Développement de nouvelles sondes per-opératoires positon pour guider la chirurgie des tumeurs solides

L exérèse des tumeurs cancéreuses est une procédure courante pour le traitement de nombreux cancers. L enjeu est de réaliser une excision la plus complète possible pour éviter les récidives tout en épargnant le plus possible les tissus sains bordant la tumeur. La détection de positons est une modalité d imagerie particulièrement adaptée au repérage de résidus tumoraux lors de l'éxerèse car sa forte sélectivité spatiale permet de s'affranchir du bruit provenant de la fixation non spécifique du radiotraceur dans les tissus situés en profondeur, offrant ainsi une meilleur sensibilité et un meilleur rapport signal sur bruit que la détection de photons gamma. L utilisation pour le contrôle d exérèse impose cependant une contrainte forte sur les dimensions du détecteur qui doit être manipulable facilement par le chirurgien et pouvoir être inséré dans des plaies opératoires potentiellement étroites. Une nouvelle génération de photodétecteurs appelés photomultiplicateurs silicium (SiPM) est particulièrement adaptée à cette application car ceux-ci allient la compacité et la robustesse des technologies silicium avec d'excellentes performances de détection. Mon travail de thèse porte sur le développement et la caractérisation de nouvelles sondes positon basées sur ces photodétecteurs. Dans un premier temps, un travail de caractérisation des SiPMs a été réalisé pour évaluer leurs performances pour la détection de positons. Deux prototypes de prototypes de détecteurs aux rôles complémentaires ont ensuite été réalisé: le premier est un imageur, basé sur l assemblage de deux scintillateurs avec une ou deux matrices de SiPMs, qui permet de réaliser rapidement l'image de la distribution de traceur sur une large surface de tissus. Le second détecteur est une sonde de comptage, constituée de fibres scintillantes couplées à des SiPMs individuels via des fibres claires et capable d'être couplée à l'outil d'exérèse. Elle permet de guider l'outil du chirurgien vers les tissus repérés préalablement avec l'imageur. La caractérisation de l imageur a montré sa capacité à détecter des résidus tumoraux de petite taille (15mg) avec une résolution submillimétrique. La sonde de comptage présente quant à elle, une efficacité de détection de 80%.Excision of cancerous tumors is a common procedure for the treatment of numerous cancers. The stake is to perform the most complete excision to prevent recurrences while preserving as much as possible surrounding healthy tissues. Positron detection is a well suited imaging modality for detection of tumor remains during excision because its strong spatial selectivity makes it insensitive to the noise coming from the non-specific accumulation of the radiotracer in healthy tissues located far from the detector, leading to a better sensitivity and a better signal-to-noise ratio than gamma photon detection. Its use for the control of excision implies however strong constraints on detector dimensions which must be easy to handle by the surgeon and easy to insert in tight surgical wound. A new generation of photodetectors called Silicon Photmultipliers (SiPMs) is particularly suited for this application because they present the compactness and robustness of silicon technologies and very good detection performances. My thesis aims to develop and characterize a new generation of new positron probes based on these photodetectors. Two prototypes of detectors with complementary roles were realized: the first one is an imaging device based on the assembly of two scintillators with one or two SiPMs arrays which allows to quickly make an image of tracer distribution along a wide surface of tissues. The second detector is a counting probe made of scintillating fibers associated with individual SiPMs through clear optical fibers and can be associated to the excision tool. It guides the surgeon tool to the tissues previously localized with the imaging probe. Characterization of the imaging probe showed its ability to detect small tumor remains (15mg) with a submillimetric resolution. The counting probe showed a detection efficiency of 80%.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Faisabilité d une sonde pixelisée autonome (PIXSIC) pour le suivi des cinétiques de fixation de radiotraceurs dans le cerveau de petits animaux éveillés et libres de leurs mouvements

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

A method based on Monte Carlo simulations and voxelized anatomical atlases to evaluate and correct uncertainties on radiotracer accumulation quantitation in beta microprobe studies in the rat brain

International audienc

The potential of the beta-Microprobe, an intracerebral radiosensitive probe, to monitor the [(18)F]MPPF binding in the rat dorsal raphe nucleus.

The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal beta-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [(18)F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using beta-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the DRN of anaesthetised rodents

Physical Characterization of a Wireless Radiotracer Detection System Based on Pixelated Silicon for in Vivo Brain Studies in Freely Moving Rats

BLUPS for the four phenotypic traits studied. Each row corresponds to one individual

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracerswith additional imaging features in freelymoving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions.Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution. (Some figures may appear in colour only in the online journal

Physical Characterization of a Wireless Radiotracer Detection System Based on Pixelated Silicon for in Vivo Brain Studies in Freely Moving Rats

An exciting challenge for neuro-physiological investigations remains the combination of brain imaging and behavioral studies, which associates molecular processes of neuronal communications to their related actions. PIXSIC presents novel strategy using a submillimeter pixellated probe for β+ radiotracer detection based on a reverse-biased, high-resistivity silicon diode; This fully autonomous detection system permits local, time resolved measurements of radiotracers in a volume of a few mm3 with the probe dipped into aqueous solutions of [18F] and [11C]. Preliminary implantation tests on a anaesthetized rats proved functionality of the PIXSIC probe in brain tissues. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with a temporal resolution of less than 2 second

X-band EPR imaging as a tool for gradient dose reconstruction in irradiated bones

PURPOSE: Various tools are currently available for dose reconstruction in individuals after accidental exposure to ionizing radiation. Among the available biological analyses, Monte Carlo simulations, and biophysical methods, such as electron paramagnetic resonance (EPR), the latter has proved its usefulness for retrospective dosimetry. Although EPR spectroscopy is probably the most sensitive technique, it does not provide spatial dosimetric data. This information is, however, highly desirable when steep dose gradient irradiations are involved. The purpose of this work was to explore the possibilities of EPR imaging (EPRI) for spatial dose reconstruction in irradiated biological material. METHODS: X-band EPRI was used to reconstruct ex vivo the relative dose distribution in human bone samples and hydroxyapatite phantoms after irradiation with brachytherapy seeds or x rays. Three situations were investigated: Homogeneous, stepwise gradient, and continuous gradient irradiation. RESULTS: EPRI gave a faithful relative spin density distribution in bone samples and in hydroxyapatite phantoms. Measured dose ratios were in close agreement with the actual delivered dose ratios. EPRI was able to distinguish the dose gradients induced by two different sources (125I and 192Ir). However, the measured spatial resolution of the system was 1.9 mm and this appeared to be a limiting factor. The method could be improved by using new signal postprocessing strategies. CONCLUSIONS: This study demonstrates that EPRI can be used to assess the regional relative dose distribution in irradiated bone samples. The method is currently applicable to ex vivo measurements of small size samples with low variation in tissue density but is likely to be adapted for in vivo application using L-band EPRI