Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18kDa Translocator Protein Radioligand [18F]DPA-714

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuroinflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuroinflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuroinflammation for detection, monitoring, and research in MS

Alien Registration- Dubois, Albertine (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/28015/thumbnail.jp

Exploitation conjointe d'informations anatomiques et fonctionnelles tridimensionnelles pour l'imagerie cérébrale post mortem chez le rongeur

L'émergence de systèmes d'imagerie anatomique (IRM) et fonctionnelle (microTEP) haute résolution pour le Rongeur rend aujourd'hui possible la réalisation d'études in vivo et répétées sur le même animal, comme par exemple le suivi longitudinal de la consommation de glucose cérébral. Cependant, ces systèmes souffrent encore de limitations technologiques telles qu'une sensibilité et une résolution spatiale limitées. Dans ce contexte, l'autoradiographie et l'histologie restent aujourd'hui les techniques de référence les plus largement utilisées pour les _études sur le petit animal en biologie. L'inconvénient majeur de ces techniques d'imagerie post mortem est qu'elles nécessitent la coupe des cerveaux, entraînant la production de centaines de coupes par animal ainsi que la perte de toute cohérence tridimensionnelle (3D). La reconstruction d'un volume biologique en 3D à partir de coupes d'autoradiographie ou d'histologie doit permettre d'améliorer notablement l'exploitation de cette information post mortem et ainsi d'ouvrir de nouvelles perspectives en termes d'analyse de données. Après avoir mis en place des systèmes d'acquisition entièrement automatisés des données (coupes 2D et photographies du plan de coupe), nous avons développé différentes stratégies de reconstruction 3D. Nous avons ainsi envisagé aussi bien la mise en correspondance anatomo-fonctionnelle que la prise en compte de l'information fournie par les photos (cohérence 3D intrinsèque au bloc photographique). Ces travaux, indispensables pour la reconstruction 3D, ont ensuite permis d'évaluer différentes méthodes d'analyse des données fonctionnelles de la plus simple et la plus opérateur-dépendante (tracé de régions d'intérêt) à la plus automatique (analyse statistique de groupes de type Statistical Parametric Mapping). Deux applications biologiques ont été étudiées : stimulation visuelle chez le rat et métabolisme chez un modèle de souris transgéniques Alzheimer. Une perspective de ce travail est le couplage en 3D des informations obtenues post mortem et acquises in vivo à une échelle macroscopique.The recent development of dedicated small animal anatomical (MRI) and functional (microPET) scanners has opened up the possibility of performing repeated functional in vivo studies in the same animal as the longitudinal follow-up of cerebral glucose metabolism. However, these systems still suffer technical limitations including a limited sensitivity and a reduced spatial resolution. Hence, autoradiography and histological studies remain the reference and widely used techniques for biological studies in small animals. The major disadvantage of these post mortem imaging techniques is that they require brain tissue sectioning, entailing the production of large numbers (up to several hundreds) of serial sections and the inherent loss of three-dimensional (3D) spatial consistency. The first step towards improving the analysis of this post mortem information was the development of reliable, automated procedures for the 3D reconstruction of the whole brain sections. We first developed an optimized data acquisition from large numbers of post mortem data (2D sections and blockface photographs). Then, we proposed different strategies of 3D reconstruction of the corresponding volumes. We also addressed the histological to autoradiographic sections and to blockface photographs co-registration problem (the photographic volume is intrinsically spatially consistent). These developments were essential for the 3D reconstruction but also enabled the evaluation of different methods of functional data analysis, from the most straightforward (manual delineation of regionsof- interest) to the most automated (Statistical Parametric Mapping-like approaches for group analysis). Two biological applications were carried out : visual stimulation in rats and cerebral metabolism in a transgenic mouse model of Alzheimer's disease. One perspective of this work is to match reconstructed post mortem data with in vivo images of the same animal.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Advanced optical simulation of scintillation detectors in GATE V8.0: first implementation of a reflectance model based on measured data

Typical PET detectors are composed of a scintillator coupled to a photodetector that detects scintillation photons produced when high energy gamma photons interact with the crystal. A critical performance factor is the collection efficiency of these scintillation photons, which can be optimized through simulation. Accurate modelling of photon interactions with crystal surfaces is essential in optical simulations, but the existing UNIFIED model in GATE is often inaccurate, especially for rough surfaces. Previously a new approach for modelling surface reflections based on measured surfaces was validated using custom Monte Carlo code. In this work, the LUT Davis model is implemented and validated in GATE and GEANT4, and is made accessible for all users in the nuclear imaging research community. Look-up-tables (LUTs) from various crystal surfaces are calculated based on measured surfaces obtained by atomic force microscopy. The LUTs include photon reflection probabilities and directions depending on incidence angle. We provide LUTs for rough and polished surfaces with different reflectors and coupling media. Validation parameters include light output measured at different depths of interaction in the crystal and photon track lengths, as both parameters are strongly dependent on reflector characteristics and distinguish between models. Results from the GATE/GEANT4 beta version are compared to those from our custom code and experimental data, as well as the UNIFIED model. GATE simulations with the LUT Davis model show average variations in light output of  <2% from the custom code and excellent agreement for track lengths with R 2  >  0.99. Experimental data agree within 9% for relative light output. The new model also simplifies surface definition, as no complex input parameters are needed. The LUT Davis model makes optical simulations for nuclear imaging detectors much more precise, especially for studies with rough crystal surfaces. It will be available in GATE V8.0

Advanced optical simulation of scintillation detectors in GATE V8.0: first implementation of a reflectance model based on measured data

International audienceTypical PET detectors are composed of a scintillator coupled to a photodetector that detects scintillation photons produced when high energy gamma photons interact with the crystal. A critical performance factor is the collection efficiency of these scintillation photons, which can be optimized through simulation. Accurate modelling of photon interactions with crystal surfaces is essential in optical simulations, but the existing UNIFIED model in GATE is often inaccurate, especially for rough surfaces. Previously a new approach for modelling surface reflections based on measured surfaces was validated using custom Monte Carlo code. In this work, the LUT Davis model is implemented and validated in GATE and GEANT4, and is made accessible for all users in the nuclear imaging research community. Look-up-tables (LUTs) from various crystal surfaces are calculated based on measured surfaces obtained by atomic force microscopy. The LUTs include photon reflection probabilities and directions depending on incidence angle. We provide LUTs for rough and polished surfaces with different reflectors and coupling media. Validation parameters include light output measured at different depths of interaction in the crystal and photon track lengths, as both parameters are strongly dependent on reflector characteristics and distinguish between models. Results from the GATE/GEANT4 beta version are compared to those from our custom code and experimental data, as well as the UNIFIED model. GATE simulations with the LUT Davis model show average variations in light output of    0.99. Experimental data agree within 9% for relative light output. The new model also simplifies surface definition, as no complex input parameters are needed. The LUT Davis model makes optical simulations for nuclear imaging detectors much more precise, especially for studies with rough crystal surfaces. It will be available in GATE V8.0

Automated indexation of metabolic changes in Alzheimer's mice using a voxel-wise approach combined to an MRI-based 3D digital atlas

International audienceBrain glucose uptake was examined in transgenic mice relevant to Alzheimer's disease (APP/PS1) and their control littermates (PS1). Glucose distribution in the brain of the resting animals was measured using 3D-reconstructed autoradiography and analysed by a voxel-wise approach using SPMMouse combined to an MRI-based 3D digital atlas. Prompt and direct indexation of metabolic changes between the two groups was achieved, showing both hypo-and hypermetabolism of glucose in the brain of APP/PS1 mice. We confirm and extend previous study, since we identified brain structures affected in this pathological model and demonstrate glucose uptake changes in structures like the olfactory bulb. Our results pave the way to complete and accurate examination of functional data from cerebral structures involved in models of neurodegenerative diseases

Co-registration of glucose metabolism with positron emission tomography and vascularity with fluorescent diffuse optical tomography in mouse tumors

BACKGROUND: Bimodal molecular imaging with fluorescence diffuse optical tomography (fDOT) and positron emission tomography (PET) has the capacity to provide multiple molecular information of mouse tumors. The objective of the present study is to co-register fDOT and PET molecular images of tumors in mice automatically. METHODS: The coordinates of bimodal fiducial markers (FM) in regions of detection were automatically detected in planar optical images (x, y positions) in laser pattern optical surface images (z position) and in 3-D PET images. A transformation matrix was calculated from the coordinates of the FM in fDOT and in PET and applied in order to co-register images of mice bearing neuroendocrine tumors. RESULTS: The method yielded accurate non-supervised co-registration of fDOT and PET images. The mean fiducial registration error was smaller than the respective voxel sizes for both modalities, allowing comparison of the distribution of contrast agents from both modalities in mice. Combined imaging depicting tumor metabolism with PET-[(18) F]2-deoxy-2-fluoro-d-glucose and blood pool with fDOT demonstrated partial overlap of the two signals. CONCLUSIONS: This automatic method for co-registration of fDOT with PET and other modalities is efficient, simple and rapid, opening up multiplexing capacities for experimental in vivo molecular imaging

Decreased metabolic response to visual stimulation in the superior colliculus of mice lacking the glial glutamate transporter GLT-1

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