Precise estimation of postoperative cup alignment from single standard X-ray radiograph with gonadal shielding

This paper addresses the problem of estimating postoperative cup alignment from single standard X-ray radiograph with gonadal shielding. The widely used procedure of evaluation of cup orientation following total hip arthroplasty using single standard anteroposterior radiograph is known inaccurate, largely due to the wide variability in individual pelvic position relative to X-ray plate. 2D-3D image registration methods have been introduced to estimate the rigid transformation between a preoperative CT volume and postoperative radiograph(s) for an accurate estimation of the postoperative cup alignment relative to an anatomical reference extracted from the CT data. However, these methods require either multiple radiographs or a radiograph-specific calibration, both of which are not avaiable for most retrospective studies. Furthermore, these methods were only evaluated on X-ray radiograph(s) without gonadal shielding. In this paper, we propose to use a hybrid 2D-3D registration scheme combining an iterative landmark-to-ray registration with a 2D-3D intensity-based registration to estimate the rigid transfromation for a precise estimation of cup alignment. Quantitative and qualitative results evaluated on clinical and cadaveric datasets are given which indicate the validity of our approach.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

Estimation of tool pose based on force-density correlation during robotic drilling

The application of image-guided systems with or without support by surgical robots relies on the accuracy of the navigation process, including patient-to-image registration. The surgeon must carry out the procedure based on the information provided by the navigation system, usually without being able to verify its correctness beyond visual inspection. Misleading surrogate parameters such as the fiducial registration error are often used to describe the success of the registration process, while a lack of methods describing the effects of navigation errors, such as those caused by tracking or calibration, may prevent the application of image guidance in certain accuracy-critical interventions. During minimally invasive mastoidectomy for cochlear implantation, a direct tunnel is drilled from the outside of the mastoid to a target on the cochlea based on registration using landmarks solely on the surface of the skull. Using this methodology, it is impossible to detect if the drill is advancing in the correct direction and that injury of the facial nerve will be avoided. To overcome this problem, a tool localization method based on drilling process information is proposed. The algorithm estimates the pose of a robot-guided surgical tool during a drilling task based on the correlation of the observed axial drilling force and the heterogeneous bone density in the mastoid extracted from 3-D image data. We present here one possible implementation of this method tested on ten tunnels drilled into three human cadaver specimens where an average tool localization accuracy of 0.29 mm was observed.

The effect of shoulder variation on IMRT and SmartArc for Head and Neck Cancer

Purpose: First, to determine an average and maximum displacement of the shoulder relative to isocenter over the course of treatment. Second, to establish the dosimetric effect of shoulder displacements relative to correct isocenter alignment on the dose delivered to the target and the surrounding structures for head and neck cancer patients. Method and Materials: The frequency of shoulder shifts of various magnitudes relative to isocenter was assessed for 4 patients using image registration software. The location of the center of the right and left humeral head relative to isocenter (usually C2) was found daily from CT on rails scans, and was compared to the location of the humeral heads relative to isocenter on the initial simulation CT. Three Baseline head and neck IMRT and SmartArc plans were generated in Pinnacle based on simulation CTs. The CT datasets (external contour and boney structures) were then modified to represent shifts of the shoulder (relative to isocenter) between 3 mm and 15 mm in the SI, AP, and LR directions. The initial plans were recalculated on the image sets with shifted shoulders. Results: On average, shoulder variation was 2-5 mm in each direction, although displacements of over 1 cm in the inferior and posterior directions occurred. Shoulder shifts induced perturbations in the dose distribution, although generally only for large shifts. Most substantially, large, superior shifts resulted in coverage loss by the 95% isodose line for targets in the lower neck. Inferior shifts elevated the dose to the brachial plexus by 0.6-4.1 Gy. SmartArc plans showed similar loss of target coverage as IMRT plans. Conclusions: The position of the shoulder can have an impact on target coverage and critical structure dose. Shoulder position may need to be considered for setup of head and neck patients depending on target location.

Improving Cervical Cancer Nodal Boost Radiation Therapy by Quantifying Uncertainties and Exploring Advanced Radiation Therapy Modalities

Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of this complex process for the purpose of improving treatment accuracy while increasing dose sparing to the surrounding normal tissues. Because external beam boosts to involved lymph nodes are given prior to the completion of ICBT, assumptions must be made about dose to positive lymph nodes from future implants. The first aim of this project was to quantify differences in nodal dose contribution between independent ICBT fractions. We retrospectively evaluated differences in the ICBT dose contribution to positive pelvic nodes for ten patients who had previously received external beam nodal boost. Our results indicate that the mean dose to the pelvic nodes differed by up to 1.9 Gy between independent ICBT fractions. The second aim is to develop and validate a volumetric method for summing dose of the normal tissues during prescription of nodal boost. The traditional method of dose summation uses the maximum point dose from each modality, which often only represents the worst case scenario. However, the worst case is often an exaggeration when highly conformal therapy methods such as intensity modulated radiation therapy (IMRT) are used. We used deformable image registration algorithms to volumetrically sum dose for the bladder and rectum and created a voxel-by-voxel validation method. The mean error in deformable image registration results of all voxels within the bladder and rectum were 5 and 6 mm, respectively. Finally, the third aim explored the potential use of proton therapy to reduce normal tissue dose. A major physical advantage of protons over photons is that protons stop after delivering dose in the tumor. Although theoretically superior to photons, proton beams are more sensitive to uncertainties caused by interfractional anatomical variations, and must be accounted for during treatment planning to ensure complete target coverage. We have demonstrated a systematic approach to determine population-based anatomical margin requirements for proton therapy. The observed optimal treatment angles for common iliac nodes were 90° (left lateral) and 180° (posterior-anterior [PA]) with additional 0.8 cm and 0.9 cm margins, respectively. For external iliac nodes, lateral and PA beams required additional 0.4 cm and 0.9 cm margins, respectively. Through this project, we have provided radiation oncologists with additional information about potential differences in nodal dose between independent ICBT insertions and volumetric total dose distribution in the bladder and rectum. We have also determined the margins needed for safe delivery of proton therapy when delivering nodal boosts to patients with cervical cancer.

Comparison of Tumor Shrinkage and Cumulative Dose Distribution for Lung Cancers

Background: The physical characteristic of protons is that they deliver most of their radiation dose to the target volume and deliver no dose to the normal tissue distal to the tumor. Previously, numerous studies have shown unique advantages of proton therapy over intensity-modulated radiation therapy (IMRT) in conforming dose to the tumor and sparing dose to the surrounding normal tissues and the critical structures in many clinical sites. However, proton therapy is known to be more sensitive to treatment uncertainties such as inter- and intra-fractional variations in patient anatomy. To date, no study has clearly demonstrated the effectiveness of proton therapy compared with the conventional IMRT under the consideration of both respiratory motion and tumor shrinkage in non-small cell lung cancer (NSCLC) patients. Purpose: This thesis investigated two questions for establishing a clinically relevant comparison of the two different modalities (IMRT and proton therapy). The first question was whether or not there are any differences in tumor shrinkage between patients randomized to IMRT versus passively scattered proton therapy (PSPT). Tumor shrinkage is considered a standard measure of radiation therapy response that has been widely used to gauge a short-term progression of radiation therapy. The second question was whether or not there are any differences between the planned dose and 5D dose under the influence of inter- and intra-fractional variations in the patient anatomy for both modalities. Methods: A total of 45 patients (25 IMRT patients and 20 PSPT patients) were used to quantify the tumor shrinkage in terms of the change of the primary gross tumor volume (GTVp). All patients were randomized to receive either IMRT or PSPT for NSCLC. Treatment planning goals were identical for both groups. All patients received 5 to 8 weekly repeated 4-dimensional computed tomography (4DCT) scans during the course of radiation treatments. The original GTVp contours were propagated to T50 of weekly 4DCT images using deformable image registration and their absolute volumes were measured. Statistical analysis was performed to compare the distribution of tumor shrinkage between the two population groups. In order to investigate the difference between the planned dose and the 5D dose with consideration of both breathing motion and anatomical change, we re-calculated new dose distributions at every phase of the breathing cycle for all available weekly 4DCT data sets which resulted 50 to 80 individual dose calculations for each of the 7 patients presented in this thesis. The newly calculated dose distributions were then deformed and accumulated to T50 of the planning 4DCT for comparison with the planned dose distribution. Results: At the end of the treatment, both IMRT and PSPT groups showed mean tumor volume reductions of 23.6% ( 19.2%) and 20.9% ( 17.0 %) respectively. Moreover, the mean difference in tumor shrinkage between two groups is 3% along with the corresponding 95% confidence interval, [-8%, 14%]. The rate of tumor shrinkage was highly correlated with the initial tumor volume size. For the planning dose and 5D dose comparison study, all 7 patients showed a mean difference of 1 % in terms of target coverage for both IMRT and PSPT treatment plans. Conclusions: The results of the tumor shrinkage investigation showed no statistically significant difference in tumor shrinkage between the IMRT and PSPT patients, and the tumor shrinkage between the two modalities is similar based on the 95% confidence interval. From the pilot study of comparing the planned dose with the 5D dose, we found the difference to be only 1%. Overall impression of the two modalities in terms of treatment response as measured by the tumor shrinkage and 5D dose under the influence of anatomical change that were designed under the same protocol (i.e. randomized trial) showed similar result.

Nonrigid Motion Compensation of Free Breathing Acquired Myocardial Perfusion Data

In this work, we present a novel method to compensate the movement in images acquired during free breathing using first-pass gadolinium enhanced, myocardial perfusion magnetic resonance imaging (MRI). First, we use independent component analysis (ICA) to identify the optimal number of independent components (ICs) that separate the breathing motion from the intensity change induced by the contrast agent. Then, synthetic images are created by recombining the ICs, but other then in previously published work (Milles et al. 2008), we omit the component related to motion, and therefore, the resulting reference image series is free of motion. Motion compensation is then achieved by using a multi-pass non-rigid image registration scheme. We tested our method on 15 distinct image series (5 patients) consisting of 58 images each and we validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration. The average correlation to the manually obtained curves before registration 0:89 0:11 was increased to 0:98 0:02

Computational methods to create and analyze a digital gene expression atlas of embryo development from microscopy images

Abstract The creation of atlases, or digital models where information from different subjects can be combined, is a field of increasing interest in biomedical imaging. When a single image does not contain enough information to appropriately describe the organism under study, it is then necessary to acquire images of several individuals, each of them containing complementary data with respect to the rest of the components in the cohort. This approach allows creating digital prototypes, ranging from anatomical atlases of human patients and organs, obtained for instance from Magnetic Resonance Imaging, to gene expression cartographies of embryo development, typically achieved from Light Microscopy. Within such context, in this PhD Thesis we propose, develop and validate new dedicated image processing methodologies that, based on image registration techniques, bring information from multiple individuals into alignment within a single digital atlas model. We also elaborate a dedicated software visualization platform to explore the resulting wealth of multi-dimensional data and novel analysis algo-rithms to automatically mine the generated resource in search of bio¬logical insights. In particular, this work focuses on gene expression data from developing zebrafish embryos imaged at the cellular resolution level with Two-Photon Laser Scanning Microscopy. Disposing of quantitative measurements relating multiple gene expressions to cell position and their evolution in time is a fundamental prerequisite to understand embryogenesis multi-scale processes. However, the number of gene expressions that can be simultaneously stained in one acquisition is limited due to optical and labeling constraints. These limitations motivate the implementation of atlasing strategies that can recreate a virtual gene expression multiplex. The developed computational tools have been tested in two different scenarios. The first one is the early zebrafish embryogenesis where the resulting atlas constitutes a link between the phenotype and the genotype at the cellular level. The second one is the late zebrafish brain where the resulting atlas allows studies relating gene expression to brain regionalization and neurogenesis. The proposed computational frameworks have been adapted to the requirements of both scenarios, such as the integration of partial views of the embryo into a whole embryo model with cellular resolution or the registration of anatom¬ical traits with deformable transformation models non-dependent on any specific labeling. The software implementation of the atlas generation tool (Match-IT) and the visualization platform (Atlas-IT) together with the gene expression atlas resources developed in this Thesis are to be made freely available to the scientific community. Lastly, a novel proof-of-concept experiment integrates for the first time 3D gene expression atlas resources with cell lineages extracted from live embryos, opening up the door to correlate genetic and cellular spatio-temporal dynamics. La creación de atlas, o modelos digitales, donde la información de distintos sujetos puede ser combinada, es un campo de creciente interés en imagen biomédica. Cuando una sola imagen no contiene suficientes datos como para describir apropiadamente el organismo objeto de estudio, se hace necesario adquirir imágenes de varios individuos, cada una de las cuales contiene información complementaria respecto al resto de componentes del grupo. De este modo, es posible crear prototipos digitales, que pueden ir desde atlas anatómicos de órganos y pacientes humanos, adquiridos por ejemplo mediante Resonancia Magnética, hasta cartografías de la expresión genética del desarrollo de embrionario, típicamente adquiridas mediante Microscopía Optica. Dentro de este contexto, en esta Tesis Doctoral se introducen, desarrollan y validan nuevos métodos de procesado de imagen que, basándose en técnicas de registro de imagen, son capaces de alinear imágenes y datos provenientes de múltiples individuos en un solo atlas digital. Además, se ha elaborado una plataforma de visualization específicamente diseñada para explorar la gran cantidad de datos, caracterizados por su multi-dimensionalidad, que resulta de estos métodos. Asimismo, se han propuesto novedosos algoritmos de análisis y minería de datos que permiten inspeccionar automáticamente los atlas generados en busca de conclusiones biológicas significativas. En particular, este trabajo se centra en datos de expresión genética del desarrollo embrionario del pez cebra, adquiridos mediante Microscopía dos fotones con resolución celular. Disponer de medidas cuantitativas que relacionen estas expresiones genéticas con las posiciones celulares y su evolución en el tiempo es un prerrequisito fundamental para comprender los procesos multi-escala característicos de la morfogénesis. Sin embargo, el número de expresiones genéticos que pueden ser simultáneamente etiquetados en una sola adquisición es reducido debido a limitaciones tanto ópticas como del etiquetado. Estas limitaciones requieren la implementación de estrategias de creación de atlas que puedan recrear un multiplexado virtual de expresiones genéticas. Las herramientas computacionales desarrolladas han sido validadas en dos escenarios distintos. El primer escenario es el desarrollo embrionario temprano del pez cebra, donde el atlas resultante permite constituir un vínculo, a nivel celular, entre el fenotipo y el genotipo de este organismo modelo. El segundo escenario corresponde a estadios tardíos del desarrollo del cerebro del pez cebra, donde el atlas resultante permite relacionar expresiones genéticas con la regionalización del cerebro y la formación de neuronas. La plataforma computacional desarrollada ha sido adaptada a los requisitos y retos planteados en ambos escenarios, como la integración, a resolución celular, de vistas parciales dentro de un modelo consistente en un embrión completo, o el alineamiento entre estructuras de referencia anatómica equivalentes, logrado mediante el uso de modelos de transformación deformables que no requieren ningún marcador específico. Está previsto poner a disposición de la comunidad científica tanto la herramienta de generación de atlas (Match-IT), como su plataforma de visualización (Atlas-IT), así como las bases de datos de expresión genética creadas a partir de estas herramientas. Por último, dentro de la presente Tesis Doctoral, se ha incluido una prueba conceptual innovadora que permite integrar los mencionados atlas de expresión genética tridimensionales dentro del linaje celular extraído de una adquisición in vivo de un embrión. Esta prueba conceptual abre la puerta a la posibilidad de correlar, por primera vez, las dinámicas espacio-temporales de genes y células.

Automatic motion compensation of free breathing acquired myocardial perfusion data by using independent component analysis

Images acquired during free breathing using first-pass gadolinium-enhanced myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic motion pattern that needs to be compensated for if a further automatic analysis of the perfusion is to be executed. In this work, we present a method to compensate this movement by combining independent component analysis (ICA) and image registration: First, we use ICA and a time?frequency analysis to identify the motion and separate it from the intensity change induced by the contrast agent. Then, synthetic reference images are created by recombining all the independent components but the one related to the motion. Therefore, the resulting image series does not exhibit motion and its images have intensities similar to those of their original counterparts. Motion compensation is then achieved by using a multi-pass image registration procedure. We tested our method on 39 image series acquired from 13 patients, covering the basal, mid and apical areas of the left heart ventricle and consisting of 58 perfusion images each. We validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and combined ICA based registration approaches and previously published motion compensation schemes. Considering run-time and accuracy, a two-step ICA based motion compensation scheme that first optimizes a translation and then for non-linear transformation performed best and achieves registration of the whole series in 32 ± 12 s on a recent workstation. The proposed scheme improves the Pearsons correlation coefficient between manually and automatically obtained time?intensity curves from .84 ± .19 before registration to .96 ± .06 after registration

Mejoras en el procesamiento de imágenes de TC para el tratamiento con radioterapia adaptativa del cáncer de próstata

El cáncer de próstata es el tipo de cáncer con mayor prevalencia entre los hombres del mundo occidental y, pese a tener una alta tasa de supervivencia relativa, es la segunda mayor causa de muerte por cáncer en este sector de la población. El tratamiento de elección frente al cáncer de próstata es, en la mayoría de los casos, la radioterapia externa. Las técnicas más modernas de radioterapia externa, como la radioterapia modulada en intensidad, permiten incrementar la dosis en el tumor mientras se reduce la dosis en el tejido sano. Sin embargo, la localización del volumen objetivo varía con el día de tratamiento, y se requieren movimientos muy pequeños de los órganos para sacar partes del volumen objetivo fuera de la región terapéutica, o para introducir tejidos sanos críticos dentro. Para evitar esto se han desarrollado técnicas más avanzadas, como la radioterapia guiada por imagen, que se define por un manejo más preciso de los movimientos internos mediante una adaptación de la planificación del tratamiento basada en la información anatómica obtenida de imágenes de tomografía computarizada (TC) previas a la sesión terapéutica. Además, la radioterapia adaptativa añade la información dosimétrica de las fracciones previas a la información anatómica. Uno de los fundamentos de la radioterapia adaptativa es el registro deformable de imágenes, de gran utilidad a la hora de modelar los desplazamientos y deformaciones de los órganos internos. Sin embargo, su utilización conlleva nuevos retos científico-tecnológicos en el procesamiento de imágenes, principalmente asociados a la variabilidad de los órganos, tanto en localización como en apariencia. El objetivo de esta tesis doctoral es mejorar los procesos clínicos de delineación automática de contornos y de cálculo de dosis acumulada para la planificación y monitorización de tratamientos con radioterapia adaptativa, a partir de nuevos métodos de procesamiento de imágenes de TC (1) en presencia de contrastes variables, y (2) cambios de apariencia del recto. Además, se pretende (3) proveer de herramientas para la evaluación de la calidad de los contornos obtenidos en el caso del gross tumor volumen (GTV). Las principales contribuciones de esta tesis doctoral son las siguientes: _ 1. La adaptación, implementación y evaluación de un algoritmo de registro basado en el flujo óptico de la fase de la imagen como herramienta para el cálculo de transformaciones no-rígidas en presencia de cambios de intensidad, y su aplicabilidad a tratamientos de radioterapia adaptativa en cáncer de próstata con uso de agentes de contraste radiológico. Los resultados demuestran que el algoritmo seleccionado presenta mejores resultados cualitativos en presencia de contraste radiológico en la vejiga, y no distorsiona la imagen forzando deformaciones poco realistas. 2. La definición, desarrollo y validación de un nuevo método de enmascaramiento de los contenidos del recto (MER), y la evaluación de su influencia en el procedimiento de radioterapia adaptativa en cáncer de próstata. Las segmentaciones obtenidas mediante el MER para la creación de máscaras homogéneas en las imágenes de sesión permiten mejorar sensiblemente los resultados de los algoritmos de registro en la región rectal. Así, el uso de la metodología propuesta incrementa el índice de volumen solapado entre los contornos manuales y automáticos del recto hasta un valor del 89%, cercano a los resultados obtenidos usando máscaras manuales para el registro de las dos imágenes. De esta manera se pueden corregir tanto el cálculo de los nuevos contornos como el cálculo de la dosis acumulada. 3. La definición de una metodología de evaluación de la calidad de los contornos del GTV, que permite la representación de la distribución espacial del error, adaptándola a volúmenes no-convexos como el formado por la próstata y las vesículas seminales. Dicha metodología de evaluación, basada en un nuevo algoritmo de reconstrucción tridimensional y una nueva métrica de cuantificación, presenta resultados precisos con una gran resolución espacial en un tiempo despreciable frente al tiempo de registro. Esta nueva metodología puede ser una herramienta útil para la comparación de distintos algoritmos de registro deformable orientados a la radioterapia adaptativa en cáncer de próstata. En conclusión, el trabajo realizado en esta tesis doctoral corrobora las hipótesis de investigación postuladas, y pretende servir como cimiento de futuros avances en el procesamiento de imagen médica en los tratamientos de radioterapia adaptativa en cáncer de próstata. Asimismo, se siguen abriendo nuevas líneas de aplicación futura de métodos de procesamiento de imágenes médicas con el fin de mejorar los procesos de radioterapia adaptativa en presencia de cambios de apariencia de los órganos, e incrementar la seguridad del paciente. I.2 Inglés Prostate cancer is the most prevalent cancer amongst men in the Western world and, despite having a relatively high survival rate, is the second leading cause of cancer death in this sector of the population. The treatment of choice against prostate cancer is, in most cases, external beam radiation therapy. The most modern techniques of external radiotherapy, as intensity modulated radiotherapy, allow increasing the dose to the tumor whilst reducing the dose to healthy tissue. However, the location of the target volume varies with the day of treatment, and very small movements of the organs are required to pull out parts of the target volume outside the therapeutic region, or to introduce critical healthy tissues inside. Advanced techniques, such as the image-guided radiotherapy (IGRT), have been developed to avoid this. IGRT is defined by more precise handling of internal movements by adapting treatment planning based on the anatomical information obtained from computed tomography (CT) images prior to the therapy session. Moreover, the adaptive radiotherapy adds dosimetric information of previous fractions to the anatomical information. One of the fundamentals of adaptive radiotherapy is deformable image registration, very useful when modeling the displacements and deformations of the internal organs. However, its use brings new scientific and technological challenges in image processing, mainly associated to the variability of the organs, both in location and appearance. The aim of this thesis is to improve clinical processes of automatic contour delineation and cumulative dose calculation for planning and monitoring of adaptive radiotherapy treatments, based on new methods of CT image processing (1) in the presence of varying contrasts, and (2) rectum appearance changes. It also aims (3) to provide tools for assessing the quality of contours obtained in the case of gross tumor volume (GTV). The main contributions of this PhD thesis are as follows: 1. The adaptation, implementation and evaluation of a registration algorithm based on the optical flow of the image phase as a tool for the calculation of non-rigid transformations in the presence of intensity changes, and its applicability to adaptive radiotherapy treatment in prostate cancer with use of radiological contrast agents. The results demonstrate that the selected algorithm shows better qualitative results in the presence of radiological contrast agents in the urinary bladder, and does not distort the image forcing unrealistic deformations. 2. The definition, development and validation of a new method for masking the contents of the rectum (MER, Spanish acronym), and assessing their impact on the process of adaptive radiotherapy in prostate cancer. The segmentations obtained by the MER for the creation of homogenous masks in the session CT images can improve significantly the results of registration algorithms in the rectal region. Thus, the use of the proposed methodology increases the volume overlap index between manual and automatic contours of the rectum to a value of 89%, close to the results obtained using manual masks for both images. In this way, both the calculation of new contours and the calculation of the accumulated dose can be corrected. 3. The definition of a methodology for assessing the quality of the contours of the GTV, which allows the representation of the spatial distribution of the error, adapting it to non-convex volumes such as that formed by the prostate and seminal vesicles. Said evaluation methodology, based on a new three-dimensional reconstruction algorithm and a new quantification metric, presents accurate results with high spatial resolution in a time negligible compared to the registration time. This new approach may be a useful tool to compare different deformable registration algorithms oriented to adaptive radiotherapy in prostate cancer In conclusion, this PhD thesis corroborates the postulated research hypotheses, and is intended to serve as a foundation for future advances in medical image processing in adaptive radiotherapy treatment in prostate cancer. In addition, it opens new future applications for medical image processing methods aimed at improving the adaptive radiotherapy processes in the presence of organ’s appearance changes, and increase the patient safety.

Validación, caracterización y aplicación clínica en neuroimagen multimodalidad de técnicas de registro basadas en Teoría de la Información

La correcta validación y evaluación de cualquier algoritmo de registro incluido en la línea de procesamiento de cualquier aplicación clínica, es fundamental para asegurar la calidad y fiabilidad de los resultados obtenidos con ellas. Ambas características son imprescindibles, además, cuando dicha aplicación se encuentra en el área de la planificación quirúrgica, en la que las decisiones médicas influyen claramente en la invasividad sobre el paciente. El registro de imágenes es un proceso de alineamiento entre dos o más de éstas de forma que las características comunes se encuentren en el mismo punto del espacio. Este proceso, por tanto, se hace imprescindible en aquellas aplicaciones en las que existe la necesidad de combinar la información disponible en diferentes modalidades (fusión de imágenes) o bien la comparación de imágenes intra-modalidad tomadas de diferentes pacientes o en diferentes momentos. En el presente Trabajo Fin de Máster, se desarrolla un conjunto de herramientas para la evaluación de algoritmos de registro y se evalúan en la aplicación sobre imágenes multimodalidad a través de dos metodologías: 1) el uso de imágenes cuya alineación se conoce a priori a través de unos marcadores fiables (fiducial markers) eliminados de las imágenes antes del proceso de validación; y 2) el uso de imágenes sintetizadas con las propiedades de cierta modalidad de interés, generadas en base a otra modalidad objetivo y cuya des-alineación es controlada y conocida a priori. Para la primera de las metodologías, se hizo uso de un proyecto (RIRE – Retrospective Image Registration Evaluation Project) ampliamente conocido y que asegura la fiabilidad de la validación al realizarse por terceros. En la segunda, se propone la utilización de una metodología de simulación de imágenes SPECT (Single Photon Emission Computed Tomography) a partir de imágenes de Resonancia Magnética (que es la referencia anatómica). Finalmente, se realiza la modularización del algoritmo de registro validado en la herramienta FocusDET, para la localización del Foco Epileptógeno (FE) en Epilepsia parcial intratable, sustituyendo a la versión anterior en la que el proceso de registro se encontraba embebido en dicho software, dificultando enormemente cualquier tarea de revisión, validación o evaluación.

Thermal imaging as a biometrics approach to facial signature authentication

This dissertation develops an image processing framework with unique feature extraction and similarity measurements for human face recognition in the thermal mid-wave infrared portion of the electromagnetic spectrum. The goals of this research is to design specialized algorithms that would extract facial vasculature information, create a thermal facial signature and identify the individual. The objective is to use such findings in support of a biometrics system for human identification with a high degree of accuracy and a high degree of reliability. This last assertion is due to the minimal to no risk for potential alteration of the intrinsic physiological characteristics seen through thermal infrared imaging. The proposed thermal facial signature recognition is fully integrated and consolidates the main and critical steps of feature extraction, registration, matching through similarity measures, and validation through testing our algorithm on a database, referred to as C-X1, provided by the Computer Vision Research Laboratory at the University of Notre Dame. Feature extraction was accomplished by first registering the infrared images to a reference image using the functional MRI of the Brain’s (FMRIB’s) Linear Image Registration Tool (FLIRT) modified to suit thermal infrared images. This was followed by segmentation of the facial region using an advanced localized contouring algorithm applied on anisotropically diffused thermal images. Thermal feature extraction from facial images was attained by performing morphological operations such as opening and top-hat segmentation to yield thermal signatures for each subject. Four thermal images taken over a period of six months were used to generate thermal signatures and a thermal template for each subject, the thermal template contains only the most prevalent and consistent features. Finally a similarity measure technique was used to match signatures to templates and the Principal Component Analysis (PCA) was used to validate the results of the matching process. Thirteen subjects were used for testing the developed technique on an in-house thermal imaging system. The matching using an Euclidean-based similarity measure showed 88% accuracy in the case of skeletonized signatures and templates, we obtained 90% accuracy for anisotropically diffused signatures and templates. We also employed the Manhattan-based similarity measure and obtained an accuracy of 90.39% for skeletonized and diffused templates and signatures. It was found that an average 18.9% improvement in the similarity measure was obtained when using diffused templates. The Euclidean- and Manhattan-based similarity measure was also applied to skeletonized signatures and templates of 25 subjects in the C-X1 database. The highly accurate results obtained in the matching process along with the generalized design process clearly demonstrate the ability of the thermal infrared system to be used on other thermal imaging based systems and related databases. A novel user-initialization registration of thermal facial images has been successfully implemented. Furthermore, the novel approach at developing a thermal signature template using four images taken at various times ensured that unforeseen changes in the vasculature did not affect the biometric matching process as it relied on consistent thermal features.

Accumulation de dose à partir de champs de déformation 4D appliqués aux traitements au CyberKnife et à l'IMRT

Le cancer pulmonaire est la principale cause de décès parmi tous les cancers au Canada. Le pronostic est généralement faible, de l'ordre de 15% de taux de survie après 5 ans. Les déplacements internes des structures anatomiques apportent une incertitude sur la précision des traitements en radio-oncologie, ce qui diminue leur efficacité. Dans cette optique, certaines techniques comme la radio-chirurgie et la radiothérapie par modulation de l'intensité (IMRT) visent à améliorer les résultats cliniques en ciblant davantage la tumeur. Ceci permet d'augmenter la dose reçue par les tissus cancéreux et de réduire celle administrée aux tissus sains avoisinants. Ce projet vise à mieux évaluer la dose réelle reçue pendant un traitement considérant une anatomie en mouvement. Pour ce faire, des plans de CyberKnife et d'IMRT sont recalculés en utilisant un algorithme Monte Carlo 4D de transport de particules qui permet d'effectuer de l'accumulation de dose dans une géométrie déformable. Un environnement de simulation a été développé afin de modéliser ces deux modalités pour comparer les distributions de doses standard et 4D. Les déformations dans le patient sont obtenues en utilisant un algorithme de recalage déformable d'image (DIR) entre les différentes phases respiratoire générées par le scan CT 4D. Ceci permet de conserver une correspondance de voxels à voxels entre la géométrie de référence et celles déformées. La DIR est calculée en utilisant la suite ANTs («Advanced Normalization Tools») et est basée sur des difféomorphismes. Une version modifiée de DOSXYZnrc de la suite EGSnrc, defDOSXYZnrc, est utilisée pour le transport de particule en 4D. Les résultats sont comparés à une planification standard afin de valider le modèle actuel qui constitue une approximation par rapport à une vraie accumulation de dose en 4D.

Three dimensional study to quantify the relationship between facial hard and soft tissue movement as a result of orthognathic surgery

Introduction Prediction of soft tissue changes following orthognathic surgery has been frequently attempted in the past decades. It has gradually progressed from the classic “cut and paste” of photographs to the computer assisted 2D surgical prediction planning; and finally, comprehensive 3D surgical planning was introduced to help surgeons and patients to decide on the magnitude and direction of surgical movements as well as the type of surgery to be considered for the correction of facial dysmorphology. A wealth of experience was gained and numerous published literature is available which has augmented the knowledge of facial soft tissue behaviour and helped to improve the ability to closely simulate facial changes following orthognathic surgery. This was particularly noticed following the introduction of the three dimensional imaging into the medical research and clinical applications. Several approaches have been considered to mathematically predict soft tissue changes in three dimensions, following orthognathic surgery. The most common are the Finite element model and Mass tensor Model. These were developed into software packages which are currently used in clinical practice. In general, these methods produce an acceptable level of prediction accuracy of soft tissue changes following orthognathic surgery. Studies, however, have shown a limited prediction accuracy at specific regions of the face, in particular the areas around the lips. Aims The aim of this project is to conduct a comprehensive assessment of hard and soft tissue changes following orthognathic surgery and introduce a new method for prediction of facial soft tissue changes.   Methodology The study was carried out on the pre- and post-operative CBCT images of 100 patients who received their orthognathic surgery treatment at Glasgow dental hospital and school, Glasgow, UK. Three groups of patients were included in the analysis; patients who underwent Le Fort I maxillary advancement surgery; bilateral sagittal split mandibular advancement surgery or bimaxillary advancement surgery. A generic facial mesh was used to standardise the information obtained from individual patient’s facial image and Principal component analysis (PCA) was applied to interpolate the correlations between the skeletal surgical displacement and the resultant soft tissue changes. The identified relationship between hard tissue and soft tissue was then applied on a new set of preoperative 3D facial images and the predicted results were compared to the actual surgical changes measured from their post-operative 3D facial images. A set of validation studies was conducted. To include: • Comparison between voxel based registration and surface registration to analyse changes following orthognathic surgery. The results showed there was no statistically significant difference between the two methods. Voxel based registration, however, showed more reliability as it preserved the link between the soft tissue and skeletal structures of the face during the image registration process. Accordingly, voxel based registration was the method of choice for superimposition of the pre- and post-operative images. The result of this study was published in a refereed journal. • Direct DICOM slice landmarking; a novel technique to quantify the direction and magnitude of skeletal surgical movements. This method represents a new approach to quantify maxillary and mandibular surgical displacement in three dimensions. The technique includes measuring the distance of corresponding landmarks digitized directly on DICOM image slices in relation to three dimensional reference planes. The accuracy of the measurements was assessed against a set of “gold standard” measurements extracted from simulated model surgery. The results confirmed the accuracy of the method within 0.34mm. Therefore, the method was applied in this study. The results of this validation were published in a peer refereed journal. • The use of a generic mesh to assess soft tissue changes using stereophotogrammetry. The generic facial mesh played a major role in the soft tissue dense correspondence analysis. The conformed generic mesh represented the geometrical information of the individual’s facial mesh on which it was conformed (elastically deformed). Therefore, the accuracy of generic mesh conformation is essential to guarantee an accurate replica of the individual facial characteristics. The results showed an acceptable overall mean error of the conformation of generic mesh 1 mm. The results of this study were accepted for publication in peer refereed scientific journal. Skeletal tissue analysis was performed using the validated “Direct DICOM slices landmarking method” while soft tissue analysis was performed using Dense correspondence analysis. The analysis of soft tissue was novel and produced a comprehensive description of facial changes in response to orthognathic surgery. The results were accepted for publication in a refereed scientific Journal. The main soft tissue changes associated with Le Fort I were advancement at the midface region combined with widening of the paranasal, upper lip and nostrils. Minor changes were noticed at the tip of the nose and oral commissures. The main soft tissue changes associated with mandibular advancement surgery were advancement and downward displacement of the chin and lower lip regions, limited widening of the lower lip and slight reversion of the lower lip vermilion combined with minimal backward displacement of the upper lip were recorded. Minimal changes were observed on the oral commissures. The main soft tissue changes associated with bimaxillary advancement surgery were generalized advancement of the middle and lower thirds of the face combined with widening of the paranasal, upper lip and nostrils regions. In Le Fort I cases, the correlation between the changes of the facial soft tissue and the skeletal surgical movements was assessed using PCA. A statistical method known as ’Leave one out cross validation’ was applied on the 30 cases which had Le Fort I osteotomy surgical procedure to effectively utilize the data for the prediction algorithm. The prediction accuracy of soft tissue changes showed a mean error ranging between (0.0006mm±0.582) at the nose region to (-0.0316mm±2.1996) at the various facial regions.

Accumulation de dose à partir de champs de déformation 4D appliqués aux traitements au CyberKnife et à l'IMRT

Le cancer pulmonaire est la principale cause de décès parmi tous les cancers au Canada. Le pronostic est généralement faible, de l'ordre de 15% de taux de survie après 5 ans. Les déplacements internes des structures anatomiques apportent une incertitude sur la précision des traitements en radio-oncologie, ce qui diminue leur efficacité. Dans cette optique, certaines techniques comme la radio-chirurgie et la radiothérapie par modulation de l'intensité (IMRT) visent à améliorer les résultats cliniques en ciblant davantage la tumeur. Ceci permet d'augmenter la dose reçue par les tissus cancéreux et de réduire celle administrée aux tissus sains avoisinants. Ce projet vise à mieux évaluer la dose réelle reçue pendant un traitement considérant une anatomie en mouvement. Pour ce faire, des plans de CyberKnife et d'IMRT sont recalculés en utilisant un algorithme Monte Carlo 4D de transport de particules qui permet d'effectuer de l'accumulation de dose dans une géométrie déformable. Un environnement de simulation a été développé afin de modéliser ces deux modalités pour comparer les distributions de doses standard et 4D. Les déformations dans le patient sont obtenues en utilisant un algorithme de recalage déformable d'image (DIR) entre les différentes phases respiratoire générées par le scan CT 4D. Ceci permet de conserver une correspondance de voxels à voxels entre la géométrie de référence et celles déformées. La DIR est calculée en utilisant la suite ANTs («Advanced Normalization Tools») et est basée sur des difféomorphismes. Une version modifiée de DOSXYZnrc de la suite EGSnrc, defDOSXYZnrc, est utilisée pour le transport de particule en 4D. Les résultats sont comparés à une planification standard afin de valider le modèle actuel qui constitue une approximation par rapport à une vraie accumulation de dose en 4D.