Publications (12)20.69 Total impact
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Article: Quantitative volumetric analysis of gliomas with sequential MRI and ¹¹C-methionine PET assessment: patterns of integration in therapy planning.
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ABSTRACT: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p < 0.001, κ = 0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.European Journal of Nuclear Medicine 01/2012; 39(5):771-81. · 4.53 Impact Factor -
Article: Evaluation of spatial resolution of a PET scanner through the simulation and experimental measurement of the recovery coefficient.
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ABSTRACT: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures. In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources. In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure. Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions.Computers in biology and medicine 12/2009; 40(1):75-80. · 1.27 Impact Factor -
Article: New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification.
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ABSTRACT: Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.NeuroImage 06/2009; 47(2):533-9. · 5.89 Impact Factor -
Article: Evaluation of CdZnTe as neutron detector around medical accelerators.
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ABSTRACT: The operation of electron linear accelerators (LINACs) and cyclotrons can produce a mixed gamma-neutron field composed of energetic neutrons coming directly from the source and scattered lower energy neutrons. The thermal neutron detection properties of a non-moderated coplanar-grid CdZnTe (CZT) gamma-ray detector close to an 18 MV electron LINAC and an 18 MeV proton cyclotron producing the radioisotope (18)F for positron emission tomography are investigated. The two accelerators are operated at conditions producing similar thermal neutron fluence rates of the order of 10(4) cm(-2) s(-1) at the measurement locations. The counting efficiency of the CZT detector using the prompt 558 keV photopeak following (113)Cd thermal neutron capture is evaluated and a good neutron detection performance is found at the two installations.Radiation Protection Dosimetry 04/2009; 133(4):193-9. · 0.82 Impact Factor -
Article: PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector.
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ABSTRACT: Non-invasive in vivo imaging of transgene expression is currently providing very important means to optimize gene therapy regimes. Results in non-human primates are considered the most predictive models for the outcome in patients. In this study, we have documented that tumour and primary cell lines from human and non-human primates are comparably gene-transduced in vitro by serotype 5 adenovirus expressing HSV1-thymidine kinase. Transgene expression can be quantified in human and monkey cultured cells by positron emission tomography (PET) imaging when transduced cells are incubated with a fluoride-18 labelled penciclovir analogue. In our hands, PET images of cell cultures estimate the number of transduced cells rather than intensity of transgene expression once a threshold of TK per cell is reached. Interestingly, in vivo systemic administration of a clinical grade recombinant adenovirus expressing TK into macaques gives rise to an intense retention of the radiotracer in the liver parenchyma, providing an experimental system to visualize transgene expression that ought to be similar in human and macaques. Such imaging methodology might contribute to improve strategies based on adenoviral vectors.Gene therapy 08/2008; 16(1):136-41. · 4.75 Impact Factor -
Article: [Use of 11C-(+)-alpha -dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease].
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ABSTRACT: This study evaluates the utility of (11)C-(+)-alpha -dihydrotetrabenazine ((11)C-(+)DTBZ) in the quantification of dopaminergic innervation by positron emission tomography (PET) in rat and monkey, two animal species used as animal models of Parkinson's disease. Healthy control animals (n = 10) and the effect of 6-hydroxidopamine (6-OHDA) neurotoxic were studied in rats. (18)F-DOPA PET studies and digital quantitative autoradiography were also carried out. Studies with Macaca fascicularis were performed in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) treated animals. In both species high quality images were generated in which clear uptake of (11)C-(+)DTBZ was found in the striatum. (11)C-(+)DTBZ uptake quantification was estimated by creating parametric images and binding potential (BP) calculation. BP in control rats was 1.10 +/- 0.16 (mean +/- standard deviation [SD], whereas 6-OHDA produced a decrease in the uptake depending on the lesion degree. Images obtained with (18)F-DOPA were not adequate for the analysis as they did not discriminate the stratum whereas digital quantitative autoradiography studies confirmed the high affinity of striatum by (11)C-(+)DTBZ. In monkeys, final BP values were 1.31 and 1.06 and MPTP treatment reduced uptake by 40 %. The quality of PET images and the decrease of uptake in 6-OHDA and MPTP lesions show that (11)C-(+)DTBZ is an adequate radiotracer for the study of dopaminergic innervation in these animal models.Revista Española de Medicina Nuclear 04/2008; 27(2):103-11. · 0.89 Impact Factor -
Article: Neutron spectrometry in a PET cyclotron with a Bonner sphere system.
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ABSTRACT: Positron emission tomography (PET) is a non-invasive medical imaging technique normally used for diagnostic purposes to determine the location and concentration of physiologically active compounds in a human body. An unshielded cyclotron is used for PET at the Clinica Universitaria de Navarra to produce short-lived positron emitting radionuclides ((15)O, (13)N, (11)C and (18)F) by bombarding appropriate target material with proton or deuteron beams with energies up to 18 and 9 MeV, respectively. Subsequent nuclear reactions may generate undesirable neutrons that should be evaluated and controlled. In this study, the neutron measurements performed with an active and a passive Bonner sphere systems at different locations outside and inside the cyclotron vault during operation have been presented. The neutron spectrum at each location was determined with an unfolding code developed by the authors.Radiation Protection Dosimetry 02/2007; 126(1-4):371-5. · 0.82 Impact Factor -
Article: Monte Carlo neutron doses estimations inside a PET cyclotron vault room.
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ABSTRACT: Neutron organ equivalent doses, effective doses and dose equivalents received inside a positron emission tomography vault room in a maximum credible accident have been estimated with the Monte Carlo code MCNPX. While an operator was inside the vault room of a Cyclone 18/9 IBA cyclotron, this was producing (18)F with 30 muA proton current in the target and the operator had to activate a stopped emergency device placed on the wall. MC simulation of the cyclotron vault were carried out to estimate the organ and tissue equivalent doses in a mathematical male mannequin simulating the operator facing the wall on which the emergency device is placed. Doses were calculated at two emergency devices for each one of the two targets of the cyclotron, which were able to produce (18)F. The maximum effective dose in the mannequin was 6.70 Sv/h and the maximum organ equivalent dose was 18.47 Sv/h in spleen.Radiation Protection Dosimetry 02/2007; 126(1-4):477-81. · 0.82 Impact Factor -
Article: [Positron emission tomography in breast cancer].
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ABSTRACT: PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer.Revista de medicina de la Universidad de Navarra 52(1):4-12. -
Article: [Quick and simple synthesis of (11)C-(+)-alpha-dihydrotetrabenazine to be used as a PET radioligand of vesicular monoamine transporters].
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ABSTRACT: Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). We have developed a new fully automated synthesis procedure to obtain 11C-(+)DTBZ quickly and simply through labelling the precursor -(+)desmethyldihy-drotetrabenazine- at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11CH3I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free 11C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11CH3I production. 11C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys. This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.Revista Española de Medicina Nuclear 27(1):13-21. · 0.89 Impact Factor -
Article: Tomografía por emisión de positrones en el cáncer de mama
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ABSTRACT: PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current diffi culties for clinical applications, fl uoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer. La PET-18FDG es una técnica de imagen que pone en evidencia los cambios del metabolismo glicolítico que de forma muy precoz se manifi estan a lo largo de todo el proceso tumoral. Su principal limitación en el cáncer de mama es la detección de lesiones tumorales de pequeño tamaño o de micrometástasis ganglionares axilares. Sin embargo ofrece una información muy importante en la estadifi cación de pacientes con alto riesgo, ante la sospecha de recidiva clínica o en la valoración de la respuesta terapéutica. Los nuevos equipos PET-TC ofrecen ventajas respecto a la técnica convencional por facilitar una mayor precisión en la localización de los focos tumorales. A pesar de ciertas difi cultades para su úso clínico en el momento actual la PET, por medio del radiofármaco fl uor-estradiol (18F-ES), ofrece la posibilidad de estudiar la presencia de receptores estrogénicos tanto en tumor primario como en sus metástasis, pudiendo ser una herramienta muy útil en el manejo terapéutico y en la valoración pronóstica del cáncer de mama.Revista de medicina, Vol. 52, Nº. 1, 2008, pags. 4-12. -
Article: New MRI, 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: Advantages to improve PET quantification
[show abstract] [hide abstract]
ABSTRACT: Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, 18F-DOPA and 11C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of 11C-DTBZ PET. A symmetric reduction in striatal 11C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.NeuroImage.
Top co-authors
Top Journals
Institutions
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2012
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Clínica Universidad de Navarra
Madrid, Madrid, Spain
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2007
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Universidad de Valladolid
- Departamento de Física Teórica, Atómica y Óptica
Valladolid, Castile and Leon, Spain
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