PeneloPET v3.0, an improved multiplatform PET Simulator

PeneloPET is a Monte Carlo simulation tool for positron emission tomography based on PENELOPE. It was developed by the Nuclear Physics Group at University Complutense of Madrid and its initial version was released in 2009. In this work, we present PeneloPET v3.0, which is now available precompiled for Microsoft Windows, MacOS and Linux OS. This new release includes improved simulations of the positron range in different materials and an accurate description of the decay cascades for many radioactive nuclei including the most common non-pure positron emitters used in PET. This enables the simulation of PET acquisitions with positron-gamma emitters. This release also includes many different fully-working examples, of both clinical and preclinical scanners, as well as several numerical phantoms. Due to the simplicity of the input the output files, and the installation process, PeneloPET v3.0 can be perfectly used not only for research, but also as an educational tool in class

Characterization of the proton pulsed beam at CMAM

In this paper, the technicalities performed to obtain a pulsed beam at the CMAM facility will be explained. The pulsed beam has been characterized with an 8 MeV proton beam, using an existing equipment at CMAM: two pairs of electrostatic plates (RASTER) that deflect the beam, commonly used for homogeneous irradiation of large areas. A pulsed beam is used in many areas such as nuclear physics, material science and, in particular, for proton-therapy medical studies. Rectangular and pyramidal functions have been used to generate different pulses and characterize the response of the RASTER. The results point out that the pulses obtained are suitable for preclinical proton-therapy studies in the FLASH regime, which consists on fractionating the dose in time with short and intense pulses. The set-up for the characterization has been a function generator and a Si-PM outside the chamber

In vivo production of fluorine-18 in a chicken egg tumor model of breast cancer for proton therapy range verification

Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in the Bragg peak area and biological washout of PET emitters. The use of contrast agents including O-18, Zn-68 or Cu-63, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of O-18-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (F-18) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough O-18 into a living organism to produce a detectable signal from F-18 after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of F-18 (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which confirms that low-energy protons can indeed produce a detectable PET signal if a suitable contrast agent is employed. Moreover, dynamic PET studies in two of the eggs evidenced a minimal effect of biological washout, with 68% retained specific F-18 activity at 8 h after irradiation. Furthermore, ex-vivo analysis of 4 irradiated tumours showed that up to 3% of oxygen atoms in the targets were replaced by O-18 from infused 18-W, and evidenced an entrapment of 59% for specific activity of F-18 after washing, supporting our hypothesis that F- ions remain trapped within the cells. An infusion of 18-W can incorporate O-18 in animal tissues by replacing regular water inside cells, producing a PET signal when irradiated with low-energy protons that could be used for range verification in protontherapy. F-18 produced inside cells remains entrapped and suffers from minimal biological washout, allowing for a sharper localization with longer PET acquisitions. Further studies must evaluate the feasibility of this technique in dosimetric conditions closer to clinical practice, in order to define potential protocols for its use in patients

Desarrollo de un libro electrónico mejorado sobre aplicaciones de la Física Nuclear a la Medicina

Proyecto de innovación docente con el objetivo de desarrollar una herramienta que facilite el aprendizaje de las aplicaciones a la Medicina de la Física Nuclear. Se ha creado el sitio web https://fisnucmed.wordpress.com/. Se abordan, entre otros contenidos, las radiaciones ionizantes y los fundamentos de la interacción de la radiación con la materia, nociones de detección de radiación e instrumentación nuclear , diagnóstico por imagen, y las modalidades de imagen PET, SPECT, CT, resonancia magnética nuclear, ultrasonidos, así como la radioterapia y en particular la hadronterapia

Simulaciones avanzadas aplicadas al diseño de escáneres y mejora de la calidad de imagen en tomografía por emisión de positrones

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Física Atómica, Molecular y Nuclear, leída el 31-03-2009Desde la aparición de los primeros escáneres PET en los años 70 del siglo pasado, la tomografía por emisión de positrones se ha extendido de manera continuada en oncología, cardiología y neurología. La utilización de esta técnica en investigación preclínica ha supuesto un gran desafío durante la última década, en que se han desarrollado escáneres PET de muy alta resolución para animales de laboratorio como ratones y ratas. En la actualidad se consiguen imágenes PET con una resolución submilimétrica con sensibilidades superiores al 10 %. Esto ha sido posible gracias al desarrollo tecnológico de los equipos de detección de rayos gamma y la electrónica de procesado. Así mismo, la aparición de computadores con gran capacidad de cálculo, unido al perfeccionamiento de los algoritmos de reconstrucción y al uso generalizado de los métodos de simulación Monte Carlo en todas las etapas del desarrollo de escáneres, ha supuesto un impulso muy importante en el desarrollo de la técnica PET. En esta tesis doctoral se ha tratado de mejorar la calidad de las imágenes PET reconstruidas. Para ello se han utilizado de manera intensiva los métodos de simulación Monte Carlo con el fin de entender a fondo los procesos que tienen lugar en la adquisición de datos PET. La simulación realista del PET nos ha permitido introducir mejoras en todas las fases del proceso de formación de la imagen, desde el diseño del escáner y los detectores que lo componen hasta el cálculo de la matriz del sistema utilizada en el proceso de reconstrucción, pasando por la adquisición y procesado de datos y la introducción de correcciones sobre los mismos. Gracias a ello, hemos conseguido imágenes con mejor resolución espacial, mejor relación señal-ruido y resultados de cuantificación más precisos y reproducibles.Depto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasTRUEpu

Monte Carlo patient study on the comparison of prompt gamma and PET imaging for range verification in proton therapy

The purpose of this work was to compare the clinical adaptation of prompt gamma (PG) imaging and positron emission tomography (PET) as independent tools for non-invasive proton beam range verification and treatment validation. The PG range correlation and its differences with PET have been modeled for the first time in a highly heterogeneous tissue environment, using different field sizes and configurations. Four patients with different tumor locations (head and neck, prostate, spine and abdomen) were chosen to compare the site-specific behaviors of the PG and PET images, using both passive scattered and pencil beam fields. Accurate reconstruction of dose, PG and PET distributions was achieved by using the planning computed tomography (CT) image in a validated GEANT4-based Monte Carlo code capable of modeling the treatment nozzle and patient anatomy in detail. The physical and biological washout phenomenon and decay half-lives for PET activity for the most abundant isotopes such as (11)C, (15)O, (13)N, (30)P and (38)K were taken into account in the data analysis. The attenuation of the gamma signal after traversing the patient geometry and respective detection efficiencies were estimated for both methods to ensure proper comparison. The projected dose, PG and PET profiles along many lines in the beam direction were analyzed to investigate the correlation consistency across the beam width. For all subjects, the PG method showed on average approximately 10 times higher gamma production rates than the PET method before, and 60 to 80 times higher production after including the washout correction and acquisition time delay. This rate strongly depended on tissue density and elemental composition. For broad passive scattered fields, it was demonstrated that large differences exist between PG and PET signal falloff positions and the correlation with the dose distribution for different lines in the beam direction. These variations also depended on the treatment site and the particular subject. Thus, similar to PET, direct range verification with PG in passive scattering is not easily viable. However, upon development of an optimized 3D PG detector, indirect range verification by comparing measured and simulated PG distributions (currently being explored for the PET method) would be more beneficial because it can avoid the inherent biological challenges of the PET imaging. The improved correlation of PG and PET with dose when using pencil beams was evident. PG imaging was found to be potentially advantageous especially for small tumors in the presence of high tissue heterogeneities. Including the effects of detector acceptance and efficiency may hold PET superior in terms of the amplitude of the detected signal (depending on the future development of PG detection technology), but the ability to perform online measurements and avoid signal disintegration (due to washout) with PG are important factors that can outweigh the benefits of higher detection sensitivity.Peer reviewe

The reliability of proton-nuclear interaction cross-section data to predict proton-induced PET images in proton therapy

In vivo PET range verification relies on the comparison of measured and simulated activity distributions. The accuracy of the simulated distribution depends on the accuracy of the Monte Carlo code, which is in turn dependent on the accuracy of the available cross-section data for β(+) isotope production. We have explored different cross-section data available in the literature for the main reaction channels ((16)O(p,pn)(15)O, (12)C(p,pn)(11)C and (16)O(p,3p3n)(11)C) contributing to the production of β(+) isotopes by proton beams in patients. Available experimental and theoretical values were implemented in the simulation and compared with measured PET images obtained with a high-resolution PET scanner. Each reaction channel was studied independently. A phantom with three different materials was built, two of them with high carbon or oxygen concentration and a third one with average soft tissue composition. Monoenergetic and SOBP field irradiations of the phantom were accomplished and measured PET images were compared with simulation results. Different cross-section values for the tissue-equivalent material lead to range differences below 1 mm when a 5 min scan time was employed and close to 5 mm differences for a 30 min scan time with 15 min delay between irradiation and scan (a typical off-line protocol). The results presented here emphasize the need of more accurate measurement of the cross-section values of the reaction channels contributing to the production of PET isotopes by proton beams before this in vivo range verification method can achieve mm accuracy.Peer reviewe

Materiales didácticos para la enseñanza de la Bioingeniería

Depto. de Estructura de la Materia, Física Térmica y ElectrónicaCAI Ciencias de la Tierra y ArqueometríaFALSEsubmitte

Cardiovascular imaging: what have we learned from animal models?

Consejería de Educación, Juventud y Deporte of Comunidad de MadridUnión EuropeaDepto. de Medicina y Cirugía AnimalFac. de VeterinariaTRUEpu