References of "Bahri, Mohamed Ali"
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See detailBrain metabolic dysfunction in Capgras delusion during Alzheimer’s disease: a positron emission tomography study
Jedidi, Haroun ULg; Daury, Noémy; Rémi, Capa et al

in American Journal of Alzheimer's Disease & Other Dementias (in press)

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since ... [more ▼]

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer’s disease (AD) and Capgras syndrome was compared with those of 24 healthy elderly subjects and 26 AD patients without delusional syndrome. Compared to the healthy and AD groups, the patient had significant hypometabolism in frontal and posterior midline structures. In light of current neural models of face perception, our patient’s Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. [less ▲]

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See detailBiodistribution and radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H: Firstin- human study.
Bretin, Florian ULg; Bahri, Mohamed Ali ULg; BERNARD, Claire ULg et al

in Molecular Imaging & Biology (in press)

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a ... [more ▼]

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [18F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body PET/CT imaging was performed over approximately 110 minutes on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1 – 156.5 MBq) of [18F]UCB-H. Major organs were delineated on CT images and time-activity curves were obtained from co-registered dynamic PET emission scans. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET-activities including voiding was simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70 kg standard male was 1.54E-02 ± 6.84E-04 mSv/MBq, with urinary bladder wall, gallbladder wall and the liver receiving the highest absorbed dose. The brain, the tracer’s main organ of interest, received an absorbed dose of 1.89E-02 ± 2.32E-03 mGy/MBq. This first human dosimetry study of [18F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for USA practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose, but showed significant differences in organ absorbed doses compared to human data. [less ▲]

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See detailEffects of α-synuclein levels on cerebral synaptic function: Validation of a novel PET radioligand for the early diagnosis of Parkinson’s disease
Tarragon Cros, Ernesto ULg; Ferrara, André ULg; Tirelli, Ezio ULg et al

Poster (2015, January 27)

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells ... [more ▼]

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells such as neurons in the substantia nigra pars compacta. The resulting loss of dopaminergic terminals in the striatum can be demonstrated in vivo using 18F-Dopa-PET (positron emission tomography). However, there’s currently no validated biomarker of the progressive synaptic dysfunction in other vulnerable areas such as the cerebral cortex. Goal In this longitudinal study, we will test the hypothesis that the loss of synaptic terminals in a mouse model of excessive α–synuclein accumulation can be demonstrated in vivo before the occurrence of behavioural disturbances using 18F-UCB-H, a new PET biomarker developed at CRC. We will also test if this new imaging modality is sensitive enough to study the effect of a disease modifying therapy such as chronic physical exercise. Methods We will use microPET for the in vivo quantification of 18F-UCB-H brain uptake in 16 wild type animals and 16 transgenic (Tg) mice overexpressing human α–syn under the mThy1 promotor every 2 months. Data will be validated against post-mortem analyses after the last PET study. Predictions We predict decreased tracer uptake over time in the basal ganglia and cerebral cortex in Tg mice as compared with WT animals. Also, we predict a relationship between 18F-UCB-H uptake levels in basal ganglia and cerebral cortex and progressive alterations in both motor and cognitive functions, respectively. Further, we also expect that chronic exercise will slow down both motor and cognitive disturbances, as well as the rate of 18F-UCB-H brain uptake decreases. Conclusion If 18F-UCB-H PET proves to be a valid biomarker for the early detection of α–synuclein accumulation in the pre-clinical model of PD, the methods will tested on human clinical populations. [less ▲]

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial
Bahri, Mohamed Ali ULg; Stifkens, Mathieu; Bastin, Christine ULg et al

Poster (2015, January 27)

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is ... [more ▼]

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling. The IF was also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The image-derived arterial IFs were showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue, 2-tissue, and Logan Plot). The three models gave similar results with both the measured and image-derived IFs. The total distribution volume of the tracer in the brain was greater than 7 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. SV2A modifications may consequently be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailRecognition of Personally Familiar Faces and Functional Connectivity in Alzheimer’s Disease
Kurth, Sophie ULg; Moyse, Evelyne ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2015), 67

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See detailChanges in cerebral metabolism in patients with a minimally conscious state responding to zolpidem.
Chatelle, Camille ULg; Thibaut, Aurore ULg; Gosseries, Olivia ULg et al

in Frontiers in Neuroscience (2014)

Background:Zolpidem,ashort-actingnon-benzodiazepineGABAagonisthypnotic,hasbeenshowntoinduceparadoxicalresponsesinsomepatientswithdisordersofconsciousness(DOC ... [more ▼]

Background:Zolpidem,ashort-actingnon-benzodiazepineGABAagonisthypnotic,hasbeenshowntoinduceparadoxicalresponsesinsomepatientswithdisordersofconsciousness(DOC),leadingtorecoveryofarousalandcognitiveabilities.Wehereassessedzolpidem-inducedchangesinregionalbrainmetabolisminthreepatientswithknownzolpidemresponseinchronicpost-anoxicminimallyconsciousstate(MCS).Methods:[18F]-fluorodeoxyglucosepositronemissiontomography(FDG-PET)andstandardizedclinicalassessmentsusingtheComaRecoveryScale-Revisedwereperformedafteradministrationof10mgzolpidemorplaceboinarandomizeddoubleblind2-dayprotocol.PETdatapreprocessingandcomparisonwithahealthyage-matchedcontrolgroupwereperformedusingstatisticalparametricmapping(SPM8).Results:Behaviorally,allpatientsrecoveredfunctionalcommunicationafteradministrationofzolpidem(i.e.,emergencefromtheMCS).FDG-PETshowedincreasedmetabolismindorsolateralprefrontalandmesiofrontalcorticesafterzolpidembutnotafterplaceboadministration.Conclusion:Ourdatashowametabolicactivationofprefrontalareas,corroboratingtheproposedmesocircuithypothesistoexplaintheparadoxicaleffectofzolpidemobservedinsomepatientswithDOC.ItalsosuggeststhekeyroleoftheprefrontalcorticesintherecoveryoffunctionalcommunicationandobjectuseinhypoxicpatientswithchronicMCS. [less ▲]

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See detailEvaluation of [18F]UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
Warnock, Geoffrey; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

in Journal of Nuclear Medicine (The) (2014), 55(8), 1336-1341

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic ... [more ▼]

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. [18F]UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A. Methods: preclinical PET studies were carried out in isoflurane anesthetized rats. Arterial input function was measured using an arteriovenous shunt and beta microprobe system. [18F]UCB-H was injected IV (140 ± 20 MBq bolus). Results: brain uptake of [18F]UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for [18F]UCB-H was calculated using Logan’s graphical analysis and the effect of LEV pretreatment on Vt measured. In control animals the mean whole-brain Vt was 9.76 ± 0.52 ml/cm3 (mean ± SD, n=4, test-retest), and the mean reproducibility in test-retest studies was 10.4 ± 6.5 %. Uptake of [18F]UCB-H was dose-dependently blocked by pretreatment with LEV (0.1 - 100 mg/kg IV). Conclusion: our results indicate that [18F]UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. This is the first PET tracer for in vivo quantification of SV2A. The necessary steps for implementation of [18F]UCB-H production under GMP conditions and first in human studies are planned. [less ▲]

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See detail[18F]UCB-H AS A NEW PET RADIOTRACER FOR SYNAPTIC VESICLE PROTEIN 2A
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, June 06)

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown ... [more ▼]

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, for example, by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease and to improve cognition in patients with amnestic mild cognitive impairment. We here aimed to investigate the cerebral distribution of [18F]UCB-H, a fluorine-18 radiolabelled PET imaging tracer, which has a high affinity with the SV2A. [18F]UCB-H was radiosynthesized under GMP conditions. Dynamic PET data of the head of four healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of [18F]UCB-H. The arterial input function was obtained by blood sampling during the dynamic PET acquisition. The analysis of the blood data reveled a consistent amount of [18F]UCB-H in whole blood and plasma which indicates a very low degree of binding of the tracer to the red blood cells. The unchanged fraction of [18F]UCB-H in plasma showed a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreased to about 50% at 10 min post injection. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue compartment, 2-tissue compartment, and Logan graphical analysis). The three models gave consistent results. The two-tissue compartment model fitted the experimental data best and provided a total distribution volume of the [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. In the future, SV2A modifications might be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailExecutive function and grey matter atrophy in healthy aging: A voxel-based morphometry analysis
Manard, Marine ULg; Bahri, Mohamed Ali ULg; Salmon, Eric ULg et al

Poster (2014, June)

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse ... [more ▼]

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse neurobiological modifications associated to normal aging, such as reduced grey and white matter volumes and cortical thickness (Raz & Rodrigue; 2006). In that context, Voxel Based Morphometry (VBM; Ashburner & Friston, 2000) and Partial Least Square (PLS; McIntoch at al., 1996, 2004) were used to investigate the effect of grey matter atrophy on executive abilities in normal aging. Methods Thirty six young (age range: 18-30) and 43 healthy older (age range: 60-78) adults were included in this study. Executive functioning was assessed by inhibition, updating and shifting tasks (Miyake et al., 2000), and a composite score for general executive ability was created. Structural high resolution T1-weighted images were acquired with a 3T head-only scanner using a standard transmit-receive quadrature head coil (Siemens, Allegra, Erlangen, Germany). The structural images were segmented using VBM8 toolbox, normalized to the MNI stereotaxic space and the resulting grey matter volume images were smoothed (Gaussian kernel: FWHM 8mm). PLS analyses were performed to determine regional grey matter volume differences between young and older adults, and next to identify the regional grey matter volumes specifically associated to executive performance in older participants (p<0.001). PLS is a validated multivariate approach that robustly identifies whole brain activity patterns correlated with behavioral data or experimental design (i.e., scores, conditions or tasks). Results Behavioral data showed a significant age-related decline in executive functioning (t=-5.43; p<.001). MRI analyses showed that significant age-related grey matter volume decrease was mostly observed across a large network including frontal, parietal, and temporal regions. Moreover significant positive correlations between the executive score and the grey matter volumes in older participants were found in a subset of these cortical areas: the inferior, middle and superior frontal cortex, the pre and postcentral gyri, the anterior and middle cingulate cortex, the inferior and superior parietal regions, the retrosplenial cortex, and finally, the inferior, middle and superior temporal regions. Discussion This study first replicated that executive abilities decline with age (Salthouse et al., 2003). This age-related executive decline is related to specific cerebral regions within a large fronto-temporo-parietal network sensitive to age. Interestingly, the areas whose atrophy is linked to executive abilities are quite similar to those evidenced in functional neuroimaging studies in young participants (see Collette & Van der Linden, 2002; Collette, Hogge, Salmon, & Van der Linden, 2006 for reviews). Therefore, using PLS multivariate analyses, we demonstrated that executive changes in normal aging are not dependent on atrophy in frontal areas only but rather comes from a grey matter volume decrease in a large antero-posterior brain network. [less ▲]

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See detail[18F]UCB-H AS A BRAIN SV2A RADIOTRACER: A FIRST CLINICAL TRIAL
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, May 27)

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the ... [more ▼]

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the brain, represents the binding site and the primary mechanism of the antiepileptic drug levetiracetam. Levetiracetam has recently been suggested to reduce synaptic deficits in a mouse Alzheimer’s disease model and to improve cognition in patients with amnestic mild cognitive impairment, suggesting a possible role for this protein in synaptic integrity. The objective of this study was to investigate the cerebral distribution of [18F]UCB-H in healthy human volunteers. Dynamic PET imaging of the head of four healthy volunteers was performed over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The input function was acquired by arterial blood sampling during the dynamic PET acquisition. Blood data analysis showed a consistent tracer amount in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. Unchanged [18F]UCB-H fraction in plasma follows a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreases to about 50% at 10 min post injection. The [18F]UCB-H PET data revealed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue compartment, 2-tissue compartment, and Logan graphical analysis). The three models gave consistent results. The two-tissue compartment model fitted the experimental data best and provided a total distribution volume of [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results indicate that [18F]UCB-H is a new radiotracer for brain SV2A proteins suitable for human studies. Further studies are warranted to assess SV2A modifications in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailQuantitative multi-parameter mapping in parkinson’s disease: preliminary results
Rouillard, Maud ULg; D'Ostilio, Kevin ULg; Albinet, Cedric et al

Poster (2014, May)

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See detailHybrid MicroPET Imaging for Dosimetric Applications in Mice: Improvement of Activity Quantification in Dynamic MicroPET Imaging for Accelerated Dosimetry Applied to 6-[ 18 F] Fluoro- L -DOPA and 2-[ 18 F]Fluoro- L -Tyrosine
Bretin, Florian ULg; Mauxion, T; Warnock, G et al

in Molecular Imaging and Biology (2014), 16(3), 383-394

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is pronetoquantificationerrorsinsmallvolumes.Hybridimaging,wheremicroPETactivitiesarecross- calibrated using post ... [more ▼]

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is pronetoquantificationerrorsinsmallvolumes.Hybridimaging,wheremicroPETactivitiesarecross- calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro-L-DOPA and 2-[18 F]fluoro-L-tyrosine and compared. Procedures: Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n=5 at each time point for 18 F-FDOPA and n=3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S- factors for the MOBY phantom were used to calculate the animal dosimetry. Results: Correlations between dose estimates based on organ harvesting and imaging was improved from r=0.997 to r=0.999 for 18 F-FDOPA and from r=0.985 to r=0.996 (p<0.0001 for all) for 18 F-FTYR by using hybrid imaging. Conclusion: Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved. [less ▲]

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See detailFunctional connectivity and recognition of familiar faces in Alzheimer’s disease
Kurth, Sophie ULg; Bahri, Mohamed Ali ULg; Moyse, Evelyne ULg et al

in Frontiers in Human Neuroscience (2014)

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