Nicolas Costes - Academia.edu (original) (raw)
Papers by Nicolas Costes
Scientific Reports, Jan 27, 2023
PET data were submitted to list mode motion correction 40 , then re-binned into 24-time frames (v... more PET data were submitted to list mode motion correction 40 , then re-binned into 24-time frames (variable length frames, 8 × 15 s, 3 × 60 s, 5 × 120 s, 1 × 300 s, 7 × 600 s) for dynamic reconstruction. Images were reconstructed using OP-OSEM 3D incorporating the system point spread function using 3 iterations of 21 subsets. Sinograms were corrected for scatter, random, normalization, and attenuation 41. Reconstructions were performed with a zoom of 2, which yielded a voxel size of 1.04 × 1.04 × 2.08 mm 3 in a matrix of 344 × 344 × 127 voxels. Gaussian post-reconstruction filtering (FWHM = 2 mm) was applied to PET images.
Research Square (Research Square), Aug 18, 2022
Background: In parallel to the traditional symptomatology, de cits in cognition (memory, attentio... more Background: In parallel to the traditional symptomatology, de cits in cognition (memory, attention, reasoning, social functioning) contribute signi cantly to disability and suffering in individuals with schizophrenia. Cognitive de cits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive de cits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial Direct Current Stimulation). However, a signi cant proportion of patients derive no cognitive bene ts after tDCS treatment. Further, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. Method: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham controlled, 4centers trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1-and 3-month follow-up. The primary outcome will be the number of responders, de ned as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive bene ts from active tDCS and whether there are changes in EAP measures in responders after active tDCS. Discussion: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a Randomized Controlled Trial (RCT) with follow-up assessments up to 3 months and a large sample size. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive de cit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia. Trial registration: ClinicalTrials.gov NCT05440955. Prospectively registered on July 1 st , 2022 Administrative Information Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modi ed to group similar items (see http://www.equator-network.org/reportingguidelines/spirit-2013-statement-de ning-standard-protocol-items-for-clinical-trials/). Original French title: E cacité et tolérance de la stimulation électrique transcrânienne fronto-temporale gauche à courant continu (tDCS) comme traitement du dé cit cognitif chez les sujets atteints de schizophrénie débutante : un essai multicentrique, randomisé, contrôlé. Trial registration {2a and 2b} Clinicaltrials.gov registration number: NCT05440955, rst posted on July 1 st , 2022 Protocol version {3} version 0.2 on June 7 th 15th, 2021, substantial modi cation n°1
PLOS ONE, Oct 17, 2014
Introduction: Preclinical in vivo imaging requires precise and reproducible delineation of brain ... more Introduction: Preclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies. Methods: High-resolution 7T 2DT2 MR images of 12 Sprague-Dawley rat brains were manually segmented into 27-VOI label volumes using detailed protocols. Automated methods were developed with 7/12 atlas datasets, i.e. the MRIs and their associated label volumes. MRIs were registered to a common space, where an MRI template and a maximum probability atlas were created. Three automated methods were tested: 1/registering individual MRIs to the template, and using a single atlas (SA), 2/using the maximum probability atlas (MP), and 3/registering the MRIs from the multi-atlas dataset to an individual MRI, propagating the label volumes and fusing them in individual MRI space (propagation & fusion, PF). Evaluation was performed on the five remaining rats which additionally underwent [ 18 F]FDG PET. Automated and manual segmentations were compared for morphometric performance (assessed by comparing volume bias and Dice overlap index) and functional performance (evaluated by comparing extracted PET measures). Results: Only the SA method showed volume bias. Dice indices were significantly different between methods (PF.MP.SA). PET regional measures were more accurate with multi-atlas methods than with SA method. Conclusions: Multi-atlas methods outperform SA for automated anatomical brain segmentation and PET measure's extraction. They perform comparably to manual segmentation for FDG-PET quantification. Multi-atlas methods are suitable for rapid reproducible VOI analyses.
Trials, Feb 24, 2023
Background In parallel to the traditional symptomatology, deficits in cognition (memory, attentio... more Background In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. Method The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1-and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.
![Research paper thumbnail of Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [<sup>11</sup>C]-(<i>R</i>)-PK11195 PET and MRI](https://attachments.academia-assets.com/119794714/thumbnails/1.jpg)
](Journal of Cerebral Blood Flow and Metabolism, Jul 20, 2016
Inflammation may play a role in the development of epilepsy after brain insults. [ 11 C]-(R)-PK11... more Inflammation may play a role in the development of epilepsy after brain insults. [ 11 C]-(R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [ 11 C]-(R)-PK11195 binding during epileptogenesis after pilocarpineinduced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 þ 6, D0 þ 35, D0 ¼ SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/ CT. On D0 þ 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to twofold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 þ 6. Some individuals showed increases at D0 þ 35. AIF models yielded more consistent increases at D0 þ 6. FA values were decreased at D0 þ 6 and had recovered by D0 þ 35. MD was increased at D0 þ 6 and more so at D0 þ 35. [ 11 C]-(R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.
Research Square (Research Square), Feb 28, 2023
Background: The low throughout of small animal positron emission tomography (PET) images acquisit... more Background: The low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design an low-cost support for whole-body PET scanning of two lying rats, and (ii) to study its impact on brain image quanti cation. Methods: A dual holder system compatible with the Siemens INVEON PET scanner was conceived and produced using a 3D printer. The developed system allows to overlap the two INVEON beds, 5 cm apart. Two cone masks can deliver gas anesthesia through the scanner's head side, and the tail veins of both rats are freely accessible on the back side of the scanner, allowing the radiotracer injection before or during the scans. Ear and tooth bars immobilize the rats' head on a stereotactic position. Six experiments of two cylindrical phantoms per session (50 ml tubes lled with different 18 F activity) were scanned solo, on upper or lower bed and duo, on both beds. Four experiments were performed on 8 Sprague Dawley male rats (330 ± 66 g). For each experiment, two rats fasted for 4 hours, received a [ 18 F]FDG dose (34.5 ± 5.5 kBq) and underwent 4 imaging conditions, starting 20 minutes after radiotracer injection: (1) One rat only for a solo test scan (2) repeated for a solo retest, (3) two rats simultaneously for a duo test, (4) repeated for a duo retest. Results: Accuracy of concentration measurement was 5.09% for one phantom in the FOV, and 4.35% for two phantoms measured simultaneously. Ratio concentration between phantoms reached an accuracy of
ABSTRACTBackgroundIn the last decades, advances in Intensive Care Unit management have led to dec... more ABSTRACTBackgroundIn the last decades, advances in Intensive Care Unit management have led to decreased mortality. However, significant morbidity remains as patients survive after a lesional coma with uncertain quality of awakening and high risk of functional disability. Predicting this level of recovery but also the functional disability of those who will awake constitutes a major challenge for medical, ethical and social perspectives. Among the huge heterogeneity of coma-related injuries, recognising the universality of a common functional pattern which may be focused on a final step of an integrated network would be of great interest for our understanding of disorders of consciousness. The objective of this study is to investigate the neural correlates of arousal and awareness in coma and post-coma to build a prognostic tool based on the detection of a common pattern between patients with a favourableversusan unfavourable outcome.Method/DesignWe will implement this objective in a...
Cerebral Cortex, 2021
Memory consolidation involves reorganization at both the synaptic and system levels. The latter i... more Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of...
![Research paper thumbnail of Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging](https://attachments.academia-assets.com/119794710/thumbnails/1.jpg)
](EJNMMI Physics, 2020
Background A valid photon attenuation correction (AC) method is instrumental for obtaining quanti... more Background A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain. Methods Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE...
Journal of Applied Physiology, 2019
Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilat... more Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilation-induced lung injury (VILI). We assessed the performance of [11C](R)-PK11195, a positron emission tomography (PET) radiotracer binding the translocator protein, to quantify macrophage lung recruitment during experimental VILI. Pigs ( n = 6) were mechanically ventilated under general anesthesia, using protective ventilation settings (baseline). Experimental VILI was performed by titrating tidal volume to reach a transpulmonary end-inspiratory pressure (∆PL) of 35–40 cmH2O. We acquired PET/computed tomography (CT) lung images at baseline and after 4 h of VILI. Lung macrophages were quantified in vivo by the standardized uptake value (SUV) of [11C](R)-PK11195 measured in PET on the whole lung and in six lung regions and ex vivo on lung pathology at the end of experiment. Lung mechanics were extracted from CT images to assess their association with the PET signal. ∆PL increased from 9 ± 1...
NeuroImage, Feb 14, 2016
To accurately quantify the radioactivity concentration measured by PET, emission data need to be ... more To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods in general demonstrated improvements compared to vendor-implemented AC, and many studies report deviations in PET uptake after AC of only a few percent from a gold standard CT-AC. Using a unified quantitative evaluation with identical metrics, subject cohort, and common CT-based reference, the aims of this study were to evaluate a selection of novel methods proposed in the literature, and identify the ones suitable for clin...
PloS one, 2016
Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians ... more Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians in their diagnosis by marking abnormal regions in an image. We propose a machine learning system based on a one-class support vector machine (OC-SVM) classifier for the detection of abnormalities in magnetic resonance images (MRI) applied to patients with intractable epilepsy. The system learns the features associated with healthy control subjects, allowing a voxelwise assessment of the deviation of a test subject pattern from the learned patterns. While any number of various features can be chosen and learned, here we focus on two texture parameters capturing image patterns associated with epileptogenic lesions on T1-weighted brain MRI e.g. heterotopia and blurred junction between the grey and white matter. The CAD output consists of patient specific 3D maps locating clusters of suspicious voxels ranked by size and degree of deviation from control patterns. System performance was evalua...
Brain structure & function, Jan 18, 2016
How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor ... more How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor information into behavioral responses is still largely unknown. Indeed, rat olfactory cortices encompass an extensive network located in the ventral part of the brain, thus complicating the use of invasive functional methods. In vivo imaging techniques that were previously developed for brain activation studies in humans have been adapted for use in rodents and facilitate the non-invasive mapping of the whole brain. In this study, we report an initial series of experiments designed to demonstrate that microPET is a powerful tool to investigate the neural processes underlying odor-induced behavioral response in a large-scale olfactory neuronal network. After the intravenous injection of [(18)F]Fluorodeoxyglucose ([(18)F]FDG), awake rats were placed in a ventilated Plexiglas cage for 50 min, where odorants were delivered every 3 min for a 10-s duration in a random order. Individual behavio...
Brain : a journal of neurology, Jan 27, 2015
Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this ... more Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervat...
Cognitive Brain Research, 2005
Using positron emission tomography (PET), we investigated the organisation of spatial versus obje... more Using positron emission tomography (PET), we investigated the organisation of spatial versus object-based visual working memory in 11 normal human subjects. The paradigm involved a conditional colour-response association task embedded within two visual working memory tasks. The subject had to remember a position (spatial) or shape (object-based) and then use this to recover the colour of the matching element for the conditional association. Activation of the nucleus accumbens and the anterior cingulate cortex was observed during the conditional associative task, indicating a possible role of these limbic structures in associative memory. When the 2 memory tasks were contrasted, we observed activation of 2 distinct cortical networks: (1) The spatial task activated a dorsal stream network distributed in the right hemisphere in the parieto-occipital cortex and the dorsal prefrontal cortex, and (2) The non spatial task activated a ventral stream network distributed in the left hemisphere in the temporo-occipital cortex, the ventral prefrontal cortex and the striatum. These results support the existence of a domain-specific dissociation with dorsal and ventral cortical systems involved respectively in spatial and non spatial working memory functions.
NeuroImage, 2010
Neuroimaging studies are increasingly performed on non-human primates, including Macaca fascicula... more Neuroimaging studies are increasingly performed on non-human primates, including Macaca fascicularis. The analysis of functional imaging studies requires a corresponding anatomical image in order to identify brain structures. In the specific case of positron emission tomography (PET), anatomical correspondence is also required for quantification and modeling of interactions between the PET ligand and its pharmacological receptors. For voxel-based statistical parametric mapping, a reference frame (template) is needed to perform spatial normalization of individual brains. In this work we introduce a specific brain template and its associated atlas, with the purpose of enabling accurate, robust and reliable normalization and anatomical labeling of Macaca fascicularis brain images. S174 NRM2010 abstracts-Poster presentations individual MRIs. By comparison of ROI volumes, ROI tracer distribution volumes and modeled binding parameters were established, and bias, standard error and intra-class coefficients (ICC) computed. Results: Fig. 1 shows the atlas, template and fusion on three orthogonal slices centered on the striatum. Visual inspections were in good agreement with the anatomy. Robustness tests were passed with success for every individual. Reproducibility was high, with bias between methods smaller than the test-retest standard error, and ICCs were over 0.7. Conclusion: A brain Macaca fascicularis template and a reference atlas were obtained and validated. These references are suitable for future voxel-based, longitudinal and multi-tracer analyses. They are also useful for quantification, for post-hoc corrections such as partial volume effect recovery, and for inter-individual comparisons.
![Research paper thumbnail of Effect of sensory stimulus on striatal dopamine release in humans and cats: a [11C]raclopride PET study](https://attachments.academia-assets.com/119794781/thumbnails/1.jpg)
](Neuroscience Letters, 2004
Background : Sensory stimulation of the forelimb extremities constitutes a well-established exper... more Background : Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. Objectives : To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [ 11 C]raclopride. Experiments in humans were paralled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [ 11 C]raclopride binding (BP raclo), a radioligand probing DA D2-receptors. Results : In humans no significant difference of BP raclo in caudate (with sensory stimulation: 2.0 ± 0.3 versus without sensory stimulation: 2.2 ± 0.3; P = 0.3) or putamen (2.6 ± 0.3 versus 2.6 ± 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP raclo was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 ± 0.4 versus without sensory stimulation: 2.1 ± 0.2; P = 0.5) and the putamen (2.5 ± 0.4 versus 2.6 ± 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 ± 0.03 versus without sensory stimulation: 2.4 ± 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 ± 0.04 versus 2.5 ± 0.06; P = 0.6). The [ 11 C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. Conclusion : This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [ 11 C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.
![Research paper thumbnail of Striatal dopamine during sensorial stimulations: A [18F]FDOPA PET study in human and cats](https://attachments.academia-assets.com/119794784/thumbnails/1.jpg)
](Neuroscience Letters, 2005
Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsila... more Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsilateral striatum and to decrease it in the homologous contralateral structure. Using positron emission tomography in both humans and cats, the present study shows that such sensory stimulations greatly reduce [ 18 F]FDOPA accumulation ipsilateral to the stimulation (by 40.4% and 26.4% in the human caudate and putamen, respectively, and by 33.3% in the cat striatum). This decrease in striatal [ 18 F]FDOPA uptake suggests a reduced DA storage resulting from the increased amine release. No change was observed in the contralateral striatum in neither human or cat suggesting, in contrast, that [ 18 F]FDOPA accumulation is not facilitated by decreased DA release. These results support the hypothesis that sensory stimulations activate a non-synaptic mode of dopamine release.
![Research paper thumbnail of Modeling [18F]MPPF Positron Emission Tomography Kinetics for the Determination of 5-Hydroxytryptamine(1A) Receptor Concentration with Multiinjection](https://attachments.academia-assets.com/119794709/thumbnails/1.jpg)
](Journal of Cerebral Blood Flow & Metabolism, 2002
The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-piry... more The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. ...
Circulation: Cardiovascular Imaging, 2009
Background— Despite the major role attributed to myocardial vagal activity in left ventricular ar... more Background— Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown. Methods and Results— Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [ 11 C]methylquinuclidinyl benzilate ([ 11 C]MQNB) in 11 patients 43�20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [ 11 C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy...
Scientific Reports, Jan 27, 2023
PET data were submitted to list mode motion correction 40 , then re-binned into 24-time frames (v... more PET data were submitted to list mode motion correction 40 , then re-binned into 24-time frames (variable length frames, 8 × 15 s, 3 × 60 s, 5 × 120 s, 1 × 300 s, 7 × 600 s) for dynamic reconstruction. Images were reconstructed using OP-OSEM 3D incorporating the system point spread function using 3 iterations of 21 subsets. Sinograms were corrected for scatter, random, normalization, and attenuation 41. Reconstructions were performed with a zoom of 2, which yielded a voxel size of 1.04 × 1.04 × 2.08 mm 3 in a matrix of 344 × 344 × 127 voxels. Gaussian post-reconstruction filtering (FWHM = 2 mm) was applied to PET images.
Research Square (Research Square), Aug 18, 2022
Background: In parallel to the traditional symptomatology, de cits in cognition (memory, attentio... more Background: In parallel to the traditional symptomatology, de cits in cognition (memory, attention, reasoning, social functioning) contribute signi cantly to disability and suffering in individuals with schizophrenia. Cognitive de cits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive de cits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial Direct Current Stimulation). However, a signi cant proportion of patients derive no cognitive bene ts after tDCS treatment. Further, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. Method: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham controlled, 4centers trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1-and 3-month follow-up. The primary outcome will be the number of responders, de ned as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive bene ts from active tDCS and whether there are changes in EAP measures in responders after active tDCS. Discussion: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a Randomized Controlled Trial (RCT) with follow-up assessments up to 3 months and a large sample size. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive de cit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia. Trial registration: ClinicalTrials.gov NCT05440955. Prospectively registered on July 1 st , 2022 Administrative Information Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modi ed to group similar items (see http://www.equator-network.org/reportingguidelines/spirit-2013-statement-de ning-standard-protocol-items-for-clinical-trials/). Original French title: E cacité et tolérance de la stimulation électrique transcrânienne fronto-temporale gauche à courant continu (tDCS) comme traitement du dé cit cognitif chez les sujets atteints de schizophrénie débutante : un essai multicentrique, randomisé, contrôlé. Trial registration {2a and 2b} Clinicaltrials.gov registration number: NCT05440955, rst posted on July 1 st , 2022 Protocol version {3} version 0.2 on June 7 th 15th, 2021, substantial modi cation n°1
PLOS ONE, Oct 17, 2014
Introduction: Preclinical in vivo imaging requires precise and reproducible delineation of brain ... more Introduction: Preclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies. Methods: High-resolution 7T 2DT2 MR images of 12 Sprague-Dawley rat brains were manually segmented into 27-VOI label volumes using detailed protocols. Automated methods were developed with 7/12 atlas datasets, i.e. the MRIs and their associated label volumes. MRIs were registered to a common space, where an MRI template and a maximum probability atlas were created. Three automated methods were tested: 1/registering individual MRIs to the template, and using a single atlas (SA), 2/using the maximum probability atlas (MP), and 3/registering the MRIs from the multi-atlas dataset to an individual MRI, propagating the label volumes and fusing them in individual MRI space (propagation & fusion, PF). Evaluation was performed on the five remaining rats which additionally underwent [ 18 F]FDG PET. Automated and manual segmentations were compared for morphometric performance (assessed by comparing volume bias and Dice overlap index) and functional performance (evaluated by comparing extracted PET measures). Results: Only the SA method showed volume bias. Dice indices were significantly different between methods (PF.MP.SA). PET regional measures were more accurate with multi-atlas methods than with SA method. Conclusions: Multi-atlas methods outperform SA for automated anatomical brain segmentation and PET measure's extraction. They perform comparably to manual segmentation for FDG-PET quantification. Multi-atlas methods are suitable for rapid reproducible VOI analyses.
Trials, Feb 24, 2023
Background In parallel to the traditional symptomatology, deficits in cognition (memory, attentio... more Background In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. Method The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1-and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.
Journal of Cerebral Blood Flow and Metabolism, Jul 20, 2016
Inflammation may play a role in the development of epilepsy after brain insults. [ 11 C]-(R)-PK11... more Inflammation may play a role in the development of epilepsy after brain insults. [ 11 C]-(R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [ 11 C]-(R)-PK11195 binding during epileptogenesis after pilocarpineinduced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 þ 6, D0 þ 35, D0 ¼ SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/ CT. On D0 þ 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to twofold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 þ 6. Some individuals showed increases at D0 þ 35. AIF models yielded more consistent increases at D0 þ 6. FA values were decreased at D0 þ 6 and had recovered by D0 þ 35. MD was increased at D0 þ 6 and more so at D0 þ 35. [ 11 C]-(R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.
Research Square (Research Square), Feb 28, 2023
Background: The low throughout of small animal positron emission tomography (PET) images acquisit... more Background: The low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design an low-cost support for whole-body PET scanning of two lying rats, and (ii) to study its impact on brain image quanti cation. Methods: A dual holder system compatible with the Siemens INVEON PET scanner was conceived and produced using a 3D printer. The developed system allows to overlap the two INVEON beds, 5 cm apart. Two cone masks can deliver gas anesthesia through the scanner's head side, and the tail veins of both rats are freely accessible on the back side of the scanner, allowing the radiotracer injection before or during the scans. Ear and tooth bars immobilize the rats' head on a stereotactic position. Six experiments of two cylindrical phantoms per session (50 ml tubes lled with different 18 F activity) were scanned solo, on upper or lower bed and duo, on both beds. Four experiments were performed on 8 Sprague Dawley male rats (330 ± 66 g). For each experiment, two rats fasted for 4 hours, received a [ 18 F]FDG dose (34.5 ± 5.5 kBq) and underwent 4 imaging conditions, starting 20 minutes after radiotracer injection: (1) One rat only for a solo test scan (2) repeated for a solo retest, (3) two rats simultaneously for a duo test, (4) repeated for a duo retest. Results: Accuracy of concentration measurement was 5.09% for one phantom in the FOV, and 4.35% for two phantoms measured simultaneously. Ratio concentration between phantoms reached an accuracy of
ABSTRACTBackgroundIn the last decades, advances in Intensive Care Unit management have led to dec... more ABSTRACTBackgroundIn the last decades, advances in Intensive Care Unit management have led to decreased mortality. However, significant morbidity remains as patients survive after a lesional coma with uncertain quality of awakening and high risk of functional disability. Predicting this level of recovery but also the functional disability of those who will awake constitutes a major challenge for medical, ethical and social perspectives. Among the huge heterogeneity of coma-related injuries, recognising the universality of a common functional pattern which may be focused on a final step of an integrated network would be of great interest for our understanding of disorders of consciousness. The objective of this study is to investigate the neural correlates of arousal and awareness in coma and post-coma to build a prognostic tool based on the detection of a common pattern between patients with a favourableversusan unfavourable outcome.Method/DesignWe will implement this objective in a...
Cerebral Cortex, 2021
Memory consolidation involves reorganization at both the synaptic and system levels. The latter i... more Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of...
EJNMMI Physics, 2020
Background A valid photon attenuation correction (AC) method is instrumental for obtaining quanti... more Background A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain. Methods Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE...
Journal of Applied Physiology, 2019
Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilat... more Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilation-induced lung injury (VILI). We assessed the performance of [11C](R)-PK11195, a positron emission tomography (PET) radiotracer binding the translocator protein, to quantify macrophage lung recruitment during experimental VILI. Pigs ( n = 6) were mechanically ventilated under general anesthesia, using protective ventilation settings (baseline). Experimental VILI was performed by titrating tidal volume to reach a transpulmonary end-inspiratory pressure (∆PL) of 35–40 cmH2O. We acquired PET/computed tomography (CT) lung images at baseline and after 4 h of VILI. Lung macrophages were quantified in vivo by the standardized uptake value (SUV) of [11C](R)-PK11195 measured in PET on the whole lung and in six lung regions and ex vivo on lung pathology at the end of experiment. Lung mechanics were extracted from CT images to assess their association with the PET signal. ∆PL increased from 9 ± 1...
NeuroImage, Feb 14, 2016
To accurately quantify the radioactivity concentration measured by PET, emission data need to be ... more To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods in general demonstrated improvements compared to vendor-implemented AC, and many studies report deviations in PET uptake after AC of only a few percent from a gold standard CT-AC. Using a unified quantitative evaluation with identical metrics, subject cohort, and common CT-based reference, the aims of this study were to evaluate a selection of novel methods proposed in the literature, and identify the ones suitable for clin...
PloS one, 2016
Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians ... more Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians in their diagnosis by marking abnormal regions in an image. We propose a machine learning system based on a one-class support vector machine (OC-SVM) classifier for the detection of abnormalities in magnetic resonance images (MRI) applied to patients with intractable epilepsy. The system learns the features associated with healthy control subjects, allowing a voxelwise assessment of the deviation of a test subject pattern from the learned patterns. While any number of various features can be chosen and learned, here we focus on two texture parameters capturing image patterns associated with epileptogenic lesions on T1-weighted brain MRI e.g. heterotopia and blurred junction between the grey and white matter. The CAD output consists of patient specific 3D maps locating clusters of suspicious voxels ranked by size and degree of deviation from control patterns. System performance was evalua...
Brain structure & function, Jan 18, 2016
How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor ... more How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor information into behavioral responses is still largely unknown. Indeed, rat olfactory cortices encompass an extensive network located in the ventral part of the brain, thus complicating the use of invasive functional methods. In vivo imaging techniques that were previously developed for brain activation studies in humans have been adapted for use in rodents and facilitate the non-invasive mapping of the whole brain. In this study, we report an initial series of experiments designed to demonstrate that microPET is a powerful tool to investigate the neural processes underlying odor-induced behavioral response in a large-scale olfactory neuronal network. After the intravenous injection of [(18)F]Fluorodeoxyglucose ([(18)F]FDG), awake rats were placed in a ventilated Plexiglas cage for 50 min, where odorants were delivered every 3 min for a 10-s duration in a random order. Individual behavio...
Brain : a journal of neurology, Jan 27, 2015
Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this ... more Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervat...
Cognitive Brain Research, 2005
Using positron emission tomography (PET), we investigated the organisation of spatial versus obje... more Using positron emission tomography (PET), we investigated the organisation of spatial versus object-based visual working memory in 11 normal human subjects. The paradigm involved a conditional colour-response association task embedded within two visual working memory tasks. The subject had to remember a position (spatial) or shape (object-based) and then use this to recover the colour of the matching element for the conditional association. Activation of the nucleus accumbens and the anterior cingulate cortex was observed during the conditional associative task, indicating a possible role of these limbic structures in associative memory. When the 2 memory tasks were contrasted, we observed activation of 2 distinct cortical networks: (1) The spatial task activated a dorsal stream network distributed in the right hemisphere in the parieto-occipital cortex and the dorsal prefrontal cortex, and (2) The non spatial task activated a ventral stream network distributed in the left hemisphere in the temporo-occipital cortex, the ventral prefrontal cortex and the striatum. These results support the existence of a domain-specific dissociation with dorsal and ventral cortical systems involved respectively in spatial and non spatial working memory functions.
NeuroImage, 2010
Neuroimaging studies are increasingly performed on non-human primates, including Macaca fascicula... more Neuroimaging studies are increasingly performed on non-human primates, including Macaca fascicularis. The analysis of functional imaging studies requires a corresponding anatomical image in order to identify brain structures. In the specific case of positron emission tomography (PET), anatomical correspondence is also required for quantification and modeling of interactions between the PET ligand and its pharmacological receptors. For voxel-based statistical parametric mapping, a reference frame (template) is needed to perform spatial normalization of individual brains. In this work we introduce a specific brain template and its associated atlas, with the purpose of enabling accurate, robust and reliable normalization and anatomical labeling of Macaca fascicularis brain images. S174 NRM2010 abstracts-Poster presentations individual MRIs. By comparison of ROI volumes, ROI tracer distribution volumes and modeled binding parameters were established, and bias, standard error and intra-class coefficients (ICC) computed. Results: Fig. 1 shows the atlas, template and fusion on three orthogonal slices centered on the striatum. Visual inspections were in good agreement with the anatomy. Robustness tests were passed with success for every individual. Reproducibility was high, with bias between methods smaller than the test-retest standard error, and ICCs were over 0.7. Conclusion: A brain Macaca fascicularis template and a reference atlas were obtained and validated. These references are suitable for future voxel-based, longitudinal and multi-tracer analyses. They are also useful for quantification, for post-hoc corrections such as partial volume effect recovery, and for inter-individual comparisons.
Neuroscience Letters, 2004
Background : Sensory stimulation of the forelimb extremities constitutes a well-established exper... more Background : Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. Objectives : To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [ 11 C]raclopride. Experiments in humans were paralled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [ 11 C]raclopride binding (BP raclo), a radioligand probing DA D2-receptors. Results : In humans no significant difference of BP raclo in caudate (with sensory stimulation: 2.0 ± 0.3 versus without sensory stimulation: 2.2 ± 0.3; P = 0.3) or putamen (2.6 ± 0.3 versus 2.6 ± 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP raclo was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 ± 0.4 versus without sensory stimulation: 2.1 ± 0.2; P = 0.5) and the putamen (2.5 ± 0.4 versus 2.6 ± 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 ± 0.03 versus without sensory stimulation: 2.4 ± 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 ± 0.04 versus 2.5 ± 0.06; P = 0.6). The [ 11 C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. Conclusion : This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [ 11 C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.
Neuroscience Letters, 2005
Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsila... more Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsilateral striatum and to decrease it in the homologous contralateral structure. Using positron emission tomography in both humans and cats, the present study shows that such sensory stimulations greatly reduce [ 18 F]FDOPA accumulation ipsilateral to the stimulation (by 40.4% and 26.4% in the human caudate and putamen, respectively, and by 33.3% in the cat striatum). This decrease in striatal [ 18 F]FDOPA uptake suggests a reduced DA storage resulting from the increased amine release. No change was observed in the contralateral striatum in neither human or cat suggesting, in contrast, that [ 18 F]FDOPA accumulation is not facilitated by decreased DA release. These results support the hypothesis that sensory stimulations activate a non-synaptic mode of dopamine release.
Journal of Cerebral Blood Flow & Metabolism, 2002
The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-piry... more The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. ...
Circulation: Cardiovascular Imaging, 2009
Background— Despite the major role attributed to myocardial vagal activity in left ventricular ar... more Background— Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown. Methods and Results— Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [ 11 C]methylquinuclidinyl benzilate ([ 11 C]MQNB) in 11 patients 43�20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [ 11 C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy...