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See detailPerformance evaluation of the General Electric eXplore CT 120 micro-CT using the vmCT phantom.
Bahri, Mohamed Ali ULg; Warnock, Geoffrey ULg; Plenevaux, Alain ULg et al

in Nuclear Instruments & Methods in Physics Research Section A (2011), 648

The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high power tube and a flat panel detector. It allows high resolution and high contrast fast CT scanning of ... [more ▼]

The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high power tube and a flat panel detector. It allows high resolution and high contrast fast CT scanning of small animals. The aim of this study was to compare the performance of the eXplore CT 120 with the one of the eXplore Ultra, its predecessor for which the methodology using the vmCT phantom was already described [1]. The phantom was imaged using typical rat (fast scan or F) or mouse (in vivo bone scan or H) scanning protocols. With the slanted edge method, a 10% modulation transfer function (MTF) was observed at 4.4 (F) and 3.9-4.4 (H) mm-1 corresponding to 114 μm resolution. A fairly larger MTF was obtained with the coil method with the MTF for the thinnest coil (3.3 mm-1 ) equal to 0.32 (F) and 0.34 (H). The geometric accuracy was better than 0.3%. There was a highly linear (R2 > 0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom. A cupping effect was clearly seen on the uniform slices and the uniformity-to-noise ratio ranged from 0.52 (F) to 0.89 (H). The air CT number depended on the amount of polycarbonate surrounding the area where it was measured: a difference as high as approximately 200 HU was observed. This hindered the calibration of this scanner in HU. This is likely due to the absence of corrections for beam hardening and scatter in the reconstruction software. However in view of the high linearity of the system, the implementation of these corrections would allow a good quality calibration of the scanner in HU. In conclusion, the eXplore CT 120 achieved a better spatial resolution than the eXplore Ultra (based on previously reported specifications) and future software developments to include beam hardening and scatter corrections will make the new generation CT scanner even more promising. [less ▲]

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See detailUse of a beta microprobe system to measure arterial input function in PET via an arteriovenous shunt in rats
Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg; Goblet, David ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2011), 1

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The ... [more ▼]

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts. In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart. Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32. IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies. [less ▲]

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See detail[18F]fallypride binding in the mouse brain: test-retest and effects of registration
Bahri, Mohamed Ali ULg; Geuzaine, Annabelle ULg; Warnock, Geoffrey ULg et al

Conference (2011, January 17)

The quantification of in vivo receptor kinetics with PET tracer experiments is an intricate and challenging problem especially for small animals such as rats and mice. A test-retest scan is usually set up ... [more ▼]

The quantification of in vivo receptor kinetics with PET tracer experiments is an intricate and challenging problem especially for small animals such as rats and mice. A test-retest scan is usually set up in order to confirm an observed experimental effect or to examine the reliability of the experiment design. Inadequate processing of the image data may also mask small effects. The purpose of this study was to investigate the effect of image registration on [18F]fallypride binding potentials calculated from PET mouse test-retest data. Sub-optimal registration affected the quantification of in vivo receptor kinetics with [18F]fallypride. The absence of anatomical information in the [18F]fallypride image and the lack of a homogeneous tracer distribution, even during the earlier minutes of the scan, lead to erroneous automatic registration. A FDG scan after each [18F]fallypride test could improve registration as FDG provides a more homogeneous brain image. Variability in the data could also result from stress induced by anaesthesia or the experimental environment. [less ▲]

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See detailImage Quality evaluation for 124I in the microPET Focus 120 scanner using the NEMA NU4-2008 phantom
Bahri, Mohamed Ali ULg; Warnock, Geoffrey ULg; Taleb, Dounia ULg et al

Conference (2011, January 17)

Physical properties of iodine-124 such as its high positron energy, corresponding large positron range in tissue and the fraction of the single γ-photons emitted may have detrimental effects on the PET ... [more ▼]

Physical properties of iodine-124 such as its high positron energy, corresponding large positron range in tissue and the fraction of the single γ-photons emitted may have detrimental effects on the PET image quality. The purpose of this work was to evaluate the image quality for iodine-124 in the small animal microPET Focus 120 scanner using the NEMA NU4-2008 image quality phantom. Although the 2 ns timing window gives higher recovery coefficients and slightly lower spill-over ratios and combined with the 350-590 keV energy window gives the lowest spill-over ratio, the combination of the 350-650 keV and 6 ns windows seems to be the best compromise to obtain images with high contrast and low noise content. [less ▲]

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See detailMemantine-induced brain activation as a model for the rapid screening of potential novel antipsychotic compounds: Exemplified by an mGlu2/3 receptor agonist
Dedeurwaerdere, S.; Wintmolders, C.; Straetemans, R. et al

in Society-for-Neuroscience Abstracts/Annual Meeting Publications (2010, November 17), 40

Schizophrenia is a severe, disabling chronic disorder affecting approximately 1% of the population. Unfortunately, patients afflicted by this difficult to treat psychiatric illness remain stigmatized and ... [more ▼]

Schizophrenia is a severe, disabling chronic disorder affecting approximately 1% of the population. Unfortunately, patients afflicted by this difficult to treat psychiatric illness remain stigmatized and are likely to suffer permanent cognitive and social deficits. Improvements and development of more robust and hopefully predictive screening assays for this disease should enhance the identification and development of novel treatments. The present study describes a rapid and robust method for the testing of potential novel antipsychotics by utilising a simplified [14C]2-deoxyglucose (2-DG) uptake autoradiography technique following memantine-induced brain activation. Male C57BL/6JCRL mice were treated with either vehicle, ketamine (30 mg/kg, s.c.) or memantine (20 mg/kg, s.c.). Both NMDA antagonists induced significant increases in 2-DG uptake in specific brain region such as lateral orbital cortex, olfactory tubercle, piriform cortex, cingulate cortex, retrosplenial cortex, lacunosum molecular layer of the hippocampus and the lateral posterior thalamic nucleus. Interestingly, memantine elicited a more robust brain activation signature with a larger dynamic window than ketamine. For further characterisation of the assay, we also tested the effect of diet (fasting versus non-fasting) and different vehicles. In addition, dedicated software, developed particularly for this assay, was evaluated for automated quantification of the brain sections. In subsequent reversal studies, we found that in accordance to the ketamine challenge model (Duncan et al. 1998), the “atypical” anti-psychotic clozapine (2.5 and 10 mg/kg, s.c.) significantly reversed memantine-induced 2-DG uptake whilst the “typical” anti-psychotic haloperidol (0.32 mg/kg, s.c.) was inactive thus further validating our choice of memantine for the challenge agent. An additional study then determined the effects of a mGlu2/3 receptor agonist on both ketamine and memantine-induced brain activation. Pre-treatment with LY404039 (10 mg/kg, s.c.) fully reversed both the ketamine and memantine-induced increase in 2-DG uptake without effects on basal 2-DG uptake. Finally, a small animal PET study was performed with [18F]-FDG in mice and rats investigating the effect of memantine (20 mg/kg) administration in vivo. This study confirmed the memantine-induced brain activation previously demonstrated by autoradiography. In conclusion, this novel pre-clinical method shows potential for the screening of compounds targeting the NMDA receptor hypofunction hypothesis of schizophrenia and may assist in translating these findings from the bench to clinic. [less ▲]

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See detailIN VIVO PET IMAGING OF THE EFFECT OF THE NMDA ANTAGONIST MEMANTINE ON GLUCOSE METABOLISM IN THE RODENT BRAIN
Warnock, Geoffrey ULg; Dedeurwaerdere, Stefanie; Bahri, Mohamed Ali ULg et al

Poster (2010, September)

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See detailTHE EFFECT OF BETA MICROPROBE IMPLANTATION ON THE BLOOD BRAIN BARRIER
Warnock, Geoffrey ULg; Dedeurwaardere, Stefanie; Bahri, Mohamed Ali ULg et al

Poster (2010, September)

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See detailClick chemistry : radiolabelling of oligonucleotides with fluorine- 18 for PET
Kaisin, Geoffroy ULg; Flagothier, Jessica ULg; Mercier, Frédéric ULg et al

Poster (2010, June)

Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET ... [more ▼]

Oligonucleotides (ONs), especially small interfering RNA (siRNA), are promising therapeutic agents, but their pharmacokinetics and biodistributions are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to image and quantify such biological processes. The challenge for the radiochemist is to introduce this short half-life isotope (t1/2(18F)=109.7 min) onto oligonucleotides or, more generally, biomolecules. The most common technique requires the coupling of a prosthetic group bearing the radiotracer with the biomolecule. Current methods for labeling ONs with fluorine-18 have sub-optimal yields and require a long synthesis time.1 Click chemistry, e.g. 1,3-dipolar Huisgen cycloaddition of azides to alkynes, could be an efficient way to increase yields and reduce synthesis time. Conjugations with ONs are usually performed at 3’-ends using a well-chosen linker in order to limit degradation by exonucleases and to avoid alteration of hybridization properties and siRNA gene silencing efficiency. This also allows the development of universal solid supports used for the solidphase synthesis of ONs. Here we report the synthesis of three alkyne-bearing linkers , the synthesis and radiosynthesis of the complementary azido-bearing prosthetic groups (1-(azidomethyl)-4-[18F]- fluorobenzene) and coupling with functionalized ONs. [less ▲]

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See detailAutomated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors
Goblet, David ULg; Thonon, David ULg; Plenevaux, Alain ULg et al

Poster (2010, May 30)

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is ... [more ▼]

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is implicated in numerous neurodegenerative disorders such as Alzheimer disease’s, dementia, depression, anxiety, schizophrenia, and Parkinson disease’s. The 5-HT1A serotonin receptors are involved in several physiological functions including sleep, mood, neurogenesis and learning [1]. Consequently, there have been huge efforts in finding ligands for this receptor. [11C]WAY-100635 is a high affinity radioligand used for quantifying serotonin 5-HT1A receptors with positron emission tomography. An 18F-labeled radioligand is advantageous because of higher specific activity and physical/nuclear properties (t1/2= 109 min, 97% of positron decay and positron energy of 635 keV maximum). [18F]MPPF, a selective 5-HT1A antagonist derived from WAY-100635, is currently one of the most successful PET ligand used for 5-HT1A receptor imaging [2]. However the affinity is lower then WAY-100635 and the amount of [18F]MPPF reaching the brain is relatively low since MPPF is a substrate for p-glycoprotein [3]. Methods: In order to improve the brain uptake of the radiotracer, a desmethylated analog has been developed in our lab and preliminary in vitro studies show positive results [4]. Nevertheless, the radiosynthesis take place in two steps as a protecting group removal is needed. A one step procedure with a MPPF derivative could be of very great interest. We have synthesized many MPPF derivatives in our lab (modification on the phenylpiperazine moiety) and developed an automated radiosynthesis procedure for the production of these radiotracers. [18F]MPPF was chosen as the model compound. We used a GE Healthcare FASTlabTM module and made modifications to the [18F]FDG synthesis sequence and cassette. [18F]MPPF was synthesized by coupling of [18F]FBA with the corresponding amine. After coupling, the crude solution was diluted with water and passed through a tC18 cartridge for prepurification. After elution, the [18F]MPPF was purified by semi-preparative HPLC. Results: Total synthesis time, including purification was approximately 100 min. [18F]FBA and [18F]MPPF were obtained at a corrected yield of 55% (n=20) and 25% (n=5) respectively. The radiochemical purity, checked by radio-TLC and UPLC, was >95%. Conclusions: We have developed an automated method for [18F]MPPF and derivatives production using a commercial synthesizer (FASTlabTM from GE Healthcare) and a conventional HPLC system resulting in good yields and high (radio)chemical purity. By simply switching the vial containing the modified amine, an 18F-labeled MPPF derivative could be obtained. Radiosynthesis is still under optimization and the radiotracers synthesized need to be tested as suitable 5-HT1A radioligands. Acknowledgement: This work was supported by the Fondation Rahier. References: [1] Filip M., Bader M. et Al, Pharmacol Rep. 2009 Sep-Oct; 61(5):761-77 [2] Aznavour N, Zimmer L. Et Al, Neuropharmacology. 2007 Mar; 52(3):695-707 [3] Laćan G., Plenevaux A. et Al, Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66 [4] Defraiteur C., Plenevaux A. et Al., Br J Pharmacol. 2007 Nov; 152(6):952-8 [less ▲]

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See detailFast Production of Highly Reactive No-Carrier-Added [18F]Fluoride for the Labeling of Radiopharmaceuticals
Lemaire, Christian ULg; Aerts, Joël ULg; Voccia, Samuel et al

in Angewandte Chemie (International ed. in English) (2010), 49

The 18F labeling of radiopharmaceuticals requires nearly anhydrous solutions of [18F]fluoride. Aqueous K2CO3 is generally used to elute [18F]fluoride from an anion-exchange resin. Replacing aqueous K2CO3 ... [more ▼]

The 18F labeling of radiopharmaceuticals requires nearly anhydrous solutions of [18F]fluoride. Aqueous K2CO3 is generally used to elute [18F]fluoride from an anion-exchange resin. Replacing aqueous K2CO3 with strong organic bases, such as the phosphazene base P2Et enabled the recovery of highly reactive [18F]fluoride and avoided the azeotropic evaporation of water, which is very difficult on a microchip device. [less ▲]

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See detailFast production of highly concentrated reactive [18F] fluoride for aliphatic and aromatic nucleophilic radiolabelling
Aerts, Joël ULg; Voccia, Samuel; Lemaire, Christian ULg et al

in Tetrahedron Letters (2010), 51

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic ... [more ▼]

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield. [less ▲]

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See detailBreakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.
Boveroux, Pierre ULg; Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg et al

in Anesthesiology (2010), 113(5), 1038-53

BACKGROUND: Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes ... [more ▼]

BACKGROUND: Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes during pharmacological modulation of the level of consciousness. METHODS: Low-frequency spontaneous blood oxygen level-dependent fluctuations were measured in 19 healthy volunteers during wakefulness, mild sedation, deep sedation with clinical unconsciousness, and subsequent recovery of consciousness. RESULTS: Propofol-induced decrease in consciousness linearly correlates with decreased corticocortical and thalamocortical connectivity in frontoparietal networks (i.e., default- and executive-control networks). Furthermore, during propofol-induced unconsciousness, a negative correlation was identified between thalamic and cortical activity in these networks. Finally, negative correlations between default network and lateral frontoparietal cortices activity, present during wakefulness, decreased proportionally to propofol-induced loss of consciousness. In contrast, connectivity was globally preserved in low-level sensory cortices, (i.e., in auditory and visual networks across sedation stages). This was paired with preserved thalamocortical connectivity in these networks. Rather, waning of consciousness was associated with a loss of cross-modal interactions between visual and auditory networks. CONCLUSIONS: Our results shed light on the functional significance of spontaneous brain activity fluctuations observed in functional magnetic resonance imaging. They suggest that propofol-induced unconsciousness could be linked to a breakdown of cerebral temporal architecture that modifies both within- and between-network connectivity and thus prevents communication between low-level sensory and higher-order frontoparietal cortices, thought to be necessary for perception of external stimuli. They emphasize the importance of thalamocortical connectivity in higher-order cognitive brain networks in the genesis of conscious perception. [less ▲]

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See detailDISPLACEMENT OF 18F-FALLYPRIDE BINDING WITH HALOPERIDOL IN A WITHIN-SUBJECT DESIGN USING A BETA MICROPROBE
Warnock, Geoffrey ULg; Goblet, David ULg; Lemaire, Christian ULg et al

in Journal of Cerebral Blood Flow & Metabolism (2009, October), 29(S1), 352-353

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