A general method for labeling siRNA by click chemistry with fluorine-18 for in vivo PET imaging

Poster (2010)

Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.

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 ▲]

Is brain activity during a Stroop inhibitory task modulated by the kind of cognitive control required?

Poster (2009, October 21)

NEMA NU4-2008 Image Quality Performance Report for the microPET Focus 120 and for Various Transmission and Reconstruction Methods

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2009), 50

This work aimed to evaluate the image quality and accuracy of attenuation and scatter corrections provided with the microPET Focus 120 scanner using the National Electrical Manufacturers Association NU4 ... [more ▼]

This work aimed to evaluate the image quality and accuracy of attenuation and scatter corrections provided with the microPET Focus 120 scanner using the National Electrical Manufacturers Association NU4-2008 image quality phantom. Methods: Attenuation correction was obtained from transmission measurements using either a 68Ge or a 57Copoint source. Fully correctedemission images were reconstructed using Fourier rebinning (FORE) and filtered backprojection (FBP). For attenuation data obtained with the 57Co source, fully corrected emission images were also reconstructed using FORE and 2-dimensional (2D) ordered-subset expectation maximization (OSEM), 3-dimensional (3D) filtered backprojection (3DRP), 3D OSEM, and 3D maximum a posteriori methods. The mean activity, the coefficients of variation (COVs) of the uniform slices, the recovery coefficients (RCs) for hot rods, and the spillover ratio (SOR) for nonemittingwater and air compartments were measured. Results: For 57Co-based attenuation correction, the mean activity value differed by less than 3% from the true activity.Measuring the attenuation with 68Ge resulted in lower reconstructed activity and higher COV. On the basis of 57Co measurements, the SORs for air and water nonemitting compartments were the closest to zero for attenuation correction. The RC measured on emission images corrected for attenuation but not for scatter did not show any significant difference linked to the transmissionmethod. However, higherRCswere noted for transmission measurement with 68Ge in coincidence with windowing when emission data were corrected for attenuation and scatter. This resulted from a lower mean value in the uniform area. 2D and 3DRP reconstructionmethods showed little effect on themean activity value, whereas iterative 3D methods gave 7%higher values. Higher RCs were found with iterative reconstruction than with FBP and 3DRP. However, the SOR seemed to be optimal with FBP. SORs were higher with iterative methods and decreased with the number of iterations. Conclusion: For studies of small rodents with the Focus 120, 57Co transmission seems to be the most suitable method for attenuation correction. FORE and 2D reconstruction methods appear to be a good compromise between overall image quality and reconstruction time: OSEM provides the largest contrasts, but FBP provides superior attenuation and scatter correction. [less ▲]

Synthesis and Evaluation of 3-(Dihydroxyboryl)benzoic Acids as d,d-Carboxypeptidase R39 Inhibitors.

in Journal of Medicinal Chemistry (2009)

Penicillin binding proteins (PBPs) catalyze steps in the biosynthesis of bacterial cell walls and are the targets for the beta-lactam antibiotics. Non-beta-lactam based antibiotics that target PBPs are of ... [more ▼]

Penicillin binding proteins (PBPs) catalyze steps in the biosynthesis of bacterial cell walls and are the targets for the beta-lactam antibiotics. Non-beta-lactam based antibiotics that target PBPs are of interest because bacteria have evolved resistance to the beta-lactam antibiotics. Boronic acids have been developed as inhibitors of the mechanistically related serine beta-lactamases and serine proteases; however, they have not been explored extensively as PBP inhibitors. Here we report aromatic boronic acid inhibitors of the d,d-carboxypeptidase R39 from Actinomadura sp. strain. Analogues of an initially identified inhibitor [3-(dihydroxyboryl)benzoic acid 1, IC(50) 400 muM] were prepared via routes involving pinacol boronate esters, which were deprotected via a two-stage procedure involving intermediate trifluorborate salts that were hydrolyzed to provide the free boronic acids. 3-(Dihydroxyboryl)benzoic acid analogues containing an amide substituent in the meta, but not ortho position were up to 17-fold more potent inhibitors of the R39 PBP and displayed some activity against other PBPs. These compounds may be useful for the development of even more potent boronic acid based PBP inhibitors with a broad spectrum of antibacterial activity. [less ▲]

Comparaison of reference tissue model versus two compartement model with input function for [18F]Fallypride modelling. A combined microPET-Beta microprobe study in rat.

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July 12), 52(S1), 108

USE OF A BETA MICROPROBE SYSTEM AS AN AFFORDABLE TRANSLATIONAL TOOL COMPARED TO PET – EXAMPLES USING FDG AND 18F-FALLYPRIDE BINDING

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 55

Modified Non-Ionic Solid Supports: a Way to High Activity Fluorine-18 Radiochemistry in Microfluidic Devices

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 12

New Improvements in the Enantioselective Synthesis of 2-[18F]Fluoro-L-Tyrosine and 6-[18F]Fluoro-L-Dopa

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 196

Are Ionic Liquid Useful for Fluorine-18 Labeling?

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 193