YAP-(S)PET: a small animal PET/SPECT scanner. Performance and applications in oncology, cardiology and neuroscience

Aims: Molecular imaging can be defined as the visual representation, characterization, and quantification of biological processes at the cellular and sub-cellular levels within intact living organisms. It is a novel multidisciplinary field, in which the produced images reflect cellular and molecular pathways and in vivo mechanisms of disease present within the context of physiological environments. The emergence of molecular imaging strategies is largely due to recent unprecedented advances in molecular and cell biology techniques, the use of transgenic animal models, availability of newer imaging drugs and probes that are highly specific, and successful development of small-animal imaging instrumentation. The YAP-(S)PET small animal scanner is part of this environment. It is a specifically built scanner able to perform both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) and simultaneous PET/SPECT acquisitions. Materials and Methods: The scanner was originally developed at the Department of Physics of the Universities of Ferrara and Pisa, Italy. From 2003, a fully engineered version of the scanner have been produced and commercialized by the small italian company I.S.E. s.r.l., Pisa, Italy. This thesis deals with the physical calibration and characterization and with pre-clinical applications of the new version the YAP-(S)PET originally developed, the YAP-(S)PET II. It is made up of four detector heads, each one composed of a 4 × 4 cm2 YAP:Ce matrix of 27 × 27 elements, 1.5 × 1.5 × 20 mm3 each, coupled to a Position Sensitive-Photomultiplier (PS-PMT). The heads can be positioned at different distances ranging from 10 to 20 cm. The four modules are positioned on a rotating gantry and opposing detectors are in time coincidence when used in PET mode. The scanner can be switched between PET and SPECT modalities simply replacing the tungsten septum used in PET with a high-resolution parallel hole collimator in front of each crystal. The peculiar YAP-(S)PET architecture provides also the capability to perform simultaneous PET/SPECT acquisitions. The hardware calibrations concerned both electronics and mechanics settings such as adjustment of PMT gain or precise positioning of the center of rotation, while the software calibrations were related to definition of crystal and energy maps, and to efficiency corrections. In PET mode, the performance of the YAP-(S)PET scanner have been evaluated following the standards proposed by the PET National Electric Manufacturers Association (NEMA) task force for small animal scanners. Since the lack of small animal SPECT performance, the SPECT performance has been evaluated by rescaling the clinical SPECT NEMA reference standards NU1-1994. For both PET and SPECT modalities, the performance were evaluated at different head-to-head distances: 10, 12.5 and 15 cm. The simultaneous PET/SPECT dual imaging acquisition modality was realized by independently acquiring single events with two opposing heads equipped with the collimators (SPECT mode), while the other couple of heads detects coincident events (PET mode). Different animal models and various isotopes and tracers have been used in the experiments performed in collaborations with several research groups. In this thesis only some of these studies are reported in order to point out the YAP-(S)PET imaging capabilities, particularly in neuro-pharmacology, psychiatry and oncology. Conclusions: In PET mode the performance evaluation has regarded the spatial resolution, sensitivity, scatter fraction and count rate. The best compromise between spatial resolution and sensitivity was obtained with a head-to-head distance of 10 cm. In this configuration, the volume resolution is about 8 microliters, the sensitivity reaches 3% at the center fo the Field of View (CFOV), the scatter fraction is 27% and the peak Noise Equivalent Count rate is about 38 kcps at an activity concentration in the FOV of about 370 kBq/ml. Also in SPECT modality, the best results are obtained for 10 cm head-to-head distance. The spatial resolution is about 2.8 mm at CFOV and the sensitivity is (3.7 E-3)% for 140-250 keV energy window. Due to reduced working space at 10 cm, particularly evident in rats experiments, the best compromise between scanner performance and rats experiments is 12.5 cm for both PET and SPECT modality. On the contrary, mice experiments can be better performed at 10 cm head-to-head distance

The experience in a Center of Excellence in Preclinical Imaging: from the set-up of the PET/SPECT laboratory to the routine experimental activity

Molecular imaging can be defined as the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. Generally speaking, molecular imaging involves specialized instrumentation, used alone or in combination with targeted imaging agents, to visualize tissue characteristics and/or biochemical markers. The field of molecular imaging is highly multidisciplinary, drawing from many areas of science, including, but not limited to, molecular biology, biochemistry, physiology, physics, engineering, genetics, mathematics, chemistry, pharmacology, immunology, and medicine. Molecular imaging of living subjects can trace its roots back to nuclear medicine, nevertheless many techniques are now possible. In fact, techniques using optical signaling, as well as signaling using magnetic resonance imaging (MRI), ultrasound (US), Raman, photoacoustics (PA), and computed tomography (CT), have also been steadily increasing. And although still in its infancy, molecular imaging is showing enormous promise in the areas of diagnostics, therapy monitoring, drug discovery and development, and understanding nanoscale reactions such as protein-protein interactions and enzymatic conversion. Biomedical research utilizing small animals such as mice and rats has expanded dramatically in the past few years as molecular biology and imaging techniques open new opportunities to investigate models of disease. The growing number of mouse and rat experiments, coupled with the increasing number of dedicated small animal imaging systems such as microPET, optical, microCT, microMRI, ultrasound and microSPECT, has led to the development of common technical centers for imaging small animals. Increasingly sophisticated molecular probes and tool sets allow researchers to examine multiple processes at once in the same animal by using different light wavelengths (optical), various molecular imaging probes (PET and SPECT) and different contrast agents (MRI and CT), as well as to define the anatomical structures in which these processes take place. This, in turn, has led to a demand for comprehensive, multimodality imaging facilities that can house animals, support imaging systems, and provide investigators with the tools, methods, and other infrastructure necessary for successful imaging experiments. The realization of the Center of Excellence in Preclinical Imaging (CEIP) is part of this expansions. The CEIP is an Academic/Industry partnership and offers to universities, research centers and companies know-how and methodologies based on imaging techniques in order to facilitate and speed up the process of development of new diagnostic and therapeutic solutions. This thesis mainly describes two topics of the experience within the CEIP: the set-up of the PET/SPECT laboratory and a few small animal imaging studies. Concerning the set-up of the PET/SPECT laboratory, we focused on radioprotection issues such as: - features of the employed sources. - Selection of the rooms reserved for radioactive employing and description of the equipment positioning. - Shielding calculation. - Evaluation of the radiation exposure to both personnel and public. - Management of the radioactive wastes and residuals. - Classification of the areas and of the workers. About animal experiments, a few case studies have been reported. - A PET study performed with [18]F and [68]Ga to assess the response to Dasatinib treatment in PC-3 prostate tumor-bearing nude mice. - A longitudinal SPECT concerning the evaluation of the $^{99m}$Tc-rhAnnexin V-128 imaging effectiveness for diagnosis and monitoring anti-rheumatic therapies in a collagen induced arthritis (CIA) model in mice. - A multimodality study realized by combining the 7 T MRI scanner with the YAP-(S)PET scanner. The PET/MRI acquisitions were performed in sequential mode with a hand-made bed support that allowed to keep the animal in a fixed position

In vivo imaging of tumor metabolism and acidosis by combining PET and MRI-CEST pH imaging

Abstract The vast majority of cancers exhibit increased glucose uptake and glycolysis regardless of oxygen availability. This metabolic shift leads to an enhanced production of lactic acid that decreases extracellular pH (pHe), a hallmark of the tumor microenvironment. In this way, dysregulated tumor pHe and upregulated glucose metabolism are linked tightly and their relative assessment may be useful to gain understanding of the underlying biology. Here we investigated noninvasively the in vivo correlation between tumor 18F-FDG uptake and extracellular pH values in a murine model of HER2+ breast cancer. Tumor extracellular pH and perfusion were assessed by acquiring MRI-CEST (chemical exchange saturation transfer) images on a 3T scanner after intravenous administration of a pH-responsive contrast agent (iopamidol). Static PET images were recorded immediately after MRI acquisitions to quantify the extent of 18F-FDG uptake. We demonstrated the occurrence of tumor pHe changes that report on acidification of the interstitial fluid caused by an accelerated glycolysis. Combined PET and MRI-CEST images reported complementary spatial information of the altered glucose metabolism. Notably, a significant inverse correlation was found between extracellular tumor pH and 18F-FDG uptake, as a high 18F-FDG uptake corresponds to lower extracellular pH values. These results show how merging the information from 18F-FDG-uptake and extracellular pH measurements can improve characterization of the tumor microenvironment. Cancer Res; 76(22); 6463–70. ©2016 AACR.</jats:p

El viaje de campaña como estrategia pedagógica para alumnos de Ciencias Naturales : La experiencia de Fisiología Vegetal

La realización de viajes de campaña constituye un aporte fundamental para los estudios de grado de algunas carreras. Específicamente para alumnos del área biológica es la oportunidad de aprender en ambientes informales, realizar actividades que no podrían ser desarrolladas en el laboratorio y permite construir conocimiento a través de interacciones con el ambiente que invitan a observar, identificar, medir y comparar. En esta presentación se describen las características del viaje de campaña al Palmar de Colón del curso de Fisiología Vegetal de la Facultad de Ciencias Naturales y Museo, con el propósito de evaluar la experiencia piloto que el equipo docente viene desarrollando y definir algunas orientaciones para mejorar su aprovechamiento. El propósito de la actividad es que los alumnos integren contenidos previos de su carrera con los específicos del curso de Fisiología Vegetal para analizar, interpretar y explicar el comportamiento adaptativo de especies en ambientes naturales. Los alumnos deben completar una guía de actividades, en la registran parámetros descriptivos de cada ambiente, rasgos morfo-fisiológicos de las especies, miden procesos vinculados con el balance de agua y carbono y discuten su posible importancia en cada ambiente. Se realiza una puesta en común sobre cada ítem fomentando la discusión e intercambio de ideas. Con el fin de que los estudiantes tengan acceso a algunos equipos utilizados en la disciplina, la cátedra aporta aquellos que permitan efectuar mediciones morfológicas y fisiológicas de caracteres y procesos vinculados con los balances de agua y carbono. Se evalúa la experiencia a través de una encuesta.Trabajos del área Ciencias NaturalesDepartamento de Ciencias Exactas y Naturale

Abriendo las compuertas del aula: la fisiología vegetal en el viaje de campaña

La experiencia educativa durante el viaje de campaña adquiere características singulares que en parte podrían explicarse por una temporalidad diferente a la usual en el aula. También, el hecho de que nuestra propuesta no supuso abordar contenidos específicos de la disciplina sino integrar los ya vistos durante la cursada contribuyó a deshacernos de estructuras conceptuales o esquemas de razonamiento rígidos y, por lo tanto, a hacernos de ideas propias. La estrategia de utilizar un proceso de investigación como hilo conductor del trabajo grupal implicó colocarnos a docentes y alumnos en una misma situación de incertidumbre, acercándonos a una construcción colectiva del conocimiento disciplinar.Eje 1: La enseñanza universitaria en el contexto actual: transformaciones y propuestas. Reflexiones y experiencias en la enseñanza de las Ciencias NaturalesSecretaría de Asuntos Académico

Integration of art and technology in personalized radiation oncology care: Experiences, evidence, and perspectives

Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as “co-stars” in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization

BIODIVERSITÀ DEL CILIEGIO CAMPANO: CONTENUTI IN ELEMENTI ESSENZIALI

The contents of some nutrients [Phosphorus (P), Potassium (K), Magnesium (Mg), Iron(Fe), Calcium(Ca), Selenium(Se), Zinc(Zn) and Sodium(Na)]  and trace metals [Vanadium (V), Nickel (Ni), Chromium (Cr), Lead (Pb), Copper (Cu), Aluminum (Al) and Cadmium (Cd)] were determined in 30 cherry accessions from a farm for collections of Campania Region. Data have highlighted a high nutrient contents in the local accessions and often higher than commercial ones. In particular, it was observed that the Bologna accession showed higher contents of P, Mg, K and Se, and also high concentrations of Ca, Na, Zn, Fe. Moreover, they are of a good quality because the concentrations of trace metals, commonly found as pollutants in the environments, did not exceed, where provided, the law limits imposed.Le contenu des éléments essentiels [Phosphore (P), Potassium (K), Magnésium (Mg), Fer (Fe),  Calcium (Ca), Sélénium (Se), Zinc (Zn) et Sodium (Na)] et des trace-éléments [Vanadium (V), Nickel (Ni), Chrome (Cr), Plomb (Pb), Cuivre (Cu), Aluminium (Al) et Cadmium (Cd)] ont été déterminées dans 30 écotypes de cerise de la Région de la Campanie. Les résultats obtenus ont montré souvent une plus grande quantité des éléments essentiels  dans les différentes écotypes locales auprès de ces commerciales. En particulier, nous avons observé que le écotype Bologne a concentrations élevées de P, Mg, K, Se, et de Ca, Na, Zn, Fe. En outre, les variétés locales analysées ont montré une bonne qualité pourquoi les concentrations des métaux en trace, et qui sont contaminants de l’ambiant,  ne dépassent pas, dans les cas prévus, les limites imposées.I contenuti di diversi nutrienti [Fosforo (P), Potassio (K), Magnesio (Mg), Ferro (Fe), Calcio (Ca), Selenio (Se), Zinco (Zn) e Sodio (Na) ] ed elementi in tracce [Vanadio (V), Nichel (Ni), Cromo (Cr), Piombo (Pb), Rame (Cu), Alluminio (Al) e Cadmio (Cd)] sono stati determinati in 30 accessioni di ciliegio della Regione Campania. I dati ottenuti hanno evidenziato contenuti elevati in nutrienti in molte delle accessioni locali e spesso anche più che in quelle commerciali. In particolare, si è osservato che l’accessione Bologna ha i contenuti maggiori di P, Mg, K e Se ed anche alte concentrazioni di Ca, Na, Zn, Fe. Inoltre, le accessioni locali finora analizzate hanno evidenziato una buona qualità in quanto le concentrazioni dei metalli in traccia, più comunemente rinvenute come contaminanti ambientali,  non superano, laddove previsti, i limiti imposti dalle normative vigenti

Silicosis in Workers Exposed to Artificial Quartz Conglomerates: Does It Differ From Chronic Simple Silicosis?

6reservedRecently, a number of reports have been published on silicosis in workers exposed to artificial quartz conglomerates containing high levels of crystalline silica particles (70-90%) used in the construction of kitchen and bathroom surfaces. Three cases of silicosis in workers exposed to artificial quartz conglomerates are reported. The diagnosis was derived from both the International Labour Office and the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) classifications and cytological analysis of bronchoalveolar lavage fluid. In 2 cases, levels of respirable silica greatly in excess of recommended standards were measured in the workplace, and cytological analysis of bronchoalveolar lavage fluid highlighted a prevalence of lymphocytes, meeting criteria for the diagnosis of accelerated silicosis. The prevention of pneumoconiosis caused by the use of innovative materials, such as artificial conglomerates with high crystalline silica content must be addressed.mixedPaolucci, V; Romeo, R; Sisinni, Ag; Bartoli, D; Mazzei, Ma; Sartorelli, PPaolucci, Valentina; Romeo, Riccardo; Sisinni, ANTONIETTA GERARDINA; Bartoli, D; Mazzei, MARIA ANTONIETTA; Sartorelli, Pietr