References of "Bahri, Mohamed Ali"
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See detailFunction–structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET
Annen, Jitka ULg; Heine, Lizette ULg; Ziegler, Erik et al

in Human Brain Mapping (2016), 37(11), 3707-3720

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See detailThe influence of COMT single nucleotide polymorphism (rs4680) on the neural substrates of working memory representations maintenance in healthy aging
Manard, Marine ULg; François, Sarah ULg; Bahri, Mohamed Ali ULg et al

Poster (2016, May 10)

The COMT val108/158met polymorphism was associated to the dopaminergic modulation in the brain, and therefore stimulated research on its influence for cognitive functioning and particularly working memory ... [more ▼]

The COMT val108/158met polymorphism was associated to the dopaminergic modulation in the brain, and therefore stimulated research on its influence for cognitive functioning and particularly working memory. First, a general advantage of carrying the met allele was reported. However, many studies used tasks that did not allow efficiently assessing the contribution of manipulation and maintenance processes in working memory, leading to divergent results, in both young and older populations, resulting in debates about the exact phenotypic effect of the COMT polymorphism. Using fMRI, this study was designed to assess the potential effect of the COMT polymorphism on age-related differences in working memory representations maintenance abilities (Sternberg paradigm). Partial Least Squares method was used to determine the brain-behavior correlations at low, intermediate, and high cognitive demands among young and older groups, homozygous for the val or for the met allele. First, young val/val showed some disadvantages at brain and behavioral level compared to their m/m counterparts. However, in older adults subgroups, the m/m participants tended to show greater age-related difference (when compared to younger adults with similar genotype), suggesting an advantage in carrying the val allele when dopamine signaling is not at optimal efficiency (optimal: young/middle adulthood vs suboptimal: childhood or older ages). These results will be discussed in regard to compensating theories and dopaminergic models accounting for the potential effect of COMT polymorphism on stability/flexibility abilities. [less ▲]

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See detailFeasibility study of repetitive diffusion MRI after Neoadjuvant radiotherapy for following tumor microenvironment.
LALLEMAND, François ULg; Leroi, Natacha ULg; Bahri, Mohamed Ali ULg et al

Conference (2016, March 22)

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence ... [more ▼]

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence of side effects or the tumor downsizing. We previously demonstrated in an in vivo model that the timing of surgery and the schedule of NeoRT influenced the tumor dissemination. Here, our aim is to evaluate with functional MRI (fMRI) the impact of the radiation treatment on the tumor microenvironment and subsequently to identify non-invasive markers helping to determine the best timing to perform surgery for avoiding tumor spreading. First, we needed to demonstrate the feasibility of repetitive MRI imaging after NeoRT in mice. Material/methods. We used two models of NeoRT we previously developed in mice: MDA-MB 231 and 4T1 cells implanted in the flank of mice. When tumors reached the planned volume, they are irradiated with 2x5 Gy and then surgically removed at different time points after RT. In the mean time between the end of RT and the surgical procedure, mice were imaged in a 9,4T Agilent® MRI. Diffusion Weighted (DW) -MRI was performed every 2 days between RT and surgery. For each tumors we acquired 8 slices of 1 mm thickness and 0.5 mm gap with an “in plane voxel resolution” of 0.5 mm. For DW-MRI, we performed FSEMS (Fast Spin Echo MultiSlice) sequences, with 9 different B-values (from 40 to 1000) and B0, in the 3 main directions. We also performed IVIM (IntraVoxel Incoherent Motion) analysis, in the aim to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. Results. As preliminary results, with the MBA-MB 231 we observed a significant increase of F at day 6 after irradiation than a decrease and stabilization until surgery. No other modifications of the MRI signal, ADC, D or D* were observed. We observed similar results with 4T1 cells, F increased at day 3 than returned to initial signal. The difference in the timing of the peak of F can be related to the difference in tumor growth between MBA-MB 231 and 4T1 (four weeks vs one week). Conclusion. For the first time, we demonstrate the feasibility of repetitive fMRI imaging in mice models after NeoRT. With these models, we show a significant peak of the perfusion factor (F) at day 6 or day 3. This change occurs between the two previous time points of surgery demonstrating a difference in the metastatic spreading. Indeed, after a NeoRT of 2X5Gy we observed more metastases in the lung when MDA-MB 231 tumor bearing mice are operated 4 days after RT compared to 11 days. These preliminary results are very promising for identifying noninvasive markers for determining the best timing for surgery. [less ▲]

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See detailEVALUATION OF SV2Alox/Cre TRANSGENIC MICE USING [18F]UCB-H IN VITRO AUTORADIOGRAPHY
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; MENTEN, Catherine ULg et al

Poster (2016, March 09)

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to study in vivo SV2A brain proteins [3, 4]. The present pilot study was undertaken to evaluate for the first time in vivo in rats SV2A expression in the Kaïnic Acid (KA) epilepsy model [5]. Although this model is well studied in mice, few reports were devoted to rats. Imaging-wise, rats are very interesting thanks to a bigger brain size (reduction of the partial volume effect). Methods Three male Sprague-Dawley were used, one injected with saline and two with multiple KA injections (3 x 5mg/kg) [6]. 75 days later, when spontaneous seizures started to appear, microPET (Focus 120 ) was performed under isoflurane anesthesia (2.5-3 % in air) for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) followed by MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed as SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results obtained in KA treated rats showed that [18F]UCB-H was able to detect important modifications for SV2A in relevant regions for epilepsy and appears as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [less ▲]

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See detailSleep, Coma, Vegetative and Minimally 4 Conscious States
Di Perri, Carol ULg; Cavaliere, Carlo; Bodart, Olivier ULg et al

in Sleep Disorders Medicine (2016)

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See detailCorrelation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness
Soddu, Andrea ULg; Gomez, Francisco; Heine, Lizette ULg et al

in Brain and Behavior (2016), 6(1), 1-15

Introduction: The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure ‘resting state’ cerebral metabolism. This technique made ... [more ▼]

Introduction: The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure ‘resting state’ cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. Objective: We assessed the possi- bility of creating functional MRI activity maps, which could estimate the rela- tive levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recogniz- ing individual networks of independent component selection in functional mag- netic resonance imaging (fMRI) resting state analysis. Methods: We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neu- ronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. Results: The results show a significant similarity with q = 0.75  0.05 for healthy controls and q = 0.58  0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG- PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. Conclusions: The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map. [less ▲]

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See detailNeural correlates of consciousness in patients who have emerged from a minimally conscious state: A cross-sectional multimodal imaging study
Di Perri, Carol ULg; Bahri, Mohamed Ali ULg; Amico, Enrico ULg et al

in Lancet Neurology (2016), 15

Background Between pathologically impaired consciousness and normal consciousness exists a scarcely researched transition zone, referred to as emergence from minimally conscious state, in which patients ... [more ▼]

Background Between pathologically impaired consciousness and normal consciousness exists a scarcely researched transition zone, referred to as emergence from minimally conscious state, in which patients regain the capacity for functional communication, object use, or both. We investigated neural correlates of consciousness in these patients compared with patients with disorders of consciousness and healthy controls, by multimodal imaging. Methods In this cross-sectional, multimodal imaging study, patients with unresponsive wakefulness syndrome, patients in a minimally conscious state, and patients who had emerged from a minimally conscious state, diagnosed with the Coma Recovery Scale–Revised, were recruited from the neurology department of the Centre Hospitalier Universitaire de Liège, Belgium. Key exclusion criteria were neuroimaging examination in an acute state, sedation or anaesthesia during scanning, large focal brain damage, motion parameters of more than 3 mm in translation and 3° in rotation, and suboptimal segmentation and normalisation. We acquired resting state functional and structural MRI data and ¹⁸F-fl uorodeoxyglucose (FDG) PET data; we used seed-based functional MRI (fMRI) analysis to investigate positive default mode network connectivity (within-network correlations) and negative default mode network connectivity (between-network anticorrelations). We correlated FDG-PET brain metabolism with fMRI connectivity. We used voxel- based morphometry to test the eff ect of anatomical deformations on functional connectivity. Findings We recruited a convenience sample of 58 patients (21 [36%] with unresponsive wakefulness syndrome, 24 [41%] in a minimally conscious state, and 13 [22%] who had emerged from a minimally conscious state) and 35 healthy controls between Oct 1, 2009, and Oct 31, 2014. We detected consciousness-level-dependent increases (from unresponsive wakefulness syndrome, minimally conscious state, emergence from minimally conscious state, to healthy controls) for positive and negative default mode network connectivity, brain metabolism, and grey matter volume (p<0·05 false discovery rate corrected for multiple comparisons). Positive default mode network connectivity diff ered between patients and controls but not among patient groups (F test p<0·0001). Negative default mode network connectivity was only detected in healthy controls and in those who had emerged from a minimally conscious state; patients with unresponsive wakefulness syndrome or in a minimally conscious state showed pathological between-network positive connectivity (hyperconnectivity; F test p<0·0001). Brain metabolism correlated with positive default mode network connectivity (Spearman’s r=0·50 [95% CI 0·26 to 0·61]; p<0·0001) and negative default mode network connectivity (Spearman’s r=–0·52 [–0·35 to –0·67); p<0·0001). Grey matter volume did not diff er between the studied groups (F test p=0·06). Interpretation Partial preservation of between-network anticorrelations, which are seemingly of neuronal origin and cannot be solely explained by morphological deformations, characterise patients who have emerged from a minimally conscious state. Conversely, patients with disorders of consciousness show pathological between-network correlations. Apart from a deeper understanding of the neural correlates of consciousness, these fi ndings have clinical implications and might be particularly relevant for outcome prediction and could inspire new therapeutic options. [less ▲]

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See detailRelationship between grey matter integrity and executive abilities in aging
Manard, Marine ULg; Bahri, Mohamed Ali ULg; Salmon, Eric ULg et al

in Brain Research (2016), 1642

This cross-sectional study was designed to investigate grey matter changes that occur in healthy aging and the relationship between grey matter characteristics and executive functioning. Thirty-six young ... [more ▼]

This cross-sectional study was designed to investigate grey matter changes that occur in healthy aging and the relationship between grey matter characteristics and executive functioning. Thirty-six young adults (18 to 30 years old) and 43 seniors (60 to 75 years old) were included. A general executive score was derived from a large battery of neuropsychological tests assessing three major aspects of executive functioning (inhibition, updating and shifting). Age-related grey matter changes were investigated by comparing young and older adults using voxel-based morphometry and voxel-based cortical thickness methods. A widespread difference in grey matter volume was found across many brain regions, whereas cortical thinning was mainly restricted to central areas. Multivariate analyses showed age-related changes in relatively similar brain regions to the respective univariate analyses but appeared more limited. Finally, in the older adult sample, a significant relationship between global executive performance and decreased grey matter volume in anterior (i.e. frontal, insular and cingulate cortex) but also some posterior brain areas (i.e. temporal and parietal cortices) as well as subcortical structures was observed. Results of this study highlight the distribution of age-related effects on grey matter volume and show that cortical atrophy does not appear primarily in “frontal” brain regions. From a cognitive viewpoint, age-related executive functioning seems to be related to grey matter volume but not to cortical thickness. Therefore, our results also highlight the influence of methodological aspects (from preprocessing to statistical analysis) on the pattern of results, which could explain the lack of consensus in literature. [less ▲]

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See detailDiffusion MRI for following tumor modifications after neoadjuvant radiotherapy.
LALLEMAND, François ULg; Leroi, Natacha ULg; Bahri, Mohamed Ali ULg et al

in Radiotherapy & Oncology (2016), 119

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is driven by the occurrence of side effects or the ... [more ▼]

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is driven by the occurrence of side effects or the tumor downsizing. Some studies demonstrated that the timing of surgery and the RT schedule could influence tumor dissemination and subsequently patient overall survival. We demonstrated the impact of NeoRT on metastatic spreading in a Scid mice model. After an irradiation of 2x5gy, we show more metastasis in the lung when the mice are operated at day 4 compared to day 11. Here, our aim is to evaluate with functional MRI (fMRI) the impact of the radiation treatment on the tumor microenvironment and subsequently to identify non-invasive markers helping to determine the best timing to perform surgery for avoiding tumor spreading. [less ▲]

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See detailContribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson’s disease
Rouillard, Maud; Audiffren, Michel; Albinet, Cédric et al

in Journal of Clinical and Experimental Neuropsychology (2016)

Introduction. Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education ... [more ▼]

Introduction. Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Method. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (1) any of these four environmental lifespan variables ; (2) demographic and clinical variables (age, gender, depression score and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Results. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and 1) education, 2) leisure activities, 3) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Conclusions. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency. [less ▲]

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See detailMultimodality imaging assessment of the deleterious role of the intraluminal thrombus on the growth of abdominal aortic aneurysm in a rat model
NCHIMI LONGANG, Alain ULg; Courtois, Audrey ULg; EL HACHEMI, Mounia ULg et al

in European Radiology (2016), 26

Objectives To evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence. Methods The post-induction ... [more ▼]

Objectives To evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence. Methods The post-induction growth of the AAA diameter was characterized using ultrasound in 22 rats. ILT was reported on 13 rats that underwent 14 magnetic resonance imaging (MRI) 2-18 days post-surgery, and on 10 rats that underwent 18 fluoro-deoxyglucose (FDG) positron emission tomography (PET)/microcomputed tomography examinations 2-27 days post-surgery. Logistic regressions were used to establish the evolution with time of AAA length, diameter, ILT thickness, volume, stratification, MRI and FDG PET signalling properties, and histological assessment of inflammatory infiltrates. Results All of the following significantly increased with time post-induction (p < 0.001): AAA length, AAA diameter, ILT maximal thickness, ILT volume, ILT iron content and related MRI signalling changes, quantitative uptake on FDG PET, and the magnitude of inflammatory infiltrates on histology. However, the aneurysm growth peak followed occurrence of ILT approximately 6 days after elastase infusion. Conclusion Our model emphasizes that occurrence of ILT precedes AAA peak growth. Aneurysm growth is associated with increasing levels of iron, signalling properties changes in both MRI and FDG PET, relating to its biological activities. [less ▲]

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See detailNeural correlates of event clusters in past and future thoughts: How the brain integrates specific episodes with autobiographical knowledge
Demblon, Julie ULg; Bahri, Mohamed Ali ULg; D'Argembeau, Arnaud ULg

in NeuroImage (2016), 127

When remembering the past or envisioning the future, events often come to mind in organized sequences or stories rather than in isolation from one another. The aim of the present fMRI study was to ... [more ▼]

When remembering the past or envisioning the future, events often come to mind in organized sequences or stories rather than in isolation from one another. The aim of the present fMRI study was to investigate the neural correlates of such event clusters. Participants were asked to consider pairs of specific past or future events: in one condition, the two events were part of the same event cluster (i.e., they were thematically and/or causally related to each other), whereas in another condition the two events only shared a surface feature (i.e., their location); a third condition was also included, in which the two events were unrelated to each other. The results showed that the processing of past and future events that were part of a same cluster was associated with higher activation in the medial prefrontal cortex (PFC), rostrolateral PFC, and left lateral temporal and parietal regions, compared to the two other conditions. Furthermore, functional connectivity analyses revealed an increased coupling between these cortical regions. These findings suggest that largely similar processes are involved in organizing events in clusters for the past and the future. The medial and rostrolateral PFC might play a pivotal role in mediating the integration of specific events with conceptual autobiographical knowledge ‘stored’ in more posterior regions. Through this integrative process, this set of brain regions might contribute to the attribution of an overarching meaning to representations of specific past and future events, by contextualizing them with respect to personal goals and general knowledge about one's life story. [less ▲]

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See detailMonte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT using gate.
Bretin, Florian; Bahri, Mohamed Ali ULg; Luxen, André ULg et al

in Medical Physics (2015), 42(10), 5711-5719

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are ... [more ▼]

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low-level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non-invasively using Monte Carlo simulations in GATE and to compare results to previously obtained experimental values. Methods: Tungsten X-ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half-value layers were simulated for spectra validation against experimentally measured values of the physical X-ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat. Results: Simulated half-value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%. Conclusions: Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup. [less ▲]

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See detailEVALUATION OF SV2Alox/Cre TRANSGENIC MOUSE USING [18F]UCB-H IN IN VITRO AUTORADIOGRAPHY
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; MENTEN, Catherine ULg et al

Poster (2015, September 04)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for the antiepileptic drug levetiracetam, showing a close relation between the epilepsy, the dysregulation of the SV2A levels and the response to antiepileptic medications. SV2A floxed-mice were developed using a cre-lox technique, leading to a strong decrease of SV2A expression in the CA3 field of the hippocampus. We aim here to validate this model using [18F]UCB-H, a novel PET imaging radiotracer with a nanomolar affinity for human SV2A. Methods: In vitro autoradiography were performed on SV2Alox/Cre+ transgenic mouse brain slices. SV2Alox/Cre- mouse was used as control. To obtain a structural reference, brain slices underwent eosin-haematoxylin staining. Images of both procedures were coregistered using π-PMOD software. Regions of interest (Dentate Gyrus, CA1, CA2 and CA3) were drawn according to a stereotaxic atlas of the mouse brain. Results: Analyses showed significant differences in radiotracer binding (p<0.001) between SV2Alox/Cre+ mouse and SV2Alox/Cre- mouse highlighting an important reduction for the labelling density in Ammon's horn, particularly in CA1, compared to Dentate Gyrus where the diminution was less marked. Conclusions: Here, we used the radiotracer [18F]UCB-H to probe the decreased expression of SV2A protein in the hippocampus of SV2Alox/Cre+ mouse versus SV2Alox/Cre- control mouse. Our results contribute to the validation of the model, and encourage us to proceed with further longitudinal and behavioural studies. [less ▲]

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See detailIn vivo quantification of dopaminergic terminals loss in Parkinson’s Disease rat model: comparison between [18F]FMT and [18F]FDOPA.
Becker, Guillaume ULg; Bahri, Mohamed Ali ULg; Michel, Anne et al

Poster (2015, September 02)

Objectives: Rat models of Parkinson’s disease (PD), such as unilaterally lesioned rats with 6-hydroxydopamine (6-OHDA), are useful to evaluate novel antiparkinsonian therapies. MicroPET imaging, using L-3 ... [more ▼]

Objectives: Rat models of Parkinson’s disease (PD), such as unilaterally lesioned rats with 6-hydroxydopamine (6-OHDA), are useful to evaluate novel antiparkinsonian therapies. MicroPET imaging, using L-3,4-dihydroxy-6-[18F]-fluoro-phenylalanine ([18F]FDOPA) allows longitudinal evaluations of DA terminals loss. However, chemical structure of [18F]FDOPA leads to suboptimal PET imaging. 18F-fluoro-m-tyrosine ([18F]FMT) is an effective PET tracer to evaluate DA terminals integrity and L-aromatic amino acid decarboxylase (AAAD) metabolic pathway. So far, there are no available quantitative PET studies comparing the two methods in hemiparkinsonian rats. In this study, we compare imaging data provided by [18F]FMT PET and [18F]FDOPA PET in 6-OHDA-lesioned rats. Methods: 10 µg of 6-OHDA were injected into the right medial forebrain bundle (MFB) of male Sprague-Dawley rats (n=8). As control, sham-treated rats (n=8) were injected with vehicle only but otherwise treated identically. Striatal DA presynaptic activity was assessed by dynamic PET with both [18F]FMT and [18F]FDOPA. Structural T2-weighted brain images were acquired on a 9.4T MRI and were used for co-registration. After normalization on a MRI template, kinetic analysis was performed by “Patlak Reference” model, using PMOD software. Six days after the last PET scan, rats were sacrificed, and striatum were rapidly removed for striatal DA and metabolites quantification. Results: Striatal accumulation was observed for both tracers. However, while the administration of [18F]FDOPA required two peripheral inhibitors (benserazide and entacapone), only benserazide is needed with [18F]FMT. As consequence of the 6-OHDA-lesion, significant decrease of both [18F]FMT and [18F]DOPA accumulation was recorded in the striatum ipsilateral to the lesion. Lesioned rats had dramatically reduced uptake constant Ki in the ipsilateral striatum compared to the contralateral striatum (p<0.001 for [18F]FMT and p<0.05 for [18F]DOPA) and to the ipsilateral striatum of sham-treated rats (p<0.001 for both tracers). The DA content in the ipsilateral striatum was significantly lower (p<0.001) than in the contralateral striatum in the 6-OHDA-injected group, whereas such difference was not measured with the sham group. This indicate that [18F]FMT PET is as effective as [18F]DOPA PET to quantify loss of DA presynaptic function in unilaterally 6-OHDA lesioned rats. Conclusions: Our results are in agreement with data reporting correlation between these two tracers in a Non-human primate model of PD. The sensitivity of the data quantification obtained in this study, confirms the interest to pursue longitudinal investigations with [18F]FMT to monitor dopaminergic dysfunction in a more progressive preclinical model of PD. [less ▲]

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See detailPrevalence of increases in functional connectivity in visual, somatosensory and language areas in congenital blindness
Heine, Lizette ULg; Bahri, Mohamed Ali ULg; cavaliere, Carlo et al

in Frontiers in Neuroanatomy (2015), 3(295),

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