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The correlation of molecular neuroimaging and behavior studies in preclinical PET imaging is of major interest to unlock progress in the understanding of brain processes and assess the validity of preclinical studies in drug development. However, fully achieving this ambition requires performing molecular images of awake and freely moving animals, whereas most of the preclinical imaging procedures are currently performed under anesthesia. To overcome this issue, the MAPSSIC project aims to develop a pixelated intracerebral probe to be implanted into awake and freely moving rats. The aforementioned probe relies on IMIC (Imageur Moléculaire Intra Cérébral), a Monolithic Active Pixel Sensor (MAPS) prototype set to directly detect positrons. The IMIC sensors were produced in 5 different configurations. Measurements using a 204Tl source showed that the sensor parameters can be optimized to boost its performance allowing to increase the sensitivity and reduce the average cluster size. In addition, comparisons between sensor configurations show a clear gain provided by the introduction of CMOS process modifications. Finally, the choice of the optimal sensor configuration will depend on the expected in vivo conditions. [ABSTRACT FROM AUTHOR]

Abstract IMIC is a Monolithic Active Pixel Sensor prototype designed for the MAPSSIC project, which aims at developing wireless intracerebral probes dedicated to image positron-emitting source activity in the brain of awake and freely moving rats. Former experiments with the PIXSIC positron probe based on a passive sensor have validated the proof of concept, but have also shown limitations with regards to the probe robustness and to its transparency to annihilation photons. The IMIC circuit features a matrix of 16 × 128 active pixels of 30 × 50 µm2 size and targets to overcome the PIXSIC probe drawbacks by exploiting a thin sensitive layer of 18 µm, still featuring an overall thickness close to 300 µm. Additionally, by using a low power (55 nW/pixel) in-pixel front-end architecture providing binary output, IMIC solves the challenge of implanting an active sensor in tissues where overheating is forbidden. The needle-shaped sensor 610 µm × 12000 µm was fabricated and tested in laboratory. The whole sensor dissipates 160 µW and its imaging capabilities were asserted with various sources: 55Fe, 90Sr and 18F. These tests also demonstrated robust count-rate measurement with IMIC in the range 10–1000 counts/matrix/s. Finally, a dedicated setup qualitatively confirmed excellent in-sensitivity to 511 keV γ -rays. In this paper, we present the sensor requirements and its detailed design. We also discuss the first characterisation results and the outlook for the integration of IMIC into an implantable probe. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this work was to demonstrate the pharmacokinetic potential of a wireless pixelated β(+)-sensitive probe (PIXSIC).Procedures: The binding of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), a 5-HT1A serotonin receptor radiopharmaceutical, was measured in anesthetized rats and compared to microPET data. The effects of a 5-HT1A antagonist injection on in vivo [(18)F]MPPF binding were monitored by PIXSIC.Results: PIXSIC allowed differentiating the radioactive kinetics according to the location of its pixels in the hippocampus, cortex, corpus callosum, and cerebellum. The device accurately detected the changes in [(18)F]MPPF binding, after 5-HT1A antagonist blockade. The time-activity curves were reproducible and consistent with kinetics obtained simultaneously with a microPET camera.Conclusions: These results demonstrate the ability of the PIXSIC device to record reliably the binding of PET ligands, with a high spatiotemporal resolution in anesthetized rodents. These first in vivo results are a key stage on the path to its implementation in awake freely moving animals. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this work was to demonstrate the pharmacokinetic potential of a wireless pixelated β-sensitive probe (PIXSIC). Procedures: The binding of 2′-methoxyphenyl-( N-2′-pyridinyl)-p-[F]fluoro-benzamidoethylpiperazine ([F]MPPF), a 5-HT serotonin receptor radiopharmaceutical, was measured in anesthetized rats and compared to microPET data. The effects of a 5-HT antagonist injection on in vivo [F]MPPF binding were monitored by PIXSIC. Results: PIXSIC allowed differentiating the radioactive kinetics according to the location of its pixels in the hippocampus, cortex, corpus callosum, and cerebellum. The device accurately detected the changes in [F]MPPF binding, after 5-HT antagonist blockade. The time-activity curves were reproducible and consistent with kinetics obtained simultaneously with a microPET camera. Conclusions: These results demonstrate the ability of the PIXSIC device to record reliably the binding of PET ligands, with a high spatiotemporal resolution in anesthetized rodents. These first in vivo results are a key stage on the path to its implementation in awake freely moving animals. [ABSTRACT FROM AUTHOR]

Abstract: Topographic representation of the outside world is a key feature of sensory systems, but so far it has been difficult to define how the activity pattern of the olfactory information is distributed at successive stages in the olfactory system. We studied odor-evoked activation patterns in the main olfactory bulb and the anterior piriform cortex of rats using functional ultrasound (fUS) imaging. fUS imaging is based on the use of ultrafast ultrasound scanners and detects variations in the local blood volume during brain activation. It makes deep brain imaging of ventral structures, such as the piriform cortex, possible. Stimulation with two different odors (hexanal and pentylacetate) induced the activation of odor-specific zones that were spatially segregated in the main olfactory bulb. Interestingly, the same odorants triggered the activation of the entire anterior piriform cortex, in all layers, with no distinguishable odor-specific areas detected in the power Doppler images. These fUS imaging results confirm the spatial distribution of odor-evoked activity in the main olfactory bulb, and furthermore, they reveal the absence of such a distribution in the anterior piriform cortex at the macroscopic scale in vivo. [Copyright &y& Elsevier]

Multimodal instrumentation is a new technical approach allowing simultaneous and complementary in vivo recordings of complementary biological parameters. To elucidate further the physiopathological mechanisms in intact small animal models, especially for brain studies, a challenging issue is the actual coupling of magnetic resonance imaging (MRI) techniques with positron emission tomography (PET): it has been shown that running the technology for radioactive imaging in a magnet alters the spatiotemporal performance of both modalities. Thus, we propose an alternative coupling of techniques that uses the β-MicroProbe instead of PET for local measurements of radioactivity coupled with MRI. We simultaneously recorded local radioactivity due to [18F]MPPF (a 5-HT1A receptor PET radiotracer) binding in the hippocampus with the β-MicroProbe and carried out anatomical MRI in the same anaesthetised rat. The comparison of [18F]MPPF kinetics obtained from animals in a magnet with kinetics from a control group outside the magnet allowed us to determine the stability of tracer biokinetic measurements over time in the magnet. We were thus able to show that the β-MicroProbe reliably measures radioactivity in rat brains under an intense magnetic field of 7 Tesla. The biological validation of a β-MicroProbe/MRI dual system reported here opens up a wide range of future multimodal approaches for functional and pharmacological measurements by the probe combined with various magnetic resonance technologies, including anatomical MRI, functional MRI and MR spectroscopy. [ABSTRACT FROM AUTHOR]

Elucidating complex physiological mechanisms in small animal in vivo requires the development of new investigatory techniques including imaging with multiple modalities. Combining exploratory techniques has the tremendous advantage to record simultaneously complementary parameters on the same animal. In this field, an exciting challenge remains in the combination of nuclear magnetic resonance (NMR) and positron emission tomography (PET) since small animals studies are limited by strict technical constraints in vivo. Coupling NMR with a radiosensitive β-MicroProbe offers therefore an interesting technical alternative. To assess the feasibility of this new dual-modality system, we designed theoretical and experimental approaches to test the ability of the β-Microprobe to quantify radioactivity concentration in an intense magnetic field. In an initial step, simulations were carried out using Geants. First, we evaluated the influence of a magnetic field on the probe detection volume. Then, the detection sensitivity and energy response of the probe were quantified. In a second step, experiments were run within a 7-T magnet to confirm our simulations results. We showed that using the probe in magnetic fields leads to a slight attenuation in sensitivity and an increase of the scintillation light yield. These data demonstrate the feasibility of combining NMR to the β-MicroProbe. [ABSTRACT FROM AUTHOR]

The aim of this study was to demonstrate the ability of a recently developed β[sup +]-range sensitive intracerebral probe (β-Microprobe) to measure the binding kinetics of [[sup 18]F]MPPF, a well-documented 5-HT[sub 1A] serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT[sub 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 β-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 β-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [[sup 18]F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [[sup 18]F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [[sup 18]F] MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT[sup 1A] antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using β-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [[sup 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 [[sup 18]F]MPPF in the DRN of anaesthetised rodents. [ABSTRACT FROM AUTHOR]

Presents a paper which describes the characteristics and performance of the per-operative compact imager (POCI) camera. Discussion on the optimal simulations and measurements; Results of the intensified position sensitive diode (IPSD); Implementation of a position sensitive diode (PSD).

Presents information on the RITM mini gamma ray-camera. How the camera works; What principle it is based on; Details on how well it performed in tests; Identification of the medical field that it is used in.

The β-microprobe is a simple and versatile technique complementary to small animal positron emission tomography (PET). It relies on local measurements of the concentration of positron-labeled molecules. So far, it has been successfully used in anesthetized rats for pharmacokinetics experiments and for the study of brain energetic metabolism. However, the ability of the technique to provide accurate quantitative measurements using 18F, 11C and 15O tracers is likely to suffer from the contribution of 511 keV gamma rays background to the signal and from the contribution of positrons from brain loci surrounding the locus of interest. The aim of the present paper is to provide a method of evaluating several parameters, which are supposed to affect the quantification of recordings performed in vivo with this methodology. We have developed realistic voxelized phantoms of the rat whole body and brain, and used them as input geometries for Monte Carlo simulations of previous β-microprobe reports. In the context of realistic experiments (binding of 11C-Raclopride to D2 dopaminergic receptors in the striatum; local glucose metabolic rate measurement with 18F-FDG and H2O15 blood flow measurements in the somatosensory cortex), we have calculated the detection efficiencies and corresponding contribution of 511 keV gammas from peripheral organs accumulation. We confirmed that the 511 keV gammas background does not impair quantification. To evaluate the contribution of positrons from adjacent structures, we have developed β-Assistant, a program based on a rat brain voxelized atlas and matrices of local detection efficiencies calculated by Monte Carlo simulations for several probe geometries. This program was used to calculate the ‘apparent sensitivity’ of the probe for each brain structure included in the detection volume. For a given localization of a probe within the brain, this allows us to quantify the different sources of beta signal. Finally, since stereotaxic accuracy is crucial for quantification in most microprobe studies, the influence of stereotaxic positioning error was studied for several realistic experiments in favorable and unfavorable experimental situations (binding of 11C-Raclopride to D2 dopaminergic receptors in the striatum; binding of 18F-MPPF to 5HT1A receptors in the dorsal raphe nucleus). [ABSTRACT FROM AUTHOR]