Contribution of high energy physics techniques to the medical imaging field

The purpose of this study was to show how advanced concepts of compact, lossless and "Time Of Flight" (TOF) capable electronics similar to those foreseen for the LHC and ILC experiments could be fairly and easily transferred to the medical imaging field through Positron Emission Tomography (PET). As a wish of explanation, the two overriding weaknesses of PET camera readout electronics, namely dead-time and timing resolution, were investigated analytically and with a Monte-Carlo simulator presently dedicated to this task. Results have shown there was room left for count rate enhancement through a huge decrease of the timing resolution well below the nanosecond. The novel electronics scheme suggested for PET in this paper has been partly inspired by the long experience led in High Energy Physics where the latter requirement is compulsory. Its structure entirely pipelined combined to a pixelation of the whole detector should allow dead-times to be suppressed, while the absence of devoted timing channel would remove the preponderant contributions to the timing resolution. To the common solution for timing would substitute an optimal filtering method witch clearly appears as a good candidate as timing resolution of a few tens of picoseconds may be achieved provided the shape of the signal is known and sufficient samples are available with enough accuracy. First investigations have yield encouraging results as a sampling frequency of 50 MHz with a 7 bits precision appears sufficient to ensure the 500ps coincidence timing resolution planed. At this point, there will be a baby step ahead to draw benefice from a TOF implementation to the design and the enormous noise variance enhancement that would come with.Comment: presented at EuroMedIm 2006 : 1st European Conference on Molecular Imaging Technology, Marseille 9-12 May 2006, 6 pp, 4 figures, submitted to NI

PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ

PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28γ, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28γ. Its recruitment to proteasome-containing complexes depends on PA28γ and its expression increases the association of PA28γ with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28γ-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28γ in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28γ interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28γ in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus

Study of secondary charged particles emission to monitor in-line dosimetry during hadrontherapy treatment

Ce travail est consacré à l'étude de faisabilité d'une imagerie par reconstruction de vertex (IRV) pour le contrôle qualité en temps réel de la thérapie par faisceau d'ions carbone. La détection de vertex d'interactions nucléaires repose sur la détection de particules secondaires : grâce à un dispositif de détection spatiale des fragments chargés (tracker), on peut reconstruire les trajectoires des particules émergeant du patient et les extrapoler jusqu'à leur point d'origine (le vertex)... Dans le cadre de notre étude, la position du vertex est déterminée de deux manières différentes : soit en calculant l'intersection de la trajectoire d'un fragment émergent avec celle de l'ion incident (connue grâce à l'utilisation d'un hodoscope de faisceau placé en amont du patient), soit grâce à l'intersection de la trajectoire de deux fragments émergents détectés en coïncidence. Notre étude de faisabilité de la technique repose sur l'outil de simulation GEANT4. La première partie de l'étude a consisté à valider cet outil grâce à plusieurs expériences réalisées au GANIL (Caen) et au GSI (Darmstadt) avec des ions carbone de différentes énergies dans des cibles d'eau ou de PMMA Par la suite, la comparaison des deux modes de détection des particules secondaires a montré que la technique utilisant l'hodoscope est la plus performante. Enfin, après l'optimisation des principaux paramètres de cette technique, une simulation réaliste montre qu'il est possible de mesurer le parcours des ions avec une précision millimétrique à l'échelle d'une tranche en énergie voire à l'échelle d'un voxel uniqueThis work is devoted to the feasibility study of interaction vertex imaging (IVI) for real-time quality assurance in hadrontherapy treatments with carbon ion beams. Nuclear interaction vertex detection is based on secondary particle detection: a device allows us to spatially detect charged particles (tracker), thus we can reconstruct the trajectories of particles emerging from the patient and then extrapolate their emission point (vertex). In our study, the vertex position is determined by two ways: either by calculating the intersection of the trajectory of an emerging fragment with the trajectory of the incident ion (measured by means of a beam hodoscope upstream of the patient), or with the intersection of two emerging particles trajectories detected in coincidence. Our feasibility study of this technique relies on the GEANT4 simulation tool. The first part of the study aimed to validate this tool with experiments performed at GANIL (Caen) and GSI (Darmstadt) using carbon ion beams at various energies and in various targets (water or PMMA). Secondly, the comparison of two different technics for secondary particles detection showed that the technique using the hodoscope is the most efficient. Finally, after the parameters optimization of this technique, a realistic simulation shows that it is possible to measure ion paths within millimeter precision during each energy slices. A control of each beam spot may also be possibl

Etude de l'émission de particules chargées secondaires dans l'optique d'un monitorage faisceau et de la dosimétrie en ligne en hadronthérapie

This work is devoted to the feasibility study of interaction vertex imaging (IVI) for real-time quality assurance in hadrontherapy treatments with carbon ion beams. Nuclear interaction vertex detection is based on secondary particle detection: a device allows us to spatially detect charged particles (tracker), thus we can reconstruct the trajectories of particles emerging from the patient and then extrapolate their emission point (vertex). In our study, the vertex position is determined by two ways: either by calculating the intersection of the trajectory of an emerging fragment with the trajectory of the incident ion (measured by means of a beam hodoscope upstream of the patient), or with the intersection of two emerging particles trajectories detected in coincidence. Our feasibility study of this technique relies on the GEANT4 simulation tool. The first part of the study aimed to validate this tool with experiments performed at GANIL (Caen) and GSI (Darmstadt) using carbon ion beams at various energies and in various targets (water or PMMA). Secondly, the comparison of two different technics for secondary particles detection showed that the technique using the hodoscope is the most efficient. Finally, after the parameters optimization of this technique, a realistic simulation shows that it is possible to measure ion paths within millimeter precision during each energy slices. A control of each beam spot may also be possible.Ce travail est consacré à l'étude de faisabilité d'une imagerie par reconstruction de vertex (IRV) pour le contrôle qualité en temps réel de la thérapie par faisceau d'ions carbone. La détection de vertex d'interactions nucléaires repose sur la détection de particules secondaires : grâce à un dispositif de détection spatiale des fragments chargés (tracker), on peut reconstruire les trajectoires des particules émergeant du patient et les extrapoler jusqu'à leur point d'origine (le vertex)... Dans le cadre de notre étude, la position du vertex est déterminée de deux manières différentes : soit en calculant l'intersection de la trajectoire d'un fragment émergent avec celle de l'ion incident (connue grâce à l'utilisation d'un hodoscope de faisceau placé en amont du patient), soit grâce à l'intersection de la trajectoire de deux fragments émergents détectés en coïncidence. Notre étude de faisabilité de la technique repose sur l'outil de simulation GEANT4. La première partie de l'étude a consisté à valider cet outil grâce à plusieurs expériences réalisées au GANIL (Caen) et au GSI (Darmstadt) avec des ions carbone de différentes énergies dans des cibles d'eau ou de PMMA Par la suite, la comparaison des deux modes de détection des particules secondaires a montré que la technique utilisant l'hodoscope est la plus performante. Enfin, après l'optimisation des principaux paramètres de cette technique, une simulation réaliste montre qu'il est possible de mesurer le parcours des ions avec une précision millimétrique à l'échelle d'une tranche en énergie voire à l'échelle d'un voxel unique

Nanofluidic fluorescence microscopy with integrated concentration gradient generation for one-shot parallel kinetic assays

International audienceWe report a simple and cost-effective nanofluidic fluorescence microscopy platform with parallel kinetic assay capability for the determination of kinetic parameters in a single run. An on-chip microfluidic concentration diluter, or gradient generator, was integrated to a biofunctionalized nanofluidic chip, enabling simultaneous interrogation of multiple biomolecular interactions with a full titration series of analyte in a single experiment. We demonstrate that since the association and dissociation phases are induced by the on-chip gradient generator and a reverse buffer flow operation, complete kinetic sensorgrams for IgG/anti-IgG interactions can be achieved within 20 min on a single device, which is at least 10 times faster than traditional kinetic techniques. This method could contribute to low-cost, rapid and high-throughput drug-screening and clinical diagnostics

Appendix A. Selection of the best tag loss and dispersal models in each site.

Selection of the best tag loss and dispersal models in each site