for the first time, measurements are carried out per-operatively on the patient, just before the resection of the brain parenchyma. This paper discloses the results of a difficult experiment and provide for the first time in-vivo data on human brain elasticity. The results point out the softness as well as the highly non-linear behavior of the brain tissue.Comment: Medical Image Analysis (2009) accept\'

Étude et réalisation d'un système de localisation en six dimensions pour la chirurgie assistée par ordinateur

Most of Computer Assisted Surgery (C.A.S.) need a six-dimensional localizer. Those systems can locate and follow in space, position and orientation of rigid bodies constituted of markers. A lot of localizers have already been used in surgery but few of them are specifically dedicated for medical applications and the answers they propose to constraints of surgery is not completely adapted. We present in this thesis an original approach to localisation. Based on a study of surgical applications using a localizer, we have defined qualitative (cumbersome, weight, shape etc...) and quantitative criteria in particular accuracy. We have indeed proposed a generic accuracy evaluation protocol for localizer in surgery. An evolution to most often used localizer (optical systems) is proposed to adapt them totally to those criteria. In particular, it appears that cost, accuracy and global ergonomics of existing system are insufficient for high demanding applications, even if they are enough for most of them. We have studied and detailed in this thesis two prototypes that allow to answer to problems posed by cost, accuracy and especially ergonomics. From a passive stereovision hard-ware which locate punctual markers, we propose an original evolution based on the localisation of linear markers which are identified by Thalès equation, which improve the global visibility. Finally, we propose two very innovating concepts of localisation which answer to the major drawback of optical system, which must have the line of sight between cameras and marker, free of all obstacles.La plupart des Gestes Médicaux-Chirurgicaux Assistés par Ordinateur (G.M.C.A.O.) nécessitent l'utilisation d'un localisateur en six-dimensions. Il s'agit d'un système permettant de déterminer et de suivre la position et l'orientation de corps rigides constitués de marqueurs dans l'espace. De nombreux localisateurs ont été utilisés en chirurgie. Très peu de systèmes sont dédiés spécifiquement à la chirurgie ainsi ils ne répondent pas entièrement de façon satisfaisante aux contraintes du domaine. Nous présentons dans cette thèse, une approche originale de la localisation. A partir d'une étude des applications chirurgicales utilisant un localisateur, nous avons défini un ensemble de critères qualitatifs (encombrement, poids, forme) et quantitatifs en particulier sur la précision pour laquelle un protocole générique d'évaluation des localisateurs pour la chirurgie est proposé. Ces critères nous ont conduit à proposer une évolution des principaux systèmes utilisés aujourd'hui (les localisateurs optiques) afin de les rendre totalement adaptés aux besoins du domaine. En particulier, il est apparu que le coût, la précision et l'ergonomie globale des systèmes existants bien que satisfaisantes dans la plupart des cas étaient insuffisantes pour des applications exigeantes. Nous avons étudié et nous détaillons dans cette thèse deux prototypes permettant de répondre aux problèmes posés par le coût, la précision et surtout l'ergonomie. A partir de la base commune d'un localisateur par stéréovision passive repérant des marqueurs ponctuels, nous proposons une évolution originale basée sur la localisation et l'identification de marqueurs linéaires par le rapport de Thalès pour améliorer la visibilité des cibles. Enfin nous proposons deux concepts très innovants de localisation répondant à l'inconvénient majeur des systèmes optiques qui doivent avoir une ligne de vue entre les caméras et les marqueurs libre de tout obstacle

Étude et réalisation d'un système de localisation en six dimensions pour la chirurgie assistée par ordinateur

GRENOBLE1-BU Médecine pharm. (385162101) / SudocGRENOBLE-MI2S (384212302) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Accuracy evaluation of a CAS system: laboratory protocol and results with 6D localizers, and clinical experiences in otorhinolaryngology

OBJECTIVES: The objective of the study reported in this article was to evaluate (1) localizer inaccuracies, one of the major sources of errors in Computer-Assisted Surgery (CAS) systems, and (2) the final errors obtained using surface-based registration in ear, nose, and throat (ENT) surgery. These objectives were met through (1) a technical evaluation of the accuracy and usability of several optical localizers under laboratory test conditions, and (2) a clinical measure of the global errors obtained when using a CAS system including one of the standard localizer systems (Flashpoint 5000) in Functional Endoscopic Sinus Surgery (FESS). PATIENTS AND METHODS: The technical evaluation of localizers consisted of series of geometric tests on four commercial systems. Clinical evaluation included the development of a laboratory CAS system using a markerless, skin surface registration method. This was based on a standard optical digitizing system (Flashpoint 5000), which eliminates the need for the second CT scan, which is normally performed specifically to process the position of the fiducial markers. Global accuracy was then evaluated on 20 patients by subjective and visual comparison when placing a calibrated pointer on anatomical landmarks. RESULTS: The results of the technical study indicate that the four commercial systems tested have levels of inaccuracy deemed acceptable for most CAS applications, including ENT surgery. The clinical study obtained a registration and calibration accuracy of less than 1.5 mm in 89.2% (SD = 0.20 mm) of the cases studied. Our markerless skin surface points registration method is reliable, and allows patient head movements during the procedure. The accuracy tests performed show that this type of system can be used for ENT surgery with satisfaction. CONCLUSION: CAS systems enable the surgeon to have a more thorough understanding of the complicated anatomy of paranasal sinuses, and may be especially helpful in revision surgery when normal anatomic landmarks are lacking. Further studies are necessary in FESS to improve the CAS systems that are currently available, and to determine whether these systems can minimize the overall risk of complications

Neuronavegación con un modelo de corrección a tiempo real con ecografía intraoperatoria

National audienceWe present our project which aims at developing, validating and proposing a prototype for a neuronavigation station able to improve the precision of the actual systems, without per-operative MRI. Our goal is to integrate, in a “classical” image guided surgery (IGS) station, a model of the deformations of the cerebral soft-tissue and more specifically the “brain shift”, phenomenon which is observed during neurosurgery. This unables the IGS stations presently commercialized around the world to take into account most of the brain open surgeries. These stations help guiding the surgeons for gestures such as biopsies or tumor resection. Starting from pre-operative medical imaging exams, the tumor is localized on the images and the surgical planning is transferred into the operating room. Because of the “brain shift”, this planning has to be updated during surgery, to ensure sufficient accuracy. The solutions proposed consist in developing a real-time mechanical model of the brain soft tissues, which will be updated with intraoperative ultrasound images, in order to estimate and compensate the mechanical deformations of the brain during surgery. We present advanced technologies for neurosurgery.Keywords: neuronavigation, brain shift, soft tissue deformation, biomechanical modelling.Presentamos nuestro proyecto que enfoca el desarrollo y validación de un prototipo para ser instalado en un neuronavegador que mejorará la precisión de los sistemas actuales sin la necesidad de RMN intraoperatoria. Nuestro objetivo es la integración, dentro de una estación “clásica” de cirugía asistida por computador (CAC), de un modelo de deformación de los tejidos cerebrales, en particular la causada por el “brain shift”. Este fenómeno impide la utilización de las estaciones de CAC en la mayoría de las cirugías “muy abiertas” del cerebro. Estas estaciones permiten ayudar en la planificación y ejecución de procedimientos quirúrgicos tales como biopsias o resección de tumores. Desde el preoperatorio el tumor es localizado en las neuroimágenes y con ayuda de ellas se efectúa la planificación quirúrgica con la cual se ingresa al quirófano. Debido al “brain shift” esta planificación inicial debe ser actualizada durante la cirugía para asegurar una precisión suficiente. La solución que proponemos consiste en el desarrollo de un modelo biomecánico en tiempo real de los tejidos cerebrales que será actualizado con las imágenes ecográficas intraoperatorias con el objetivo de estimar y compensar las deformaciones del cerebro durante la cirugía.Palabras clave: neuronavegación, desplazamiento encefálico, deformación de tejidos blandos, modelamiento biomecánic

Neuronavegación con un modelo de corrección a tiempo real con ecografía intraoperatoria

National audienceWe present our project which aims at developing, validating and proposing a prototype for a neuronavigation station able to improve the precision of the actual systems, without per-operative MRI. Our goal is to integrate, in a “classical” image guided surgery (IGS) station, a model of the deformations of the cerebral soft-tissue and more specifically the “brain shift”, phenomenon which is observed during neurosurgery. This unables the IGS stations presently commercialized around the world to take into account most of the brain open surgeries. These stations help guiding the surgeons for gestures such as biopsies or tumor resection. Starting from pre-operative medical imaging exams, the tumor is localized on the images and the surgical planning is transferred into the operating room. Because of the “brain shift”, this planning has to be updated during surgery, to ensure sufficient accuracy. The solutions proposed consist in developing a real-time mechanical model of the brain soft tissues, which will be updated with intraoperative ultrasound images, in order to estimate and compensate the mechanical deformations of the brain during surgery. We present advanced technologies for neurosurgery.Keywords: neuronavigation, brain shift, soft tissue deformation, biomechanical modelling.Presentamos nuestro proyecto que enfoca el desarrollo y validación de un prototipo para ser instalado en un neuronavegador que mejorará la precisión de los sistemas actuales sin la necesidad de RMN intraoperatoria. Nuestro objetivo es la integración, dentro de una estación “clásica” de cirugía asistida por computador (CAC), de un modelo de deformación de los tejidos cerebrales, en particular la causada por el “brain shift”. Este fenómeno impide la utilización de las estaciones de CAC en la mayoría de las cirugías “muy abiertas” del cerebro. Estas estaciones permiten ayudar en la planificación y ejecución de procedimientos quirúrgicos tales como biopsias o resección de tumores. Desde el preoperatorio el tumor es localizado en las neuroimágenes y con ayuda de ellas se efectúa la planificación quirúrgica con la cual se ingresa al quirófano. Debido al “brain shift” esta planificación inicial debe ser actualizada durante la cirugía para asegurar una precisión suficiente. La solución que proponemos consiste en el desarrollo de un modelo biomecánico en tiempo real de los tejidos cerebrales que será actualizado con las imágenes ecográficas intraoperatorias con el objetivo de estimar y compensar las deformaciones del cerebro durante la cirugía.Palabras clave: neuronavegación, desplazamiento encefálico, deformación de tejidos blandos, modelamiento biomecánic

Neuronavegación con un modelo de corrección a tiempo real con ecografía intraoperatoria

National audienceWe present our project which aims at developing, validating and proposing a prototype for a neuronavigation station able to improve the precision of the actual systems, without per-operative MRI. Our goal is to integrate, in a “classical” image guided surgery (IGS) station, a model of the deformations of the cerebral soft-tissue and more specifically the “brain shift”, phenomenon which is observed during neurosurgery. This unables the IGS stations presently commercialized around the world to take into account most of the brain open surgeries. These stations help guiding the surgeons for gestures such as biopsies or tumor resection. Starting from pre-operative medical imaging exams, the tumor is localized on the images and the surgical planning is transferred into the operating room. Because of the “brain shift”, this planning has to be updated during surgery, to ensure sufficient accuracy. The solutions proposed consist in developing a real-time mechanical model of the brain soft tissues, which will be updated with intraoperative ultrasound images, in order to estimate and compensate the mechanical deformations of the brain during surgery. We present advanced technologies for neurosurgery.Presentamos nuestro proyecto que enfoca el desarrollo y validación de un prototipo para ser instalado en un neuronavegador que mejorará la precisión de los sistemas actuales sin la necesidad de RMN intraoperatoria. Nuestro objetivo es la integración, dentro de una estación “clásica” de cirugía asistida por computador (CAC), de un modelo de deformación de los tejidos cerebrales, en particular la causada por el “brain shift”. Este fenómeno impide la utilización de las estaciones de CAC en la mayoría de las cirugías “muy abiertas” del cerebro. Estas estaciones permiten ayudar en la planificación y ejecución de procedimientos quirúrgicos tales como biopsias o resección de tumores. Desde el preoperatorio el tumor es localizado en las neuroimágenes y con ayuda de ellas se efectúa la planificación quirúrgica con la cual se ingresa al quirófano. Debido al “brain shift” esta planificación inicial debe ser actualizada durante la cirugía para asegurar una precisión suficiente. La solución que proponemos consiste en el desarrollo de un modelo biomecánico en tiempo real de los tejidos cerebrales que será actualizado con las imágenes ecográficas intraoperatorias con el objetivo de estimar y compensar las deformaciones del cerebro durante la cirugía

Morphogenetic processes: application to cambial growth dynamics.

Both the physiological and the pathological morphogenetic processes that we can meet in embryogenesis, neogenesis and degenerative dysgenesis present common features: they are ruled by three different kinds of mechanisms, one related to cell migration, the second to cell differentiation and the third to cell proliferation. We deal here with an application to the cambial growth which essentially involves the third type of mechanism. Woody plants produce secondary tissue (secondary xylem and phloem) from a meristematic tissue called vascular cambium, responsible for the radial growth of a tree. This paper focuses on the formation of secondary xylem, considered in two dimensions in a cross-section framework. A new discrete modelling approach is used, based on the cellular scale, in order to attain a more accurate understanding of how the elementary microscopic behaviour of each cell takes part in the macroscopic morphogenesis. The mathematical model essentially uses an occurrence method simulating the main features of radial growth with simple geometric rules, such as Thom's division rule (Thom,1972)to account for the cell proliferation. The study applies to concrete instances in which the changes made in the geometrical cellular patterns of the vascular cambium clearly affect the shape of the tree, as in Pinus radiata (D. Don.)

Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine

International audienceChronic ingestion of environmental heavy metals such as lead (Pb) and cadmium (Cd) causes various well-documented pathologies in specific target organs following their intestinal absorption and subsequent accumulation. However, little is known about the direct impact of the non-absorbed heavy metals on the small intestine and the colon homeostasis. The aim of our study was to compare the specific bioaccumulation and retention of Cd and Pb and their effect on the essential metal balance in primary organs, with those occurring specifically in the gastrointestinal tract of mice. Various doses of Cd (5, 20 and 100 mg l−1) and Pb (100 and 500 mg l−1) chloride salts were provided in drinking water for subchronic to chronic exposures (4, 8 and 12 weeks). In contrast to a clear dose- and time-dependent accumulation in target organs, results showed that intestines are poor accumulators for Cd and Pb. Notwithstanding, changes in gene expression of representative intestinal markers revealed that the transport-, oxidative- and inflammatory status of the gut epithelium of the duodenum, ileum and colon were specifically affected by both heavy metal species. Additionally, in vivo comet assay used to evaluate the impact of heavy metals on DNA damage showed clear genotoxic activities of Cd, on both the upper and distal parts of the gastrointestinal tract. Altogether, these results outline the resilience of the gut which balances the various effects of chronic Cd and Pb in the intestinal mucosa. Collectively, it provides useful information for the risk assessment of heavy metals in gut homeostasis and further disease’s susceptibility

Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability

Abstract Nonsense-mediated mRNA decay (NMD) is responsible for the degradation of mRNAs with a premature termination codon (PTC). The role of this system in cancer is still quite poorly understood. In the present study, we evaluated the functional consequences of NMD activity in a subgroup of colorectal cancers (CRC) characterized by high levels of mRNAs with a PTC due to widespread instability in microsatellite sequences (MSI). In comparison to microsatellite stable (MSS) CRC, MSI CRC expressed increased levels of two critical activators of the NMD system, UPF1/2 and SMG1/6/7. Suppression of NMD activity led to the re-expression of dozens of PTC mRNAs. Amongst these, several encoded mutant proteins with putative deleterious activity against MSI tumorigenesis (e.g., HSP110DE9 chaperone mutant). Inhibition of NMD in vivo using amlexanox reduced MSI tumor growth, but not that of MSS tumors. These results suggest that inhibition of the oncogenic activity of NMD may be an effective strategy for the personalized treatment of MSI CRC