The RTT80 cone beam x-ray computed tomography system, developed by Rapiscan Systems Ltd, uses switched x-ray sources and fixed offset detector rings to remove the time consuming mechanical rotations of earlier imaging systems. This system produces three-dimensional images in real time. A Geant4 Monte Carlo simulation has been developed to investigate scattered radiation in the uncollimated detector machine, showing high levels of scatter behind highly attenuating objects. A new scatter correction method is proposed which estimates scatter to each detector, in each projection, from 1cm³ voxels of the computerised object. The scatter distributions from different materials are pre-determined using a Geant4 Monte Carlo simulation. The intensity of scatter from each voxel is based on measured data. The method is applied to two simulated test objects, a water box simulated with a monoenergetic input spectrum and a test suitcase simulated with a polyenergetic spectrum. The test suitcase is broken down into separate components to analyse the method further. The results show that the method performs well for low attenuating objects, but the results are sensitive to the intensity values. However, the method provides a good basis for a scatter correction method.

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C-arm Cone Beam CT (CBCT) systems – due to compact size, flexible geometry and low radiation exposure – inaugurated the era of on-board 3D image guidance in therapeutic and surgical procedures. Leksell Gamma Knife Icon by Elekta introduced an integrated CBCT system to determine patient position prior to surgical session, thus advancing to a paradigm shift in facilitating frameless stereotactic radiosurgeries. While CBCT offers a quick imaging facility with high spatial accuracy, the quantitative values tend to be distorted due to various physics based artifacts such as scatter, beam hardening and cone beam effect. Several 3D reconstruction algorithms targeting these artifacts involve an accurate and fast segmentation of craniofacial CBCT images into air, tissue and bone. The objective of the thesis is to investigate the performance of deep learning based convolutional neural networks (CNN) in relation to conventional image processing and machine learning algorithms in segmenting CBCT images. CBCT data for training and testing procedures was provided by Elekta. A framework of segmentation algorithms including multilevel automatic thresholding, fuzzy clustering, multilayer perceptron and CNN is developed and tested against pre-defined evaluation metrics carrying pixel-wise prediction accuracy, statistical tests and execution times among others. CNN has proven its ability to outperform other segmentation algorithms throughout the evaluation metrics except for execution times. Mean segmentation error for CNN is found to be 0.4% with a standard deviation of 0.07%, followed by fuzzy clustering with mean segmentation error of 0.8% and a standard deviation of 0.12%. CNN based segmentation takes 500s compared to multilevel thresholding which requires ~1s on similar sized CBCT image. The present work demonstrates the ability of CNN in handling artifacts and noise in CBCT images and maintaining a high semantic segmentation performance. However, further efforts targeting CNN execution speed are required to utilize the segmentation framework within real-time 3D reconstruction algorithms. / C-arm Cone Beam CT (CBCT) system har tack vare sitt kompakta format, flexibla geometri och låga strålningsdos startat en era av inbyggda 3D bildtagningssystem för styrning av terapeutiska och kirurgiska ingripanden. Elektas Leksell Gamma Knife Icon introducerade ett integrerat CBCT-system för att bestämma patientens position för operationer och på så sätt gå in i en paradigm av ramlös stereotaktisk strålkirurgi. Även om CBCT erbjuder snabb bildtagning med hög spatiel noggrannhet så tenderar de kvantitativa värdena att störas av olika artefakter som spridning, beam hardening och cone beam effekten. Ett flertal 3D rekonstruktionsalgorithmer som försöker reducera dessa artefakter kräver en noggrann och snabb segmentering av kraniofaciala CBCT-bilder i luft, mjukvävnad och ben. Målet med den här avhandlingen är att undersöka hur djupa neurala nätverk baserade på faltning (convolutional neural networks, CNN) presterar i jämförelse med konventionella bildbehandlings- och maskininlärningalgorithmer för segmentering av CBCT-bilder. CBCT-data för träning och testning tillhandahölls av Elekta. Ett ramverk för segmenteringsalgorithmer inklusive flernivåströskling (multilevel automatic thresholding), suddig klustring (fuzzy clustering), flerlagersperceptroner (multilayer perceptron) och CNN utvecklas och testas mot fördefinerade utvärderingskriterier som pixelvis noggrannhet, statistiska tester och körtid. CNN presterade bäst i alla metriker förutom körtid. Det genomsnittliga segmenteringsfelet för CNN var 0.4% med en standardavvikelse på 0.07%, följt av suddig klustring med ett medelfel på 0.8% och en standardavvikelse på 0.12%. CNN kräver 500 sekunder jämfört med ungefär 1 sekund för den snabbaste algorithmen, flernivåströskling på lika stora CBCT-volymer. Arbetet visar CNNs förmåga att handera artefakter och brus i CBCT-bilder och bibehålla en högkvalitativ semantisk segmentering. Vidare arbete behövs dock för att förbättra presetandan hos algorithmen för att metoden ska vara applicerbar i realtidsrekonstruktionsalgorithmer.

The objective of this work is to develop an on-line planning and delivery technique for palliative radiotherapy of spinal metastases using a linear accelerator capable of cone-beam CT (CBCT) imaging. This technique integrates all preparation and delivery steps into a single session equivalent to an initial treatment session. The key technical challenges pertaining to the development and implementation of this novel treatment technique are related to CBCT image performance, efficient system integration, development of on-line planning tools and design of novel quality assurance (QA) phantoms and processes. Hardware and software image corrections were first implemented to make CBCT images suitable for target definition and planning. These corrections reduced CBCT non-uniformity and improved CBCT-number accuracy. The on-line treatment technique workflow and the integration of all the subsystems involved in the process were assessed on a customized spine phantom constructed for the study. The challenges related to the routine QA of the highly integrated on-line treatment technique were addressed with the construction and validation of an integral test phantom. This phantom, which contains point detectors (diodes) allows for real-time QA of the entire image guidance, planning and treatment process in terms of dose delivery accuracy. The integral test phantom was also effective for the QA of high-dose, high-precision spinal radiosurgery. Simulation of the on-line treatment technique on patient data showed that the planning step was the one of the most time consuming tasks due predominantly to manual target definition. A semi-automatic method for detection and identification of vertebrae on CBCT images was developed and validated to streamline vertebra segmentation and improve the on-line treatment efficiency. With a single patient setup at the treatment unit, patient motion during the on-line process represents the main source of geometric uncertainty for dose delivery. Spine intra-fraction motion was assessed on CBCT for a group of 49 patients treated with a palliative intent. The use of surface marker tracking as a surrogate for spine motion was also evaluated. Finally, the complete on-line planning and delivery technique was implemented in a research ethics board (REB) approved clinical study at the Princess Margaret Hospital and 7 patients have been successfully treated at the time of this report with this novel treatment approach.

The purpose of this work is to present the development and validation of a novel method for reconstructing time-dependent, or 4D, cone-beam CT (4DCBCT) images. 4DCBCT can have a variety of applications in the radiotherapy of moving targets, such as lung tumors, including treatment planning, dose verification, and real time treatment adaptation. However, in its current incarnation it suffers from poor reconstruction quality and limited temporal resolution that may restrict its efficacy. Our algorithm remedies these issues by deforming a previously acquired high quality reference fan-beam CT (FBCT) to match the projection data in the 4DCBCT data-set, essentially creating a 3D animation of the moving patient anatomy. This approach combines the high image quality of the FBCT with the fine temporal resolution of the raw 4DCBCT projection data-set. Deformation of the reference CT is accomplished via a patient specific motion model. The motion model is constrained spatially using eigenvectors generated by a principal component analysis (PCA) of patient motion data, and is regularized in time using parametric functions of a patient breathing surrogate recorded simultaneously with 4DCBCT acquisition. The parametric motion model is constrained using forward iterative projection matching (FIPM), a scheme which iteratively alters model parameters until digitally reconstructed radiographs (DRRs) cast through the deforming CT optimally match the projections in the raw 4DCBCT data-set. We term our method FIPM-PCA 4DCBCT. In developing our algorithm we proceed through three stages of development. In the first, we establish the mathematical groundwork for the algorithm and perform proof of concept testing on simulated data. In the second, we tune the algorithm for real world use; specifically we improve our DRR algorithm to achieve maximal realism by incorporating physical principles of image formation combined with empirical measurements of system properties. In the third stage we test our algorithm on actual patient data and evaluate its performance against gold standard and ground truth data-sets. In this phase we use our method to track the motion of an implanted fiducial marker and observe agreement with our gold standard data that is typically within a millimeter.

A reabilitação dos pacientes com fissura de lábio e palato teve significativa evolução nas últimas décadas, sendo o desenvolvimento do enxerto ósseo alveolar muito importante para este avanço. É um procedimento que requer atenção rigorosa aos detalhes, por esta razão os exames de imagem são de grande auxílio. As Tomografias Computadorizadas enriqueceram os métodos de diagnóstico, despertando o interesse nos estudos desta modalidade de exame dentro da abordagem terapêutica da fissura labiopalatina. Este trabalho tem por objetivo desenvolver uma metodologia para avaliar o volume da fenda alvelar, por meio de Tomografia Computadorizada por Feixe Cônico. Utilizou-se o Software Open Source OsiriXTM DICOM Viewer Apple Inc, Versão 3.7.1 32 bits, um software de domínio público e que pode ser baixado gratuitamente na internet. Este software permite a visualização e manipulação de arquivos de tomografia computadorizada, desde de que os mesmos sejam salvos no formato DICOM, oferecendo possibilidade de mensuração tanto de medidas lineares, como de cálculo de área e de volume, sempre em proporções reais (1:1). A amostra foi constituída pelas imagens tomográficas de 30 pacientes, sendo 24 portadores de fissuras unilaterais e 6 de bilaterais, com idade média de 09 anos e 09 meses, sendo 19 do gênero masculino e 11 do feminino. Após a importação dos arquivos, foram utilizadas ferramentas do software OsiriXTM por 2 examinadores, em tempos distintos, para se proceder à mensuração do volume da fenda alveolar nos cortes axiais, a qual foi delimitada por meio da demarcação de pontos e limites pré-determinados. Foi realizada a análise pelo Teste da Estatística Alfa de Cronbach, que comprovou o elevado grau de reprodutibilidade e confiabilidade do método proposto (p<0,001). O volume médio encontrado foi de 0,92 ± 0,31 cm3, sendo que em relação aos tipos de fenda observou-se que as fissuras unilaterais apresentaram maior volume do que as bilaterais (p=0,019). Não houve diferenças quanto ao gênero, faixa etária e lado da fissura. Concluiu-se que o software OsiriXTM é eficiente em mensurar o volume da fenda alveolar; o método proposto pode ser reproduzido e o volume médio da fenda alveolar das fissuras unilaterais é maior que o das bilaterais. / Rehabilitation of patients with cleft lip and palate has evolved significantly in recent decades, due to development of the alveolar bone graft procedures. It is a procedure that requires strict attention to detail, and for this reason imaging exams are of great help. Computerized Tomography has enriched the diagnostic methods, arousing interest in studies of this method of examination in the therapeutic treatment of cleft lip and palate. This study aims to develop a methodology to assess the volume of the alveolar cleft, using Cone Beam Computerized Tomography. The 32-bit OsiriX® DICOM Viewer (Apple, Inc., version 3.7.1) open source softtware, a public domain program which can be downloaded for free from the Internet, was used. This software enables the visualization and manipulation of Computerized Tomography files as long as they are saved in the DICOM format, offering possibilities both for making linear measurements and also for calculating area and volume, always in real proportions (1:1). The sample was composed of tomographic images of 30 patients: 24 with unilateral and 6 with bilateral cleft , with average age of 9 years and 9 months, 19 male and 11 female. After importing the files, 2 examiners used tools from the OsiriXTM software, at different times, to measure the volume of the alveolar cleft lip and palate along the axial cuts, which was delimited using demarcation points and predetermined limits. Statistical analysis was performed using Cronbachs Alpha test, which demonstrated the high degree of reproducibility and reliability of the proposed method (p<0,001). The mean volume found was 0.92 ± 0.31 cm3 and, in relation to the type of cleft observed, the unilateral clefts presented larger volume than the bilaterals (p=0,019). There were no differences regarding gender, age range, and side of the cleft. It was concluded that the OsiriXTM software is efficient for measuring the volume of alveolar cleft; that the proposed method can be reproduced; and, that the mean volume of the alveolar unilateral cleft is greater than bilateral clefts.

As fissuras de rebordo alveolar e palato duro estão entre as malformações mais frequentes do corpo humano, podendo causar extensas deformidades ósseas faciais, com implicações biopsíquico-sociais marcantes. A avaliação da extensão desses defeitos ósseos, através de exames por imagem, tem sido feita com o objetivo de diagnosticar e planejar a terapêutica reabilitadora dos pacientes. O presente estudo tem por objetivo desenvolver uma metodologia de pós-processamento de imagens tomográficas para avaliação volumétrica de defeitos ósseos confeccionados em palato duro e rebordo alveolar de crânios macerados, mimetizando fissuras trans-forâmens unilaterais, e verificar a aplicabilidade clínica do Tomógrafo Computadorizado espiral Multislice e do tomógrafo computadorizado por feixe cônico na análise desses defeitos. Para tanto, nove crânios provenientes da Faculdade Cathedral, da cidade de Boa Vista- RR, foram escaneados em um Tomógrafo Computadorizado Multislice pertencente ao Hospital Geral de Roraima e em um tomógrafo computadorizado por feixe cônico de uma clínica privada, na cidade de Fortaleza-CE. As imagens foram, posteriormente, encaminhadas para análise ao Laboratório em Terceira Dimensão(LAB-3D) da Faculdade de Odontologia da USP, utilizando-se uma estação de trabalho independente e aplicando-se programas específicos de computação gráfica. Todas as imagens foram analisadas por dois examinadores, individualmente e em tempos distintos, por duas vezes, com o objetivo de processarmos análises intra e interexaminadores. Para a análise da metodologia de processamento de imagens, comparamos os resultados obtidos pelo Tomógrafo multislice utilizando crânios sem cera e com cera de modelagem número 07, na região do defeito ósseo, para auxiliar no seu delineamento, durante o pós-processamento das imagens tomográficas. Foram também avaliados os resultados volumétricos obtidos nos dois tipos de tomógrafos,com o objetivo de verificar a aplicabilidade dessas tecnologias na avaliação volumétrica dos defeitos ósseos fissurais e de comparar os resultados obtidos por cada uma delas. Todos os resultados foram comparados com os valores estabelecidos pelo padrão - ouro de nossa análise, que foram obtidos através do princípio de Arquimedes de deslocamento de água dos modelos de cera que foram utilizados. Os resultados estatísticos demonstraram que a metodologia de processamento das imagens tomográficas apresentou uma eficácia bastante elevada (p=0,995), sendo considerada eficiente na avaliação volumétrica de defeitos ósseos fissurais. Com relação aos tomógrafos utilizados, observamos que tanto o multislice como o por feixe cônico também apresentaram resultados satisfatórios, apresentando grande confiabilidade para o estudo do volume dos defeitos ósseos fissurais (p=0,997 e p=0,981, respectivamente), não havendo diferença nos resultados encontrados por eles. As análises intra e interobservadores nos dois tipos de tomógrafos não demonstraram diferença estatisticamente significativa. Os resultados evidenciaram que, independente do tipo de tomógrafo utilizado e do avaliador, as medidas obtidas são estatisticamente iguais às conseguidas pelo padrão-ouro de nossa análise. A aplicabilidade clínica de nossa pesquisa demonstrou ser direta e imediata, sendo importante no processo diagnóstico/terapêutico dos pacientes portadores de fissuras de rebordo alveolar e palato duro. / Oral clefts are one of the most frequent malformations of the human body, causing extensive facial bone deformities, compromising biological, psychic and social the individuals affected. Multislice CT and CBCT have been used to assess the volume of bone defect with the goal of diagnosis and rehabilitative therapy planning of the patients. The aim of this study were to develop a methodology for post-processing of tomographic images for volumetric assessment of bone defects made in the hard palate and alveolar ridge of dry skulls, mimicking unilateral trans-foramen clefts; and to determine the clinical applicability of multislice spiral computed tomography, and cone beam computed tomography in the analysis of these defects. Nine dry skulls from the Cathedral College in Boa Vista-RR were scanned on a multislice CT scanner at the Hospital Geral de Roraima and a cone beam computed tomography in a private clinic in Fortaleza-CE. The images were sent for analysis at Three Dimensional Laboratory (LAD-3D) of the Dentistry School, São Paulo University, using an independent workstation and implementing specific computer graphics programs. All images were analyzed by two examiners at different times and twice to proceed the intra and inter-examiners analysis. For analysis the methodology of image processing, we compared the results obtained by multislice CT using skulls with and without wax model in the region of bone defect. It was also analyzed the same images in both types of CT scanners in order to determine the applicability of these radiographic techniques in assessing volume of the clefts and to compare the results. All results were compared with the gold standard of our analysis, which was obtained by Archimedes principle of water displacement of wax models. The statistical results showed that the post processing methodology of tomographic images showed a high efficiency (p = 0.995) and was considered an efficient method for volumetric assessment of fissure bone defects. It was also observed that both multislice CT and cone beam CT showed excellent results with high reliability in the study of the volume of bone defects (p = 0.997 and p = 0.981, respectively), with no difference in performance between them. Analysis of intra-and inter-observer in the two types of CT scanners showed no statistically significant difference. The results demonstrate that independent of the type of CT scanner and the appraiser, the measurements are statistically equal to the gold standard obtained by our analysis. The clinical applicability of our research has shown to be immediate and direct, and it is important for the diagnostic and therapeutic process of patients with oral cleft.

<p>Contemporary algorithms employed for reconstruction of 3D volumes from helical cone beam projections are so called non-exact algorithms. This means that the reconstructed volumes will contain artifacts irrespective of the detector resolution and number of projections angles employed in the process.</p><p>It has been proposed that these artifacts can be suppressed using an iterative scheme which comprises computation of projections from the already reconstructed volume as well as the non-exact reconstruction itself.</p><p>The purpose of the present work is to examine if the iterative scheme can be applied to the non-exact reconstruction method PI-original in order to improve the reconstruction result. An important part in this implementation is a careful design of the projection operator, as a poorly designed projection operator may result in aliasing and/or other artifacts in the reconstruction result. Since the projection data is truncated, special care must be taken along the boundaries of the detector. Three different ways of handling this interpolation problem is proposed and examined.</p><p>The results show that artifacts caused by the PI-original method can indeed be reduced by the iterative scheme. However, each iteration requires at least three times more processing time than the initial reconstruction, which may call for certain compromises, smartness and/or parallelization in the innermost loops. Furthermore, at higher cone angles certain types of artifacts seem to grow by each iteration instead of being suppressed.</p>

Contemporary algorithms employed for reconstruction of 3D volumes from helical cone beam projections are so called non-exact algorithms. This means that the reconstructed volumes will contain artifacts irrespective of the detector resolution and number of projections angles employed in the process. It has been proposed that these artifacts can be suppressed using an iterative scheme which comprises computation of projections from the already reconstructed volume as well as the non-exact reconstruction itself. The purpose of the present work is to examine if the iterative scheme can be applied to the non-exact reconstruction method PI-original in order to improve the reconstruction result. An important part in this implementation is a careful design of the projection operator, as a poorly designed projection operator may result in aliasing and/or other artifacts in the reconstruction result. Since the projection data is truncated, special care must be taken along the boundaries of the detector. Three different ways of handling this interpolation problem is proposed and examined. The results show that artifacts caused by the PI-original method can indeed be reduced by the iterative scheme. However, each iteration requires at least three times more processing time than the initial reconstruction, which may call for certain compromises, smartness and/or parallelization in the innermost loops. Furthermore, at higher cone angles certain types of artifacts seem to grow by each iteration instead of being suppressed.

<p>Digital tomosynthesis (DTS) is a quasi-three-dimensional (3D) imaging technique which reconstructs images from a limited angle of cone-beam projections with shorter acquisition time, lower imaging dose, and less mechanical constraint than full cone-beam CT (CBCT). However, DTS images reconstructed by the conventional filtered back projection method have low plane-to-plane resolution, and they do not provide full volumetric information for target localization due to the limited angle of the DTS acquisition. </p><p>This dissertation presents the optimization and clinical implementation of image guided radiation therapy using limited-angle projections.</p><p>A hybrid multiresolution rigid-body registration technique was developed to automatically register reference DTS images with on-board DTS images to guide patient positioning in radiation therapy. This hybrid registration technique uses a faster but less accurate static method to achieve an initial registration, followed by a slower but more accurate adaptive method to fine tune the registration. A multiresolution scheme is employed in the registration to further improve the registration accuracy, robustness and efficiency. Normalized mutual information is selected as the criterion for the similarity measure, and the downhill simplex method is used as the search engine. This technique was tested using image data both from an anthropomorphic chest phantom and from head-and-neck cancer patients. The effects of the scan angle and the region-of-interest size on the registration accuracy and robustness were investigated. The average capture ranges in single-axis simulations with a 44° scan angle and a large ROI covering the entire DTS volume were between -31 and +34 deg for rotations and between -89 and +78 mm for translations in the phantom study, and between -38 and +38 deg for rotations and between -58 and +65 mm for translations in the patient study.</p><p>Additionally, a novel limited-angle CBCT estimation method using a deformation field map was developed to optimally estimate volumetric information of organ deformation for soft tissue alignment in image guided radiation therapy. The deformation field map is solved by using prior information, a deformation model, and new projection data. Patients' previous CBCT data are used as the prior information, and the new patient volume to be estimated is considered as a deformation of the prior patient volume. The deformation field is solved by minimizing bending energy and maintaining new projection data fidelity using a nonlinear conjugate gradient method. The new patient CBCT volume is then obtained by deforming the prior patient CBCT volume according to the solution to the deformation field. The method was tested for different scan angles in 2D and 3D cases using simulated and real projections of a Shepp-Logan phantom, liver, prostate and head-and-neck patient data. Hardware acceleration and multiresolution scheme are used to accelerate the 3D estimation process. The accuracy of the estimation was evaluated by comparing organ volume, similarity and pixel value differences between limited-angle CBCT and full-rotation CBCT images. Results showed that the respiratory motion in the liver patient, rectum volume change in the prostate patient, and the weight loss and airway volume change in the head-and-neck patient were accurately estimated in the 60° CBCT images. This new estimation method is able to optimally estimate the volumetric information using 60-degree projection images. It is both technically and clinically feasible for image-guidance in radiation therapy.</p> / Dissertation