Low-cost MR-compatible moving heart phantom.

For the development and evaluation of cardiac magnetic resonance (MR) imaging sequences and methodologies, the availability of a periodically moving phantom to model respiratory and cardiac motion would be of substantial benefit. Given the specific physical boundary conditions in an MR environment, the choice of materials and power source of such phantoms is heavily restricted. Sophisticated commercial solutions are available; however, they are often relatively costly and user-specific modifications may not easily be implemented. We therefore sought to construct a low-cost MR-compatible motion phantom that could be easily reproduced and had design flexibility. A commercially available K'NEX construction set (Hyper Space Training Tower, K'NEX Industries, Inc., Hatfield, PA) was used to construct a periodically moving phantom head. The phantom head performs a translation with a superimposed rotation, driven by a motor over a 2-m rigid rod. To synchronize the MR data acquisition with phantom motion (without introducing radiofrequency-related image artifacts), a fiberoptic control unit generates periodic trigger pulses synchronized to the phantom motion. Total material costs of the phantom are US$ < 200.00, and a total of 80 man-hours were required to design and construct the original phantom. With schematics of the present solution, the phantom reproduction may be achieved in approximately 15 man-hours. The presented MR-compatible periodically moving phantom can easily be reproduced, and user-specific modifications may be implemented. Such an approach allows a detailed investigation of motion-related phenomena in MR images.

Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images.

This paper presents a validation study on statistical nonsupervised brain tissue classification techniques in magnetic resonance (MR) images. Several image models assuming different hypotheses regarding the intensity distribution model, the spatial model and the number of classes are assessed. The methods are tested on simulated data for which the classification ground truth is known. Different noise and intensity nonuniformities are added to simulate real imaging conditions. No enhancement of the image quality is considered either before or during the classification process. This way, the accuracy of the methods and their robustness against image artifacts are tested. Classification is also performed on real data where a quantitative validation compares the methods' results with an estimated ground truth from manual segmentations by experts. Validity of the various classification methods in the labeling of the image as well as in the tissue volume is estimated with different local and global measures. Results demonstrate that methods relying on both intensity and spatial information are more robust to noise and field inhomogeneities. We also demonstrate that partial volume is not perfectly modeled, even though methods that account for mixture classes outperform methods that only consider pure Gaussian classes. Finally, we show that simulated data results can also be extended to real data.

Population receptive field estimates of human auditory cortex.

Here we describe a method for measuring tonotopic maps and estimating bandwidth for voxels in human primary auditory cortex (PAC) using a modification of the population Receptive Field (pRF) model, developed for retinotopic mapping in visual cortex by Dumoulin and Wandell (2008). The pRF method reliably estimates tonotopic maps in the presence of acoustic scanner noise, and has two advantages over phase-encoding techniques. First, the stimulus design is flexible and need not be a frequency progression, thereby reducing biases due to habituation, expectation, and estimation artifacts, as well as reducing the effects of spatio-temporal BOLD nonlinearities. Second, the pRF method can provide estimates of bandwidth as a function of frequency. We find that bandwidth estimates are narrower for voxels within the PAC than in surrounding auditory responsive regions (non-PAC).

Multi-slice three-dimensional myocardial strain tensor quantification using zHARP.

In this article we propose a novel method for calculating cardiac 3-D strain. The method requires the acquisition of myocardial short-axis (SA) slices only and produces the 3-D strain tensor at every point within every pair of slices. Three-dimensional displacement is calculated from SA slices using zHARP which is then used for calculating the local displacement gradient and thus the local strain tensor. There are three main advantages of this method. First, the 3-D strain tensor is calculated for every pixel without interpolation; this is unprecedented in cardiac MR imaging. Second, this method is fast, in part because there is no need to acquire long-axis (LA) slices. Third, the method is accurate because the 3-D displacement components are acquired simultaneously and therefore reduces motion artifacts without the need for registration. This article presents the theory of computing 3-D strain from two slices using zHARP, the imaging protocol, and both phantom and in-vivo validation.

Motion artifact reduction and vessel enhancement for free-breathing navigator-gated coronary MRA using 3D k-space reordering.

Breathing-induced bulk motion of the myocardium during data acquisition may cause severe image artifacts in coronary magnetic resonance angiography (MRA). Current motion compensation strategies include breath-holding or free-breathing MR navigator gating and tracking techniques. Navigator-based techniques have been further refined by the applications of sophisticated 2D k-space reordering techniques. A further improvement in image quality and a reduction of relative scanning duration may be expected from a 3D k-space reordering scheme. Therefore, a 3D k-space reordered acquisition scheme including a 3D navigator gated and corrected segmented k-space gradient echo imaging sequence for coronary MRA was implemented. This new zonal motion-adapted acquisition and reordering technique (ZMART) was developed on the basis of a numerical simulation of the Bloch equations. The technique was implemented on a commercial 1.5T MR system, and first phantom and in vivo experiments were performed. Consistent with the results of the theoretical findings, the results obtained in the phantom studies demonstrate a significant reduction of motion artifacts when compared to conventional (non-k-space reordered) gating techniques. Preliminary in vivo findings also compare favorably with the phantom experiments and theoretical considerations. Magn Reson Med 45:645-652, 2001.

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2×2×3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p<0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies.

Intrinsic ROS-production capacity of nanoparticles

Engineered nanomaterials (ENMs) exhibit special physicochemical properties and thus are finding their way into an increasing number of industries, enabling products with improved properties. Their increased use brings a greater likelihood of exposure to the nanoparticles (NPs) that could be released during the life cycle of nano-abled products. The field of nanotoxicology has emerged as a consequence of the development of these novel materials, and it has gained ever more attention due to the urgent need to gather information on exposure to them and to understand the potential hazards they engender. However, current studies on nanotoxicity tend to focus on pristine ENMs, and they use these toxicity results to generalize risk assessments on human exposure to NPs. ENMs released into the environment can interact with their surroundings, change characteristics and exhibit toxicity effects distinct from those of pristine ENMs. Furthermore, NPs' large surface areas provide extra-large potential interfaces, thus promoting more significant interactions between NPs and other co-existing species. In such processes, other species can attach to a NP's surface and modify its surface functionality, in addition to the toxicity in normally exhibits. One particular occupational health scenario involves NPs and low-volatile organic compounds (LVOC), a common type of pollutant existing around many potential sources of NPs. LVOC can coat a NP's surface and then dominate its toxicity. One important mechanism in nanotoxicology is the creation of reactive oxygen species (ROS) on a NP's surface; LVOC can modify the production of these ROS. In summary, nanotoxicity research should not be limited to the toxicity of pristine NPs, nor use their toxicity to evaluate the health effects of exposure to environmental NPs. Instead, the interactions which NPs have with other environmental species should also be considered and researched. The potential health effects of exposure to NPs should be derived from these real world NPs with characteristics modified by the environment and their distinct toxicity. Failure to suitably address toxicity results could lead to an inappropriate treatment of nano- release, affect the environment and public health and put a blemish on the development of sustainable nanotechnologies as a whole. The main objective of this thesis is to demonstrate a process for coating NP surfaces with LVOC using a well-controlled laboratory design and, with regard to these NPs' capacity to generate ROS, explore the consequences of changing particle toxicity. The dynamic coating system developed yielded stable and replicable coating performance, simulating an important realistic scenario. Clear changes in the size distribution of airborne NPs were observed using a scanning mobility particle sizer, were confirmed using both liquid nanotracking analyses and transmission electron microscopy (TEM) imaging, and were verified thanks to the LVOC coating. Coating thicknesses corresponded to the amount of coating material used and were controlled using the parameters of the LVOC generator. The capacity of pristine silver NPs (Ag NPs) to generate ROS was reduced when they were given a passive coating of inert paraffin: this coating blocked the reactive zones on the particle surfaces. In contrast, a coating of active reduced-anthraquinone contributed to redox reactions and generated ROS itself, despite the fact that ROS generation due to oxidation by Ag NPs themselves was quenched. Further objectives of this thesis included development of ROS methodology and the analysis of ROS case studies. Since the capacity of NPs to create ROS is an important effect in nanotoxicity, we attempted to refine and standardize the use of 2'7-dichlorodihydrofluorescin (DCFH) as a chemical tailored for the characterization of NPs' capacity for ROS generation. Previous studies had reported a wide variety of results, which were due to a number of insufficiently well controlled factors. We therefore cross-compared chemicals and concentrations, explored ways of dispersing NP samples in liquid solutions, identified sources of contradictions in the literature and investigated ways of reducing artificial results. The most robust results were obtained by sonicating an optimal sample of NPs in a DCFH-HRP solution made of 5,M DCFH and 0.5 unit/ml horseradish peroxidase (HRP). Our findings explained how the major reasons for previously conflicting results were the different experimental approaches used and the potential artifacts appearing when using high sample concentrations. Applying our advanced DCFH protocol with other physicochemical characterizations and biological analyses, we conducted several case studies, characterizing aerosols and NP samples. Exposure to aged brake wear dust engenders a risk of potential deleterious health effects in occupational scenarios. We performed microscopy and elemental analyses, as well as ROS measurements, with acellular and cellular DCFH assays. TEM images revealed samples to be heterogeneous mixtures with few particles in the nano-scale. Metallic and non-metallic elements were identified, primarily iron, carbon and oxygen. Moderate amounts of ROS were detected in the cell-free fluorescent tests; however, exposed cells were not dramatically activated. In addition to their highly aged state due to oxidation, the reason aged brake wear samples caused less oxidative stress than fresh brake wear samples may be because of their larger size and thus smaller relative reactive surface area. Other case studies involving welding fumes and differently charged NPs confirmed the performance of our DCFH assay and found ROS generation linked to varying characteristics, especially the surface functionality of the samples. Les nanomatériaux manufacturés (ENM) présentent des propriétés physico-chimiques particulières et ont donc trouvés des applications dans un nombre croissant de secteurs, permettant de réaliser des produits ayant des propriétés améliorées. Leur utilisation accrue engendre un plus grand risque pour les êtres humains d'être exposés à des nanoparticules (NP) qui sont libérées au long de leur cycle de vie. En conséquence, la nanotoxicologie a émergé et gagné de plus en plus d'attention dû à la nécessité de recueillir les renseignements nécessaires sur l'exposition et les risques associés à ces nouveaux matériaux. Cependant, les études actuelles sur la nanotoxicité ont tendance à se concentrer sur les ENM et utiliser ces résultats toxicologiques pour généraliser l'évaluation des risques sur l'exposition humaine aux NP. Les ENM libérés dans l'environnement peuvent interagir avec l'environnement, changeant leurs caractéristiques, et montrer des effets de toxicité distincts par rapport aux ENM originaux. Par ailleurs, la grande surface des NP fournit une grande interface avec l'extérieur, favorisant les interactions entre les NP et les autres espèces présentes. Dans ce processus, d'autres espèces peuvent s'attacher à la surface des NP et modifier leur fonctionnalité de surface ainsi que leur toxicité. Un scénario d'exposition professionnel particulier implique à la fois des NP et des composés organiques peu volatils (LVOC), un type commun de polluant associé à de nombreuses sources de NP. Les LVOC peuvent se déposer sur la surface des NP et donc dominer la toxicité globale de la particule. Un mécanisme important en nanotoxicologie est la création d'espèces réactives d'oxygène (ROS) sur la surface des particules, et les LVOC peuvent modifier cette production de ROS. En résumé, la recherche en nanotoxicité ne devrait pas être limitée à la toxicité des ENM originaux, ni utiliser leur toxicité pour évaluer les effets sur la santé de l'exposition aux NP de l'environnement; mais les interactions que les NP ont avec d'autres espèces environnementales doivent être envisagées et étudiées. Les effets possibles sur la santé de l'exposition aux NP devraient être dérivés de ces NP aux caractéristiques modifiées et à la toxicité distincte. L'utilisation de résultats de toxicité inappropriés peut conduire à une mauvaise prise en charge de l'exposition aux NP, de détériorer l'environnement et la santé publique et d'entraver le développement durable des industries de la nanotechnologie dans leur ensemble. L'objectif principal de cette thèse est de démontrer le processus de déposition des LVOC sur la surface des NP en utilisant un environnement de laboratoire bien contrôlé et d'explorer les conséquences du changement de toxicité des particules sur leur capacité à générer des ROS. Le système de déposition dynamique développé a abouti à des performances de revêtement stables et reproductibles, en simulant des scénarios réalistes importants. Des changements clairs dans la distribution de taille des NP en suspension ont été observés par spectrométrie de mobilité électrique des particules, confirmé à la fois par la méthode dite liquid nanotracking analysis et par microscopie électronique à transmission (MET), et a été vérifié comme provenant du revêtement par LVOC. La correspondance entre l'épaisseur de revêtement et la quantité de matériau de revêtement disponible a été démontré et a pu être contrôlé par les paramètres du générateur de LVOC. La génération de ROS dû aux NP d'argent (Ag NP) a été diminuée par un revêtement passif de paraffine inerte bloquant les zones réactives à la surface des particules. Au contraire, le revêtement actif d'anthraquinone réduit a contribué aux réactions redox et a généré des ROS, même lorsque la production de ROS par oxydation des Ag NP avec l'oxygène a été désactivé. Les objectifs associés comprennent le développement de la méthodologie et des études de cas spécifique aux ROS. Etant donné que la capacité des NP à générer des ROS contribue grandement à la nanotoxicité, nous avons tenté de définir un standard pour l'utilisation de 27- dichlorodihydrofluorescine (DCFH) adapté pour caractériser la génération de ROS par les NP. Des etudes antérieures ont rapporté une grande variété de résultats différents, ce qui était dû à un contrôle insuffisant des plusieurs facteurs. Nous avons donc comparé les produits chimiques et les concentrations utilisés, exploré les moyens de dispersion des échantillons HP en solution liquide, investigué les sources de conflits identifiées dans les littératures et étudié les moyens de réduire les résultats artificiels. De très bon résultats ont été obtenus par sonication d'une quantité optimale d'échantillons de NP en solution dans du DCFH-HRP, fait de 5 nM de DCFH et de 0,5 unité/ml de Peroxydase de raifort (HRP). Notre étude a démontré que les principales raisons causant les conflits entre les études précédemment conduites dans la littérature étaient dues aux différentes approches expérimentales et à des artefacts potentiels dus à des concentrations élevées de NP dans les échantillons. Utilisant notre protocole DCFH avancé avec d'autres caractérisations physico-chimiques et analyses biologiques, nous avons mené plusieurs études de cas, caractérisant les échantillons d'aérosols et les NP. La vielle poussière de frein en particulier présente un risque élevé d'exposition dans les scénarios professionnels, avec des effets potentiels néfastes sur la santé. Nous avons effectué des analyses d'éléments et de microscopie ainsi que la mesure de ROS avec DCFH cellulaire et acellulaire. Les résultats de MET ont révélé que les échantillons se présentent sous la forme de mélanges de particules hétérogènes, desquels une faible proportion se trouve dans l'échelle nano. Des éléments métalliques et non métalliques ont été identifiés, principalement du fer, du carbone et de l'oxygène. Une quantité modérée de ROS a été détectée dans le test fluorescent acellulaire; cependant les cellules exposées n'ont pas été très fortement activées. La raison pour laquelle les échantillons de vielle poussière de frein causent un stress oxydatif inférieur par rapport à la poussière de frein nouvelle peut-être à cause de leur plus grande taille engendrant une surface réactive proportionnellement plus petite, ainsi que leur état d'oxydation avancé diminuant la réactivité. D'autres études de cas sur les fumées de soudage et sur des NP différemment chargées ont confirmé la performance de notre test DCFH et ont trouvé que la génération de ROS est liée à certaines caractéristiques, notamment la fonctionnalité de surface des échantillons.

MorphoGraphX: A platform for quantifying morphogenesis in 4D.

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX ( www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software's modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth.

Development of cardiovascular magnetic resonance imaging techniques for improved characterization of atherosclerotic disease

Atherosclerosis is a chronic cardiovascular disease that involves the thicken¬ing of the artery walls as well as the formation of plaques (lesions) causing the narrowing of the lumens, in vessels such as the aorta, the coronary and the carotid arteries. Magnetic resonance imaging (MRI) is a promising modality for the assessment of atherosclerosis, as it is a non-invasive and patient-friendly procedure that does not use ionizing radiation. MRI offers high soft tissue con¬trast already without the need of intravenous contrast media; while modifica¬tion of the MR pulse sequences allows for further adjustment of the contrast for specific diagnostic needs. As such, MRI can create angiographic images of the vessel lumens to assess stenoses at the late stage of the disease, as well as blood flow-suppressed images for the early investigation of the vessel wall and the characterization of the atherosclerotic plaques. However, despite the great technical progress that occurred over the past two decades, MRI is intrinsically a low sensitive technique and some limitations still exist in terms of accuracy and performance. A major challenge for coronary artery imaging is respiratory motion. State- of-the-art diaphragmatic navigators rely on an indirect measure of motion, per¬form a ID correction, and have long and unpredictable scan time. In response, self-navigation (SM) strategies have recently been introduced that offer 100% scan efficiency and increased ease of use. SN detects respiratory motion di¬rectly from the image data obtained at the level of the heart, and retrospectively corrects the same data before final image reconstruction. Thus, SN holds po-tential for multi-dimensional motion compensation. To this regard, this thesis presents novel SN methods that estimate 2D and 3D motion parameters from aliased sub-images that are obtained from the same raw data composing the final image. Combination of all corrected sub-images produces a final image with reduced motion artifacts for the visualization of the coronaries. The first study (section 2.2, 2D Self-Navigation with Compressed Sensing) consists of a method for 2D translational motion compensation. Here, the use of com- pressed sensing (CS) reconstruction is proposed and investigated to support motion detection by reducing aliasing artifacts. In healthy human subjects, CS demonstrated an improvement in motion detection accuracy with simula¬tions on in vivo data, while improved coronary artery visualization was demon¬strated on in vivo free-breathing acquisitions. However, the motion of the heart induced by respiration has been shown to occur in three dimensions and to be more complex than a simple translation. Therefore, the second study (section 2.3,3D Self-Navigation) consists of a method for 3D affine motion correction rather than 2D only. Here, different techniques were adopted to reduce background signal contribution in respiratory motion tracking, as this can be adversely affected by the static tissue that surrounds the heart. The proposed method demonstrated to improve conspicuity and vi¬sualization of coronary arteries in healthy and cardiovascular disease patient cohorts in comparison to a conventional ID SN method. In the third study (section 2.4, 3D Self-Navigation with Compressed Sensing), the same tracking methods were used to obtain sub-images sorted according to the respiratory position. Then, instead of motion correction, a compressed sensing reconstruction was performed on all sorted sub-image data. This process ex¬ploits the consistency of the sorted data to reduce aliasing artifacts such that the sub-image corresponding to the end-expiratory phase can directly be used to visualize the coronaries. In a healthy volunteer cohort, this strategy improved conspicuity and visualization of the coronary arteries when compared to a con¬ventional ID SN method. For the visualization of the vessel wall and atherosclerotic plaques, the state- of-the-art dual inversion recovery (DIR) technique is able to suppress the signal coming from flowing blood and provide positive wall-lumen contrast. How¬ever, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. In response and as a fourth study of this thesis (chapter 3, Vessel Wall MRI of the Carotid Arteries), a phase-sensitive DIR method has been implemented and tested in the carotid arteries of a healthy volunteer cohort. By exploiting the phase information of images acquired after DIR, the proposed phase-sensitive method enhances wall-lumen contrast while widens the window of opportunity for image acquisition. As a result, a 3-fold increase in volumetric coverage is obtained at no extra cost in scanning time, while image quality is improved. In conclusion, this thesis presented novel methods to address some of the main challenges for MRI of atherosclerosis: the suppression of motion and flow artifacts for improved visualization of vessel lumens, walls and plaques. Such methods showed to significantly improve image quality in human healthy sub¬jects, as well as scan efficiency and ease-of-use of MRI. Extensive validation is now warranted in patient populations to ascertain their diagnostic perfor¬mance. Eventually, these methods may bring the use of atherosclerosis MRI closer to the clinical practice. Résumé L'athérosclérose est une maladie cardiovasculaire chronique qui implique le épaississement de la paroi des artères, ainsi que la formation de plaques (lé¬sions) provoquant le rétrécissement des lumières, dans des vaisseaux tels que l'aorte, les coronaires et les artères carotides. L'imagerie par résonance magné¬tique (IRM) est une modalité prometteuse pour l'évaluation de l'athérosclérose, car il s'agit d'une procédure non-invasive et conviviale pour les patients, qui n'utilise pas des rayonnements ionisants. L'IRM offre un contraste des tissus mous très élevé sans avoir besoin de médias de contraste intraveineux, tan¬dis que la modification des séquences d'impulsions de RM permet en outre le réglage du contraste pour des besoins diagnostiques spécifiques. À ce titre, l'IRM peut créer des images angiographiques des lumières des vaisseaux pour évaluer les sténoses à la fin du stade de la maladie, ainsi que des images avec suppression du flux sanguin pour une première enquête des parois des vais¬seaux et une caractérisation des plaques d'athérosclérose. Cependant, malgré les grands progrès techniques qui ont eu lieu au cours des deux dernières dé¬cennies, l'IRM est une technique peu sensible et certaines limitations existent encore en termes de précision et de performance. Un des principaux défis pour l'imagerie de l'artère coronaire est le mou¬vement respiratoire. Les navigateurs diaphragmatiques de pointe comptent sur une mesure indirecte de mouvement, effectuent une correction 1D, et ont un temps d'acquisition long et imprévisible. En réponse, les stratégies d'auto- navigation (self-navigation: SN) ont été introduites récemment et offrent 100% d'efficacité d'acquisition et une meilleure facilité d'utilisation. Les SN détectent le mouvement respiratoire directement à partir des données brutes de l'image obtenue au niveau du coeur, et rétrospectivement corrigent ces mêmes données avant la reconstruction finale de l'image. Ainsi, les SN détiennent un poten¬tiel pour une compensation multidimensionnelle du mouvement. A cet égard, cette thèse présente de nouvelles méthodes SN qui estiment les paramètres de mouvement 2D et 3D à partir de sous-images qui sont obtenues à partir des mêmes données brutes qui composent l'image finale. La combinaison de toutes les sous-images corrigées produit une image finale pour la visualisation des coronaires ou les artefacts du mouvement sont réduits. La première étude (section 2.2,2D Self-Navigation with Compressed Sensing) traite d'une méthode pour une compensation 2D de mouvement de translation. Ici, on étudie l'utilisation de la reconstruction d'acquisition comprimée (compressed sensing: CS) pour soutenir la détection de mouvement en réduisant les artefacts de sous-échantillonnage. Chez des sujets humains sains, CS a démontré une amélioration de la précision de la détection de mouvement avec des simula¬tions sur des données in vivo, tandis que la visualisation de l'artère coronaire sur des acquisitions de respiration libre in vivo a aussi été améliorée. Pourtant, le mouvement du coeur induite par la respiration se produit en trois dimensions et il est plus complexe qu'un simple déplacement. Par conséquent, la deuxième étude (section 2.3, 3D Self-Navigation) traite d'une méthode de cor¬rection du mouvement 3D plutôt que 2D uniquement. Ici, différentes tech¬niques ont été adoptées pour réduire la contribution du signal du fond dans le suivi de mouvement respiratoire, qui peut être influencé négativement par le tissu statique qui entoure le coeur. La méthode proposée a démontré une amélioration, par rapport à la procédure classique SN de correction 1D, de la visualisation des artères coronaires dans le groupe de sujets sains et des pa¬tients avec maladies cardio-vasculaires. Dans la troisième étude (section 2.4,3D Self-Navigation with Compressed Sensing), les mêmes méthodes de suivi ont été utilisées pour obtenir des sous-images triées selon la position respiratoire. Au lieu de la correction du mouvement, une reconstruction de CS a été réalisée sur toutes les sous-images triées. Cette procédure exploite la cohérence des données pour réduire les artefacts de sous- échantillonnage de telle sorte que la sous-image correspondant à la phase de fin d'expiration peut directement être utilisée pour visualiser les coronaires. Dans un échantillon de volontaires en bonne santé, cette stratégie a amélioré la netteté et la visualisation des artères coronaires par rapport à une méthode classique SN ID. Pour la visualisation des parois des vaisseaux et de plaques d'athérosclérose, la technique de pointe avec double récupération d'inversion (DIR) est capa¬ble de supprimer le signal provenant du sang et de fournir un contraste posi¬tif entre la paroi et la lumière. Pourtant, il est difficile d'obtenir un contraste optimal car cela est soumis à la variabilité du rythme cardiaque. Par ailleurs, l'imagerie DIR est inefficace du point de vue du temps et les acquisitions "mul- tislice" peuvent conduire à des temps de scan prolongés. En réponse à ce prob¬lème et comme quatrième étude de cette thèse (chapitre 3, Vessel Wall MRI of the Carotid Arteries), une méthode de DIR phase-sensitive a été implémenté et testé

Cardiovascular magnetic resonance imaging techniques for motion-suppressed multi-dimensional coronary artery imaging with high spatial and temporal resolution

L'imagerie par résonance magnétique (IRM) peut fournir aux cardiologues des informations diagnostiques importantes sur l'état de la maladie de l'artère coronarienne dans les patients. Le défi majeur pour l'IRM cardiaque est de gérer toutes les sources de mouvement qui peuvent affecter la qualité des images en réduisant l'information diagnostique. Cette thèse a donc comme but de développer des nouvelles techniques d'acquisitions des images IRM, en changeant les techniques de compensation du mouvement, pour en augmenter l'efficacité, la flexibilité, la robustesse et pour obtenir plus d'information sur le tissu et plus d'information temporelle. Les techniques proposées favorisent donc l'avancement de l'imagerie des coronaires dans une direction plus maniable et multi-usage qui peut facilement être transférée dans l'environnement clinique. La première partie de la thèse s'est concentrée sur l'étude du mouvement des artères coronariennes sur des patients en utilisant la techniques d'imagerie standard (rayons x), pour mesurer la précision avec laquelle les artères coronariennes retournent dans la même position battement après battement (repositionnement des coronaires). Nous avons découvert qu'il y a des intervalles dans le cycle cardiaque, tôt dans la systole et à moitié de la diastole, où le repositionnement des coronaires est au minimum. En réponse nous avons développé une nouvelle séquence d'acquisition (T2-post) capable d'acquérir les données aussi tôt dans la systole. Cette séquence a été testée sur des volontaires sains et on a pu constater que la qualité de visualisation des artère coronariennes est égale à celle obtenue avec les techniques standard. De plus, le rapport signal sur bruit fourni par la séquence d'acquisition proposée est supérieur à celui obtenu avec les techniques d'imagerie standard. La deuxième partie de la thèse a exploré un paradigme d'acquisition des images cardiaques complètement nouveau pour l'imagerie du coeur entier. La technique proposée dans ce travail acquiert les données sans arrêt (free-running) au lieu d'être synchronisée avec le mouvement cardiaque. De cette façon, l'efficacité de la séquence d'acquisition est augmentée de manière significative et les images produites représentent le coeur entier dans toutes les phases cardiaques (quatre dimensions, 4D). Par ailleurs, l'auto-navigation de la respiration permet d'effectuer cette acquisition en respiration libre. Cette technologie rend possible de visualiser et évaluer l'anatomie du coeur et de ses vaisseaux ainsi que la fonction cardiaque en quatre dimensions et avec une très haute résolution spatiale et temporelle, sans la nécessité d'injecter un moyen de contraste. Le pas essentiel qui a permis le développement de cette technique est l'utilisation d'une trajectoire d'acquisition radiale 3D basée sur l'angle d'or. Avec cette trajectoire, il est possible d'acquérir continûment les données d'espace k, puis de réordonner les données et choisir les paramètres temporel des images 4D a posteriori. L'acquisition 4D a été aussi couplée avec un algorithme de reconstructions itératif (compressed sensing) qui permet d'augmenter la résolution temporelle tout en augmentant la qualité des images. Grâce aux images 4D, il est possible maintenant de visualiser les artères coronariennes entières dans chaque phase du cycle cardiaque et, avec les mêmes données, de visualiser et mesurer la fonction cardiaque. La qualité des artères coronariennes dans les images 4D est la même que dans les images obtenues avec une acquisition 3D standard, acquise en diastole Par ailleurs, les valeurs de fonction cardiaque mesurées au moyen des images 4D concorde avec les valeurs obtenues avec les images 2D standard. Finalement, dans la dernière partie de la thèse une technique d'acquisition a temps d'écho ultra-court (UTE) a été développée pour la visualisation in vivo des calcifications des artères coronariennes. Des études récentes ont démontré que les acquisitions UTE permettent de visualiser les calcifications dans des plaques athérosclérotiques ex vivo. Cepandent le mouvement du coeur a entravé jusqu'à maintenant l'utilisation des techniques UTE in vivo. Pour résoudre ce problème nous avons développé une séquence d'acquisition UTE avec trajectoire radiale 3D et l'avons testée sur des volontaires. La technique proposée utilise une auto-navigation 3D pour corriger le mouvement respiratoire et est synchronisée avec l'ECG. Trois échos sont acquis pour extraire le signal de la calcification avec des composants au T2 très court tout en permettant de séparer le signal de la graisse depuis le signal de l'eau. Les résultats sont encore préliminaires mais on peut affirmer que la technique développé peut potentiellement montrer les calcifications des artères coronariennes in vivo. En conclusion, ce travail de thèse présente trois nouvelles techniques pour l'IRM du coeur entier capables d'améliorer la visualisation et la caractérisation de la maladie athérosclérotique des coronaires. Ces techniques fournissent des informations anatomiques et fonctionnelles en quatre dimensions et des informations sur la composition du tissu auparavant indisponibles. CORONARY artery magnetic resonance imaging (MRI) has the potential to provide the cardiologist with relevant diagnostic information relative to coronary artery disease of patients. The major challenge of cardiac MRI, though, is dealing with all sources of motions that can corrupt the images affecting the diagnostic information provided. The current thesis, thus, focused on the development of new MRI techniques that change the standard approach to cardiac motion compensation in order to increase the efficiency of cardioavscular MRI, to provide more flexibility and robustness, new temporal information and new tissue information. The proposed approaches help in advancing coronary magnetic resonance angiography (MRA) in the direction of an easy-to-use and multipurpose tool that can be translated to the clinical environment. The first part of the thesis focused on the study of coronary artery motion through gold standard imaging techniques (x-ray angiography) in patients, in order to measure the precision with which the coronary arteries assume the same position beat after beat (coronary artery repositioning). We learned that intervals with minimal coronary artery repositioning occur in peak systole and in mid diastole and we responded with a new pulse sequence (T2~post) that is able to provide peak-systolic imaging. Such a sequence was tested in healthy volunteers and, from the image quality comparison, we learned that the proposed approach provides coronary artery visualization and contrast-to-noise ratio (CNR) comparable with the standard acquisition approach, but with increased signal-to-noise ratio (SNR). The second part of the thesis explored a completely new paradigm for whole- heart cardiovascular MRI. The proposed techniques acquires the data continuously (free-running), instead of being triggered, thus increasing the efficiency of the acquisition and providing four dimensional images of the whole heart, while respiratory self navigation allows for the scan to be performed in free breathing. This enabling technology allows for anatomical and functional evaluation in four dimensions, with high spatial and temporal resolution and without the need for contrast agent injection. The enabling step is the use of a golden-angle based 3D radial trajectory, which allows for a continuous sampling of the k-space and a retrospective selection of the timing parameters of the reconstructed dataset. The free-running 4D acquisition was then combined with a compressed sensing reconstruction algorithm that further increases the temporal resolution of the 4D dataset, while at the same time increasing the overall image quality by removing undersampling artifacts. The obtained 4D images provide visualization of the whole coronary artery tree in each phases of the cardiac cycle and, at the same time, allow for the assessment of the cardiac function with a single free- breathing scan. The quality of the coronary arteries provided by the frames of the free-running 4D acquisition is in line with the one obtained with the standard ECG-triggered one, and the cardiac function evaluation matched the one measured with gold-standard stack of 2D cine approaches. Finally, the last part of the thesis focused on the development of ultrashort echo time (UTE) acquisition scheme for in vivo detection of calcification in the coronary arteries. Recent studies showed that UTE imaging allows for the coronary artery plaque calcification ex vivo, since it is able to detect the short T2 components of the calcification. The heart motion, though, prevented this technique from being applied in vivo. An ECG-triggered self-navigated 3D radial triple- echo UTE acquisition has then been developed and tested in healthy volunteers. The proposed sequence combines a 3D self-navigation approach with a 3D radial UTE acquisition enabling data collection during free breathing. Three echoes are simultaneously acquired to extract the short T2 components of the calcification while a water and fat separation technique allows for proper visualization of the coronary arteries. Even though the results are still preliminary, the proposed sequence showed great potential for the in vivo visualization of coronary artery calcification. In conclusion, the thesis presents three novel MRI approaches aimed at improved characterization and assessment of atherosclerotic coronary artery disease. These approaches provide new anatomical and functional information in four dimensions, and support tissue characterization for coronary artery plaques.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Combined T2 -preparation and two-dimensional pencil-beam inner volume selection.

PURPOSE: To improve coronary magnetic resonance angiography (MRA) by combining a two-dimensional (2D) spatially selective radiofrequency (RF) pulse with a T2 -preparation module ("2D-T2 -Prep"). METHODS: An adiabatic T2 -Prep was modified so that the first and last pulses were of differing spatial selectivity. The first RF pulse was replaced by a 2D pulse, such that a pencil-beam volume is excited. The last RF pulse remains nonselective, thus restoring the T2 -prepared pencil-beam, while tipping the (formerly longitudinal) magnetization outside of the pencil-beam into the transverse plane, where it is then spoiled. Thus, only a cylinder of T2 -prepared tissue remains for imaging. Numerical simulations were followed by phantom validation and in vivo coronary MRA, where the technique was quantitatively evaluated. Reduced field-of-view (rFoV) images were similarly studied. RESULTS: In vivo, full field-of-view 2D-T2 -Prep significantly improved vessel sharpness as compared to conventional T2 -Prep, without adversely affecting signal-to-noise (SNR) or contrast-to-noise ratios (CNR). It also reduced respiratory motion artifacts. In rFoV images, the SNR, CNR, and vessel sharpness decreased, although scan time reduction was 60%. CONCLUSION: When compared with conventional T2 -Prep, the 2D-T2 -Prep improves vessel sharpness and decreases respiratory ghosting while preserving both SNR and CNR. It may also acquire rFoV images for accelerated data acquisition.

Clinical Use of EEG in the ICU: Technical Setting.

Neurophysiology is an essential tool for clinicians dealing with patients in the intensive care unit. Because of consciousness disorders, clinical examination is frequently limited. In this setting, neurophysiological examination provides valuable information about seizure detection, treatment guidance, and neurological outcome. However, to acquire reliable signals, some technical precautions need to be known. EEG is prone to artifacts, and the intensive care unit environment is rich in artifact sources (electrical devices including mechanical ventilation, dialysis, and sedative medications, and frequent noise, etc.). This review will discuss and summarize the current technical guidelines for EEG acquisition and also some practical pitfalls specific for the intensive care unit.

Prospective motion correction with FID-triggered image navigators

In this work, we propose a method for prospective motion correction in MRI using a novel image navigator module, which is triggered by a free induction decay (FID) navigator. Only when motion occurs, the image navigator is run and new positional information is obtained through image registration. The image navigator was specifically designed to match the impact on the magnetization and the acoustic noise of the host sequence. This detection-correction scheme was implemented for an MP-RAGE sequence and 5 healthy volunteers were scanned at 3T while performing various head movements. The correction performance was demonstrated through automated brain segmentation and an image quality index whose results are sensitive to motion artifacts.