Fast optimized Monte Carlo phase-space generation and dose prediction for low energy x-ray intra-operative radiation therapy

Low energy x-ray intra-operative radiation therapy (IORT) is used mostly for breast cancer treatment with spherical applicators. X-ray IORT treatment delivered during surgery (ex: INTRABEAM (R), Carl Zeiss) can benefit from accurate and fast dose prediction in a patient 3D volume. However, full Monte Carlo (MC) simulations are time-consuming and no commercial treatment planning system (TPS) was available for this treatment delivery technique. Therefore, the aim of this work is to develop a dose computation tool based on MC phase space information, which computes fast and accurate dose distributions for spherical and needle INTRABEAM (R) applicators. First, a database of monoenergetic phase-space (PHSP) files and depth dose profiles (DDPs) in water for each applicator is generated at factory and stored for on-site use. During commissioning of a given INTRABEAM (R) unit, the proposed fast and optimized phase-space (FOPS) generation process creates a phase-space at the exit of the applicator considered, by fitting the energy spectrum of the source to a combination of the monoenergetic precomputed phase-spaces, by means of a genetic algorithm, with simple experimental data of DDPs in water provided by the user. An in-house hybrid MC (HMC) algorithm which takes into account condensed history simulations of photoelectric, Rayleigh and Compton interactions for x-rays up to 1 MeV computes the dose from the optimized phase-space file. The whole process has been validated against radiochromic films in water as well as reference MC simulations performed with pen Easy in heterogeneous phantoms. From the pre-computed monoenergetic PHSP files and DDPs, building the PHSP file optimized to a particular depth-dose curve in water only takes a few minutes in a single core ([email protected] GHz), for all the applicators considered in this work, and this needs to be done only when the x-ray source (XRS) is replaced. Once the phase-space file is ready, the HMC code is able to compute dose distributions within 10 min. For all the applicators, more than 95% of voxels from dose distributions computed with the FOPS+hybrid code agreed within 7%-0.5 mm with both reference MC simulations and measurements. The method proposed has been fully validated and it is now implemented into radiance (GMV SA, Spain), the first commercial IORT TPS

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

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Sin / Sense

Sexto desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume

Implementación y validación de herramientas de dosimetría ultra-rápida para IORT

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Física Atómica, Molecular y Nuclear, leída el 09-06-2017Intraoperative Radiation Therapy (IORT) is a special modality for cancer treatment that delivers a single high dose of radiation directly to the exposed tumor bed during the tumor resection surgery. One of the main limitations in IORT lies in the difficulties that the planning process entails, which limits the use of this technique, and a treatment planning has not been available in IORT up to now. Recently, a new tool has been introduced: radiance, the first Treatment Planning System (TPS) specifically designed for IORT. The main goal of this thesis has been the development, implementation and evaluation of a dosimetric tool capable of providing a realistic dose distribution from any intraoperative electron radiotherapy (IOERT) dedicated accelerator or Intrabeam applicator that can be used for dose treatment planning in the operating room (OR) during an IORT treatment. This dosimetric tool has been separated in three phases. First, a database of monoenergetic phase space (PHSP) files and depth dose profiles (DDPs) in water was computed with penEasy from detailed simulations of each IOERT accelerator and Intrabeam applicator. Then, the energy spectrum of these monoenergetic simulations was tuned for each device using simple experimental DDPs provided by the manufacturer to the user, obtaining an optimized PHSP file that reproduces the user's data. Finally, dose was calculated from this optimized PHSP file with an accelerated version of DPM in the case of electrons, or with the Hybrid Monte Carlo (HMC) code we have developed, in the case of the Intrabeam. The tools described in this thesis have been proven to be fast and accurate enough to be used as a TPS for any IORT device. They have been incorporated into radiance as the dose calculation algorithms of the TPS.La radioterapia intraoperatoria (IORT) es una modalidad de tratamiento que consiste en irradiar directamente el lecho tumoral expuesto durante la cirugía con una dosis única y localizada [Palta et al., 1995, Beddar et al., 2006, Calvo et al., 1993, 2013, Lamanna et al., 2012]. A pesar de las ventajas que ofrece esta técnica, hasta hace poco la IORT carecía de las herramientas de plani cación y dosimetría que se emplean regularmente en radioterapia externa. Para remediar esta carencia, se creó radiance R , el primer plani cador de tratamientos para IORT [Pascau et al., 2012, Valdivieso-Casique et al., 2015]. El principal objetivo de esta tesis ha sido el desarrollo, implementación y validación de una herramienta de cálculo de dosis capaz de proporcionar una dosis realista de cualquier acelerador dedicado de IORT con electrones o con el sistema IntrabeamR que pueda ser usada para plani car el tratamiento dentro del quirófano durante una intervención de IORT. Esta herramienta dosimétrica se ha separado en tres fases. Primero, se ha generado una base de datos con penEasy [Sempau et al., 2011, Badal Soler et al., 2008] a partir de simulaciones detalladas de aceleradores de electrones y aplicadores de IntrabeamR , compuesta por espacios de fase (PHSP) monoenergéticos y per les de dosis en profundidad (DDPs) en agua. Después, con un proceso de ajuste en el que necesitamos únicamente la DDP experimental de cada máquina, obtenemos un PHSP optimizado que reproduce la dosis experimental. Finalmente, la dosis se calcula a partir de este PHSP, bien con una versión acelerada de DPM [Sempau et al., 2000] en el caso de trabajar con electrones, o bien con el Monte Carlo Híbrido (HMC) que hemos desarrollado [Vidal et al., 2014b,a, Udías et al., 2017b] para el IntrabeamR...Depto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasTRUEsubmitte

RADIANCE-A planning software for intra-operative radiation therapy

In the last decades accumulated clinical evidence has proven that intra-operative radiation therapy (IORT) is a very valuable technique. In spite of that, planning technology has not evolved since its conception, being outdated in comparison to current state of the art in other radiotherapy techniques and therefore slowing down the adoption of IORT. RADIANCE is an IORT planning system, CE and FDA certified, developed by a consortium of companies, hospitals and universities to overcome such technological backwardness. RADIANCE provides all basic radiotherapy planning tools which are specifically adapted to IORT. These include, but are not limited to image visualization, contouring, dose calculation algorithms-Pencil Beam (PB) and Monte Carlo (MC), DVH calculation and reporting. Other new tools, such as surgical simulation tools have been developed to deal with specific conditions of the technique. Planning with preoperative images (preplanning) has been evaluated and the validity of the system being proven in terms of documentation, treatment preparation, learning as well as improvement of surgeons/radiation oncologists (ROs) communication process. Preliminary studies on Navigation systems envisage benefits on how the specialist to accurately/safely apply the pre-plan into the treatment, updating the plan as needed. Improvements on the usability of this kind of systems and workflow are needed to make them more practical. Preliminary studies on Intraoperative imaging could provide an improved anatomy for the dose computation, comparing it with the previous pre-plan, although not all devices in the market provide good characteristics to do so. DICOM.RT standard, for radiotherapy information exchange, has been updated to cover IORT particularities and enabling the possibility of dose summation with external radiotherapy. The effect of this planning technology on the global risk of the IORT technique has been assessed and documented as part of a failure mode and effect analysis (FMEA). Having these technological innovations and their clinical evaluation (including risk analysis) we consider that RADIANCE is a very valuable tool to the specialist covering the demands from professional societies (AAPM, ICRU, EURATOM) for current radiotherapy procedures

XIORT-MC: A real-time MC-based dose computation tool for low- energy X-rays intraoperative radiation therapy

El texto completo de este trabajo no se encuentra disponible por no haber sido facilitado aún por su autor, por restricciones de copyright, o por no existir una versión digitalPurpose The INTRABEAM system is a miniature accelerator for low-energy X-ray Intra-Operative Radiation Therapy (IORT), and it could benefit from a fast and accurate dose computation tool. With regards to accuracy, dose computed with Monte Carlo (MC) simulations are the gold standard, however, they require a large computational effort and consequently they are not suitable for real-time dose planning. This work presents a comparison of the implementation on Graphics Processing Unit (GPU) of two different dose calculation algorithms based on MC phase-space (PHSP) information to compute dose distributions for the INTRABEAM device within seconds and with the accuracy of realistic MC simulations. Methods The MC-based algorithms we present incorporate photoelectric, Compton and Rayleigh effects for the interaction of low-energy X-rays. XIORT-MC (X-ray Intra-Operative Radiation Therapy Monte Carlo) includes two dose calculation algorithms; a Woodcock-based MC algorithm (WC-MC) and a Hybrid MC algorithm (HMC), and it is implemented in CPU and in GPU. Detailed MC simulations have been generated to validate our tool in homogeneous and heterogeneous conditions with all INTRABEAM applicators, including three clinically realistic CT-based simulations. A performance study has been done to determine the acceleration reached with the code, in both CPU and GPU implementations. Results Dose distributions were obtained with the HMC and the WC-MC and compared to standard reference MC simulations with more than 95% voxels fulfilling a 7%-0.5 mm gamma evaluation in all the cases considered. The CPU-HMC is 100 times more efficient than the reference MC, and the CPU-WC-MC is about 50 times more efficient. With the GPU implementation, the particle tracking of the WC-MC is faster than the HMC, with the extraction of the particle's information from the PHSP file taking a major part of the time. However, thanks to the variance reduction techniques implemented in the HMC, up to 400 times less particles are needed in the HMC to reach the same level of noise than the WC-MC. Therefore, in our implementation for INTRABEAM energies, the HMC is about 1.3 times more efficient than the WC-MC in an NVIDIA GeForce GTX 1080 Ti card and about 5.5 times more efficient in an NVIDIA GeForce RTX 3090. Dose with noise below 5% has been obtained in realistic situations in less than 5 s with the WC-MC and in less than 0.5 s with the HMC. Conclusions The XIORT-MC is a dose computation tool designed to take full advantage of modern GPUs, making possible to obtain MC-grade accurate dose distributions within seconds. Its high speed allows a real-time dose calculation that includes the realistic effects of the beam in voxelized geometries of patients. It can be used as a dose-planning tool in the operating room during a XIORT treatment with any INTRABEAM device.Gobierno de EspañaComunidad de MadridUnión EuropeaUniversidad Complutense de MadridDepto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasInstituto de Física de Partículas y del Cosmos (IPARCOS)TRUEpu

Mathematics of Artificial Intelligence

Este proyecto de innovación docente de la Universidad Complutense de Madrid ha desarrollado una serie de contenidos online con elementos interactivos, integrados en la plataforma libretext.org, que permita a los estudiantes el aprendizaje de los fundamentos matemáticos de la inteligencia artificial de una manera autónoma, clara y sencilla.This teaching innovation project at the Complutense University of Madrid has developed a series of online content with interactive elements, integrated into the libretext.org platform, which allows students to learn the mathematical foundations of artificial intelligence in an autonomous way, clear and simple.Depto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasFALSEUniversidad Complutense de Madridsubmitte