References of "Bahri, Mohamed Ali"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailBrain metabolic dysfunction in Capgras syndrome during Alzheimer’s disease: a positron emission tomography study
Jedidi, Haroun ULg; Daury, Noémy; Cappa, Rémi et al

Poster (2013, June)

Detailed reference viewed: 47 (16 ULg)
Full Text
Peer Reviewed
See detailPreclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H
Bretin, Florian ULg; Warnock, Geoffrey; Bahri, Mohamed Ali ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2013), 3(1), 35

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to ... [more ▼]

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods: Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results: Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions: This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666. [less ▲]

Detailed reference viewed: 44 (15 ULg)
Full Text
Peer Reviewed
See detailBrain dead yet mind alive: A positron emission tomography case study of brain metabolism in Cotard’s syndrome
Charland-Verville, Vanessa ULg; Bruno, Marie-Aurélie ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2013), 49(7), 1997-1999

Detailed reference viewed: 39 (9 ULg)
Peer Reviewed
See detailImpairment of two memory cerebral networks in Alzheimer's disease
Bastin, Christine ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

in Proceedings of the Annual Meeting of the Belgian Association for Psychological Sciences (2013)

Detailed reference viewed: 8 (3 ULg)
See detailRadiosynthesis and first small animal microPET imaging of [18F]UCB-H, a new fluorine-18 labelled tracer targeting synaptic vesicle protein 2A (SV2A)
Aerts, Joël ULg; Otabashi, Muhamed; Giacomelli, Fabrice ULg et al

Conference (2013)

Aim. We report the radiosynthesis and first rat microPET imaging of a new fluorine-18 tracer targeting the synaptic vesicle protein 2A, SV2A, identified as the binding site of the antiepileptic drug ... [more ▼]

Aim. We report the radiosynthesis and first rat microPET imaging of a new fluorine-18 tracer targeting the synaptic vesicle protein 2A, SV2A, identified as the binding site of the antiepileptic drug levetiracetam. Materials and Method. Two different nucleophilic radiosynthesis pathways were tested to obtain [18F]UCB-H, a no-carrier-added tracer in the 2-[18F]fluoropyridine family. The methods were automated on FastLab™ synthesizers. PET studies in rodents were carried out using male SD rats, imaged under isoflurane anaesthesia in a Siemens Concorde Focus 120 microPET scanner. Arterial input function was measured using an arteriovenous shunt method and beta microprobe system. All animal protocols were reviewed and accepted by animal ethical committees. Results and conclusion. A radiosynthesis yield of 30% was obtained (uncorrected for decay, 150 minutes of synthesis). Analytical methods were developed and validated to demonstrate that the quality of the tracer solution was compatible with in vivo injection. After intravenous injection, the tracer rapidly entered the brain, followed by rapid washout. PET imaging revealed high uptake of the tracer in the brain and spinal cord, matching the expected SV2A homogeneous distribution. Results indicate that [18F]UCB-H is suitable to quantify SV2A proteins in vivo and to estimate target occupancy of drugs targeting SV2A. Acknowledgments. The authors thank UCB Pharma SA Belgium for collaboration and the Walloon Region Belgium and the FRNS Belgium for financial support. [less ▲]

Detailed reference viewed: 25 (6 ULg)
Full Text
Peer Reviewed
See detailMetabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults
Yakushev, Igor; Chételat, Gael; Fischer F.U. et al

in NeuroImage (2013), 79

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes ... [more ▼]

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1±5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0.01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions. [less ▲]

Detailed reference viewed: 40 (16 ULg)
Full Text
Peer Reviewed
See detailRelationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity
Chételat, Gael; Landeau, Brigitte; Salmon, Eric ULg et al

in NeuroImage (2013), 76

Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related ... [more ▼]

Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centres (n=49/48 in Centre 1/2) were analyzed. WM volume from T1-weighted MRI (Centre 1), fractional anisotropy from diffusion-tensor imaging (Centre 2), and resting-state fMRI data (Centre 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes. [less ▲]

Detailed reference viewed: 37 (11 ULg)
Full Text
Peer Reviewed
See detailEpisodic autobiographical memory in amnestic Mild Cognitive Impairment: What are the neural correlates?
Bastin, Christine ULg; Feyers, Dorothée ULg; Jedidi, Haroun ULg et al

in Human Brain Mapping (2013), 34

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to ... [more ▼]

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to identify (via FDG-PET) the neural substrates of impaired episodic specificity of autobiographical memories in 35 aMCI patients compared with 24 healthy elderly controls. Significant correlations between regional cerebral activity and the proportion of episodic details in autobiographical memories from two life periods were found in specific regions of an autobiographical brain network. In aMCI patients, more than in controls, specifically episodic memories from early adulthood were associated with metabolic activity in the cuneus and in parietal regions. We hypothesized that variable retrieval of episodic autobiographical memories in our aMCI patients would be related to their variable capacity to reactivate specific sensory-perceptual and contextual details of early adulthood events linked to reduced (occipito-parietal) visual imagery and less efficient (parietal) attentional processes. For recent memories (last year), a correlation emerged between the proportion of episodic details and activity in lateral temporal regions and the temporo-parietal junction. Accordingly, variable episodic memory for recent events may be related to the efficiency of controlled search through general events likely to provide cues for the retrieval of episodic details and to the ability to establish a self perspective favouring recollection. [less ▲]

Detailed reference viewed: 89 (34 ULg)
Full Text
Peer Reviewed
See detailVerbal learning in Alzheimer’s disease and mild cognitive impairment:fine-grained acquisition and short-delay consolidation performance and neural correlates
Genon, Sarah ULg; Collette, Fabienne ULg; Moulin, Chris et al

in Neurobiology of Aging (2013), 34

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 ... [more ▼]

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 Alzheimer’s disease (AD) patients, 16 patients with mild cognitive impairment (MCI) who progressed to dementia (MCI-AD), 15 MCI patients who remained stable (MCI-S, 4–8 years of follow-up), and 20 healthy older participants. Acquisition and short-delay consolidation were calculated respectively as mean gained (MG) and lost (ML) access to items of the California Verbal Learning Task. MG performance suggests that acquisition is impaired in AD patients even at predementia stage (MCI-AD). ML performance suggests that short-delay consolidation is deficient only in confirmed AD patients. Variations in acquisition performance in control participants are related to metabolic activity in the anterior parietal cortex, an area supporting task-positive attentional processes. In contrast, the acquisition deficit is related to decreased activity in the lateral temporal cortex, an area supporting semantic processes, in patients at an early stage of AD and is related to metabolic activity in the hippocampus, an area supporting associative processes, in confirmed AD patients. [less ▲]

Detailed reference viewed: 63 (15 ULg)
Full Text
Peer Reviewed
See detailPerformance Evaluation of the GE eXplore CT 120 Micro-CT for Various Scanning Protocols
Bahri, Mohamed Ali ULg; Bretin, Florian ULg; Warnock, Geoffrey ULg et al

Poster (2012, November 03)

The aim of this study was to evaluate the performance of the General Electric (GE) eXplore CT 120 micro-CT using the same methodology and image quality assurance vmCT phantom developed for the GE eXplore ... [more ▼]

The aim of this study was to evaluate the performance of the General Electric (GE) eXplore CT 120 micro-CT using the same methodology and image quality assurance vmCT phantom developed for the GE eXplore Ultra. In addition, Quality assurance in Radiology and Medicine (QRM) low contrast and bar pattern phantoms were used. The phantoms were imaged using the six protocols regularly used in our laboratory (Fast scan 220 (P1) or 360 (P2): 70 kV, 32 mA, 220 or 360 views; Soft tissue fast scan (P3): 70 kV, 50 mA, 220 views, Soft tissue step & shoot (P4): 80 kV, 32 mA, 220 views; Low Noise (P5): 100 kV, 50 mA, 720 views and In Vivo Bone scan (P6): 100 kV, 50 mA, 360 views). Data were reconstructed with an isotropic voxel size of 100 µm (50 µm when protocol detector-binning was reduced to 2x2). The MTF obtained with the slanted edge and coil methods agreed very well. A 10% modulation transfer function (MTF) was observed in the range 3.6-4.8 mm-1 (P1&2 = 4.2; P3&4 = 4.8; P5 = 3.6 and P6 = 3.8), corresponding to 95-138 µm resolutions. The smallest bars visually observed on the QRM pattern phantom image were 100 µm. The geometric accuracy was better than 0.1%. A highly linear (R2 > 0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom was observed with a voltage dependent slope. A cupping effect was observed on the uniform slices. This effect was clearly highlighted by the uniformity-to-noise ratio (P1 = 0.58, P2&3&4 = 0.75, P5 = 1.35 and P6 = 2.74) especially for the low-noise protocols P5 and P6. The best low contrast discrimination was observed for P2 and P5 protocols. In conclusion the eXplore CT 120 achieved a resolution in the range 95-138 µm. It was found to be linear and geometrically accurate. The major difference between the protocols was the noise level which limits the detectability of low contrasts. [less ▲]

Detailed reference viewed: 204 (16 ULg)
Full Text
Peer Reviewed
See detailDosimetry for 6-[18F]Fluoro-L-DOPA in Humans Based on Biodistribution in Mice
Bretin, Florian ULg; Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, October)

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid ... [more ▼]

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid method combining dynamic PET followed by organ harvesting. Materials and methods. The tissue distribution of F-DOPA over time was determined in isoflurane-anaesthetized mice. Radioassay was performed on harvested organs at 2, 5, 10, 30, 60 and 120 minutes post administration (n = 5 at each time point). Dynamic PET images were acquired in list-mode with a Siemens FOCUS 120 microPET for 120 minutes after injection and followed by radioassay of harvested organs (n = 4). List-mode data were histogrammed in 6*5s, 6*10s, 3*20s, 5*30s, 5*60s, 8*150s, 6*300s, 6*600s 3D sinograms. Final images were obtained using filtered backprojection with correction for all physical effects except for scatter. Attenuation correction resulted from a pre-injection transmission scan with a cobalt-57 point source. Organs were manually delineated. The organ time-activity-curves (TACs) from both methods were extrapolated from a simulated 35 g standard mouse to a 70 kg standard male human using a technique based on organ to bodyweight ratios. A bladder voiding scenario was used to simulate excretion every 2 h. The absorbed doses in major human organs were calculated using the extrapolated TACs with the commercially available software OLINDA/EXM (Version 1.1). Results. The extrapolated organ activity curves obtained using the harvesting and imaging methods showed a high correlation (r = 0.94 ± 0.05, p < 0.001). However, TACs from PET alone under- or overestimated the activity in individual organs in contrast to TACs obtained using the cross-calibration of the PET data with the activity in post-scan dissected organs. Those organs in the excretion pathways, comprising bladder wall, kidneys and liver, received the highest organ doses. The total body absorbed dose was 0.0118 mGy/MBq for both the imaging based and harvesting based methods. The effective dose was 0.0193 mSv/MBq for the hybrid imaging-harvesting technique and 0.0189 mSv/MBq for the pure harvesting technique. Conclusion. The doses obtained agreed well with the few results available in the literature. The hybrid technique combining dynamic PET scanning followed by organ harvesting appeared to be a good alternative to the gold standard ex vivo radioassay method. It is much faster and minimizes the effect of some weakness of the pure imaging technique, such as partial volume effect. [less ▲]

Detailed reference viewed: 33 (7 ULg)
Full Text
Peer Reviewed
See detailIn Ovo PET Imaging Of A Human Colorectal Carcinoma Model In Chicken Chorioallantoic Membrane
Warnock, Geoffrey ULg; Turtoi, Andrei ULg; Blomme, Arnaud ULg et al

Poster (2012, October)

Aim. The objective of this study was to use in vivo PET/CT imaging as a validation tool for a novel human colorectal carcinoma model being developed in chicken chorioallantoic membrane (CAM). For this ... [more ▼]

Aim. The objective of this study was to use in vivo PET/CT imaging as a validation tool for a novel human colorectal carcinoma model being developed in chicken chorioallantoic membrane (CAM). For this initial pilot study a cell line modeling colon cancer was selected and imaged using [18F]fluorodeoxyglucose (FDG). <br />Materials and methods. A window was made in the shell of fertilized chicken eggs and 3x106 SW1222 human colorectal carcinoma cells were implanted at day 10 post-fertilization. On day 17 the shell window was enlarged to allow direct injection of FDG (12.2 ± 4.5 MBq/egg) into a CAM blood vessel. During injection the egg was warmed on a heating pad. A mixture of ketamine/medetomidine (50 :1 mg/ml, 0.2 ml/egg) was injected into the albumin in some eggs to assess the effect of anesthesia. After FDG injection the egg was returned to the incubator for a 45 min uptake period before imaging. Imaging was performed on a Siemens Focus 120 microPET with structural CT on a General Electric eXplore CT120. A Minerve cell system allowed reproducible positioning between modalities. PET data was acquired in list mode before histogramming into a single 10 min frame for reconstruction using a 3D maximum a posteriori (MAP) method with all corrections except scatter. A standard 100 µm (theoretical) image resolution protocol (70 kV, 50 mA, 32 ms, 220 views) was used to obtain structural CT data. Image coregistration was performed in PMOD version 3.3. In a separate egg, the influence of added contrast on the CT data was investigated by adding iodinated contrast agent (Iobitridol 35 mgI/ml) to the albumin. <br />Results. FDG uptake was clear in chick and tumor, with notably high uptake at the major joints. Tumors were identified by localization of FDG uptake on the surface of the CAM. A lack of soft tissue contrast between tumor, CAM and albumin made precise structural identification of the tumor difficult. Anesthesia was crucial to image quality in both PET and CT. CT contrast between the soft tissues of the chick and surrounding albumin/structures was improved by addition of contrast agent. <br />Conclusion. For the first time we demonstrate successful imaging of FDG uptake in a human colorectal carcinoma chicken CAM model in ovo. Methods to improve structural data are under investigation and will be used in further studies. With such improvement, this model could be of great value to PET oncology imaging. [less ▲]

Detailed reference viewed: 155 (52 ULg)
Full Text
Peer Reviewed
See detailPerformance Measurements of the microPET FOCUS 120 for Iodine-124 Imaging
Taleb, Dounia ULg; Bahri, Mohamed Ali ULg; Seret, Alain ULg et al

in IEEE Transactions on Nuclear Science (2012), PP

This study aimed to evaluate the performance of the microPET FOCUS 120 for 124I in terms of counting rate capability and image quality using the NEMA NU 4-2008 methodology. Scanner sensitivity was ... [more ▼]

This study aimed to evaluate the performance of the microPET FOCUS 120 for 124I in terms of counting rate capability and image quality using the NEMA NU 4-2008 methodology. Scanner sensitivity was measured for 124I for comparison and reached 75 cps/kBq, respectively, with the usual 350-650 keV energy window (EW) and 6 ns time window (TW). The noise equivalent count rate (NECR) index was defined as: NECR = RT2/(RP+RGP) (T = true, P = prompt, GP = γ-prompt). A rat phantom maximum NECR of 48 kcps was obtained for the 250-590 keV EW with 6 ns TW. An almost identical maximum NECR of 43 kcps was recorded for 350-590 and 350-650 keV EW and 6 ns TW. The 2 ns TW reduced the sensitivity and NECR by 40-50% for all EW. The mouse phantom NECR study was limited because of the maximum available activity concentration of 124I. The 250-590 keV EW showed the largest scatter and γ-prompt plus scatter fractions with 25.7% and 43%, respectively, for the rat phantom and 12.2% and 27% for the mouse phantom. With the 350-590 keV EW, these fractions decreased to 20% and 33.5% for the rat phantom and to 10% and 21% for the mouse phantom. The image quality was investigated with the NEMA NU 4-2008 dedicated phantom for four (two analytic and two iterative) 2D or 3D reconstruction methods. The lowest spillover ratios (SOR) for the phantom non-emitting regions were obtained for the 350-590 and 350-650 keV EWs. Recovery coefficients (RC) of the hot rods were the highest for the 350-590 keV EW except for the 1 mm rod. Scatter correction led to a large decrease in RC. The combination of the 350-590 keV EW with 6 ns TW appeared to be a good compromise between counting rate capability and image quality for the FOCUS 120, especially when maximum a posteriori reconstruction was used without scatter correction. Moreover this combination enabled the best quantification with an error as low as 0.36%. [less ▲]

Detailed reference viewed: 32 (7 ULg)
Full Text
Peer Reviewed
See detailCHARACTERIZATION OF A NOVEL RADIOTRACER TARGETING SYNAPTIC VESICLE PROTEIN 2A (SV2A)
Warnock, Geoffrey ULg; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, September)

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been ... [more ▼]

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been demonstrated to be involved in vesicle trafficking. Their implication in epilepsy makes them an interesting therapeutic target, and the widespread distribution of SV2A in particular may provide an opportunity to develop a PET-based measure of neuronal function in brain diseases. [18F]UCB-H is a fluorine-18 radiolabelled PET imaging agent with a nanomolar affinity for the human SV2A protein. Preclinical PET studies in rodents were carried out using male SD rats, imaged under isoflurane anaesthesia in a Siemens Concorde Focus 120 microPET scanner. Arterial input function was measured using an arteriovenous shunt method and beta microprobe system. [18F]UCB-H was injected IV (3.8 ± 0.54 mCi bolus, specific activity 8.5 ± 0.86 Ci/Emol immediately after synthesis) and dynamic PET data acquired in list mode for 90 min. Images were reconstructed using filtered back projection with correction for all physical effects except scatter. These scans revealed high uptake of [18F]UCB-H in brain and spinal cord, matching the expected homogeneous distribution of SV2A in the rodent brain [2]. Notably, the kinetics of [18F]UCB-H uptake in the brain were fast, peaking at up to 30 % ID/cm3 before a rapid decline. Metabolism of [18F]UCB-H in vivo followed a typical pattern of rapid initial metabolism followed by a reducing rate of metabolism over time, with less than 20% of the activity in plasma attributable to the parent compound after 30 minutes, and was highly reproducible between subjects. One major metabolite was identified. The uptake of [18F]UCB-H in the brain over time was well fitted by a classical 1-tissue compartment model. Mean parameter estimates (mean ± SD, n=7, whole brain VOI) were K1: 3.58 ± 0.65 ml/cm3/min, k2: 0.21 ± 0.03 min-1, Vt: 17.21 ± 2.52 ml/cm3. Uptake of [18F]UCB-H was blocked by pretreatment with brivaracetam (21 mg/kg IV, 10 min prior to [18F]UCB-H), a recently described high affinity SV2A ligand with a 20-fold higher affinity for SV2A than levetiracetam [3]. In contrast, pretreatment with ucb-100230-1, a diastereoisomer of brivaracetam with 3200-fold lower affinity for SV2A [3], had no clear effect of the brain uptake of [18F]UCB-H. Our results indicate that [18F]UCB-H is a suitable radiotracer for the quantification of SV2A proteins in vivo and for estimating target occupancy of drugs targeting SV2A. 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 have been completed and first in human studies are planned. References [1] Lynch, B.A. et al. (2004) PNAS 101(26):9861-6. [2] Janz, R. & Sudhof, T.C. (1999) Neuroscience 94(4):1279-1290.[3] Gillard, M. et al. (2011) Eur J Pharmacol 664:36-44. [less ▲]

Detailed reference viewed: 119 (23 ULg)
Full Text
Peer Reviewed
See detailMicroPET Focus 120 scanner use at high-­‐count rate
Bahri, Mohamed Ali ULg; Warnock, Geoffrey ULg; Taleb, Dounia ULg et al

Poster (2012, September)

Kinetic modeling of physiological processes using imaging techniques requires an accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The IF ... [more ▼]

Kinetic modeling of physiological processes using imaging techniques requires an accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The IF can be obtained by manual blood sampling, can be derived from PET images, or continuously measured by the use of small counting systems such as beta microprobes [1]. However, some beta microprobe systems can suffering from high background counts and low sensitivity compared to PET can obligate the use of activities higher than those typical for the imaging system. In the present study, the NEMA NU4-2008 image quality (IQ) phantom [2] was used to evaluate the image quality of the microPET Focus 120 at high activity values. Attenuation correction was obtained from transmission measurement using 57Co point source. Eight emission scans of 20 minutes were performed at decreasing activity starting from 109 MBq to 3.7 MBq (total activity in the field-of-view). To study the effect of normalization in high count rate studies, several normalization scans were performed using activities ranging between 18 and 212 MBq. Images were reconstructed with all corrections using Fourier rebinning and filtered backprojection. The mean activity and the coefficients of variation of the uniform slices were measured. All high activity reconstructed images showed a detector-block-patterned artifact with an overestimation of the counts when normalization activity is higher than that used in the IQ phantom and underestimation of the counts when normalization activity is below the activity used in the IQ phantom. Using the same high activity for acquisition and normalization considerably reduces the patterned-artifact but does not eliminate it entirely. The observed artifact is due to pulse pile-up in the detectors at high count-rates. A dedicated rejection of the pulse pile-up does not appear to have been implemented for the microPET Focus 120. An alternative would be to re-calibrate the detectors with higher activity values to prevent any pile-up effect or to create an attenuation volume into which phantoms or small animals could be inserted thus decreasing the artifact. This latter option is under development. References: [1] G. Warnock et al, European Journal of Nuclear Medicine and Molecular Imaging Research, 1-13 (2011) [2] NEMA Standards Publication NU4-2008. Rosslyn, VA: National Electrical Manufacturers Association; (2008). [less ▲]

Detailed reference viewed: 123 (10 ULg)
Full Text
Peer Reviewed
See detailSmall animal imaging with human PET
Bahri, Mohamed Ali ULg; Tombuloglu, S; Warnock, Geoffrey ULg et al

Poster (2012, September)

PET studies provide valuable information in the assessment of animal models for human diseases. MicroPET systems provide the high resolution needed to explore small organs but suffer from a reduced axial ... [more ▼]

PET studies provide valuable information in the assessment of animal models for human diseases. MicroPET systems provide the high resolution needed to explore small organs but suffer from a reduced axial FOV. Multiple bed positions are then used to obtain whole body scans resulting in increased scan time and incomplete dynamic data. In contrast, human PET systems have larger axial FOV but a lower resolution. In this study, an image-based model of the scanner spatial response function combined with a 3D-OSEM reconstruction algorithm were used to improve spatial resolution of the Siemens ECAT EXACT HR+ PET scanner. A stationary double Gaussian model [1] of the ECAT EXACT HR+ point spread function was derived from 18F point source measurements performed at different radial and axial locations in the scanner FOV. This model was used in a 3D-OSEM reconstruction (3D-OSEM-RM). Sinograms were normalized and attenuation and scatter corrected using the Siemens ECAT tools before reconstruction. Both NEMA NU 2-1994 performance phantoms and NEMA NU4-2008 image quality phantom mimicking small animals were used to evaluate the accuracy of corrections for physical effects and the overall image quality. A 50 min dynamic FDG rat study was conducted on the ECAT HR+ and reconstructed with 3D-OSEM-RM. The images were used to compute the metabolic rate of glucose (MRglu) in multiple brain structures. These images were also visually compared to the static image obtained with a FOCUS 120 microPET immediately after the HR+ dynamic scan. The standard deviations of the two Gaussians used to model the transaxial (axial) resolution in a central FOV of 5 cm radius were σ1 = 1.6 (2.75) mm and σ2 = 3.66 (4.16) mm, and the ratio of the weights between the first and second Gaussians was ρ = 0.2 (0.7). Image uniformity and accuracy of scatter and attenuation corrections, evaluated following NEMA NU 2-1994, were found to be very similar between 3D-OSEM, 3D-OSEM-RM, 2D- and 3D-FBP reconstructed images. When using the NEMA NU4-2008 image quality phantom a significant increase of the hot rod recovery coefficient was observed. This effect was rod size dependent and amounted to 17-35% for the 3D-OSEM-RM compared to the 3D-OSEM and to 35-62% compared to the FBP reconstructions. Nevertheless the values obtained with 3D-OSEM-RM were around 20-35% lower than those obtained with the FOCUS 120 microPET scanner. Most of the small brain structures observed on microPET images were also visible on the images obtained with the HR+ scanner and 3D-OSEM-RM. Rat cerebral MRglu values calculated on 3D-OSEM-RM images were in the range of published values [2] (e.g. whole brain = 25.34 μmol/min/100g). Using an approximate model of the ECAT EXACT HR+ spatial response in 3D-OSEM resulted in sufficient image quality for dynamic whole body scans of small rodents, despite the large FOV, and resulted in improved contrast compared to images generated using the built-in software. This methodology will be applied for future small animal dosimetry and modeling studies in our laboratory. [1] Comtat et al. IEEE Nucl Sci Symp Conf Record. pp. 4120-4123 (2008) [2] Schiffer et al. J Nucl Med 48:277-287 (2007) [less ▲]

Detailed reference viewed: 135 (14 ULg)