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Buvat I.,CNRS In-Vivo Molecular Imaging
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2016

In Emission Tomography images are reconstructed by solving an inverse problem: the three-dimensional activity map producing the signal observed by the gamma camera or the Positron Emission Tomography (PET) detector is estimated given a model of the imaging system response. This model gives the set of probabilities Rij that a γ or β + emission occurring at point j in the volume of interest be detected in detection element i. Thorough modeling of this R system matrix (SM) is essential for ensuring the most accurate possible estimate of the activity distribution within the object of interest. Thirty years from now, it was proposed to calculate the system matrix R based on Monte Carlo simulations, as opposed to using analytical geometrical models, for increased accuracy. A lot of progress has been made since the initial idea and using simulations for enhanced SPECT and PET image reconstruction has become a reality. In this paper, we review the rationale for this approach, explain the advantages and limitations, the performance that can be achieved, and the challenges that remain to be solved. © 2015 Elsevier B.V. All rights reserved.

PubMed | CNRS In-Vivo Molecular Imaging
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2016

Cyclosporin A (CsA) and dipyridamole (DPy) are potent inhibitors of the P-glycoprotein (P-gp; ABCB1) in vitro. Their efficacy at inhibiting P-gp at the blood-brain barrier (BBB) is difficult to predict. Efficient and readily available (i.e. marketed) P-gp inhibitors are needed as probes to investigate the role of P-gp at the human BBB. In this study, the P-gp inhibition potency at the BBB of therapeutic doses of CsA or DPy was evaluated in baboons using Positron Emission Tomography (PET) imaging with [(11)C]-N-desmethyl-loperamide ([(11)C]dLop), a radiolabeled P-gp substrate. The preparation of dLop as authentic standard and [(11)C]dLop as radiotracer were revisited so as to improve their production yields. [(11)C]dLop PET imaging was performed in the absence (n=3, baseline condition) and the presence of CsA (15mg/kg/h i.v., n=3). Three animals were injected with i.v. DPy at either 0.56 or 0.96 or 2mg/kg (n=1), corresponding to the usual, maximal and twice the maximal dose in patients, respectively, administered immediately before PET. [(11)C]dLop brain kinetics as well as [(11)C]dLop kinetics and radiometabolites in arterial plasma were measured to calculate [(11)C]dLop area-under the time-activity curve from 10 to 30min in the brain (AUCbrain) and in plasma (AUCplasma). [(11)C]dLop brain uptake was described by AUCR=AUCbrain/AUCplasma. CsA as well as DPy did not measurably influence [(11)C]dLop plasma kinetics and metabolism. Baseline AUCR (0.850.29) was significantly enhanced in the presence of CsA (AUCR=10.83.6). Injection of pharmacologic dose of DPy did not enhance [(11)C]dLop brain distribution with AUCR being 1.2, 0.9 and 1.1 after administration of 0.56, 0.96 and 2mg/kg DPy doses, respectively. We used [(11)C]dLop PET imaging in baboons, a relevant in vivo model of P-gp function at the BBB, to show the P-gp inhibition potency of therapeutic dose CsA. Despite in vitro P-gp inhibition potency, usual doses DPy are not likely to inhibit P-gp function at the BBB.

PubMed | CNRS In-Vivo Molecular Imaging, Hopital Necker and French Institute of Health and Medical Research
Type: Comparative Study | Journal: European journal of radiology | Year: 2016

This study was undertaken to evaluate the impact of free-breathing (FB) vs. Apnea on Shear-wave elastography (SWE) measurements. Quantitative liver-stiffness measurements were obtained during FB and Apnea for 97 patients with various body-morphologies and liver textures. Quality indexes of FB and Apnea elasticity maps (percentage of non-filling (PNF), temporal (TV) and spatial (SV) variabilities) were computed. SWE measurements were also obtained from an homogeneous phantom at rest and during a mechanically-induced motion. Liver-stiffness values estimated from FB and Apnea acquisitions were correlated, particularly for homogeneous livers (r=0.76, P<0.001) and favorable body-morphologies (r=0.68, P<0.001). However FB values were consistently 20-25% lower than Apnea ones (P<0.001). FB also systematically resulted in degradation of TV (P<0.005) and PNF (P<0.001) compared to Apnea but had no impact on SV. With the phantom, no differences between SWE measurements at rest and during motion were observed. Apnea and FB measurements are highly correlated, although FB data quality is degraded compared to Apnea and estimated stiffness in FB is systematically lower than in Apnea. These discrepancies between rest and motion states were observed for patients but not for phantom data, suggesting that patient breath-holding impacts liver stiffness.

PubMed | CNRS In-Vivo Molecular Imaging
Type: | Journal: The international journal of neuropsychopharmacology | Year: 2016

The neuroinflammatory response to morphine exposure modulates its antinociceptive effects, tolerance, and dependence. Positron emission tomography radioligands for translocator protein-18kDa such as [[Morphine significantly increased [[

PubMed | CNRS In-Vivo Molecular Imaging and French Institute of Health and Medical Research
Type: | Journal: Physics in medicine and biology | Year: 2016

Dynamic Contrast Enhanced Ultrasound has been proposed to monitor tumor therapy, in complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a tumor model of mouse, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated. Coefficients of variation (CV) of tissue blood volume (BV) and tissue blood flow (BF) based-parameters were estimated inside 32 sub-regions of the tumors, comparing the log-normal (LN) model with a one-compartment model fed by an arterial input function (AIF) and improved by the introduction of a time delay parameter. Relative perfusion parameters were also estimated by normalization of the LN parameters and normalization of the one-compartment parameters estimated with the AIF, using a reference tissue (RT) region. A direct estimation (rRTd) of relative parameters based on the one-compartment model without using the AIF was also obtained by using the kinetics inside the RT region. Results on test-retest studies show that absolute regional parameters have high CV, whatever the approach, with median values of about 30% for BV, and 40% for BF. The positive impact of normalization was established, showing a coherent estimation of relative parameters, with reduced CV (about 20% for BV and 30% for BF using the rRTd approach). These values were significantly lower (p<0.05) when compared to CV of absolute parameters. The rRTd approach provided the smallest CV and should be preferred for estimating relative perfusion parameters.

PubMed | CNRS In-Vivo Molecular Imaging, University of Munster and Service Hospitalier Frederic Joliot
Type: | Journal: Cancer research | Year: 2017

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, non-invasive imaging by positron emission tomography (PET) with [

PubMed | CNRS In-Vivo Molecular Imaging, French Institute of Health and Medical Research and Paris-Sorbonne University
Type: | Journal: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine | Year: 2017

Vocal fold motion was analyzed during free breathing using two-dimensional dynamic ultrasound imaging. Two cadavers were first analyzed to define easily identifiable landmarks. Motion of the laryngeal tract was then analyzed in an axial plane. Left and right arytenoids and thyroid cartilage were defined on images corresponding to abduction and adduction of the laryngeal tract. Associated area measurements were established for 50 healthy subjects. All area indices were significantly larger during abduction than adduction. Symmetry of motion was established by comparing each hemi-larynx, and mobility fractions were defined. Normal values of laryngeal motion during free breathing were thus established.

PubMed | CNRS In-Vivo Molecular Imaging, University of Porto and University Paris Diderot
Type: | Journal: Drug and alcohol dependence | Year: 2016

A growing area of research suggests that neuroimmunity may impact the pharmacology of opioids. Microglia is a key component of the brain immunity. Preclinical and clinical studies have demonstrated that microglial modulators may improve morphine-induced analgesia and prevent the development of tolerance and dependence. Positron emission tomography (PET) using translocator protein 18kDa (TSPO) radioligand is a clinically validated strategy for the non-invasive detection of microglial activation. We hypothesized that TSPO PET imaging may be used to study the neuroimmune component of opioid tolerance and withdrawal.Healthy rats (n=6 in each group) received either saline or escalating doses of morphine (10-40mg/kg) on five days to achieve tolerance and a withdrawal syndrome after morphine discontinuation. MicroPET imaging with [The baseline binding of [Morphine tolerance and withdrawal did not detectably activate microglia and had no impact on [

PubMed | CNRS In-Vivo Molecular Imaging and CIC Biomagune
Type: | Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism | Year: 2017

Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the invivo expression of CB2R with [

PubMed | CNRS In-Vivo Molecular Imaging, Federal University of Minas Gerais, French National Center for Scientific Research, Multicenter Neuroimaging Platform and 4 more.
Type: Journal Article | Journal: Brain : a journal of neurology | Year: 2016

While emerging evidence suggests that neuroinflammation plays a crucial role in Alzheimers disease, the impact of the microglia response in Alzheimers disease remains a matter of debate. We aimed to study microglial activation in early Alzheimers disease and its impact on clinical progression using a second-generation 18-kDa translocator protein positron emission tomography radiotracer together with amyloid imaging using Pittsburgh compound B positron emission tomography. We enrolled 96 subjects, 64 patients with Alzheimers disease and 32 controls, from the IMABio3 study, who had both (11)C-Pittsburgh compound B and (18)F-DPA-714 positron emission tomography imaging. Patients with Alzheimers disease were classified as prodromal Alzheimers disease (n = 38) and Alzheimers disease dementia (n = 26). Translocator protein-binding was measured using a simple ratio method with cerebellar grey matter as reference tissue, taking into account regional atrophy. Images were analysed at the regional (volume of interest) and at the voxel level. Translocator protein genotyping allowed the classification of all subjects in high, mixed and low affinity binders. Thirty high+mixed affinity binders patients with Alzheimers disease were dichotomized into slow decliners (n = 10) or fast decliners (n = 20) after 2 years of follow-up. All patients with Alzheimers disease had an amyloid positive Pittsburgh compound B positron emission tomography. Among controls, eight had positive amyloid scans (n = 6 high+mixed affinity binders), defined as amyloidosis controls, and were analysed separately. By both volumes of interest and voxel-wise comparison, 18-kDa translocator protein-binding was higher in high affinity binders, mixed affinity binders and high+mixed affinity binders Alzheimers disease groups compared to controls, especially at the prodromal stage, involving the temporo-parietal cortex. Translocator protein-binding was positively correlated with Mini-Mental State Examination scores and grey matter volume, as well as with Pittsburgh compound B binding. Amyloidosis controls displayed higher translocator protein-binding than controls, especially in the frontal cortex. We found higher translocator protein-binding in slow decliners than fast decliners, with no difference in Pittsburgh compound B binding. Microglial activation appears at the prodromal and possibly at the preclinical stage of Alzheimers disease, and seems to play a protective role in the clinical progression of the disease at these early stages. The extent of microglial activation appears to differ between patients, and could explain the overlap in translocator protein binding values between patients with Alzheimers disease and amyloidosis controls.

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