Bone quality influences bone strength with important consequences for osteoporosis, fracture risk and dental implant success. Whilst imaging that is capable of capturing bone structure in 3D is becoming more common, quantitative clinical measures of bone quality rely on bone quantity, not structure. If bone quality could be more accurately measured, and the influence of bone architecture better understood, strength may be better predicted. This thesis presents methods for making structural comparisons between successive micro-CT images of loaded bone and explores the limitations of these. I present a novel method to detect where damage occurs in loaded rat vertebrae based on multiscale rigid registration and difference measures. Together these methods represent a quantitative approach to image guided failure analysis. Time-lapsed micro-CT images of 14 successively loaded rat vertebrae were acquired and damaged regions found using these. Using a random forest classifier I tested whether the damaged regions could be predicted by several commonly used structural measures (bone area and volume), three-dimensional texture measures (co-occurrence matrices and fractal dimension) and a more novel type of architectural measure (based on the structure tensor). A combination of parameters was able to predict damage regions with specificities in the range 70-90% and sensitivities of 60-70%.Using ovariectomised rats as a model of osteoporosis I have performed a pilot experiment to investigate how changes in bone quality might effect our results. The wider applicability of my methods are demonstrated by applying them to dental cone beam images of healthy and osteoporotic patients.

This thesis proposes a multidirectional methodological framework for a comprehensive ergonomic analysis and modelling of workflow for multi-modal vascular image-guided procedures (IGPs). Two approaches are employed to analyse the workflow: Discrete Event Simulation (DES) and purpose-oriented physical models. In contrast to previous studies, the proposed methodology looks in detail the actions carried out within the intervention rooms and the clinical experience during the procedures with three main objectives: to provide a deeper understanding of vascular procedures, to predict the impact of protocol modifications and to offer a framework to develop new image-guided protocols for the alternative use of Magnetic Resonance (MR) imaging in comparison with X-Ray Digital Subtraction Angiography (DSA). The methodological framework includes an assessment of commercial simulation software packages to evaluate their fitness to the specific requirements of this research. The novel methodology is applied to several cases studies of common vascular IGPs. In addition, a case of MR – guided focused ultrasound intervention demonstrates how it is possible to extend the framework to study non-vascular IGPs. The multi-disciplinary methodological framework described opens a new way to understand IGPs that could be used in prospective applications such as medical education and medical devices regulations.

<p>In this project several tests were performed to evaluate the performance of an On-Board Imager® (OBI) mounted on a clinical linear accelerator. The measurements were divided into three parts; geometric accuracy, image registration and couch shift accuracy, and image quality. A cube phantom containing a radiation opaque marker was used to study the agreement with treatment isocenter for both kV-images and cone-beam CT (CBCT) images. The long term stability was investigated by acquiring frontal and lateral kV images twice a week over a 3 month period. Stability in vertical and longitudinal robotic arm motion as well as the stability of the center-of-rotation was evaluated. Further, the agreement of kV image and CBCT center with MV image center was examined.</p><p>A marker seed phantom was used to evaluate and compare the three applications in image registration; 2D/2D, 2D/3D and 3D/3D. Image registration using kV-kV image sets were compared with MV MV and MV-kV image sets. Further, the accuracy in 2D/2D matches with images acquired at non-orthogonal gantry angles was evaluated. The image quality in CBCT images was evaluated using a Catphan® phantom. Hounsfield unit (HU) uniformity and linearity was compared with planning CT. HU accuracy is crucial for dose verification using CBCT data.</p><p>The geometric measurements showed good long term stability and accurate position reproducibility after robotic arm motions. A systematic error of about 1 mm in lateral direction of the kV-image center was detected. A small difference between kV and CBCT center was observed and related to a lateral kV detector offset. The vector disagreement between kV- and MV-image centers was  2 mm at some gantry angles. Image registration with the different match applications worked sufficiently. 2D/3D match was seen to correct more accurately than 2D/2D match for large translational and rotational shifts. CBCT images acquired with full-fan mode showed good HU uniformity but half fan images were less uniform. In the soft tissue region the HU agreement with planning CT was reasonable while a larger disagreement was observed at higher densities. This work shows that the OBI is robust and stable in its performance. With regular QC and calibrations the geometric precision of the OBI can be maintained within 1 mm of treatment isocenter.</p>

Ce document constitue une synth`ese de travaux de recherche en vue de l'obten- tion du diplˆome d'habilitation `a diriger les recherches. A la suite ce cette in- troduction r ́edig ́ee en franc ̧ais, le reste de ce document sera en anglais. Je suis actuellement charg ́e de recherches INRIA au centre de Rennes Bretagne Atlantique. J'ai rejoint en Septembre 2001 l' ́equipe Vista dirig ́ee par Patrick Bouthemy, puis l' ́equipe Visages dirig ́ee par Christian Barillot en Janvier 2004. Depuis Janvier 2010, je travaille dans l' ́equipe-projet Serpico dirig ́ee par Charles Kervrann dont l'objet est l'imagerie et la mod ́elisation de la dynamique intra- cellulaire. Parmi mes activit ́es pass ́ees, ce document va se concentrer uniquement sur les activit ́es portant sur la neurochirurgie guid ́ee par l'image. En parti- culier, les travaux effectu ́es sur le recalage non-rigide ne seront pas pr ́esent ́es ici. Concernant le recalage, ces travaux ont commenc ́e pendant ma th`ese avec le d ́eveloppement d'une m ́ethode de recalage 3D bas ́e sur le flot optique [72], l'incorporation de contraintes locales dans ce processus de recalage [74] et la validation de m ́ethodes de recalage inter-sujets [71]. J'ai poursuivi ces travaux apr`es mon recrutement avec Anne Cuzol et Etienne M ́emin sur la mod ́elisation fluide du recalage [44], avec Nicolas Courty sur l'acc ́el ́eration temps-r ́eel de m ́ethode de recalage [42], et sur l' ́evaluation des m ́ethodes de recalage dans deux contextes : celui de l'implantation d' ́electrodes profondes [29] et le re- calage inter-sujets [92]. L'utilisation de syst`emes dits de neuronavigation est maintenant courante dans les services de neurochirurgie. Les b ́en ́efices, attendus ou report ́es dans la litt ́erature, sont une r ́eduction de la mortalit ́e et de la morbidit ́e, une am ́elio- ration de la pr ́ecision, une r ́eduction de la dur ́ee d'intervention, des couˆts d'hospitalisation. Tous ces b ́en ́efices ne sont pas `a l'heure actuelle d ́emontr ́es `a ma connaissance, mais cette question d ́epasse largement le cadre de ce doc- ument. Ces syst`emes de neuronavigation permettent l'utilisation du planning chirurgical pendant l'intervention, dans la mesure ou` le patient est mis en cor- respondance g ́eom ́etrique avec les images pr ́eop ́eratoires `a partir desquelles est pr ́epar ́ee l'intervention. Ces informations multimodales sont maintenant couramment utilis ́ees, com- prenant des informations anatomiques, vasculaires, fonctionnelles. La fusion de ces informations permet de pr ́eparer le geste chirurgical : ou` est la cible, quelle est la voie d'abord, quelles zones ́eviter. Ces informations peuvent main- tenant ˆetre utilis ́ees en salle d'op ́eration et visualis ́ees dans les oculaires du mi- croscope chirurgical grˆace au syst`eme de neuronavigation. Malheureusement, cela suppose qu'il existe une transformation rigide entre le patient et les im- ages pr ́eop ́eratoires. Alors que cela peut ˆetre consid ́er ́e comme exact avant l'intervention, cette hypoth`ese tombe rapidement sous l'effet de la d ́eformation des tissus mous. Ces d ́eformations, qui doivent ˆetre consid ́er ́ees comme un ph ́enom`ene spatio-temporel, interviennent sous l'effet de plusieurs facteurs, dont la gravit ́e, la perte de liquide c ́ephalo-rachidien, l'administration de pro- duits anesth ́esiants ou diur ́etiques, etc. Ces d ́eformations sont tr`es difficiles `a mod ́eliser et pr ́edire. De plus, il s'agit d'un ph ́enom`ene spatio-temporel, dont l'amplitude peut varier consid ́era- blement en fonction de plusieurs facteurs. Pour corriger ces d ́eformations, l'imagerie intra-op ́eratoire apparait comme la seule piste possible.

Recent progress in the overlay and registration of digital information on the users workspace in a spatially meaningful way has allowed mixed reality (MR) to become a more effective operational medium. In the area of medical surgery, surgeons are conveyed with information such as the incisions location, regions to be avoided, diseased tissues, etc, while staying in and keeping their original working environment. The main objective of this Thesis is identifying theoretical and practical basis for how mixed reality interfaces might provide support and augmentation maximizing the continuity of interaction. We start proposing a set of design principles organized in a design space which allows to identify continuity interaction properties at an early stage of the development system. Once the abstract design possibilities have been identified and a concrete design decision has been taken, an implementational strategy can be developed. Two approaches were investigated: markerless and marker-based. The last one is used to provide surgeons with guidance on an osteotomy task in the maxillo-facial surgery. The evaluation process applies usability tests with users to validate the augmented guidance in different scenarios and to study the influence of different design variables in the final user interaction. As a result we have found a model to describe the contribution factors of each variable for the continuity of the user interaction. We suggest that this methodology can be applied mainly to those applications in which smooth connections and interactions, with virtual and real environments, are critical for the system; i.e. surgery, drivers applications or pilot simulations.

Recent progress in the overlay and registration of digital information on the users workspace in a spatially meaningful way has allowed mixed reality (MR) to become a more effective operational medium. In the area of medical surgery, surgeons are conveyed with information such as the incisions location, regions to be avoided, diseased tissues, etc, while staying in and keeping their original working environment. The main objective of this Thesis is identifying theoretical and practical basis for how mixed reality interfaces might provide support and augmentation maximizing the continuity of interaction. We start proposing a set of design principles organized in a design space which allows to identify continuity interaction properties at an early stage of the development system. Once the abstract design possibilities have been identified and a concrete design decision has been taken, an implementational strategy can be developed. Two approaches were investigated: markerless and marker-based. The last one is used to provide surgeons with guidance on an osteotomy task in the maxillo-facial surgery. The evaluation process applies usability tests with users to validate the augmented guidance in different scenarios and to study the influence of different design variables in the final user interaction. As a result we have found a model to describe the contribution factors of each variable for the continuity of the user interaction. We suggest that this methodology can be applied mainly to those applications in which smooth connections and interactions, with virtual and real environments, are critical for the system; i.e. surgery, drivers applications or pilot simulations.

In this project several tests were performed to evaluate the performance of an On-Board Imager® (OBI) mounted on a clinical linear accelerator. The measurements were divided into three parts; geometric accuracy, image registration and couch shift accuracy, and image quality. A cube phantom containing a radiation opaque marker was used to study the agreement with treatment isocenter for both kV-images and cone-beam CT (CBCT) images. The long term stability was investigated by acquiring frontal and lateral kV images twice a week over a 3 month period. Stability in vertical and longitudinal robotic arm motion as well as the stability of the center-of-rotation was evaluated. Further, the agreement of kV image and CBCT center with MV image center was examined. A marker seed phantom was used to evaluate and compare the three applications in image registration; 2D/2D, 2D/3D and 3D/3D. Image registration using kV-kV image sets were compared with MV MV and MV-kV image sets. Further, the accuracy in 2D/2D matches with images acquired at non-orthogonal gantry angles was evaluated. The image quality in CBCT images was evaluated using a Catphan® phantom. Hounsfield unit (HU) uniformity and linearity was compared with planning CT. HU accuracy is crucial for dose verification using CBCT data. The geometric measurements showed good long term stability and accurate position reproducibility after robotic arm motions. A systematic error of about 1 mm in lateral direction of the kV-image center was detected. A small difference between kV and CBCT center was observed and related to a lateral kV detector offset. The vector disagreement between kV- and MV-image centers was  2 mm at some gantry angles. Image registration with the different match applications worked sufficiently. 2D/3D match was seen to correct more accurately than 2D/2D match for large translational and rotational shifts. CBCT images acquired with full-fan mode showed good HU uniformity but half fan images were less uniform. In the soft tissue region the HU agreement with planning CT was reasonable while a larger disagreement was observed at higher densities. This work shows that the OBI is robust and stable in its performance. With regular QC and calibrations the geometric precision of the OBI can be maintained within 1 mm of treatment isocenter.

<p>Imaging respiratory induced tumor motion in the radiation therapy treatment room could eliminate the necessity for large motion encompassing margins that result in excessive irradiation of healthy tissues. Currently available image guidance technologies are ill-suited for this task. Two-dimensional fluoroscopic images are acquired with sufficient speed to image respiratory motion. However, volume information is not present, and soft tissue structures are often not visible because a large volume is projected onto a single plane. Currently available volumetric imaging modalities are not acquired with sufficient speed to capture full motion trajectory information. Four-dimensional cone-beam computed tomography (4D CBCT) using a gantry mounted 2D flat panel imaging device has been proposed but has been limited by high doses, long scan times and severe under-sampling artifacts. The focus of the work completed in this thesis was to find ways to improve 4D imaging using a gantry mounted 2D kV imaging system. Specifically, the goals were to investigate methods for minimizing imaging dose and scan time while achieving consistent, controllable, high quality 4D images.</p><p>First, we introduced four-dimensional digital tomosynthesis (4D DTS) and characterized its potential for 3D motion analysis using a motion phantom. The motion phantom was programmed to exhibit motion profiles with various known amplitudes in all three dimensions and scanned using a 2D kV imaging system mounted on a linear accelerator. Two arcs of projection data centered about the anterior-posterior and lateral axes were used to reconstruct phase resolved DTS coronal and sagittal images. Respiratory signals were obtained by analyzing projection data, and these signals were used to derive phases for each of the projection images. Projection images were sorted according to phase, and DTS phase images were reconstructed for each phase bin. 4D DTS target location accuracies for peak inhalation and peak exhalation in all three dimensions were limited only by the 0.5 mm pixel resolution for all DTS scan angles. The average localization errors for all phases of an assymetric motion profile with a 2 cm peak-to-peak amplitude were 0.68, 0.67 and 1.85 mm for 60 <super> o <super/> 4D DTS, 360<super> o <super/> CBCT and 4DCT, respectively. Motion artifacts for 4D DTS were found to be substantially less than those seen in 4DCT, which is the current clinical standard in 4D imaging. </p><p>We then developed a comprehensive framework for relating patient respiratory parameters with acquisition and reconstruction parameters for slow gantry rotation 4D DTS and 4D CBCT imaging. This framework was validated and optimized with phantom and lung patient studies. The framework facilitates calculation of optimal frame rates and gantry rotation speeds based on patient specific respiratory parameters and required temporal resolution (task dependent). We also conducted lung patient studies to investigate required scan angles for 4D DTS and achievable dose and scan times for 4D DTS and 4D CBCT using the optimized framework. This explicit and comprehensive framework of relationships allowed us to demonstrate that under-sampling artifacts can be controlled, and 4D CBCT images can be acquired using lower doses than previously reported. We reconstructed 4D CBCT images of three patients with accumulated doses of 4.8 to 5.7 cGy. These doses are three times less than the doses used for the only previously reported 4D CBCT investigation that did not report images characterized by severe under-sampling artifacts. </p><p>We found that scan times for 200<super> o <super/> 4D CBCT imaging using acquisition sequences optimized for reduction of imaging dose and under-sampling artifacts were necessarily between 4 and 7 minutes (depending on patient respiration). The results from lung patient studies concluded that scan times could be reduced using 4D DTS. Patient 4D DTS studies demonstrated that tumor visibility for the lung patients we studied could be achieved using 30<super> o <super/> scan angles for coronal views. Scan times for those cases were between 41 and 50 seconds. Additional dose reductions were also demonstrated. Image doses were between 1.56 and 2.13 cGy. These doses are well below doses for standard CBCT scans. The techniques developed and reported in this thesis demonstrate how respiratory motion can be imaged in the radiotherapy treatment room using clinically feasible imaging doses and scan times.</p> / Dissertation

Modern image-guided surgery aids minimally-invasive, high-precision procedures that increase efficacy of treatment. This thesis investigates two research aims to improve precision and integration of intraoperative cone-beam CT (CBCT) imaging in guidance of head and neck (H&N) surgery. First, marker configurations were examined to identify arrangements that minimize target registration error (TRE). Best arrangements minimized the distance between the configuration centroid and surgical target while maximizing marker separation. Configurations of few markers could minimized TRE with more markers providing improved uniformity. Second, an algorithm for automatic registration of image and world reference frames was pursued to streamline integration of CBCT with real-time tracking and provide automatic updates per scan. Markers visible to the tracking and imaging systems are automatically co-localized and registered with equivalent accuracy and superior reproducibility compared to conventional registration. Such work helps the implementation of CBCT in H&N surgery to maximize surgical precision and exploit intraoperative image guidance.

This thesis presents the first work, to our knowledge, to evaluate the potential of Optical Coherence Tomography (OCT) as an intravascular imaging modality to characterize and guide interventions on chronic total occlusions (CTOs) in arteries. An ex vivo imaging study using OCT is presented that characterizes various pathologies associated with peripheral CTOs and illustrates the ability to differentiate between the vessel wall and the occluded lumen. We also found that, while OCT could image approximately 1mm through tissue, it was effective for imaging deeper through clarified microchannels seen within the occluded lumen. While others had reported observing such microchannels within the lumen before, little was known about the global architecture of these channels. This motivated a study of the global morphology of microchannels in occlusions using micro computed tomography (microCT). In this microCT study, we found that microchannels within the occluded lumen of the artery appeared to be continuous over several millimeters. However, these channels also exited the artery frequently, suggesting the need for some form of imaging guidance. As a potential intravascular imaging set-up, a forward-viewing OCT catheter was built. This catheter uses a novel scanning mechanism that combines high voltage and a dissipative polymer to achieve fast compact actuation. Doppler OCT results are presented using this catheter to image flow in the forward direction. Doppler OCT imaging of microchannels in vivo is also shown in a surgically exposed occluded artery in situ.