In vivo PET quantification of the dopamine transporter in rat brain with [¹⁸F]LBT-999.

INTRODUCTION: We examined whether [(18)F]LBT-999 ((E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane) is an efficient positron emission tomography (PET) tracer for the quantification of the dopamine transporter (DAT) in the healthy rat brain. METHODS: PET studies were performed using several experimental designs, i.e. test-retest, co-injection with different doses of unlabelled LBT, displacement with GBR12909 and pre-injection of amphetamine. RESULTS: The uptake of [(18)F]LBT-999 confirmed its specific binding to the DAT. The non-displaceable uptake (BP(ND)) in the striatum, between 5.37 and 4.39, was highly reproducible and reliable, and was decreased by 90% by acute injection of GBR12909. In the substantia nigra/ventral tegmental area (SN/VTA), the variability was higher and the reliability was lower. Pre-injection of amphetamine induced decrease of [(18)F]LBT-999 BP(ND) of 50% in the striatum. CONCLUSIONS: [(18)F]LBT-999 allows the quantification of the DAT in living rat brain with high reproducibility, sensitivity and specificity. It could be used to quantify the DAT in rodent models, thereby allowing to study neurodegenerative and neuropsychiatric diseases

4DGVF-based filtering of vector-valued images

International audienceIn this paper, we propose a new method for vector-valued image restoration in order to reduce noise while simultaneously sharpening vector edges. Our approach is a coupled anisotropic diffusion and shock filtering scheme that exploits a new robust 4DGVF vector field tailored for vector-valued images. The proposed scheme sharpens edges in directions diffused from the entire spatio-spectral information available with a more precise and a more stable sharpening effect along the iterative processing. We validate our method on color images as well as on realistic simulations of dynamic PET images

4DGVF segmentation of vector-valued images

International audienceIn this paper, we extend the gradient vector flow field to the vector-valued case for robust variational segmentation of 4D images with active surfaces. Instead of only exploiting scalar edge strength in order to identify vector edges, we propagate both directions and amplitudes of vector gradients computed from the analysis of a structure tensor of the vector-valued image. To reduce contributions from noise in the calculation of the structure tensor, image channels are weighted according to a blind estimator of contrast that take profit of the deformable models framework. The proposed 4DGVF vector field is validated on synthetic image datasets and applied to biological volume delineation in dynamic PET imaging

4-D Gradient Vector Flow : segmentation par surface active pour images multi-composantes

National audienceDans cet article, nous généralisons le flux de vecteurs gradients à la segmentation par surface active d'images 3-D à valeurs vectorielles. Nous basons notre méthode sur la définition d'un tenseur de structure multi-composantes pondéré exploitant l'intégralité de l'information de l'image pour réduire la sensibilité au bruit et améliorer la précision du modèle. Appliquée à la segmentation de volumes biologiques en imagerie par tomographie d'émission de positrons (TEP) dynamique, nous validons notre méthode sur des simulations Monte Carlo réalistes d'images TEP de fantômes numériques

Approche 4DGVF pour la restauration d'images multi-composantes

National audienceDans cet article, nous proposons une nouvelle méthode pour la restauration d'images multi-composantes afin de diminuer le bruit tout en rehaussant simultanément les contours. Notre approche repose sur un filtrage couplant diffusion anisotrope et filtre de choc qui exploite un nouveau champ de decteurs 4DGVF robuste adapté aux images multi-composantes. Le schéma proposé permet de rehausser les contours dans des directions calculées à partir de l'intégralité de l'information spatio-spectrale disponible et d'obtenir un rehaussement plus précis et plus stable au cours du traitement itératif. Nous validons notre méthode sur des images couleurs ainsi que des simulations réalistes d'images TEP dynamiques du cerveau

Variational segmentation of vector-valued images with gradient vector flow

International audienceIn this paper, we extend the gradient vector flow field for robust variational segmentation of vector-valued images. Rather than using scalar edge information, we define a vectorial edge map derived from a weighted local structure tensor of the image that enables the diffusion of the gradient vectors in accurate directions through the 4DGVF equation. To reduce the contribution of noise in the structure tensor, image channels are weighted according to a blind estimator of contrast. The method is applied to biological volume delineation in dynamic PET imaging, and validated on realistic Monte Carlo simulations of numerical phantoms as well as on real images

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the ‘‘time of diagnosis’’ phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatory foci are crucial for an adequate care for patients. In brain diseases, in vivo positron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia. Recently, TSPO has been introduced as a possible molecular target for PSIDs PET imaging, making this protein a potential biomarker to address disease heterogeneity, to assist in patient stratification, and to contribute to predicting treatment response. In this review, we summarized the major research advances recently made in the field of TSPO PET imaging in PSIDs. Promising preliminary results have been reported in bowel, cardiovascular, and rheumatic inflammatory diseases, consolidated by preclinical studies. Limitations of TSPO PET imaging in PSIDs, regarding both its large expression in healthy peripheral tissues, unlike in central nervous system, and the production of peripheral radiolabeled metabolites, are also discussed, regarding their possible consequences on TSPO PET signal’s quantification

The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4′-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease

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