Using Magnetic Resonance Images for planning treatments in External Radiotherapy - Validation procedures for planning "MRI-only"

Ana Catarina Freire Moreira Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI-only" Dissertation submitted to Faculdade de Ciências da Universidade do Porto to obtain a Master's degree in Medical Physics Supervisor: João António Miranda dos Santos, Assessor de Saúde (Física Médica) no Instituto Português de Oncologia Francisco Gentil, EPE e Professor Afiliado da Universidade do Porto (ICBAS) Co-Supervisor: Joana Borges Lencart e Silva Assessora de Saúde (Directora do Serviço de Física Médica) no Instituto Português de Oncologia Francisco Gentil, EPE Departamento de Física e Astronomia Faculdade de Ciências da Universidade do Porto September 2013 i ii Acknowledgments During this project I had the support and help of several people, without whom it would have been easy to accomplish my master thesis. I wish to thank to Dr. João Santos, to accept guide this thesis, for all the support, knowledge and availability expended throughout this project as well as to Dr. Joana Lencart for help in performing the experimental component and have afforded me the opportunity to integrate the field of radiotherapy. Other important person, who could not fail to thank, is Dr. Helena Pereira, Service director of External Radiotherapy, who authorized this study using data (nonconfidential) of the patients. At Sune K. Buhl of the Department of Oncology (52AA) of Herlev Ringvej University Hospital in Copenhagen, my huge thank you for having given me access to their own version of the script of camouflages the MR images, which served as the basis of one used in this thesis. I would like to thank the service team of Medical Physics IPO Porto in particular to the Physicist Luís Cunha for his help in adapting the script and, as might be expected, to understand the occupation of his office. I also wanted to thank the technologists of Radiology and Radiotherapy for understanding and cooperation during the acquisition of CT and MR images. I also thank dosimetrist Fatima Borges helped me some times during the planning steps. My thanks to all. iii iv Communications Influence of the organ CT units assignment for MRI only based external radiotherapy treatment planning, A.C. Moreira, J. Lencart, J.A.M. Santos, International Conference on Medical Physics (ICMP 2013), Brighton, 31st - 4th September 2013. (POSTER PRESENTATION) Uso exclusivo de imagens de Ressonância Magnética no plano de tratamento de Radioterapia Externa – “MRI only”, A.C. Moreira, J. Lencart, J.A.M. Santos, 1º Encontro Nacional de Física Médica e Engenharia Biomédica, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., 7th - 9th November 2013. (POSTER PRESENTATION) v vi Abstract In External Radiotherapy (ER) the calculation of the dose distribution is based on the knowledge of interaction between the ionizing radiation and tissue. This interaction depends not only on the geometry and the energy spectrum of the beam but also on the electronic density (related to the attenuation coefficient) geometrical distribution of the various types of tissues. Therefore, computed tomography images (CT) are used as a support for dose distribution calculation, which combine the information of the location of the organs with the information of the electronic density (and attenuation coefficient) of the different tissues. However, regarding to various soft tissues, which have attenuation coefficients very similar, the CT images have a low contrast resolution between different soft tissues being sometimes difficult to distinguish the borders between organs at risk and tumour. Some examples are brain, prostate or gynecological tumours. In these cases, and given its high contrast resolution, one uses the image of Magnetic Resonance Imaging (MRI) as an aid in contouring both the organs at risk and the volumes to be treated, using the registration and fusion of CT and MR image sets. If there are already MR images of the patient, presumably their usage will be possible for the delineation of volumes and by the planning system to implement the treatment plan for radiotherapy. Some studies have already been made on the exclusive use of MR images for the planning of a radiotherapy treatment on brain tumours [Prabhakar et al., 2007; Karlsson et al., 2009; Jonsson et al., 2010], on which the distribution of the electronic density necessary for the planning is integrated in the MRI using various methods. It is this perspective that governs the objectives of this work. This procedure is not yet established in common clinical practice nor is part of the External Radiotherapy protocols due to the lack of a universal consensus as to its applicability. Hence the importance of this study as a possible contribution to a future application. KEYWORDS: External Radiotherapy (ER), Computed Tomography (CT), electronic density, attenuation coefficient, Magnetic Resonance Imaging (MRI). vii viii Resumo Em Radioterapia Externa (RE) o cálculo de distribuição de dose baseia-se na interação entre a radiação ionizante e os tecidos, interação essa que depende não só da geometria e do espectro de energias do feixe como da densidade eletrónica (relacionada com o coeficiente de atenuação) dos tecidos irradiados. Assim, utilizamse como suporte para o cálculo, imagens de tomografia computorizada (CT), que aliam a informação da localização dos órgãos à informação da densidade eletrónica (e coeficiente de atenuação) dos diferentes tecidos. No entanto, no que toca aos diferentes tecidos moles, os quais têm coeficientes de atenuação muito próximos, as imagens de CT têm uma baixa resolução de contraste entre os tecidos moles sendo, por vezes, difícil distinguir as fronteiras entre órgãos de risco e tumor. São exemplo disso, lesões cerebrais, tumores da próstata ou ginecológicos. Nestes casos, e dada a sua elevada resolução de contraste, utiliza-se a imagem de Ressonância Magnética (MR) como auxiliar na marcação, tantos dos órgão de risco como dos volumes a tratar, recorrendo ao registo e fusão dos conjuntos de imagens de CT e MR. Existindo já imagens de MR do doente, é em princípio possível a sua utilização para a marcação dos volumes e utilização pelo sistema de planeamento para a execução do plano de tratamento de Radioterapia. Já têm sido feitos alguns estudos de utilização apenas de imagens de MR para planeamento de tratamentos de radioterapia a tumores cerebrais [Prabhakar et al., 2007; Karlsson et al., 2009; Jonsson et al., 2010], nos quais as distribuições de densidades eletrónicas necessárias para o planeamento são integradas nas imagens de MR, utilizando vários métodos. É nesta perspetiva que se rege os objetivos deste trabalho. Este procedimento não está ainda estabelecido na prática clínica nem faz parte dos protocolos de RE por ainda não haver um consenso universal quanto à sua aplicabilidade. Daí a importância da sua realização, com um possível contributo para uma futura aplicação. PALAVRAS-CHAVE: Radioterapia Externa, Tomografia Computorizada (CT), densidade eletrónica, coeficiente de atenuação, Imagem de Ressonância Magnética (MRI). xv Fig. 3.10Helical CT design [adapted from Bushberg et al., 2002]. ............................ 47 Fig. 3.11Scheme of a multiple detector arrays of computed tomography scanners [adapted from Bushberg et al., 2002]. ......................................................................... 48 Fig. 3.12Thermoplastic mask used for immobilization of brain and head and neck patients. ...................................................................................................................... 50 Fig. 3.13A: MR scanner (GE Signa® HDxt 3.0T scanner). B: Axial brain MRI. ......... 51 Fig. 3.14Hydrogen protons under the action of an external magnetic field B0 [adapted from Dougherty, 2009]. ............................................................................................... 53 Fig. 3.15The effect of a radiofrequency pulse, at the Larmor frequency, on the magnetization [adapted from Dougherty, 2009]. .......................................................... 54 Fig. 3.16Diagram of DICOM Standard [adapted from Medical-Nema]. ..................... 60 Fig. 3.17Example of some attributes of a script from a DICOM image. ..................... 62 Chapter 4 Fig. 4.1Plan 1: Steps in the conventional radiotherapy workflow with CT and MRI; and Plan 2: the proposed new radiotherapy workflow based on MRI only. ......................... 69 Fig. 4.2Phantom used in the study. .......................................................................... 71 Fig. 4.3Vaseline markers in the phantom. ................................................................ 72 Fig. 4.4A: Axial CT volumes; B: Sagittal CT volumes. .............................................. 74 Fig. 4.5Axial MRI volumes. ....................................................................................... 75 Fig. 4.6Comparison of Isodose distributions between: A-CT based plan and B-MRI based plan (HU mean). ............................................................................................... 77 Fig. 4.7Dose–Volume histograms for Spine, Lungs, planning target volume (PTV) and Clinical Target Volume (CTV) between CT–based plan (plan 1) and MRI–based (HU mean) plan (plan 2). .................................................................................................... 77 Fig. 4.8Comparison of Isodose distributions between: A-CT based plan and B-MRI based plan (wba). ....................................................................................................... 78 Fig. 4.9Dose–Volume histograms for Spine, Lungs, planning target volume (PTV) and Clinical Target Volume (CTV) between CT–based plan (plan 1) and MRI–based (wba) plan (plan 3). ............................................................................................................... 78 Chapter 5 Fig. 5.1Variation of Hounsfield Units for the brain. .................................................... 82 Fig. 5.2Variation of Hounsfield Units for the prostate. ............................................... 82 Fig. 5.3Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the PTV in brain lesions. ......................................................................................... 83 xvi Fig. 5.4Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the brain. ................................................................................................................. 83 Fig. 5.5Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the brainstem. ......................................................................................................... 84 xvii xviii List of tables Chapter 2 Tab. 2.1Typical parameters of the beam from a field of cm and with a sourcesurface distance (Source-Surface Distance-SSD) of 100 cm. ..................................... 17 Chapter 3 Tab. 3.1CT numbers of various tissues]. .................................................................. 37 Tab. 3.2The UID values that are registered and used throughout the Parts of the DICOM Standard to CT and MRI ................................................................................ 63 Tab. 3.3Study Roots Identifiers................................................................................. 63 Chapter 5 Tab. 5.1Age of patients used in the study. ................................................................ 81 Tab. 5.3Percentage of Relative dose (minimum, maximum and mean) obtained in each of the plans: plan 1CT, plan 2-MRI (HU mean) and plan 3-MRI (wba). ............. 85 xix xx List of acronyms % Percentage µ Linear attenuation coefficient 0 Degrees 2D Two dimensions 3D Three dimensions AAA Anisotropic Analytical Algorithm AAPM American Association of Physicists in Medicine ACR American College of Radiology ALARA As Low As Reasonable Achievable B0 External Magnetic Field B1 Magnetic Field C Carbon Ion CE Compton Effect cm centimetres CT Computerized Tomography CTV Clinical Target Volume DICOM Digital Imaging and Communication in Medicine dmax Maximum Distance DMLC Dynamic Multi-Leaf Collimator DVH Dose-Volume Histogram E Photon Energy ER External Radiotherapy F Fluor Ion FID Free Induction Decay FRFSE Fast Relaxation Fast Spin Echo FSE Fast Spin Echo g grammas GE Gradient-Echo GHz Giga Hertz GTV Gross Tumour Volume H Hydrogen proton H2O Water HU Hounsfield Units I Final intensity of the beam xxi I0 Initial intensity of the beam IORT Intraoperative Radiation Therapy ICRU International Committee on Radiation Units and Measurements IGRT Image Guided Radiotherapy IMAT Intensity Modulated Arc Therapy IMRT Intensity Modulated Radiation Therapy ITV Internal Target Volume IV Irradiated Volume KeV Kilo Electron-Volt Linac Linear accelerator M0 Total Magnetization MeV Mega Electron-Volt MHz Mega Hertz min Minutes mm millimetres ms milliseconds MR Magnetic Resonance MRI Magnetic Resonance Imaging MSF Multiple-Static-Field MU Monitor Units Mxy Transversal Magnetization Mz Longitudinal Magnetization Na Sodium Ion NEMA National Electrical Manufactures Association NMR Nuclear Magnetic Resonance OAR Organ at Risk P Phosphor Ion PACS Picture Archiving and Communication System PBC Pencil Beam Convolution PDD Percentage Depth Dose PE Photoelectric Effect PET Positron Emission Tomography PTV Planning Target Volume RF Radio Frequency RTP Radiotherapy Treatment Planning RX X-Rays SE Spin-Echo xxii SOP Service-Object Pairs SPECT Single-Proton Emission Computed Tomography SSD Source-Surface Distance T Tesla TE Echo time TR Repetition time T1 Time Constant of longitudinal relaxation T2 Time Constant of transversal relaxation TBI Total Body Irradiation TPS Treatment Planning System TV Treated Volume UID Unique Identifiers US Ultra Sounds VMAT Volumetric Modulated Arc Therapy VOI Volumes of Interest w Larmor Frequency Z Atomic number Zeff Effective atomic number Material thickness Bulk density of the material xxiii FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 1 Chapter 1 INTRODUCTION FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 8 been treated in the past at the External Radiotherapy Department of IPOPFG, EPE. It has been submitted to the IPOPFG Ethical Commission before the acquisition of the CT and MR images, which in turn authorized using these to perform this work. 1.3 Thesis organization The work is structured into six distinct chapters. This being the first, where are contained: the introduction to the theme, the objectives set for the project and a brief description of the organization of the thesis. The second chapter presents the theoretical foundations on the issues discussed, highlighting the key procedures followed along planning in External Radiotherapy. The third chapter is devoted to the importance of images in TPS, referring to the physical principles of the two methods most commonly used in planning: CT and MR. The fourth chapter is dedicated to the presentation of the materials and methods used where a detailed description is made of the entire experimental component of the work. The presentation and analysis of the results of this investigation are made in the fifth chapter, which is described in detail the entire practical component developed in this project. The conclusions structured according to the results found in the study and hypotheses, as well as suggestions for future works are presented in chapter six. In the last part, are the references used in this study. The Matlab™ (v.R2010b) script used, as well as several of the graphical results for the percentage of relative dose and the development of Hounsfield units is attached. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 9 Chapter 2 BACKGROUND: “THEORETICAL FOUNDATIONS” FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 10 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 11 2. Background: “Theoretical Foundations” In this chapter are described some theoretical notions of some concepts and processes which develop in the treatment by external radiotherapy, important for a better understanding of the work developed. 2.1 Radiotherapy – General Aspects Radiotherapy is one of the main modalities used in the treatment of most cancer pathologies. In contrast with other medical specialities, which are based essentially on clinical knowledge and medical experience, radiotherapy, from the use of ionizing radiation for the treatment of cancer, depends also very much on modern technology. The current advances in radiation oncology are mainly boosted by the technological development of procedures in radiotherapy equipment and the quality/accuracy of radiological imaging. These in turn allow improving the results of treatments, in particular, in terms of accuracy [Podgorsak, 2005]. Radiotherapy can be given in two different ways - from outside the body (external radiotherapy) or inside the body (internal radiotherapy). External Radiotherapy usually involves using a machine called a linear accelerator (linac), which focuses high-energy radiation beams onto the area requiring treatment. External beam radiotherapy usually involves a series of daily treatments over a number of days or weeks [Podgorsak, 2005, Mayles et al., 2007]. However, External Radiotherapy also comports the internal irradiation into the body, in a modality denominated as Intraoperative radiotherapy (IORT), which delivers a concentrated dose of radiation therapy to a tumor bed during surgery. Internal Radiotherapy (known as Brachytherapy) can involve placing a small piece of radioactive material temporarily or permanently inside the body near the cancerous cells [Podgorsak, 2005, Mayles et al., 2007]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 12 2.1.1 Procedures in the planning of treatment in External Radiotherapy The planning process of the treatment is crucial to achieve a better choice of the appropriate treatment for the patient. The process is used to determine the number of radiation beams to be used to administer a given radiation dose to the patient, with the aim to control or remove a tumour [AAPM Task Group 53 Report, 1998]. The term 'planning of the treatment' has been sometimes interpreted as a process that is primarily designed for the analysis of dosimetric procedures, such as: computer calculations of the dose distribution, calculating the time of treatment and configurations of Monitor Units (Monitor Units - MU). In reality, the planning of the treatment is a much more extensive method than just the realization of dose calculation, because it encompasses all the steps involved in patient plan [AAPM Task Group 53 Report, 1998]. It consists of three essential steps that will be described below, taking into account the diagram on figure 1. Fig. 2.1Plan of Procedures in Radiotherapy [adapted from Doobs, 1999]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 13 2.1.1.1 Preliminary Planning In this first phase, the planning includes three basic stages that influence the entire treatment. Firstly proceeds to a clinical state of the patient's pathology, and then considering the problem in question, defines the goal of therapy. This step is very important because it influences the choice of the volume to be treated, the dose administered and the treatment technique. Finally made is the choice of the type of treatments to adopt (alone or concomitant): surgery, radiotherapy and chemotherapy. 2.1.1.2 Planning of the treatment This is a crucial step in the whole process because the location of the tumour is determined, the volumes are defined and the technique and the beams are chosen, entrusting them to computing and dose distribution that will be administered on target volume. Treatment planning is the process of determining the most appropriate way to irradiate the patient. It is a combination of the following five essential steps [Mayles et al., 2007]: 1. Make sure the patient is positioned in the correct way taking into account the method of immobilization for the treatment to be feasible. 2. Define the tumoral volume and organs at risk 3. Choosing the appropriate type of beam; 4. Evaluation of the dose distribution; 5. Calculate and adjust the treatment machine settings to administer the absolute dose required. Before carrying out the planning is important to determine the nature and extent of the tumour through various diagnostic techniques. Occasionally it is possible to perform a diagnostic test so that it contains the required information to the follow up of the planning. However, in most situations a new image is required for planning because the diagnosis and planning requirements are completely different. While for FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 14 the diagnosis it is required for an image without artefact and suitable enhancement of the tumour for a planning image it is indispensable a three-dimensional model, which is geometrically accurate in relation to the exact position of the patient in the treatment together with a mean of transference of the three-dimensional coordinate system for the therapy machine [Mayles et al., 2007].  Image Acquisition / Definition of volumes The position, in which the image used for planning is acquired, will have to be maintained on the treatment, since the plan is done taking into account that position, hence the importance of this step in the whole process. Taking this into consideration, it is the acquisition of the image where the size, extent and location of the tumour (target volume) are determined, as well as its relationship with so-called normal organs and external anatomy of the surface [AAPM Task Group 53 Report, 1998]. The accuracy of the data about the tumour, the target volumes and organs at risk are acquired under the same conditions, as those used for the subsequent treatment. The techniques usually used are: CT, MRI, Ultrasound (US), image by positron emission tomography (PET) and CT image by emission of a single photon (SPECT). These methods offer a wide range of anatomical, functional and metabolic information on the tumour volume. Most of times one resorts to fusion of some of these techniques with CT images to optimize the quality and the effectiveness of the treatment planning (standard technique used in the planning system in radiotherapy) [Doobs, 1999]. Having the images acquired, one proceeds to the delimitation of the volumes which is a significant pre-requisite for the planning of the treatment and for the accurate determination of the dose. Report 50 from 1993 and Report 62 from 1999 of The International Committee on Radiation Units and Measurements (ICRU), define and describe the various target volumes and critical structures that help in the process of treatment planning and provide a basis for the comparison of the results of the treatments [BIR, 2003; Podgorsak, 2005]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 15 Initially should be defined and delimited two volumes: GTV (Gross Tumor Volume) and the Clinical Target Volume (CTV). During the process of the planning of the treatment, other volumes are also determined: Planning Target Volume (PTV) and the organs at risk (Organs at Risk-OAR's). Figure 2.2 shows how the different volumes are related to each other. As a result of the treatment planning, some more volumes could be defined: Volume Treaty (Treated Volume) and Irradiated Volume (Irradiated Volume). A B Fig. 2.2A: Schematic representation of the relations between different volumes. GTVgross tumour volume, CTV-clinical target volume, ITV-internal target volume, PTV-planning target volume, OAR-organs at risk. B: Axial planning CT slice showing PTV and CTV. The Gross Tumour Volume (GTV) is the observable or palpable mass and it consists essentially of the primary tumour. The GTV almost always corresponds to parts of the malignant growth where the density of tumour cells is increased. Therefore, an appropriate dose should be delivered to the whole GTV [ICRU Report 50, 1993; ICRU Report 62, 1999]. The clinical target volume (CTV) is the volume of tissue containing GTV plus subclinical malignant tumour that should be eliminated. The CTV is, as the GTV, a merely anatomic and clinical concept and can be defined as a volume that includes FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 16 suspicious structures in addition to any tumour known[ICRU Report 50, 1993; ICRU Report 62, 1999]. The Internal Target Volume (ITV) is composed of the CTV plus an internal margin. The internal margin is designed to take into account the variations in the size and position of the CTV in relation to the frame of reference of the patient (usually defined by the bone anatomy), this is, the changes due to movements of organs such as respiration and the rectal and bladder content [ICRU Report 50, 1993; ICRU Report 62, 1999]. The Planning Target Volume (PTV) is a volumetric expansion taking into account the uncertainties in the position of the CTV from day to day. More specifically, an internal margin is added to compensate for the physiological changes in the size, shape and position of the internal anatomy. The PTV is therefore a geometric concept, and is used to ensure that the CTV receives the prescribed dose. In terms of planning, it is used to set the dose to be supplied during treatment. Its shape and size depend fundamentally on CTV and the technique used in the treatment [ICRU Report 50, 1993; ICRU Report 62, 1999]. The Treated Volume (TV) is the volume which is surrounded by an isodose defined by the oncologist, which is suitable to achieve the purpose of the treatment (e.g., curative, palliative). On the other hand, Irradiated Volume (Irradiated Volume) is defined as the entire volume of tissue which receives a dose that is considered significant in relation to the tolerance of the healthy tissue [ICRU Report 50, 1993; ICRU Report 62, 1999]. The OAR’s are volumes which radiation sensitivity is such that the dose received from a treatment can be significant in comparison with its tolerance, which leads to a change in the arrangement of the beam or a change in the prescription of the dose. For example, in the case of prostate tumours, two of organs at risk will be the bladder and rectum [Podgorsak, 2005]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 17  Choice of technique and beam An important goal of the planning of the treatment in radiotherapy is projecting a beam configuration which will provide a uniform dose on the target volume of planning (PTV) ensuring that the normal tissue receives a fairly lower dose and that the critical organs receive the lowest dose possible. This is achieved through the choice of: the type of treatment (electrons or photons), the energy beam, the beam arrangement, the use of wedges or blocks compensating etc [Mayles et al., 2007]. However, these goals are not always met, and sometimes it is necessary to a commitment, depending on the ultimate goal of every radiotherapy treatment. For example, if the treatment is palliative (where the aim is to decrease the symptoms due to the malignant disease, such as pain), radiation effects in the long run may not be a consideration and a simple beam arrangement will be enough. Moreover, if the treatment is radical, this is, aimed at controlling the tumour location; the long-term effects should be taken into account, which may result in a more complex scheme of radiotherapy [Mayles et al., 2007]. The equipment used in treatment, which is chosen in accordance with the energy of beam must then be selected according to certain characteristics, such as the percentage depth dose (Percentage Depth Dose, PDD) and the height / depth of the build-up region (maximum depth for which we have the maximum dose deposition), which vary with the energy and beam size (Table 2.1). Other factors such as the shade in the definition of the beam, the portal image, the existence of independent collimators or multi-leafs collimators should also be considered [Mayles et al., 2007]. Energy (MeV) dmax(cm) % Depth dose to 5cm % Depth dose to 10cm 4 1.0 83.9 63.0 6 1.5 86.9 67.5 8 2.0 89.6 71.0 10 2.3 91.4 73.0 15 2.9 94.5 77.0 25 3.8 98.5 83.0 Tab. 2.1Typical parameters of the beam from a field of cm and with a source-surface distance (Source-Surface Distance-SSD) of 100 cm [adapted from Mayles et al., 2007]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 24 Ideally, the density of the tissue and the exact composition of each of these voxels must be considered. However, in practice, many simplifications have to be made. The calculations of dose distribution have evolved from simple 2D models through 3D models, to techniques of Monte Carlo 3D with greater computing power in order to increase the speed of calculation. The conventional plans and some 3D plans use a direct approach, i.e., the best planning is achieved by trial-and-error method. Another approach is to use the inverse planning in which the objectives and constraints are defined first and only then the beam configuration and the weights of the fields are determined by computer [Podgorsak, 2005]. As the majority of the treatments is done with beams of photons, and not with electron beams (which are used for superficial lesions, in regions with little bone tissue,…), one will only mention the calculation algorithms for beams of photons. Among the various methods available for calculating the dose are only exposed in a very brief way, the two most commonly used in the Eclipse Treatment Planning Software from Varian Medical Systems (Palo Alto, CA) (software used in this work), Pencil Beam Convolution (PBC) and Analytical Anisotropic Algorithm (AAA). As already mentioned, calculation algorithms have been incorporated into the treatment planning software to report for contributions from tissues of different densities that are near, far, and enclosing the site of interest. The heterogeneity corrections in the PBC model are based on dose values calculated in a water equivalent material multiplied by a heterogeneity correction factor generated from an electron density matrix derived from a CT value matrix [Carrasco et al., 2004]. The AAPM Task Group 65 reported the observations by many investigators who demonstrated experimentally or by theoretical analysis that the PBC algorithm (path length based) does not work in regions of electron disequilibrium, and compute incorrect doses within or near to a low density medium, principally when the field size is small [AAPM Task Group 65 Report, 2004]. The recently published, AAPM Task Group 101 report recommends the utilization of algorithms that account for 3D scatter integration such as convolution/superposition, and algorithms that account for better photon and electron transport such as Monte Carlo [AAPM Task Group 101 Report, 2010]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 25 The AAA is a pencil beam superposition-convolution algorithm for dose calculations [Ulmer et al., 1996; Fogliata, et al., 2006], available in the Eclipse treatment planning software, that has shown excellent accuracy overall and a great ability to handle small fields in inhomogeneous media. Dose distributions calculated by the AAA algorithm have been studied by several investigators [Cozzi et al., 2008; Ronde et al., 2009] and in the heterogeneous media; the AAA algorithm has been shown to be consistently more accurate than pencil beam convolution [Bragg et al., 2008; Ronde et al., 2009]. 2.1.1.3 Treatment After all the planning phases are completed, one proceeds to the treatment. During this period it is important to monitorize the treatment in order to verify the possibility of implementation during the treatment period. There are several geometric factors that tend to compromise the quality of treatment, such as patient movement, tattoos by the labelling with respect to the internal anatomy and inaccurate beam alignment. In situations where the fields are more complex and the patient's anatomy which is less favourable, these problems tend to be more probable. Then, in order to avoid such situations, it uses the portal image, cone beam CT, among others, where it records an image serving as a reference for checking geometric allowing evaluating the degree to which the actual treatment corresponds to the treatment plan [AAPM Report No.24, Task Group 28, 2010]. If any change occurs in the patient, which influence any dosimetric parameter, one must modify the plan to ensure the probity of the therapy or correct the patient positioning. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 26 2.1.2 Using MRI as an aid to External Radiotherapy Treatment Planning The accurate delineation of tumour volumes and critical structures is a crucial component of treatment planning. The use of a single imaging study to accomplish the delineation is not always sufficient and it is necessary to resort to other types of image [Schlegel et al., 2006]. MRI has been used for the diagnosis and monitoring of a wide range of conditions and treatments. MRI offers several advantages over other imaging techniques with particular reference to CT. As known widely, the MRI is devoid of harmful radiation when compared to CT scanning. This is of particular use in malignant tumor cases where repeated imaging may be necessary to monitor the progress of the disorder. Additional advantage is offered by the ability to directly obtain images in planes other than axially, as with CT. The high contrast resolution noted with MRI over CT offers better clarity and easier diagnosis and demarcation of soft tissues or lesions in most situations [Koshy et al., 2011]. Currently, MRI is used for:  Delineation of soft tissues;  To determine extent and spread of disease;  Staging of different tumors;  Obtaining functional and metabolic information;  Monitoring the response to treatment. Nowadays, the planning systems have the ability to combine the information from different imaging studies using the process of image fusion or registration [Podgorsak, 2005]. Image registration is the process of superimposing two or more images from different imaging modalities, into one single image with just one coordinate (x, y and z) system. The original image is often referred to as the ‘reference image’ and the second image as the ‘target image’ [Cherry et al., 2009]. The process is simplified if external markers can be attached to the patient, using internal anatomic markers, e.g. the rib cage, ventricles, bone surfaces are more frequently used [Dougherty, 2009]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 27 The high contrast in soft tissues, in some areas, such as the brain, causes the MRI is one of the most used techniques for image registration, allowing small lesions are seen more easily. CT/MR image registration or fusion (figure 2.8) combines the accurate volume definition from MR with the electron density information available from CT. The MR data set is superimposed on the CT data set through a series of translations, rotations and scaling. This process allows the visualization of both studies side by side in the same imaging plane even if the patient has been scanned in a completely different treatment position [Podgorsak, 2005]. Magnetic resonance imaging has considerable potential for treatment planning. The superior soft tissues contrast provided by MR and the ability to vary contrast by manipulation of the imaging parameters facilitate optimal tumour evaluation. Together with its 3D multi-planar imaging capability, MR can provide advantages over reconstructed CT images. Fig. 2.8Pelvic CT/MR image registration. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 28 2.1.3 Using MRI alone in External Radiotherapy Treatment Planning Introduction of newer methods of MRI, which offer better imaging options, have increased the popularity of MRI. MR imaging is now able to offer better options in terms of tumor delineation and identifying the extent, spread, and involvement of neighboring structures when compared to other modalities. While image distortion was one of the problems that commonly restricted the use of MRI, options such as phased array and faster sequences have reduced the disadvantages of MRI [Jacobs et al., 2007]. Newer concepts such as diffusion-weighted and perfusion-weighted imaging and proton spectroscopy have changed the scenario of soft tissue imaging to a major extent [Jacobs et al., 2007]. Further studies and further improvements in the field of imaging technology can enhance the use of MRI, making it the imaging modality of choice in almost all cancers in the body [Koshy et al., 2011]. Today, the MRI is still a technique complementary imaging in treatment planning for external beam radiotherapy, and MRI alone cannot be used for radiotherapy planning, for several reasons [Podgorsak, 2005]:  The physical dimensions of the MRI scanner and its accessories limit the use of immobilization devices and compromise treatment positions;  There is no electron density information available for heterogeneity corrections on the dose calculations;  MRI is prone to geometrical artefacts and distortions that may affect the accuracy of the dose distribution calculation and the treatment. However, the use of MRI alone in the assessment of brain lesions, prostate tumors or gynecological for radiotherapy has been questioned by many [Stanescu et al., 2006a, 2006b, 2008; Chen et al.,2004a, 2004b, Prabhakar et al., 2007; Jonsson et al., 2010]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 29 CT is considered superior in certain aspects as MRI is associated with geometric distortion and MRI can neither provide information about bone structure nor help assess the electron density of the body tissues. But, MRI is superior in certain aspects. These include better contrast than CT when demarcating the soft tissues, more precise delineation of normal critical structures, and more accurate definition of treatment volumes. In most of these cases, as it is soft tissue, it resorts, already referred to, fusion between CT and MRI. A particular reason for image fusion is that MR images are inherently prone to distortions that can alter the local topography targeted by the radiation treatment. Imprecise localization of the target may lead to an overall reduction in treatment accuracy and efficiency [Stanescu et al., 2008]. The replacement of the current CT/MRI-based RTP based procedure by MRI alone eliminates the sessions of CT (without exposure to x-rays) and, consequently, the image fusion process. Furthermore, any incidental errors caused by patient interprocedure positioning and image fusion will be deleted. As a result, the improved target localization is expected to lead to a higher local tumor control and reduced normal tissue complications. The MRI alone in treatment planning should result in a reduction in margins added to account for delineation uncertainties and less normal tissues irradiated, reducing treatment toxicity, and remove some systematic registration errors that occur when combining MR and CT. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 30 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 31 Chapter 3 IMAGING MODALITIES IN RADIOTHERAPY FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 32 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 33 3. Imaging modalities in radiotherapy In this chapter, it is held a brief exposure of the main types of image used in RTP, making reference to the physical principles of each one of them as well as the importance of its applicability. The acquisition of medical images is one of the key procedures in the treatment plan in ER, having as purpose three important facts [Mayles et al, 2007]:  The evaluation of the position and size of the target volume in relation to the remaining anatomical structures, in particular the components of risk;  Acquisition of data required for an accurate calculation of the dose distribution;  Obtaining accurate information for the set up of the patient during the treatment. The guarantee of the quality of the image is essential to ensure the integrity between the planning and implementation of treatment. As has already been explained in the previous chapter, the techniques commonly used in planning systems are: the CT, MRI, Ultrasound, image by positron emission (PET) and CT image by issuing a single photon (SPECT). As was also said, it is often made the fusion between them to get a greater efficiency in the treatment. In accordance with the work carried out it is only made a description of the standard technique used (CT) and the MRI, complementary technique and that is intended to be implemented as practice in planning. 3.1 Computerized Tomography 3.1.1 Physical principles There is an abundant literature on the whole physics that involves the CT [Bushberg et al., 2002; Hsieh, 2009; Kak et al., 2001; Kalender, 2011] and as such it would necessary more than one subsection of this work to detail all the information. However, it is described in a concise way the physical principles that derive from this technique of image acquisition, so that the process in question may be understood. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 40 Through the analysis of the graph depicted in figure 3.3, it is observed that from a certain value of energy, in the order of 75 KeV, the X-ray production occurs predominantly through the Compton Effect (being lower the likelihood of X-ray production from the Photoelectric Effect). Therefore, the images per CT derive its contrast from the influence of this type of interaction, having a good contrast for lower energies and a less reasonable contrast for higher energies. In the region of higher energies, where the CE is dominant, the attenuation coefficient varies very little with the energy of X-rays. As this process is directly proportional to electronic density, this plays a dominant role in the formation of medical image in CT. Fig. 3.4Dependence of the material (effective atomic number and electronic density) [adapted from Webb, 2003]. 3.1.1.4 CT Scanners Generations To understand better this imaging modality is important to know its evolution over time, which allows not only their presentation, but also the reinforcement of several key concepts in CT imaging. This section describes the evolution of CT scanners over the last 40 years. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 41  First Generation The first generation of CT scanners employed a rotate/translate, pencil beam system in 1971. The x-ray source and detector were linearly translated to acquire individual measurements. After the linear measurements were completed, both the xray tube and the detector were rotated 1 deg to the next angular position to acquire the next set of measurements (figure 3.4) [Bushberg et al., 2002; Hsieh, 2009]. Fig. 3.5First Generation CT scan geometry [adapted from Hsieh, 2009]. Although clinical results from the first-generation scanners were promising, there remained a serious image quality issue associated with patient motion during the 4-6 min data acquisition. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 42  Second Generation In order to reduce the acquisition time comes the 2nd generation scanner in 1974. Although this was still a translation/rotation scanner, the number of rotation steps was reduced by the use of multiple pencil beams. A second-generation scanner with 3 narrow beams and 3 detectors is shown in figure 3.5 [Hsieh, 2009; Goldman, 2007]. Fig. 3.6Second Generation CT scan geometry [adapted from Goldman, 2007]. The shortest scan time with a second generation scanner was 18 seconds per slice, 15 times faster than with the first generation system. Incorporating an array of detectors instead of just one required the use of a narrow fan beam of radiation. Although a narrow fan beam provides excellent scatter rejection compared with plain film imaging, it does allow more scattered radiation to be detected than was the case with the pencil beam used in first generation CT [Bushberg et al., 2002]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 43  Third Generation The translational motion of first and second generation CT scanners was a fundamental impediment to fast scanning. Faster scans required the elimination of translation motion and the use of smoother and simpler pure rotational motion. This goal is accomplished by widening the x-ray beam into a fan beam encompassing the entire patient width and using an array of detectors to intercept the beam (Figure 3.6). The early third-generation CT scanners, was installed in late 1975. [Bushberg et al., 2002: Hsieh, 2009; Goldman, 2007]. Fig. 3.7Third Generation CT scan geometry [adapted from Goldman, 2007]. The detector array is rigidly linked to the x-ray tube, so that both the tube and the detectors rotate together around the patient. The motion of third generation CT is "rotate/rotate" referring to the rotation of the x-ray tube and the rotation of the detector array [Goldman, 2007]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 44 Third-generation CT requires extremely high detector stability and matching of detector responses. First and second generation detectors were dynamically recalibrated at the beginning of each translation, before passing into the patient’s shadow. Also, each detector measured rays passing through all voxels, so that any detector error or drift was spread evenly across the image and generally was not visible [Goldman, 2007]. The introduction of ‘slip ring’ technology was also a key to the success of helical or spiral CT. Due of the inherent advantages of the third-generation technology, nearly all of the state-of-the-art scanners on the market today are third generation [Hsieh, 2009].  Fourth Generation Several technology challenges in the design of the third-generation CT, including detector stability and aliasing, led to investigations, in 1976, of the fourth generation concept [Hsieh, 2009]. In this geometry, the detector forms an enclosed ring and remains stationary during the entire scan, while the x-ray tube rotates about the patient. Unlike the third generation scanner, a projection is formed with signals measured on a single detector as the x-ray beam sweeps across the object. The projection, therefore, forms a fan with its vertex at the detector, as shown by the shaded area in figure 3.7 [Hsieh, 2009]. Fig. 3.8Fourth Generation CT scan geometry [adapted from Hsieh, 2009]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 45 Drawbacks of early fourth generation CT included size and geometric dose efficiency. Because the tube rotated inside the detector ring, a large ring diameter (170–180 cm) was needed to maintain acceptable tube–skin distances. On the other hand, acceptable spatial resolution limited detector apertures to 4 mm. Consequently, even allowing for 10% space between detectors, 1,200 or more detectors were needed to fill the ring, but cost considerations initially limited the number to 600. The result was gaps between detectors and low geometric dose efficiency ( 50%). A later, alternate design used a smaller ring placed closer to the patient, with the tube rotating outside the ring; during tube rotation, the part of the ring between the tube and the patient would tilt out of the way of the x-ray beam (the peculiar wobbling motion of the ring was called nutation) [Goldman, 2007]. Another disadvantage of fourth generation geometry was scatter. The scatterabsorbing septa used in third generation designs could not be used, because the septa would necessarily be aimed at the center of the ring, which was the source of the scatter (patient’s location); that is, they would preferentially transmit scatter rather than primary x-rays. The elimination of scatter was never truly solved in fourth generation designs [Goldman, 2007].  Fifth Generation The fifth generation scanner was known as the electron beam computed tomography (EBCT), or electron beam tomography (EBT), and was built between 1980 and 1984 for cardiac applications [Goldman, 2007; Hsieh, 2009]. To “freeze” cardiac motion, a complete set of projections must be collected within 20 to 50 ms. This is clearly very challenging for conventional third or fourth generation types of scanners due to the enormous centripetal force placed on the x-ray tube and the detector. In the electron-beam scanner, the rotation of the source is provided by the sweeping motion of the electron beam (instead of the mechanical motion of the x-ray tube), as show in figure 3.8 [Hsieh, 2009]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 46 Fig. 3.9Fifth Generation CT scan geometry (or Electron Beam Scanner) [adapted from Hsieh, 2009]. The X-rays are produced from the focal track as a high energy electron beam strikes the tungsten. There are no moving parts to this scanner gantry. The electron beam is produced in a cone-like structure (a vacuum enclosure) behind the gantry and is electronically steered around the patient so that it strikes the annular tungsten target [Bushberg et al., 2002].  Sixth Generation In the early 1990s, the design of third and fourth generation scanners evolved to incorporate slip ring technology [Bushberg et al., 2002]. A slip ring is a circular contact with sliding brushes that allows the gantry to rotate continually. The use of slip-ring technology eliminated the inertial limitations at the end of each slice acquisition, and the rotating gantry was free to rotate continuously throughout the entire patient examination. This design made it possible to achieve greater rotational velocities than with systems not using a slip ring, allowing shorter scan times [Bushberg et al., 2002]. Helical CT (also inaccurately called spiral CT) scanners acquire data while the table is moving; as a result, the x-ray source moves in a helical pattern around the patient being scanned. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 47 Helical CT scanners use either third or fourth generation slip-ring designs. By avoiding the time required to translate the patient table, the total scan time required to image the patient can be much shorter (e.g., 30 seconds for the entire abdomen). In some instances the entire scan can be performed within a single breath-hold of the patient, avoiding inconsistent levels of inspiration. With helical computed tomographic scanners, the x-ray tube rotates around the patient while the patient and the table are translated through the gantry. The net effect of these two motions results in the x-ray tube traveling in a helical path around the patient (figure 3.9). Fig. 3.10Helical CT design [adapted from Bushberg et al., 2002]. The commencement of helical scanning has introduced many different considerations for data acquisition. In order to produce reconstructions of planar sections of the patient, the raw data from the helical data set are interpolated to approximate the acquisition of planar reconstruction data [Bushberg et al., 2002].  Seventh Generation The seventh generation of CT scanners is the last and new technology use in CT scanners, and is used as multiple detector arrays. This uses several, closely spaced, complete detector arrays. With no table translation (nonhelical acquisition), each detector array acquires a separate axial CT image. With a helical acquisition on a multiple detector array system, table speed and detector pitch can be increased, increasing the coverage for a given period of time [Bushberg et al., 2002]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 48 The X-ray tubes designed for CT have impressive heat storage and cooling capabilities, although the instantaneous production of x-rays (i.e., x-rays per millampere-second) is constrained by the physics governing x-ray production. An approach to overcoming x-ray tube output limitations is to make better use of the x-rays that are produced by the x-ray tube. When multiple detector arrays are used (Figure 3.10), the collimator spacing is wider and therefore more of the x-rays that are produced by the x-ray tube are used in producing image data. With conventional, single detector array scanners, opening up the collimator increases the slice thickness, which is good for improving the utilization of the x-ray beam but reduces spatial resolution in the slice thickness dimension. With the introduction of multiple detector arrays, the slice thickness is determined by the detector size and not by the collimator. This represents a major shift in CT technology [Bushberg et al., 2002]. Fig. 3.11Scheme of a multiple detector arrays of computed tomography scanners [adapted from Bushberg et al., 2002]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 49 3.1.2 Applicability in TPS The CT is considered the gold standard technique in the planning system of treatment, due to the many advantages that it has, in particular, the geometric precision [Mayles et al,2007]. CT provides transverse slices of the human anatomy by reconstructing the attenuation of a narrow beam of X -rays through the different tissues, which contain anatomical images of very high resolution and contrast, based on the electron density, useful in the calculation of dose. CT images also give excellent soft tissue contrast, allowing for greatly improved tumors localization and definition. Patient contours can be obtained easily from the CT data on each transverse CT slice — in particular, the patient’s skin contour, target and any organs of interest. The CT numbers associated with each pixel (reconstruction element) may be converted to electron density values. The use of CT scans for treatment planning has become well established and has been shown to provide significant improvement in treatment accuracy [Podgosark, 2005; Cherry et al, 2009]. According to the pathology in question, a protocol is followed with the steps that must be taken to ensure that no failures occur on subsequent treatment. Initially, the patient is placed on the stretcher/bed of the CT machine where one gets the first image for the positioning of the body and subsequent alignment of lasers. Then, the most important phase of the acquisition comes, which is the marking with reference points on the skin (wire metal) and the appeal to masks and immobilization supports. These tags serve as guidance for the dosimetry allowing the location of the contours of the body. Typically, the wire is placed on the patient on the transverse plane parallel to the isocentre plane. Immobilization devices are usually made of carbon fibre which allows that there is no disturbance of the dose distribution during the treatment. The mask is made individually for each patient being used during the entire treatment. Patients to be treated in the head and neck or brain areas are usually immobilized with a plastic mask that, when heated, can be moulded to the patient’s contour. The mask is affixed directly on to the treatment table or to a plastic plate that lies under the patient, thereby preventing movement, as seen in figure 3.11. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 56 Therefore, T1 weighted images acquired on different MR scanners are often obtained using slightly different values of the echo (TE) and repetition (TR) times, resulting in images with subtle differences in contrast [Mayles et al., 2007]. Usually, when one wants to show a good anatomical delineation, a weight in T1 (short TE and TR) is made, if the interest is greater in the functional part weight is done at T2 (long TE and TR). For example, a T1-weighted image, tissues with long T1 appear with hypointense and tissues with short T1, with hyperintense. In T2 weighted images, tissues with short T2 appear hypointense and tissues with long T2 appear hyperintense [Liang et al, 2000]. To summarize, nuclear spins in the presence of an external magnetic field, B0, align either with or opposed to the magnetic field. The parallel and anti-parallel spins almost cancel each other out, leaving a relatively small number of excess spins aligned parallel with the main magnetic field. If a radiofrequency signal is applied at the Larmor frequency, the individual spins resonate, absorbing the applied energy, and precess in phase. Depending on the magnetic field of the applied pulse and its length, the protons flip towards the x–y plane producing transverse magnetization. The transverse magnetization induces a voltage in an antenna or receiver coil in the x–y plane, often the same coil used to transmit the radiofrequency excitation pulse; this induced signal eventually becomes the MR signal. When the radiofrequency pulse is turned off, the protons de-phase as they try to realign with B0. Two phenomena occur simultaneously. Transverse magnetization decreases (T2 decay), while longitudinal magnetization increases (T1 recovery) [Dougherty, 2009]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 57 3.2.2 Applicability in TPS Magnetic resonance imaging has considerable potential for treatment planning. Currently, the use of MRI has been frequent due not only to the high capacity that this technique has in highlighting areas of tumours and soft tissues, as well as its ability to vary the contrast of the image from the variation of their parameters. Together with its 3D multi-planar imaging capability, MR can provide advantages over reconstructed CT images. Used in conjunction with CT, MRI can provide both complementary and supplementary information for the localization and characterization of tumours and surrounding normal tissues [Mayles et al, 2007]. The process of image fusion, between these two forms of acquisition, combines the exact definition of the tumour volume (obtained in MRI) with the information available from the density of electrons (acquired in CT). The data set of MRI is overlaid on the data of CT defined through a series of translations, rotations and scale. This process allows the visualization of both methods on the same image plane. However, there is a high potential of introduction of problems during the registration of these two techniques, because it becomes difficult to coordinate the image sets, which may lead to a substantial disagreement about the target location, leading to errors in treatment. The fact that the MRI does not submit information on the electronic density of the volumes in question, necessary to calculate the dose, is one of the most striking aspects that makes its exclusive use in TPS be rejected. The introduction of MRI in RTP is also severely affected by distortions in geometry that are caused by the heterogeneity of the static magnetic field and by nonlinearities of gradient magnetic fields from the magnetic resonance device, as well as by disturbances induced by the magnetic field of the object to be treated, in this case, the human body. These differences of the magnetic field and field gradient will lead to distortions in the image, which severity depends on the type of sequence of impulses and the manipulation of their parameters (constants of relaxation - T1 and T2, proton density, etc.) [Moerland, 1996]. Being the great aim of radiotherapy the administration of a large quantity of dose on tumour volume, thus sparing the surrounding healthy tissues, the exact region to be treated is of highest importance. Hence these distortions represent a major obstacle in the plan, since they will provide spatial information inaccurate, preventing a precise correlation of the image. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 58 In addition to this problem there are others which undertake the use of MRI in the treatment plan, one of them being the lack of information about the electronic density required to dose calculation. As the CT depends on the attenuation of RX by tissues as a function of the atomic number and electrons density, it can be automatically obtained by Hounsfield Units. The same does not happen with the MRI, which as has already been said, is derived from the density of protons and of constants of relaxation [Mayles et al., 2007]. Another obstacle that arises is the low signal in the bone, which is important to limit the areas of heterogeneities as the interfaces bone-tissue and bone-air fundamental in dose calculation. On the other hand, as these are not visible as well as the landmarks, it leads to the limited registration of the image. Taking into account all the aspects mentioned, the MRI has been used in TPS only as a complementary technique, but in spite of everything it holds a strong potential for further application in the treatment planning in radiotherapy. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 59 3.3 Medical Imaging storage files - DICOM (Digital Imaging Communications in Medicine) Throughout this chapter one has addressed two of the image techniques used in the system of planning in Radiotherapy. After the acquisition, the images are transferred to the system for subsequent planning and then follow for the treatment place. The whole journey that the image suffers along the plane of procedures implies that there is, in addition to a communication system and network storage (Picture Achieving and Communication System-PACS), a common format that allows the correspondence between each station so that, in a safe manner, it is permitted the transference of data corresponding to each one of the patients. This communication is safeguarded by a pattern called DICOM - Digital Imaging and communications in Medicine. The DICOM format was published in 1993 taking into account the standard developed by the American College of Radiology (ACR) and the National Electrical Manufacturers Association (NEMA) who in 1983 formed a working group with the objective of developing a model that would allow the exchange of images. This standard is defined as a set of standards for treatment, storage and transfer of medical images and associated information, in an electronic format, and was created with the purpose of standardizing the formatting of diagnostic images allowing these to be exchanged between equipments, computers and hospitals [Medical-NEMA]. Compliance with this standard enables an open architecture for imaging systems, bridging hardware and software entities and allowing interoperability for the transfer of medical images and associated information between disparate systems [Dreyer et al., 2006]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 60 3.3.1 DICOM Standard The DICOM standard is divided into a number of parts each of which describes a particular component (figure 3.15). Fig. 3.16Diagram of DICOM Standard [adapted from Medical-Nema]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 61 The different parts [Alarcón, 2013] that comprise the DICOM Standard v.3 are interrelated and including a generally consist of:  Part 1: provides an overview Standard general, its history, development and objectives, containing a brief description of the objectives of each part of it.  Part 2: define the principles that must meet all the implementations who say they support the standard. - Requirements in accordance - Conformance statements - Although DICOM does not specify any validation procedure or test to ensure that conformity  Part 3: specifies the number of information objects and classes. So information objects as classes provide abstract definition real entities, applicable for image communication medical and related information.  Part 4: defines the number of classes of service. A service class associates one or more items of information with one or more commands, which were used on those objects.  Part 5: specifies how DICOM applications must build and encoding the data set resulting from the use of objects information and service classes. Also specifies techniques supported by image compression standard.  Part 6: Data Dictionary. Defines the collection of all elements DICOM.  Part 7: Message Exchange. Specifies both the service and the protocol used by an application in medical imaging environment, to exchange messages. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 62  Part 8: Specifies the services and higher layer protocols, needed to support communication between DICOM applications a network environment. The DICOM standard has become an essential component for the integration of systems of digital images in medicine, offering solutions for many applications related to network communication, as well as offline. 3.3.2 IOD – Information Objects An object information (IOD) is a collection of pieces of information related, grouped into smaller entities called entities of information. Each of these entities contains information about an item, such as patient information (age, sex, ID), an image type and associated parameters (CT, MRI, US), etc. These are grouped in the form of a list of data, called attributes, and each one of these is given a reference number called tag (figure 3.16). Fig. 3.17Example of some attributes of a script from a DICOM image. Two fundamental components of DICOM are the information object class and the service class. Information objects define the contents of a set of images and their relationship, and the service classes describe what to do with these objects. The service classes and information object classes are combined to form the fundamental units of DICOM, called service-object pairs (SOPs) [Huang, 2004]. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 63 According to the type of image, their attributes are different, for example, to differentiate a CT image of an MR image, there is a tag with a number (UIDUnique Identifier) that identifies the type of image in question. The attribute mentioned in the table below (table 3.2) with respect to the SOP Class UID and always have the same UID for the same class of imaging (CT, MRI, PET, etc.). Tag Attribute name UID value UID name (0002,0002) Media Storage SOP Class UID 1.2.840.10008.5.1.4.1.1.2 CT Image Storage 1.2.840.10008.5.1.4.1.1.4 MR Image Storage Tab. 3.2The UID values that are registered and used throughout the Parts of the DICOM Standard to CT and MRI [adapted from DICOM-Dictionary]. However, it is necessary to understand that all the attributes that are distinguished with the termination UID are unique and characteristic of a single image, and there is no other value equal to the same tag in another image. There are three important attributes that define the uniqueness of a picture, i.e. are unique and work as an ID and are designated by Study Roots Identifiers. These in their turn are distinguished into three levels: Study, Series and Image (table 3.3). Name Tag STUDY level Study Instance UID (0020,000D) SERIES level Series Instance UID (0020,000E) IMAGE level SOP Instance UID (0008,0018) Tab. 3.3Study Roots Identifiers [adapted from DICOM-Conformance]. With the exception of the Study Instance UID, which remains equal for the same case study, this is, for the same patient, for the remaining, the UID value will vary from image to image, even if they belong to the same class (CT, MRI, etc.). FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 64 In addition, for each modality, the DICOM defines precisely the data elements that are mandatory, optional (i.e., can be omitted) or required under certain circumstances, this is, in the case of a CT image, for example, the attribute that affects the current in the X-ray tube (tag: 0018,1151) will not be present in the script of an MR image. In the same way that the echo time (tag: 0018, 0081) that appears in the script of the MRI does not appear in CT image. 3.3.3 Conformance Statements It is important to understand that the DICOM requires that there is a declaration of conformity [DICOM Conformance Statement] that must explain what DICOM services and options are supported, which extensions and peculiarities were implemented by the supplier, and how the device communicates with other DICOM systems. In theory, when comparing two declarations of conformity it is possible to determine if the two devices compatible with DICOM are capable of fully communicate with each other or not [DICOM-offis, DICOM-Conformance]. This document describes:  SOP supported.  Syntax transfer.  Paper to perform in each.  A way to implement the network with the exceptions that could be, and if there is a possibility of a physical link  Describe the configurable elements of implementation: - Application name. - Presentation Management.  If the system supports extended character sets. Generally, these documents include more information with more detailed description. The more complete the information will be easier to achieve connectivity and interoperability implementation. In practice, however, the declarations of conformity are only understandable by specialists since they are complex and require a thorough knowledge of these resources. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 65 Chapter 4 MATERIALS AND METHODS FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 72 4.2.2 Imaging Initially, the images were acquired on a GE Lightspeed® CT scanner with 2.5mm and 120 kVp, which followed directly to the TPS. Then, it proceeded to the acquisition of MRI Images. At this stage it was necessary to place markers were possible to be visible in the images without causing artifact. Likewise, would have a similar size and positioning1 of the metallic markers used in the CT images, so that the source of the images were the same in each of the two modes. The markers used were made with a hematocrit tube with vaseline and sealed at both extremities as shown in figure 4.3. Fig. 4.3Vaseline markers in the phantom. Two sequences were acquired for MR images on a GE Signa® HDxt 3.0T scanner. A T1-weighted with Fast Relaxation Fast Spin Echo sequence (FRFSE) and a T2-weighted with Fast Spin Echo sequence (FSE). However, for further planning, we used the T1-weighted images, because these images emphasized better markers.Both reference scans were imported via DICOM into the treatment planning system, EclipseTM v. 10.0 (Varian Medical Systems, Palo Alto, CA). 1 The positioning of the phantom was made with recourse to external lasers (LAP™). However, these lasers are never used. Their existence is due to the possibility of a future use utilize "MRI only" in TPS. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 73 One important aspect that has been mentioned is the fact the Eclipse supports multi-modality (CT, MRI, PET) image registration using a mutual information algorithm. However, only accepts CT images for the calculation of the dose distribution. To overcome this problem, the MRI reference scan was camouflaged as a CT scan by modifying several attributes in the DICOM header. Changing the parameters of the DICOM header was done in MATLAB™ (v.R2010b) with the adaptation of a script given by Sune K. Buhl (Department of Oncology (52AA), Herlev Ringvej University Hospital, Copenhagen). To understand, more precisely, this process of "camouflage", the script was divided into four fundamental parts: 1. Setting of the paths of the MRI and CT folders; 2. Loading data from DICOM header of a CT image, which are then copied to the pseudo-CT; 3. Saving MRI variables to be added to the pseudo-CT images; 4. Changing information on the pseudo-CT and save the final images. The main changes occurred in the parameters with new unique identifiers-UID (because with this identification tags are unique to a particular type of image). Thus, from the dicomuid command generated three new UID's to the SeriesInstaceUID, the StudyInstanceUID and the SOPInsstanceUID attributes. Moreover, tags such as (0002,0002) corresponding to the Media Storage SOP Class UID, which takes a different value according to the image mode in question has also been necessary to modify by changing the value of MR image (1.2. 840.10008.5.1.4.1.1.4) to the value of a CT image (1.2.840.10008.5.1.4.1.1.2). As can see in the attached script (appendix A), other parameters were changed/added, which is the case of those which relate exclusively to CT images. Thus, the MRI scan appeared throughout the system as a CT scan. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 74 4.2.3 Structure definition and treatment plan 4.2.3.1 CT based RTP With the images in Eclipse started by mark the reference point (origin) taking into account the metallic markers. Then proceeded to limit the volumes of interest (lungs, spine and CTV) have been obtained automatically from each electronic density. The exception was the marking of the PTV which was done manually from the standard margins between CTV and PTV ( 1mm). A B Fig. 4.4A: Axial CT volumes; B: Sagittal CT volumes. The next step was the setting of the beam angles that was made in a simplified form as it is a phantom. In the choice of treatment technique there were not any special criteria, thus opted by applying the technique of conformal radiotherapy, creating four fields at 0 º, 80 º, 130 º and 330 º as seen in Figure 4.6. The energy of the beams was 6 MeV which used a Trilogy linac. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 75 4.2.3.2 MRI-only based RTP Initially, when importing the pseudo-CT (MRI) for the planning system, this had made an automatic registration of images. This process would facilitate the marking of the contours in the images, causing them to stay exactly the same position in both images. However, due to some artifact generated in the MRI image, the image appeared slightly distorted, which made the structures would not be positioned correctly. Then, the external contours (body) and the internal contours as used in CT-based treatment planning were used for MRI based treatment planning by manually copying target and critical structure contours from CT to MRI, and adjust according the same coordinates of CT. The plan transfer is done with regard to the isocenter, which was set to be at the center of mass of the PTV. Although manually transferring internal contours could introduce some small errors, it was considered to be more reliable to use the same internal structure contours for our plan comparison than using new contours generated independently on MRI because this would introduce additional and potentially more significant uncertainties in the contours between MRI-only based and CT-based treatment planning. Fig. 4.5Axial MRI volumes. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 76 The next step was the treatment plan, the main objective is to compare the two techniques, and it then proceeded to exact copy of the plan madein CT (keeping the same beam, the same weights, etc.) for MRI. Being, in reality, an MR image and not a CT image, there is no information about the electron density of the structures. Therefore, then became the assignment of the CT values or Hounsfield Units; it was possible to calculate the dose distribution in this plane. We created two plans equal to CT-based treatment planning, only changing the HU:  In the first plan (plan 2), which is called the plane MRI-based HU mean, the HU is given, taking into account the mean HU values of each of the volumes in the CT images. For lungs the average value was -650 HU for the spine was 890 HU for the CTV was 1000HU and body was 20HU.  In the second plane (plane 3), MRI-based wba (w-water, b-bone and aair) differentiated three types of materials: water, bone and air, with the respective values: 0 HU, 1000HU and -1000HU. Thus it is considered air into the lungs, bone for the spine, and water for the remaining structures (PTV, CTV and body). 4.2.4 Dose calculation and plan comparison Once the images and all contours of interest are available and the assign de CT values, to proceeded the dose calculation. The dose calculation was performed using Anisotropic Analytical Algorithm (AAA) v. 10.0.28 with four fields to the both three plans:  Plan 1: CT-based treatment planning;  Plan 2: MRI-based treatment planning HU mean;  Plan 3: MRI-based treatment planning wba. The evaluation of the plans was made by comparing the Dose-Volume Histograms (DVH) as well as from Isodose curves. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 77 4.2.4.1 CT-based plan VS MRI-based plan with HU mean In Figure 4.6 depicts the Isodose curves between the CT-based plan and the MRI-based plan with HU mean. It can be seen that the two plans look very similar in terms of Isodose distributions and they are acceptable according to clinical criteria. A B Fig. 4.6Comparison of Isodose distributions between: A-CT based plan and B-MRI based plan (HU mean). The DVH’s are shown below for the same plans. The histogram is represents in terms of percentage of relative dose. The differences for de spine are most evident, but the lines of the other volumes are coincident for both plans. Again the differences are clinically insignificant. Fig. 4.7Dose–Volume histograms for Spine, Lungs, planning target volume (PTV) and Clinical Target Volume (CTV) between CT–based plan (plan 1) and MRI–based (HU mean) plan (plan 2). FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 78 4.2.4.2 CT-based plan VS MRI-based plan with wba As the above comparison, results are also quite similar between the CT-based plan and the MRI-based plan with wba, in terms of isodose curves (figure 4.8) and for appreciation from the DVH's (figure 4.9). A B Fig. 4.8Comparison of Isodose distributions between: A-CT based plan and B-MRI based plan (wba). Fig. 4.9Dose–Volume histograms for Spine, Lungs, planning target volume (PTV) and Clinical Target Volume (CTV) between CT–based plan (plan 1) and MRI–based (wba) plan (plan 3). FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 79 Chapter 5 RESULTS AND DISCUSSION FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 80 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 81 5. Results and discussion Throughout this project, one of the aspects that most curiosity was aroused to understand what would be the best way to assign the HU distribution in MR images, i.e., on what fundament was based on the choice of the values that were as close as possible the real values obtained from the CT images. So, one decided to perform two different approaches, in studying real cases of patients already treated: five patients with brain lesions and two with lesions in the prostate (table 5.1), using only the CT images. Patient No. Brain Prostate 1 30 73 2 55 77 3 59 - 4 65 - 5 74 - Tab. 5.1Age of patients used in the study. With planning already done, then were created two new plans, corresponding to each of the approaches, exactly equal to the original plan, which only made the change of HU's. In the first approach was started by differentiating means, taking into account the three types of materials: water, bone and air, 0HU, 1000HU, and -1000HU, respectively. In this plan was designated CT-wba. Likewise, the second plane (CT-HU (mean)) has moved the HU, but this time by assigning the mean value of HU. These values were obtained as follows: for each patient and for each of the respective structures was acquired a significant number of HU's along the series of original CT slices, then proceeded to calculate the average of those values . These values were obtained not only for the patients used in the calculation of the dose, but to a larger sample of patients. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 88 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 89 6. Conclusion and Future Work The evolution of technology over the years has allowed a substantial improvement in the quality of care in Radiotherapy. It was with this intention that this work emerged. Increasingly focuses on the quality of images in order to make an accurate treatment planning, eliminating the entire tumor volume, while preserving the quality of life of the patient. The investigation of the state of the art enabled realizes that there are few published articles on the subject as well as diverse approaches in other countries. Most of them prove that this procedure can be successfully applied. Likewise, the results obtained with the realization of this study confirm precisely the same. MRI has proven to be the best imaging technique in precise delineation of target volumes, notably in areas of soft tissue. A major obstacle in the use of MRI in TPS was the lack of information on the electronic density of the tissues, which is essential for calculating the dose. This work demonstrated that this problem can be easily overcome with the manual assignment of Hounsfield Units values. Nevertheless, there are still some adversities, such as deformities due to inhomogeneities in the image field and the lack of reference images (portal image, OBI ...) during treatment, which must be ascertained that there are no objections to the application. The results are focused on the feasibility of implementation of MRI as a exclusive technique for the treatment planning dosimetry in external beam radiotherapy, saving an additional CT examination. The implementation of MRI as an exclusive technique in the treatment plan in External Radiotherapy is still a possibility, not a certainty, in most radiotherapy services in Portugal. More studies should be conducted in phantoms and real patients for this technique could become integrated into international protocols radiotherapy. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 90 This is the idea that is intended retain, i.e., which extends the study trying to perfect the method, so that, in the very near future, the "MRI only" be applicable in the treatment planning in External Radiotherapy. FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 91 REFERENCES FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 92 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 93 References Alarcón J I J, Introducción al Control de Calidad en Radiología Digital: Conectividad DICOM (Tema 5). Spanish Society of Medical Physics, 2013. 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FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 104 path(path, path_MR); inputdir_MR = path_MR; Dicomfiles_CT = dir(fullfile(inputdir_CT,'*.dcm')); Dicomfiles_MR = dir(fullfile(inputdir_MR,'*.dcm')); % Loading local CTtemplate.dcm: originalCT = dicominfo('IM1ct.dcm'); % Creating new UNIQUE dicom UID's: uid1 = dicomuid; uid2 = dicomuid; uid3 = dicomuid; % Loading original MR-images and saving (via Dicomwrite) with the CTdicom: for p = 1:length(Dicomfiles_MR) fname = Dicomfiles_MR(p).name; info = dicominfo(fname); %Reading dicom info t = (dicomread(fname)); s = info.InstanceNumber; dicomwrite(t,['C:\Users\Utilizador\Desktop\SE0\temp\temp' num2str(s) '.dcm'],originalCT,'CreateMode','create'); % Saving MRI variables to be added to the MRasCT images: BitDepth = info.BitDepth; BitsStored = info.BitsStored; HighBit = info.HighBit; coor = info.ImagePositionPatient; orien = info.ImageOrientationPatient; location = info.SliceLocation; pixelspace=info.PixelSpacing; slicethickness = info.SliceThickness; SeriesTime_MR=info.SeriesTime; SeriesNumber_MR=info.SeriesNumber; StudyID_MR=info.StudyID; PatientBirthDate_MR=info.PatientBirthDate; PatientSex_MR=info.PatientSex; StudyDescription_MR=info.StudyDescription; PatientID_MR=info.PatientID; PatientName_MR=info.PatientName; %FamilyName_MR=info.FamilyName; % Loading info on the 'CT' (MR) images: infoMR_to_CT = dicominfo(['temp' num2str(s) '.dcm']); % Setting MRasCT variables: infoMR_to_CT.PatientID=PatientID_MR; infoMR_to_CT.PatientName=PatientName_MR; infoMR_to_CT.FamilyName=FamilyName_MR; infoMR_to_CT.StudyDescription=StudyDescription_MR; infoMR_to_CT.PatientSex = PatientSex_MR; infoMR_to_CT.PatientBirthDate = PatientBirthDate_MR; infoMR_to_CT.SeriesTime = SeriesTime_MR; infoMR_to_CT.SeriesNumber = SeriesNumber_MR; infoMR_to_CT.PatientID = ID; FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 105 infoMR_to_CT.PatientName.GivenName = GivenName; infoMR_to_CT.PatientName.FamilyName = FamilyName; infoMR_to_CT.StudyID = StudyID_MR; infoMR_to_CT.SeriesInstanceUID = uid1; infoMR_to_CT.StudyInstanceUID = uid2; infoMR_to_CT.SOPInstanceUID = uid3; infoMR_to_CT.MediaStorageSOPClassUID ='1.2.840.10008.5.1.4.1.1.2'; infoMR_to_CT.MediaStorageSOPInstanceUID = uid3; infoMR_to_CT.SliceLocation = location; infoMR_to_CT.SliceThickness = slicethickness; infoMR_to_CT.ImagePositionPatient = coor; infoMR_to_CT.ImageOrientationPatatient = orien; infoMR_to_CT.BitDepth = BitDepth; infoMR_to_CT.PixelSpacing = pixelspace; infoMR_to_CT.BitsStored = BitsStored; infoMR_to_CT.HighBit = HighBit; infoMR_to_CT.RescaleIntercept = 0; infoMR_to_CT.RescaleSlope = 9; % Saving final MRasCT images: dicomwrite(t,['C:\Users\Utilizador\Desktop\SE0\CT\' num2str(s)'.dcm'],infoMR_to_CT,'CreateMode','create'); end FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 106 FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 107 APPENDIX B B.1 Graphics B.1.1 Percentage of Relative Dose (mean) B.1.1.1 Prostate Tumors Graphs 1Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the prostate and the bladder. 100 100 100 100,4 100,5 100 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) PROSTATA -PTV 73 years 77 years 26,1 25,9 25,6 28,3 28,3 27,8 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) BLADDER 73 years 77 years FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 108 Graphs 2Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the head of right and left femur. Graphs 3Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the penile bulb and the rectum. 44,8 46,7 43,6 51,8 53,4 49,7 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) HEAD OF THE RIGHT FEMUR 73 years 77 years 42,8 43,6 41 50,6 51,9 48,7 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) HEAD OF THE LEFT FEMUR 73 years 77 years 60,4 62,3 61,5 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) PENILE BULB 77 years 49 49,2 49 42,1 42,4 41,9 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) RECTUM 73 years 77 years FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 109 B.1.1.2 Brain Tumors Graphs 4Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the chiasmus and the spinal cord. Graphs 5Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the right and left orbit. 10,3 10,4 10,3 43,8 43,9 43,8 32,1 32,1 32,1 64 64,1 63,8 6,5 6,5 6,5 0 10 20 30 40 50 60 70 80 90 100 110 CT CT-wba CT-HU (mean) % Relative Dose (mean) CHIASMUS 30 years 55 years 59 years 65 years 74 years 0,5 0,5 0,5 0 0 0 0 0 0 0,8 0,8 0,8 0 0 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 CT CT-wba CT-HU (mean) % Relative Dose (mean) SPINAL CORD 30 years 55 years 59 years 65 years 74 years 1,3 1,2 1,2 0 0 0 8,7 7,5 8,6 11,2 11 11 0,8 0,8 0,8 0 10 20 30 CT CT-wba CT-HU (mean) % Relative Dose (mean) RIGHT ORBIT 30 years 55 years 59 years 65 years 74 years 1,7 1,6 1,7 17 17,1 17 13,5 13,5 13,5 4,5 4,5 4,5 1 1 1 0 10 20 30 CT CT-wba CT-HU (mean) % Relative Dose (mean) LEFT ORBIT 30 years 55 years 59 years 65 years 74 years FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 110 Graphs 6Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the right and left lens. Graphs 7Percentage of Relative Mean Dose between CT, CT-wba and CT-HU (mean) of the right and left optical nerve. 1,2 1,2 1,2 0 0 0 8 7,9 7,9 5,1 5,1 5 0,7 0,7 0,7 0 10 20 30 CT CT-wba CT-HU (mean) % Relative Dose (mean) RIGHT LENS 30 years 55 years 59 years 65 years 74 years 1,5 1,5 1,5 8,3 8,4 8,3 6,7 6,7 6,7 2,8 2,8 2,8 0,9 0,9 0,9 0 10 20 30 CT CT-wba CT-HU (mean) % Relative Dose (mean) LEFT LENS 30 years 55 years 59 years 65 years 74 years 2 2 2 0 0 0 11,8 11,8 11,8 19,5 19,2 19,2 1,5 1,5 1,5 0 10 20 30 CT CT-wba CT-HU (mean) % Relative Dose (mean) RIGHT OPTICAL NERVE 30 years 55 years 59 years 65 years 74 years 2,7 2,7 2,7 64 63,4 63,5 18,2 18,3 18,3 15,8 15,3 15,4 2 1,9 2 0 10 20 30 40 50 60 70 CT CT-wba CT-HU (mean) % Relative Dose (mean) LEFT OPTICAL NERVE 30 years 55 years 59 years 65 years 74 years FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 111 B.1.2 Variation of Hounsfield Units according to the patients’ age Graphs 8Variation of Hounsfield Units of the brain and the chiasmus. Graphs 9Variation of Hounsfield Units of the brainstem and the spinal cord. 52,79 41,78 43,63 38,05 32,86 40,04 35,06 0 10 20 30 40 50 60 30 53 55 56 59 65 74 HU (mean) Ages BRAIN 32,87 22,53 22,63 17,96 15,15 15,50 15,73 0 10 20 30 40 30 53 55 56 59 65 74 HU (mean) Ages CHIASMUS 44,62 31,82 42,14 36,58 32,64 40,20 37,33 0 10 20 30 40 50 30 53 55 56 59 65 74 HU (mean) Ages BRAINSTEM 44,02 34,79 51,46 42,77 0 20 40 60 30 53 65 74 HU (mean) Ages SPINAL CORD FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 112 Graphs 10Variation of Hounsfield Units of the right and left lens. Graphs 11Variation of Hounsfield Units of the right and left optic nerve. 80,10 75,08 80,00 73,03 80,05 24,50 0 20 40 60 80 100 30 53 56 59 65 74 HU (mean) Ages RIGHT LENS 78,17 82,40 76,83 85,63 80,70 80,20 50,90 0 20 40 60 80 100 30 53 55 56 59 65 74 HU (mean) Ages LEFT LENS 30,73 20,30 34,20 19,27 35,65 23,95 0 10 20 30 40 30 53 56 59 65 74 HU (mean) Ages RIGHT OPTIC NERVE 40,43 18,75 14,55 30,85 28,57 31,45 35,80 0 10 20 30 40 50 30 53 55 56 59 65 74 HU (mean) Ages LEFT OPTIC NERVE FCUP Using Magnetic Resonance Images for planning treatments in External Radiotherapyvalidation procedures for planning "MRI only" 113 Graphs 12Variation of Hounsfield Units of the right and left orbit. Graphs 13Variation of Hounsfield Units of the right and left inner ear. 17,62 20,05 24,78 17,05 24,90 19,77 0 5 10 15 20 25 30 30 53 56 59 65 74 HU (mean) Ages RIGHT ORBIT 24,00 18,65 18,83 31,63 19,22 22,66 20,76 0 10 20 30 40 30 53 55 56 59 65 74 HU (mean) Ages LEFT ORBIT 421,83 1.280,07 1.308,62 1.151,58 0 500 1000 1500 30 53 56 59 HU (mean) Ages RIGHT INNER EAR 644,77 931,43 1.337,62 1.044,08 0 500 1000 1500 30 53 56 59 HU (mean) Ages LEFT INNER EAR