Publicação
Assessment of the easyPET-3D system performance: NEMA NU 4-2008 standards and animal model
| Resumo: | Positron emission tomography (PET), dedicated to non-invasive in vivo imaging of animal models, is an essential tool in research activities, contributing to the characterization of models of human pathologies, development and validation of new medicines and radiotracers, and evaluation of the efficacy and safety of novel therapies. To guarantee accurate quantification leading to robust, reproducible, and reliable experimental results, evaluating the performance of these preclinical tomographs is mandatory, particularly in new models or when hardware/software improvements are made. Therefore, the main aim of this thesis is to evaluate the performance of the easyPET.3D, an innovative highresolution PET system dedicated to mice imaging. Hence, a preliminary experimental study was carried out to optimize the sensitivity and spatial resolution by studying the operating parameters related to motor motion. Subsequently, the scanner's performance was evaluated following the National Electrical Manufacturers Association (NEMA) NU 4-2008 Standards. It provides a comprehensive set of procedures for evaluating small animal PET scanner’s performance, assessing key characteristics like spatial resolution, sensitivity, count rate, scatter fraction, and image quality. In addition, in vivo studies in an animal model (several strains of mice) were conducted with different radiotracers to demonstrate the performance of the PET tomograph in distinct applications. To achieve the best image detail and signal strength, the easyPET.3D’s fan motor, responsible for the fan rotation during acquisition, should operate at 20 steps per second, with a step angle ranging from 0.014° to 0.056°. The axial motor, which performs the axial rotation during acquisition, may operate between 0.9° and 9.0° (faster or slower acquisition), according to the study purpose. Furthermore, it was determined that an energy window of 200–750 keV maximizes the sensitivity (x 3) without significantly deteriorating the scatter fraction (+ 35%). In contrast, the acquisition protocol made it difficult to conclude about the positron range effect. Regarding the evaluation of the performance of easyPET.3D by NEMA recommendations, the spatial resolution is 0.81 mm3 in the centre of the field-of-view, the absolute sensitivity peak corresponds to 0.23%, the noise equivalent count rate is 913 counts per second reached at 18 MBq, the uniformity result is 17.6%, the recovery coefficients are 0.21 for the smaller capillary (1 mm) and 0.85 for the larger capillary (5 mm), and spill-over ratios are 0.49 and 0.40 for water and air, respectively. Despite the low sensitivity, the linearity of easyPET.3D is suitable for activities typically used in PET studies of small animals (7–8 MBq), and its submillimetre spatial resolution is comparable to commercially available systems, whose cost is much higher (x 10). A global protocol was developed for animal preparation and care before, during and after a PET study with the gold standard radiotracer 2-Deoxy-2-[¹⁸F]fluoroglucose. Afterwards, healthy mice were administered with different tracers to assess their respective biodistribution patterns. The visualization of small structures, such as the striatum in the brain, the wall of the left ventricle, and the vertebrae, proved the high-resolution of easyPET.3D and its potential for application in animal models. Finally, longitudinal PET studies were carried out on groups of animals included in preclinical investigations in oncology and neurology. The equipment differentiated benign from malignant lesions and malignant from necrotic tissue for an early and precise therapeutic decision. Moreover, structural brain lesions induced by an acute and low dose of cocaine were correlated with changes in brain metabolism signalled by the system. In conclusion, the results obtained in this thesis demonstrate that, in terms of performance, the easyPET.3D is comparable to established commercial systems, revealing potential for application in preclinical research. However, additional evaluation studies must be performed to validate the preliminary results obtained and increase the application prospects of this high-resolution, compact, and cost-effective PET system. |
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| Autores principais: | Ribeiro, Fabiana de Meneses |
| Assunto: | EasyPET PET Small animal imaging Preclinical Performance evaluation NEMA High resolution |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Positron emission tomography (PET), dedicated to non-invasive in vivo imaging of animal models, is an essential tool in research activities, contributing to the characterization of models of human pathologies, development and validation of new medicines and radiotracers, and evaluation of the efficacy and safety of novel therapies. To guarantee accurate quantification leading to robust, reproducible, and reliable experimental results, evaluating the performance of these preclinical tomographs is mandatory, particularly in new models or when hardware/software improvements are made. Therefore, the main aim of this thesis is to evaluate the performance of the easyPET.3D, an innovative highresolution PET system dedicated to mice imaging. Hence, a preliminary experimental study was carried out to optimize the sensitivity and spatial resolution by studying the operating parameters related to motor motion. Subsequently, the scanner's performance was evaluated following the National Electrical Manufacturers Association (NEMA) NU 4-2008 Standards. It provides a comprehensive set of procedures for evaluating small animal PET scanner’s performance, assessing key characteristics like spatial resolution, sensitivity, count rate, scatter fraction, and image quality. In addition, in vivo studies in an animal model (several strains of mice) were conducted with different radiotracers to demonstrate the performance of the PET tomograph in distinct applications. To achieve the best image detail and signal strength, the easyPET.3D’s fan motor, responsible for the fan rotation during acquisition, should operate at 20 steps per second, with a step angle ranging from 0.014° to 0.056°. The axial motor, which performs the axial rotation during acquisition, may operate between 0.9° and 9.0° (faster or slower acquisition), according to the study purpose. Furthermore, it was determined that an energy window of 200–750 keV maximizes the sensitivity (x 3) without significantly deteriorating the scatter fraction (+ 35%). In contrast, the acquisition protocol made it difficult to conclude about the positron range effect. Regarding the evaluation of the performance of easyPET.3D by NEMA recommendations, the spatial resolution is 0.81 mm3 in the centre of the field-of-view, the absolute sensitivity peak corresponds to 0.23%, the noise equivalent count rate is 913 counts per second reached at 18 MBq, the uniformity result is 17.6%, the recovery coefficients are 0.21 for the smaller capillary (1 mm) and 0.85 for the larger capillary (5 mm), and spill-over ratios are 0.49 and 0.40 for water and air, respectively. Despite the low sensitivity, the linearity of easyPET.3D is suitable for activities typically used in PET studies of small animals (7–8 MBq), and its submillimetre spatial resolution is comparable to commercially available systems, whose cost is much higher (x 10). A global protocol was developed for animal preparation and care before, during and after a PET study with the gold standard radiotracer 2-Deoxy-2-[¹⁸F]fluoroglucose. Afterwards, healthy mice were administered with different tracers to assess their respective biodistribution patterns. The visualization of small structures, such as the striatum in the brain, the wall of the left ventricle, and the vertebrae, proved the high-resolution of easyPET.3D and its potential for application in animal models. Finally, longitudinal PET studies were carried out on groups of animals included in preclinical investigations in oncology and neurology. The equipment differentiated benign from malignant lesions and malignant from necrotic tissue for an early and precise therapeutic decision. Moreover, structural brain lesions induced by an acute and low dose of cocaine were correlated with changes in brain metabolism signalled by the system. In conclusion, the results obtained in this thesis demonstrate that, in terms of performance, the easyPET.3D is comparable to established commercial systems, revealing potential for application in preclinical research. However, additional evaluation studies must be performed to validate the preliminary results obtained and increase the application prospects of this high-resolution, compact, and cost-effective PET system. |
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