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Helbert, Alexandre. "L'imagerie moléculaire de contraste ultrasonore en oncologie : Utilisation des microbulles BR55 ciblant le VEGFR2 dans la détection de l’angiogenèse tumorale, le guidage thérapeutique et l'évaluation de l'efficacité de traitements antiangiogéniques et cytotoxiques". Electronic Thesis or Diss., Lyon, 2022. http://www.theses.fr/2022LYSE1076.
Pełny tekst źródłaUltrasound contrast imaging has grown considerably in recent decades. Several intravascular ultrasound contrast agents, encapsulated gas microbubbles, have been marketed for applications such as cardiovascular imaging and radiology. Following the demonstration of their effectiveness, further research was conducted. A new generation of microbubbles has been developed : targeted microbubbles. Their particularity is to contain, on their shell, a ligand that can bind to specific vascular markers of a pathology such as markers of tumor angiogenesis. To date, only one molecular ultrasound contrast agent, the so-called BR55, has been tested in humans for the detection of tumors of the prostate, breast and ovary. The objective of this work was to explore the possibilities of BR55, beyond diagnosis. The experimental work was performed on rodent models. In the first part of this work, it was necessary to master the use of ultrasound molecular contrast imaging in order to guarantee the robustness of the experiments performed and of the results obtained. BR55 has the particularity of being able to bind to a receptor, VEGFR2, overexpressed in the process of tumor angiogenesis. The BR55 microbubbles attached to this receptor allow visualization of the lesion by contrast imaging. The second part of this work was to follow the evolution of VEGFR2 expression during an antiangiogenic treatment targeting this receptor. We were able to demonstrate the precocity with which the monitoring of VEGFR2 expression by BR55 can objectify the tumor response to treatment. Finally, we used BR55 microbubbles to guide a focused ultrasound therapy to target the localization of doxorubicin release from sonosensitive liposomes. Not only was it possible to perform the treatment guidance by ultrasound molecular contrast imaging, but again the use of BR55 allowed to follow the response to the treatment. The results presented in this thesis pave the way for potential new uses of BR55 for therapeutic monitoring and guidance of treatments by ultrasound molecular contrast imaging
Novell, Anthony. "Imagerie de contraste ultrasonore avec transducteurs capacitifs micro-usinés". Phd thesis, Tours, 2011. http://tel.archives-ouvertes.fr/tel-00665141.
Pełny tekst źródłaBouakaz, Ayache. "Produits de contraste ultrasonore : évaluation acoustique in vitro et application". Lyon, INSA, 1996. http://www.theses.fr/1996ISAL0058.
Pełny tekst źródłaIt's usually more difficult for a radiologist to interpret ultrasonic images than other records issued from other imaging modalities. Indeed, the ultrasonic record has no familiar landmarks for the uninitiated observer. As for other imaging techniques, the use of contrast agents could be considered. Typically, contrast ultrasound involves the injection of echo-producing microbubbles into the bloodstream to enhance the ultrasound echogenicity of a certain structure in the body. In the first part of this study, we proposed a theoretical approach for acoustic characterization of ultrasound contrast agents. Simultaneously, an experimental procedure was developed to quantify the ultrasonic properties of contrast agents in vitro. This was carried out by determining their acoustic parameters. The backscatter coefficient (BC), attenuation coefficient and scattering to attenuation ratio (STAR) were defined to quantify the ultrasonic effectiveness of the contrast agent. The experimental conditions correspond to the clinical reality. The experimental determination of ultrasonic properties is important for an appropriate use of the contrast agent. Afterwards, a method is presented and used to determine the acoustic contribution of a contrast agent to the image enhancement. Optimal values of the acoustic properties necessary to get a visible enhancement of the image are deduced. At last, we propose a newer clinical application using contrast agent. This has been done in intravascular echography and the contrast has been proved useful for this application
Mulé, Sébastien. "Méthodologie pour l’évaluation de la microcirculation en imagerie ultrasonore de contraste". Paris 11, 2008. http://www.theses.fr/2008PA112033.
Pełny tekst źródłaContrast-enhanced ultrasound (CEUS) imaging is a modality of growing interest in human and small animal studies for the estimation of microcirculation parameters. Nevertheless, estimated microcirculation parameters are still impaired by several artefacts: the contrast agent concentration, microbubble attenuation and motion that is present in the acquisitions. The aim of this work is to propose a methodology for assessing microcirculation in small animal CEUS studies by investigating original methods to correct for these artefacts. An a posteriori frame selection method has been proposed. This method, based on a Principal Component Analysis and that integrates a priori information about the respiratory frequency, allows the selection of the frames acquired at the same respiratory phase. A method for estimating microbubble attenuation in vivo has also been developed. This method provides a dynamic microbubble-specific sequence without shadowing artefacts and therefore more reliable than available from original sequences. These methods, which have been implemented in a user friendly software, have been applied and validated in renal perfusion studies in a murine and a porcine model. Especially, their interest in assessing tumor microcirculation and the efficacy of an antiangiogenic treatment has been highlighted
Le, Marrec Loïc. "Investigation ultrasonore, qualitative et quantitative, d'objets à fort contraste". Aix-Marseille 2, 2004. http://theses.univ-amu.fr.lama.univ-amu.fr/2004AIX22103.pdf.
Pełny tekst źródłaBerti, Romain. "Caractérisation d'agents de contraste ultrasonore pour l'imagerie et la thérapie". Paris 6, 2010. http://www.theses.fr/2010PA066711.
Pełny tekst źródłaDurning, Bruno. "Simulation, estimation spectrale et imagerie des agents de contraste ultrasonores". Lyon 1, 2006. http://www.theses.fr/2006LYO10097.
Pełny tekst źródłaIn this work, we contribute to make ultrasound contrast agent simpler and more effective to use. First we developed a Simulator of Echo Contrast Imaging (SECI). SECI can simulate ultrasound imaging with contrast agent. It takes into account the probe, the propagating medium, the individual, non linear, response of each bubble. Simulations of bubbles alone, have also been performed, at different MI, transmit frequency, and radius. Then, we validate SECI by comparison with in-vitro experiments. An experimental study of the influence of the MI over the contrast agent behavior has been done. Finally, visualization techniques, based on spectral estimation, auto-regressive modelization, and atomical projection have been tested on in-vitro and in-vivo acquisition
Aired-Selmani, Leila. "Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés". Thesis, Tours, 2013. http://www.theses.fr/2013TOUR3301/document.
Pełny tekst źródłaSince they were introducted, contrast agents have revolutionized the ultrasound imaging. They are composed of tiny gaseous microbubbles and when injected intravenously into the blood, they improve the ultrasound image. Targeted imaging is another application based on the physical characteristics of contrast agents. This approach is based on the ligands incorporation into the microbubbles shell. The microbubble attach to the molecular factors overexpressed by endothelial cells, covering the inner wall of blood vessels. To distinguish these microbubbles from those freely circulating, attached microbubble have to produce an acoustic signal that is sufficiently strong. However, the low microbubbles adhesion induces a decrease of the acoustic signal. To make it possible, it is important to determine the effect of the elastic wall on their acoustic response. This thesis aimed to study the effect of elastic walls on the ultrasonic behavior of targeted microbubbles. First, a theoretical model describing a wall with finite thickness was developed. It has been shown that the scattered echo amplitude by a microbubble near a wall with finite thickness is small in comparison to the echo from a microbubble located in an infinite fluid. Furthermore, and in order to account for the effect of blood vessel wall, the mechanical properties of the wall have been incorporated into the model. The results showed that the resonane frequency of a microbubble near the wall is higher than the resonanace of the same microbubble in an infinite medium. Subsequently, we studied the effect of three types of walls on the microbubble behavior including the wall of OptiCell chamber which is commonly used in ultrasonic experiments. We have shown that microbubbles near the OptiCell wall diffuses a higher echo than those far from the wall when the excitation frequency is above the microbubble resonance frequency. On the other side, we observed that small microbubbles to the presence of the wall. Afterward, we developed a model describing a microbubble attached to the wall. We have shown that the microbubble in direct contact with the wall induces a decrease of the echo amplitude compared to the same bubble in infinite liquid. Moreover, the direct contact of the bubble with the wall generates an increase of the resonance frequency relative to a bubble without direct contact. Finally, an experimental study has shown the advantage of the subharmonic imaging to differentiate attached microbubbles from the free ones
Gerfault, Laurent. "Imagerie des produits de contraste ultrasonore : simulation et approche de la perfusion myocardique". Lyon, INSA, 2000. http://www.theses.fr/2000ISAL0041.
Pełny tekst źródłaLike other imaging modalities (MRI or X-Ray), ultrasound scanning has become a contrast imaging modality. It consists in the enhancement of standard ultrasound imaging using an intra-veinously injected ultrasound contrast agent (USCA). Video intensity and Doppler signals of perfused region, reached by the contrast agent, are enhanced. Then, contrast imaging allows a better visualization of perfusion of different organs, and the approach of functional imaging like myocardial perfusion study. In vitro efficiency of USCA has been demonstrated, but its in vivo use has shown a decrease of efficiency. This work studies the interactions between contrast agent and intra-corporal medium, and the influence of measurement method in the aims of understanding this lack of efficiency. The influences of intra-corporal medium actions (pulmonary filtering, dilution of USCA bolus, diffusion of internal gas of USCA micro particles cardiac pressure) and ultrasound waves are inspected to evaluate physical modifications of USCA in in-vivo conditions. The impact of these physical changes on acoustical responses of USCA is then studied. As clinical evaluation is performed on echographic images, simulations of echographic signals are computed. Finally, the feasibility of absolute measurement of blood flow rate is evaluated. A comparison between a newly developed fluid dynamics based model of bolus dilution and acoustical measurements made on a circulating tubular phantom is made. Our conclusions are applied to the study of myocardial perfusion using an isolated pig heart model
Pauzin, Marie-Christine. "Modélisation du comportement dynamique d'un agent de contraste ultrasonore". Phd thesis, Université de Provence - Aix-Marseille I, 2009. http://tel.archives-ouvertes.fr/tel-00430076.
Pełny tekst źródłaHoeffel, Christine. "Echographie de contraste et microcirculation tissulaire abdominale. Aspects fondamentaux et applications cliniques". Reims, 2009. http://theses.univ-reims.fr/exl-doc/GED00001104.pdf.
Pełny tekst źródłaThe aim of this work was to study the potential for contrast-enhanced functional ultrasound imaging (Cefui) to assess the abdominal microcirculation, according to three major axes of research: 1) The first axis consisted in proposing and validating a new method improving non invasive contrast-enhanced renal blood flow measurements, using the mean signal intensity in a feeding artery in order to normalize contrast-enhanced renal blood flow estimation. However, while these ex vivo results suggest that this technique has great potentials, other parameters, mainly ultrasound beam attenuation, must be taken into account to obtain reproducible measurements. 2) The second axis consisted in evaluating qualitative abdominal Cefui for tumoral detection. For the detection of liver metastases from carcinoid tumor, the first study reports sensitivity values for contrast-enhanced ultrasound similar to those obtained with enhanced computed tomography. The second study demonstrates that Cefui provides high specificity and predictive values for the early detection of residual tumor after radiofrequency ablation of renal tumors even though its sensitivity remains lower than that of contrast-enhanced CT. 3) The third axis deals with added diagnostic value in terms of characterization of renal tumors of quantitative assessment of tumor perfusion compared to that of qualitative analysis. Abdominal Cefui has unique advantages including low cost, availability, absence of renal toxicity and radiation, and excellent temporal resolution. However, it still requires improvements and standardization to be reproducible and be transferred to the clinical setting. It may somehow yield quantitative information with respect to abdominal organs microcirculation. Further studies correlating Cefui results with those of other functional imaging methods are needed
Kanbar, Emma. "Génération et optimisation du signal sous-harmonique des agents de constraste ultrasonore". Thesis, Tours, 2017. http://www.theses.fr/2017TOUR3311/document.
Pełny tekst źródłaNo summary available
Lebel, Réjean. "Imagerie moléculaire de la MMP-2". Thèse, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6644.
Pełny tekst źródłaKissi, Adelaïde. "Equations aux dérivées partielles et classification non exclusive pour l'analyse d'images échographiques de contraste". Tours, 2006. http://www.theses.fr/2006TOUR3306.
Pełny tekst źródłaColorectal carcinoma is a prevalent disease in Europe and United States. Despite of progress in detection, the prognosis of survival is weak : over 50% of patients will survive for five years, with the majority dying within the first two years. More than 30 % of carcinoma spread in liver, from overt micro metastasis, due to specific drainage of blood or to specific liver cells. The particular vascularization of liver by two different systems ( hepatic artery and portal vein) implies some changes in the balance between these two systems during the development of tumour. It is often accepted that for small liver lesions ( below 1 mm), blood supply is provided by portal vein. But, with the growing up of these tumours, an arterial supply is required entailing increase in arterial blood flow. It is therefore essential to depict these blood flow changes to detect and characterize lesions by imaging this specific vascularization. An early detection and a precise quantification of their vascularization would improve the diagnosis. Various methods could be used for this application. One of them is the Doppler sonography that allows the depiction of vascularity but is limited by its lack of sensibility and specifity. The nonlinear imaging, a contrast specific imaging technique, overcomes theses limitations, by the use of ultrasound contrast agents (microbubbles), improving tumours detection and characterization. As they are strictly intravascular, a perfect image of micro as macro vascularization can be made providing a quantitative study of perfusion. Thus, the purpose of my thesis was to quantify the liver arterial perfusion from the analysis of the image enhancement, in power Doppler mode, after an injection of ultrasound contrast agents. The perfusion has been estimated, in a regional basis (often the lesion), to extract physiological parameters in this area with two methods: a fully-automated tracking of lesion in image sequences via a segmentation based on a modification of the well known fuzzy competitive agglomerative clustering coupled with an anisotropic diffusion and a region of interest repositioning with optical flow estimation from structure tensor field. The method has been tested on varied lesions (metastasis, adenoma, focal nodular hyperplasia) and the results show that the assessment of lesion vascularization from our segmentation process can potentially be used for the diagnostic of liver carcinoma
Lucidarme, Olivier. "Quantification non invasive de la microcirculation par imagerie ultrasonore fonctionnelle de contraste avec les techniques de destruction reperfusion". Paris 12, 2003. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002118320204611&vid=upec.
Pełny tekst źródłaOur aim was to study the potential for quantitative contrast enhanced functional ultrasound imaging (fUSI) to assess microcirculation. We described in vitro and in vivo the "entrance in the section phenomenon" that introduces a distortion of the refilling curves when the vessels that feed the region or interest have previouslv traveled across the ultrasound tield. We validated in vitro a b model based on the destruction phase of microhuhbles during ultrasound emission. This model allows the estimation of quantitative flow data during acquisitions of only 1 or 2 seconds. We finally studied a non tumor angiogenesis model in 36 mice. Ultrasound measurement (during the destruction phase) ot' the Uractional blood volume in a gel impregnated with growth exhihited a higher correlation vith the fractional vascularized area of gel than with the microvascular density. Microbubble velocity assessed on fUSI did not change as mi crocirculation increased
Lucidarme, Olivier Berger Geneviève. "Quantification non invasive de la microcirculation par imagerie ultrasonore fonctionnelle de contraste avec les techniques de destruction reperfusion". Créteil : Université de Paris-Val-de-Marne, 2003. http://doxa.scd.univ-paris12.fr:80/theses/th0211832.pdf.
Pełny tekst źródłaRobert, Philippe. "Adaptation des stratégies d'utilisation des agents de contraste en IRM : exemples pour la caractérisation morphologique, structurelle ou cellulaire des tissus avec des chélates de gadolinium". Paris 11, 2004. http://www.theses.fr/2004PA112245.
Pełny tekst źródłaThe MRI is a noninvasive and new technology which gives very numerous diagnostic information. It was initially used for anatomical investigations of organs but has now extended its application field to structural and functional imaging of tissues. The introduction of MR contrast agents has participated in this extension of the MRI indications by giving the images a strong and dynamic exogen contrast. This increased signal can be devoted to enhance the distinction between two different macroscopic structures (morphological imaging), to give information on the tissue functionality (structural and functional imaging) or to vizualize a microscopic phenomenon at the cellular or molecular scale (cellular and molecular imaging). We chose examples of applications in each of these three types of examinations by analysing the specific cases of (1) MR angiography, (2) tumoral imaging and (3) specific imaging of a cell carrier overexpressed in some tumors. We studied the key issues of imaging protocols in each case by comparing three different gadolinium chelates (small non specific macromolecule and functionalised chelates). We proposed a new approach in the use of contrast media such as the administration protocol (dosage, injection rate, volume), the delay between the injection and the imaging or the MRI sequence (k-space acquisition strategy, spatial resolution)
Boyer, Laure. "Imagerie multiparamétrique en échographie de contraste ultrasonore (DCE-US) pour caractériser la vascularisation tumorale : de la modélisation numérique à l'expérimentation préclinique". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS161.
Pełny tekst źródłaEvaluation of tumor vascularization by dynamic contrast-enhanced ultrasonography showed interest for the assessment of the effectiveness of anti-angiogenic treatments. Nevertheless, this technique raises many questions about the sensitivity of quantification methods of the ultrasound signal. To address this issue, this thesis focused on the development of the first digital modeling of blood flow and contrast agents in vascular networks to study the methods of quantification of the ultrasound signal and theirs sensitivity according to variations of tumor network volume and blood velocity. A first step of the thesis was to validate by an experimental comparison, the assumptions of the digital modeling and mainly the taking into account of the blood as a homogeneous Newtonian fluid. Digital modeling allowed to highlight parameters sensitive to the modification of the blood flow which are in the case of the semi-quantitative method the area under the enhancement curve, the maximum of the enhancement curve and the slope of the enhancement curve. When it comes to follow variations of the tumor vascular volume, it appears that the quantitative method by deconvolution of the arterial function is more sensitive. The quantification methods have also been investigated throught an in vivo study of 44 mice. This digital approach of the flow of the contrast agents is promising and may eventually enable a more extensive evaluation of other quantification methods developed in dynamic contrast-enhanced ultrasonography to date
Guez, Alexandre. "Contribution à la conception, synthèse et évaluation d'agents de contraste pour l'imagerie des plaques d'athérome". Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066570.
Pełny tekst źródłaMolecular imaging is a new domain of biomedical research which can be defined as the non-invasive observation of a biological process within the living body. This technique requires the use of a contrast agent, a molecule composed of a vector targeting a biomolecule specifically expressed during the studied biological process, and a contrastophore allowing the acquisition of the signal. The aim of this work is to develop a contrast agent to diagnose the presence of atheromatous plaques. Indeed, atherosclerosis is an inflammatory chronic disease, characterized by the accumulation of cholesterol, in the form of plaques called "atheroma", in the wall of the average and broad arteries. The major complications of atherosclerosis arise when these plaques block the blood flow, locally or after they break free and are released in the artery. These phenomena of thrombosis are at the origin of myocardial and cerebral infarctions, first causes of death in all developed countries. We chose the peptide as tool of vectorisation, and my work consisted of studying and characterizing the interaction of these peptides to three different biomarkers of atherosclerosis. Secondly, I used various tools developed in our lab to conduct a pharmacomodulation campaign based on these compounds, in order to improve their physicochemical properties. We also achieved the synthesis of the tracer Ga-P04087 who answers all the criteria of the specifications and who is now in preclinical phase
Richard, Sophie. "Elaboration de nanoplateformes bimodales pour l’imagerie moléculaire des cancers". Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCD099.
Pełny tekst źródłaEarly diagnosis of cancer and development of personalized medicine is a major challenge. These issues require the development of new tools which are able to target relevant biomarkers in order to access of diagnostic using imaging techniques. The objective of this work is to develop new contrast agents for molecular imaging of cancers. To this aim, the functionalized iron oxide nanoplateformes with caffeic acid were synthesized and coupled to an antibody labeled with a fluorophore. These nanoplateformes were characterized by different techniques and evaluated on in vitro and in vivo conditions. An improvement was made with the use of PEG chains and a novel antibody. Results of this work is the obtention of a T₂ MRI contrast agents targeting endothelin receptor. Using a new wayof synthesis, different sizes of iron oxide nanoparticles have been developed and coupled to apeptide for targeting the neoangiogenesis : the cycloRGD. These nanoparticles have proven to be excellent T₂ MRI contrast agents managing a passive targeting. Persistent luminescence nanoparticles were also synthesized. These 6 nm nanoparticles offer the advantage of limiting the absorption of luminescence by the tissues and prevent the excitation in situ, limiting the autofluorescence of the tissues. Finally, the combination of these two types of nanoparticles has been studied to obtain bimodal nanoparticles combining MRI and persistent luminescence imaging
Dizeux, Alexandre. "Caractérisation ultrasonore de l'angiogenèse, de l'élasticité et de la microstructure tumorale sous l'effet de thérapies conventionnelles et innovantes". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066113/document.
Pełny tekst źródłaTumor development is complex process made possible thanks to the microenvironment surrounding tumor cell. Modifications induced by tumor cells on their environment enable their own development by remodeling tissues sustaining them and by creating a new vascular network (angiogenesis). The use of several antiangiogenic therapies, inhibiting the sprout of a new vascular network, has been authorized in clinic. These therapies induce strong modifications in tumors at the functional level and following tumor size changes are is not sufficient to fully characterize tumor modifications. The main goal of this thesis was to use different ultrasound-based imaging modalities in order to assess their sensitivity to modifications induced in murine tumor model (colorectal and lung carcinomas) during different type of therapy (chemical: cytotoxic, antiangiogenic / physical: cold plasma, sonosensitization). Modifications of the spatial distribution of microvessels and their functionality were characterized using contrast-enhanced ultrasound (CEUS), alteration of tumor microstructure was assessed using spectral analysis of radiofrequency signal, known as quantitative ultrasound (QUS) and finally variations of mechanical properties in tumor tissues were measured in shear wave elastography (SWE). In order to better understand the origin of the modifications observed in vivo, standard parameters such as level of fibrosis and necrosis were characterize ex vivo in tumor tissue using immunochemistry as gold standard
Hingot, Vincent. "Development of ultrasound localization microscopy to measure cerebral perfusion during stroke : a study in mouse models prior to its translation in humans". Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS562.
Pełny tekst źródłaUltrasonography is a medical imaging technique that uses ultrasound. A typical examination is based on two main modes, B-mode for anatomical imaging and Doppler mode for blood flowimaging. In the context of cerebrovascular diseases, ultrasonography is used primarily to estimate alterations in blood flow in major cerebral arteries through transcranial Doppler. However, the low quality of the images through the skull does not allow ultrasound to be as efficient as magnetic resonance imaging. Recent advances in ultrasound have led to the emergence of new modes of imaging, particularly a super-resolution ultrasound technique that increases the resolution and contrast of vascular imaging. It is based on the rapid imaging of microbubbles commonly used as contrast agents for ultrasound. This method has shown that it can image even the smallest vessels and allows to perform cerebral perfusion imaging more effectively than Transcranial Doppler. This would allow earlier and more effective management of stroke patients. Before being used in a medical context, this ultrasound super-resolution technique must be better understood, better realized, and adapted to the particular context of cerebrovascular diseases. In particular, this manuscript will discuss how to best form images, and will look at the actual performance of super-resolved imaging. We will also discuss the possibilities of correcting artefacts due to physiological movements and the possibilities of using super-resolved imaging in various organs, particularly the kidneys, tumors and spinal cord. Finally, imaging of models of cerebral ischemia in rodents will enable the construction of vascular biomarkers suitable for the diagnosis of cerebrovascular pathologies and should aid translation into human patients
Girard, Olivier Maciej. "Apport d’antennes miniatures en matériau supraconducteur en Imagerie par Résonance Magnétique du ciblage moléculaire et cellulaire chez le petit animal". Paris 11, 2008. http://www.theses.fr/2008PA112037.
Pełny tekst źródłaMagnetic Resonance Imaging (MRI) on small animal models is increasingly needed in biomedical research to develop new diagnostic means. However this technique suffers from a lack of specificity which is still to be improved to detect early degenerative diseases such as cancer. Molecular imaging using targeted Contrast Agents (CA) is a promising tool to reach this goal. We present hereby a cross-disciplinary work with this purpose. A first issue of this work deals with contrast physical principles involved in MRI. A theoretical study allows evidencing the presence of an optimal field strength (~1-1. 5 T) for paramagnetic targeted CA detection. This is validated experimentally. Highly sensitive detection coils made of superconductive material are presented and fully implemented in a clinical 1. 5 T MRI system. An original characterization method of such coils is developed to manage their performances and in order to be used as a tool for new coil designs. This method accounts for the nonlinear behavior of the material. Two in vivo experimental studies are presented in the last part of this work. They were performed on mouse-implanted human tumor models using a new generation of CA developed by Guerbet, a firm involved in this work. It was not possible to validate undoubtedly the specificity of this CA from these first results. However the methodological improvements of this work will allow rationalizing imaging protocols in the near future, and will lead to significant progress in this field of research
Gargam, Nicolas. "Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112118.
Pełny tekst źródłaFollowing the recent advances in nuclear medicine, magnetic resonance imaging has rapidly become an emerging technique for molecular imaging since it constitutes a contemporary issue for the improvement of the diagnosis and the post-treatment follow-up of pathologies such as cancer and Alzheimer’s disease. However, this technique suffers from both the weak amount of in vivo receptors and the low sensitivity of MRI for the detection of exogenous contrast agents. Thus, the literature shows an increasing interest for the development of novel contrast agents which can carry several thousands of contrastophores and new techniques are needed to evaluate the efficiency of these contrast agents. Indeed, when a targeted contrast agent is injected intraveneously, many biochemical process can occur simultaneously (extravasation, specific binding on receptors, internalization inside cells, …), which can make the contrast uptake mechanisms difficult to investigate. Hence, we developed a new method of cellular observation allowing to characterize the contrast agent by MRI, by imitating some of the in vitro mechanisms that occur in vivo. Using this technique, we also avoided problems that are linked to the experimentation on small animal in terms of resolution, signal to noise ratio and inter-animal reproducibility.Our approach was based on the design and fabrication of a microhistological device that allows to detect a living cells’ monolayer - whose thickness is above 10 microns - in a microfluidic environment. After having fully characterized our method with cells that had internalized a commercial contrast agent (Dotarem), we used it to evaluate the dynamic uptake of a new contrast agent developed and synthetized in Guerbet : a paramagnetic nanoemulsion functionalized with RGD peptides to target the avb3 integrins that play a capital role in the tumor angiogenesis process. In a microfluidic channel, we prepared an endothelial cell monolayer and applied a flow of contrast agent over the cell layer. We were able to follow-up by MRI the uptake of the contrast agent by the cell surface receptors. Besides demonstrating the specificity of the contrast agent as well as traditional in vitro techniques, our technique provides an additional information level since it is able to evaluate the kinetic constants and the affinity of the contrast agents toward the receptors. These experiments were done under physiological conditions close to the ones existing in vivo in terms of cell arrangement, concentration and flow velocity of the contrast agent
Beilvert, Anne. "Synthèse, caractérisation et évaluation in vitro et in vivo d'agents de contraste pour l'imagerie moléculaire du coeur lipidique de la plaque d'athérosclérose". Paris 13, 2011. http://www.theses.fr/2011PA132004.
Pełny tekst źródłaImaging and quantifying the lipid core is a key to evaluate the risk of rupture of the atherosclerotic plaque. My goal is to develop MR contrast agent that will target the lipid core inside the atherosclerotic plaque. Our hypothesis is to mimic apolipoprotein A1 and mimetic D-4F behavior with lipids. D-4F is a soluble alpha helix peptide that binds to lipids via a cluster of aromatic amino acids. We believe that using a single aromatic amino acid or a combination of aromatic amino acids on a MR platform will efficiently target the lipid core. First, we developed a micellar platform functionalized with tyrosin-O-methylester. This compound was successfully tested in an ApoE-/- mouse model under western diet that develops atherosclerotic plaque. Then, we generalized this approach with a polysaccharide based MR contrast agent. Tyrosine-O-methylester was coupled to this platform as well as trityrosine and L-4F peptide. These compounds were evaluated first by surface plasmon resonance (SPR) on immobilized lipoproteins and then in the ApoE-/- mouse model. In vivo results indicate an enhancement in the atherosclerotic plaque and in the lipid core that validates our hypothesis
Fantoni, Frédéric. "Méthodes d'illumination et de détection innovantes pour l'amélioration du contraste et de la résolution en imagerie moléculaire de fluorescence en rétrodiffusion". Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENU034/document.
Pełny tekst źródłaIntraoperative fluorescence imaging in reflectance geometry is an attractive imaging modality to noninvasively monitor fluorescence-targeted tumors. However, in some situations, this kind of imaging suffers from a lack of depth penetration and a poor resolution due to the diffusive nature of photons in tissue. The objective of the thesis was to tackle these limitations. Rather than using a wide-field illumination like usual systems, the technique developed relies on the scanning of the medium with a laser line illumination and the acquisition of images at each position of excitation. Several detection schemes are proposed to take advantage of the stack of images acquired to enhance the resolution and the contrast of the final image. These detection techniques were tested both in simulation with the NIRFAST software and a Monte-Carlo algorithm and experimentally. The experimental validation was performed on tissue-like phantoms and in vivo with a preliminary testing. The results are compared to those obtained with a classical wide-field illumination. As they enhance both the contrast and the resolution, these methods allow us to image deeper targets by reducing the negative effects of parasite signals and diffusion
Bonnard, Thomas. "Mise au point de microparticules polysaccharides injectables pour l'imagerie moléculaire de pathologies artérielles". Thesis, Paris 13, 2014. http://www.theses.fr/2014PA132015/document.
Pełny tekst źródłaCardiovascular diseases and their consequences constitute nowadays a major health issue. Their treatment could be substantially improved with the development of new non invasive diagnostic techniques. The aim of this doctoral project is to develop injectable into blood stream polysaccharide microparticles that would permit molecular imaging of arterial pathologies. From an emulsion- crosslinking process, we synthesized these microparticles which are on the one hand functionalized with fucoidan to target P-Selectin which is expressed at damaged arterial wall, and on the other hand combined with contrast agents to bring an imaging signal. We developed 2 molecular imaging tools dedicated to 2 classical medical imaging modalities. In order to track the microparticles by single photon emission computed tomography, we radiolabeled them with technetium 99m and to detect them by MRI, we loaded them with superparamagnetic nanoparticles of iron oxide. We then have validated the efficiency of these 2 molecular imaging tools with preclinical studies of in vivo small animal imaging of arterial disease models. The obtained results are very promising and these 2 molecular imaging tools have a strong clinical potential for the diagnosis of arterial pathologies. We also have observed that the microparticles tend to migrate though the damaged arterial wall. This specific property could turn out to be very interesting for future works which will consist in using this technology to convey therapeutic molecules directly into the core of the arterial pathologies
Gauthier, Marianne. "Etude de l’influence de l’entrée artérielle tumorale par modélisation numérique et in vitro en imagerie de contraste ultrasonore. : application clinique pour l’évaluation des thérapies ciblées en cancérologie". Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T088.
Pełny tekst źródłaDynamic contrast-enhanced ultrasonography (DCE-US) is currently used as a functional imaging technique for evaluating anti-angiogenic therapies. A mathematical model has been developed by the UPRES EA 4040, Paris-Sud university and the Gustave Roussy Institute to evaluate semi-quantitative microvascularization parameters directly from time-intensity curves. But DCE-US evaluation of such parameters does not yet take into account physiological variations of the patient or even the way the contrast agent is injected as opposed to other functional modalities (dynamic magnetic resonance imaging or perfusion scintigraphy). The aim of my PhD was to develop a deconvolution process dedicated to the DCE-US imaging, which is currently used as a routine method in other imaging modalities. Such a process would allow access to quantitatively-defined microvascularization parameters since it would provide absolute evaluation of the tumor blood flow, the tumor blood volume and the mean transit time. This PhD has been led according to three main goals. First, we developed a deconvolution method involving the creation of a quantification tool and validation through studies of the microvascularization parameter variability. Evaluation and comparison of intra-operator variabilities demonstrated a decrease in the coefficients of variation from 30% to 13% when microvascularization parameters were extracted using the deconvolution process. Secondly, we evaluated sources of variation that influence microvascularization parameters concerning both the experimental conditions and the physiological conditions of the tumor. Finally, we performed a retrospective study involving 12 patients for whom we evaluated the benefit of the deconvolution process: we compared the evolution of the quantitative and semi-quantitative microvascularization parameters based on tumor responses evaluated by the RECIST criteria obtained through a scan performed after 2 months. Deconvolution is a promising process that may allow an earlier, more robust evaluation of anti-angiogenic treatments than the DCE-US method in current clinical use
Jahanbin, Tania. "Conception et développement in vitro d'agents de contraste hautement efficace en IRM : apport de la dynamique moléculaire sur le signal RMN". Toulouse 3, 2014. http://thesesups.ups-tlse.fr/2566/.
Pełny tekst źródłaThe objective of this thesis is design and development of two types of MRI contrast agents (CA) with high efficiency, including macromolecule and nanoparticles. The first substance is Gd(III)-meso-tetra(4-pyridyl)porphyrin (Gd(TPyP)). Its efficiency has been compared with two metalloporphyrin compounds, Mn(III)-meso-tetra(4-sulfonatophenyl) porphyrin (Mn(TSPP)) and Fe(II)-meso-tetra(N-methylpyridiniumyl)porphyrin (Fe(TMPyP)) in presence of two magnetic field of 20 and 60 MHz. Among the metallated porphyrins, Gd(TPyP) exhibits the highest r1 of 24 mM-1s-1 (6-fold higher compared to r1 of Gd-DOTA). In the next step, Gd(TPyP) has been conjugated to chitosan nanoparticles in order to improve its biocompatibility and water solubility. The small water-soluble Gd(TPyP)-conjugated chitosan nanoparticles (~40 nm) show higher (56%) r1 of 38 mM-1. S-1 at 3T than the one of Gd(TPyP) in ethanol and 9-fold greater than r1 of Gd-DOTA. The second complex developed as CA is MnxZn1-xS ( 0. 1 =x=0. 3) nanoparticles while the majority of Mn atoms localized on/ or close to the surface of ZnS nanoparticles to enhance their efficiency as MRI CA. Mn:ZnS nanoparticles exhibits higher r1 compared with the one of commercial Mn-DPDP (r1=2. 8 mM-1s-1 at 42 MHz), which significantly increases from 20. 34 to 75. 5 mM-1s-1 with Mn content in the range of 0. 1-0. 3. Thereafter, effect of particle size on relaxivity of Mn0. 3Zn0. 7S has been investigated. We observed that r1 decreases with increasing particle size due to decreasing the surface to volume ratio from 75. 5 to 42. 81 mM-1s-1. In order to obtain the insight through the relaxivity of Mn:ZnS nanoparticles, computational technique has been carried out to predict the interaction and dynamic of Mn:ZnS and solvent (water) via molecular dynamic simulations (MDs). Thereby, MnxZn1-xS with different dopnat contents ( 0. 1 =x=0. 3) has been modeled via MDs. We achieved to reproduce the crystal structure of MnZnS precisely, within a few percent of experimental values. The study has been completed successfully by adding MnZnS nanoparticles in aqueous solution
Robert, Fabrice. "Etude chez le rat, de l'influence de la masse moléculaire sur la pharmacocinétique de polymères Dextran-Dota-Gadolinium utilisés comme produits de contraste en imagerie par résonance magnétique". Paris 5, 1997. http://www.theses.fr/1997PA05P146.
Pełny tekst źródłaChahid, Bochra. "Développement et caractérisation de nouveaux agents de contraste lipidiques ultrasensibles pour l'imagerie par résonnance magnétique destinés à l'imagerie moléculaire". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA114867/document.
Pełny tekst źródłaThe effect of paramagnetic compounds in the chemical shift of endogenous protons, i.e., their resonance frequency, widely used in conventional NMR, can also be a tool to modulate the contrast in magnetic resonance imaging (MRI) by achieving frequency-encoded images depending on the nature or the environment of the entity or tissue to be revealed. This approach involves the transfer of magnetization by chemical exchange of protons also referred to as "Chemical Exchange Saturation Transfer" (CEST). The principle consists in selectively saturate by applying a radio frequency pulse, the signal of labile protons transiently belonging to the structure of the contrast agent or to the water molecules which are associated transiently to it. The image then results from the alteration of the signal of the exchanged protons. The method is based on the actual existence of two sets of protons or pools with two distinct resonance frequencies, one corresponding to the protons associated with the contrast agent and the other represented by the surrounding bulk water.LipoCEST systems, liposomes encapsulating a paramagnetic lanthanide complex, allows such a differentiation of two proton pools constituted on one hand by the water molecules contained in the inner cavity of the liposomes (with a resonance frequency changed by the paramagnetic agent ) and on the other hand by the water present outside the vesicle structure. The sensitivity of such systems is mainly due to the large number of protons in the inner pool. The nature of the paramagnetic agent plays a role in the selectivity of the CEST effect while the nature of the liposome membrane and related permeability behavior controls the proton exchange kinetics between the two water pools. These two parameters must be selected and adjusted to provide effective CEST contrast.The work in this thesis aimed at such a development by optimizing liposome systems for MRI-CEST after intravenous administration. Therefore, the diameter of the liposomes was set below 200 nm and their surface covered by chains of poly (ethylene glycol) to ensure stability in the blood compartment. The choice of chemical shift agents based on lanthanide complexes, mainly thulium-based derivatives, was established from their structural and magnetic properties. The methodology specially developed to encapsulate these entities into vesicles of different membrane composition and permeability to water allowed to generate a new LipoCEST contrast agent
Vaillant, Solenne. "Suivi in vivo de cellules immunitaires par imagerie multimodale". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS021/document.
Pełny tekst źródłaRecent clinical trial results have demonstrated the efficacy of immunotherapy in cancer patients. This type of therapy involves treating cancer cells by stimulating the patient's immune defenses. The aim of this thesis project is to develop a biomarker of efficacy for this therapy, in order to better understand the biological mechanisms involved, and to have an early and non-invasive indicator of the patient’s response to immunotherapy. To do this, two imaging techniques (MRI and PET) were used as in vivo monitoring tools for the biodistribution of different populations of immune cells. The first step of this work was to establish different protocols for labeling immune cells. For the PET approach, the immune cells were labeled with Zirconium 89; and for MRI, two labeling techniques were studied: the first uses iron nanoparticles, and the other uses micelles loaded with Fluorine 19. After validation of their non-toxicity, the sensitivity of each labeling was evaluated in vitro, then in vivo in a second step, thus making it possible to study the biodistribution of the immune cells after different types of injections. The labeling with Zirconium 89 was then tested on different animal models of immunotherapies (PD1/PDL1 for example). Finally, since direct markings do not allow optimal cellular monitoring in the long term, a cell labeling approach using reporter genes has been considered. It involved modifying the genome of the immune cells so that they could express an enzyme (for example the viral thymidine kinase HSV1-TK) or a transporter (such as the NIS iodine transporter) allowing the internalization of a radioactive tracer in vivo, and thus be able to carry out indirect labeling of the cells
Malikidogo, Kyangwi Patrick. "Agents de contraste pour la détection quantitative du Zn(II) par IRM". Thesis, Orléans, 2017. http://www.theses.fr/2017ORLE2074.
Pełny tekst źródłaMagnetic Resonance Imaging (MRI) has long been devoted to obtain anatomical and functional images. Recently the development of molecular imaging, which seeks to obtain biochemical and physiopathological information, requires the use of a probe specific to the molecular event to be detected. This has led to the development of new “smart” Gd(III)-based contrast agents.Zn(II) detection remains of prime importance due to its implication in biological processes and diseases. One of the major challenges is its quantitative detection. To this aim, we have developed an approach based on bimodal probes which differs only by the Ln(III) used : Gd(III) for MRI (responsive technique) and 165Er(III) forsingle photon emission computed tomography (quantitative technique). These probes are based on apyridine-Ln(III) unit linked to a DPA (dipicolylamide) motif for Zn(II) complexation through a spacer.First, we have optimized the Zn(II) response of the Gd(III) complexes. We have improved the thermodynamic stability of the Ln(III) complexes by adding a carboxylate function to the ligand. This family of complexes respond to Zn(II) in the presence of HSA (Human Serum Albumin) by changes of the rotational correlation time. We have then performed a structural study to point out important parameters to optimize the Zn(II)response and/or the selectivity, especially versus Cu(II). We have also developed a family of molecules responding to Zn(II) by modest variation of the hydration number q. Finally, we validated the use of 165Er(III) for the in vitro quantitative detection of Zn(II)
Sirol, Marc. "Caractérisation de l'athérothrombose en imagerie par résonance magnétique : rôle de l'imagerie moléculaire pour l'évaluation de la plaque vulnérable". Paris 7, 2007. http://www.theses.fr/2007PA077177.
Pełny tekst źródłaDespite advances in our understanding of the pathogenesis of atherosclerosis and its thrombotic complications remain the leading cause of mortality in Western societies. Identification of high-risk atherosclerotic lesions prone to rupture and thrombosis may greatly decrease the morbidity and mortality associated with atherosclerosis. High-resolution MRI has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor its progression. The development of MRI contrast agents that specifically target components of the atherosclerotic plaque may enable non-invasive detection of high-risk lesions. This research focuses on the use of molecular imaging for the identification of high risk or vulnerable plaques in vivo. We demonstrated the ability of fibrin-targeted MR contrast agent (EP-2104R) for detection and age determination of carotid thrombus. In addition, Gadofluorine-enhanced MRI demonstrated its ability of identifying lipid-rich plaques as well as neovessel high density areas in vivo. We established the superiority of molecular imaging compared to high resolution MRI or contrast-enhanced MRI for plaque characterization. This technique allow for allow the identification of high-risk atherosclerotic lesions in-vivo, using a variety of molecules present in atherosclerotic plaques that may serve as targets for specific contrast agents. Ultimately, such agents may enable treatment of "high-risk" patients prior to lesion progression and occurrence of complications, and may allow for better stratification of "high-risk" plaque and "high-risk" patients
Boucher, Marianne. "Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS234/document.
Pełny tekst źródłaThis work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be acheived with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magnetotactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bilipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionnalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high effciency molecular imaging probes have been investigated with magnetotactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energétique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as effcient blood pool agent after intravenous injection. Afterward, we applied the concept of producing engineered MRI molecular imaging probes in a single step by bacteria, to a mouse model of glioblastoma. Knowing that tumor cells can be actively targeted through anb3 integrins by RGD, we produced RGD functionnalized magnetosomes. We started from showing these RGD magnetosomes have a good affnity for U87 cell in vitro, prior to demonstrate it in vivo on orthotopic U87 mouse model. This in vivo affnity being fnally cross-validated with histology
Gross, Dominique. "Conception et évaluation d'une sonde CMUT mixte dédiée à la thérapie ciblée à guidage ultrasonore". Thesis, Tours, 2015. http://www.theses.fr/2015TOUR3313/document.
Pełny tekst źródłaPresented for the first time in 1994, capacitive micromachined ultrasonic transducers (CMUT) are a promising alternative to the piezoelectric technology for electroacoustic transduction. Particularly, their intrinsic design flexibility and miniaturization capability are strong advantages for the manufacturing of high-end Ultrasound-guided Focused Ultrasound (USgFUS) probes. The work presented in this Ph.D. dissertation is devoted to the f irst development of a USgFUS CMUT probe. After a general introduction of the CMUT technology and the context of this research project, the development is reported starting from the preliminary numerical studies to the most advanced characterizations of the fabricated device. The first results demonstrate the benefits of this technology for the targeted applications
Marty, Benjamin. "Développements de stratégies de quantification et de dispositifs expérimentaux pour l'IRM moléculaire de biomarqueurs endovasculaires et intratissulaires de pathologies cérébrales". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112087.
Pełny tekst źródłaIn this thesis, which was part of the Iseult/INUMAC project, we propose several methodological and technological developments aiming to allow MRI to become a quantitative tool for molecular imaging of brain pathologies. To do so, we developed a quantification strategy based on T1 and T2 mapping sequences in order to acquire quantitative concentration maps of paramagnetic and superparamagnetic contrast agents with excellent sensitivity, high spatial resolution and temporal resolution compatible with in vivo imaging. This general methodology allowed us to address several issues specific to molecular imaging of cerebral pathologies using MRI. First, we focused on the imaging of a vascular biomarker of tumor angiogenesis on a glioblastoma mouse model. We studied the binding of a paramagnetic emulsion, functionalized using RGD peptides, on alpha-nu-beta-3 integrin over-expressed at the surface of freshly formed endothelial cells. Then, we focused on the delivery of contrast agents to brain parenchyma. A system was developed and optimized to open transiently and non-invasively rodents blood brain barrier (BBB) using focalized ultrasound monitored by MRI. The BBB opening features and closure dynamics induced by this protocol were extensively characterized. In another study, we measured the apparent diffusion coefficient of contrast agents with different sizes in cerebral tissues of healthy rats. From these measures we could estimate the time necessary for these particles to reach their targets once the BBB is crossed. These parameters are highly valuable in the context of drug delivery to the brain. They might indeed be used by pharmaceutical industries to optimize the design of diagnostic and therapeutic agents dedicated to cerebral diseases
Azizian, Kalkhoran Mohammad. "Design and development of a universal handheld probe for optoacoustic-ultrasonic 3D imaging". Thesis, Lyon, 2017. http://www.theses.fr/2017LYSEI027/document.
Pełny tekst źródłaWhen the interest is in multiscale and multipurpose imaging, there exists such a will in integrating multi-modalilties into a synergistic paradigm in order to leverage the diagnostic values of the interrogating agents. Employing multiple wavelengths radiation, optoacoustic imaging benefits from the optical contrast to specifically resolve molecular structure of tissue in a non-invasive manner. Hybridizing optoacoustic and ultrasound imaging comes with the promises of delivering the complementary morphological, functional and metabolic information of the tissue. This dissertation is mainly devoted to the design and characterization of a hybridized universal handheld probe for optoacoustic ultrasound volumetric imaging and developing adaptive reconstruction algorithms toward the physical requirements of the designed system. The distinguishing features of this dissertation are the introduction of a new geometry for optoacoustic ultrasonic handheld probe and systematic assessments based on pre and post reconstruction methods. To avoid the biased interpretation, a de facto performance assessment being capable of evaluating the potentials of the designed probe in an unbiased manner must be practiced. The aforementioned features establish a framework for characterization of the imaging system performance in an accurate manner. Moreover, it allows further task performance optimization as well. Correspondingly, two advanced reconstruction algorithms have been elaborated towards the requirement of the designed optoacoustic-ultrasound (OPUS) imaging system in order to maximize its ability to produce images with homogeneous contrast and resolution over the entire volume of interest. This interest is mainly due to the fact that the medical data analysis pipeline is often carried out in challenging conditions, since one has to deal with noise, low contrast, limited projections and undesirable transformations operated by the acquisition system. The presented thesis shows how reconstruction artifacts can be reduced by compensating for the detecting aperture properties and alleviate artifacts due to sparse angular sampling. In pursuit of transferring this methodology to clinic and validating the theoretical results, a synthetic imaging platform was developed. Using the measurement system, the evolution of a novel sparse annular geometry and its dynamics has been investigated and a proof of concept was demonstrated via experimental measurement with the intention of benchmarking progress
Asquier, Nicolas. "Etude des moyens de caractérisation de l’ouverture de la barrière hémato-encéphalique induite par un dispositif ultrasonore implantable". Electronic Thesis or Diss., Lyon, 2019. https://n2t.net/ark:/47881/m6rn376t.
Pełny tekst źródłaThe blood-brain barrier (BBB) is a natural protection of the central nervous system. However, it limits the delivery of many drugs to the brain tissues. It can be temporarily disrupted by ultrasound exposure combined with intravenous injection of microbubbles. In this manuscript, BBB disruption with an implantable unfocused ultrasound device is studied. An automatic method for quantifying the volume of BBB disruption using MR images from a phase 1/2a clinical study in patients with reccurent glioblastoma was assessed and validated. A correlation between the probability of disruption and the local acoustic pressure was found. Microbubbles cavitation activity was studied in vitro to better understand its effect on BBB disruption. The uncertainty on the amplitudes of cavitation signals recorded with a passive single-element detector (PCD) through the skull was quantified. A position-based correction of the PCD signal was assessed and validated. The effect of the volume of a cavitation cloud in the unfocused ultrasound field on the signal amplitude recorded by the PCD during the clinical treatment was discussed. Two methods for localizing and discriminating cavitation sources in a transcranial context were evaluated by simulations and in vitro
Bonnet, Samuel. "Ciblage moléculaire de l'athérosclérose par des nanoparticules fonctionnalisées avec des anticorps humains : développement et applications d'un protocole d'IRM paramétrique chez le petit animal". Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0436.
Pełny tekst źródłaThe project will address the problem of unstable atherosclerotic plaque rupture, which is the mechanistic cause of about 70 % of all sudden and often fatal heart attacks. Atherosclerotic lesions are lipid-rich focal thickenings in the walls of the arteries. Engineering targeted contrast agents to assess the components that underlie the risk of rupture is of crucial interest. Molecular imaging requires highly sensitive and specific probes grafted with ligands for targeting. Here single chains fragments variables of human antibodies (scFv) are proposed as specific ligands to functionalize multi-modal nanoparticles loaded with (1) iron oxide for non-invasive in vivo magnetic resonance imaging (MRI) and (2) Near InfraRed (NIR) fluorophores for fluorescence imaging at the tissular and cellular level. Iron oxide-based particles (USPIOs) are used in MRI for their superparamagnetic properties which locally induce (in the tissues where they accumulate) an hyposignal. These particles are also characterized by their ability to reduce the tissue values of a temporal physical parameter called T2 *. The quantitative evaluation of the accumulation of USPIOs in atheroma plaque by parametric MRI has been a growing field of investigation for about ten years. Although the pre-clinical research of new molecular imaging probes dedicated to atherosclerosis is very active, it also requires the development and validation of robust parametric imaging protocols dedicated to small animals. The aim of this thesis was to develop imaging tools allowing the preclinical characterization of atheromatous plaque in small animals (imaging protocol and targeting contrast agents). The first part of the project allowed the synthesis and characterization of different multimodal contrast agents (MRI / PIR). In a second step, work has been devoted to the production of recombinant human antibodies specific for atheroma plaque (scFv). In a quality state of mind approach inspired by the "Six Sigma" method, a parametric MRI imaging protocol was developed and validated to allow a robust characterization of the T2 * values of atheromatous plaque in ApoE-/- mice. In a final step, the scFv products were functionalized on the USPIOs by different grafting pathways. Thanks to the validated imaging protocol, the accumulation of targeting contrast agents into the atheroma plaque during time was finally assessed in vivo in ApoE-/- mice
Errico, Claudia. "Ultrasound sensitive agents for transcranial functional imaging, super-resolution microscopy and drug delivery". Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC013.
Pełny tekst źródłaThis thesis focuses on two main branches of the application of ultrasound contrast agents: microbubbles-aided ultrafast ultrasound imaging of the brain and ultrasound-triggered drug delivery for cancer therapy. At first, gas-filled microbubbles have been used to retrieve the brain activation through the skull in large animais. With this approach we have been able to non-invasively reconstruct the cerebral network of the brain, as well as retrieve its hemodynamic response to specific evoked tasks with high spatiotemporal resolution. The validation of this novel functional ultrasound (fUS) imaging approach was facilitated by the high sensitivity of the ultrasensitive Doppler technique able to detect subtle hemodynamic changes due to the neurovascular coupling. These resuits suggested that combining microbubbles injections with ultrafast imaging may help to fully compensate for the attenuation from the skull. Indeed, by combining both, we preserved resolution and increased penetration depth. The injection of ultrasound contrast agents has also lead to outstanding resuits in ultrafast ultrasound imaging by breaking the diffraction barrier and move beyond the half-wavelength limit in resolution. We have demonstrated that cerebral microvessels of 9pm in diameter can me distinguished via ultrafast ultrasound localization microscopy (uULM). Millions of blinking sources were localized in space and in time in few seconds in a higher dimensional space, leading to super-resolved images (microbubble density map) of the whole rat brain with a spatial resolution of À/10. Moreover, a displacement vector allowed microbubbles-tracking within frames yielding to in-plane velocity measurements retrieving a large dynamic of cerebral blood velocities. Next, we have exploited how we can spatiotemporally control the vaporization of composite perfluorocarbon (PFC) microdroplets when their activation is triggered by short ultrasound pulses. The concept 'chemistry in-situ' is introduced as we have been able to control a spontaneous chemical reaction in-vitro. Moreover, a new microfluidic device in glass has been proposed to robustly produce monodisperse droplets for future in-vivo applications of the chemistry in situ. This new device presents 128-parallel generators with two pressurized rivers. Eventually, new ultrafast ultrasound monitoring sequences have been developed in order to control and monitor the release of composite droplets
Asquier, Nicolas. "Etude des moyens de caractérisation de l’ouverture de la barrière hémato-encéphalique induite par un dispositif ultrasonore implantable". Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1330/document.
Pełny tekst źródłaThe blood-brain barrier (BBB) is a natural protection of the central nervous system. However, it limits the delivery of many drugs to the brain tissues. It can be temporarily disrupted by ultrasound exposure combined with intravenous injection of microbubbles. In this manuscript, BBB disruption with an implantable unfocused ultrasound device is studied. An automatic method for quantifying the volume of BBB disruption using MR images from a phase 1/2a clinical study in patients with reccurent glioblastoma was assessed and validated. A correlation between the probability of disruption and the local acoustic pressure was found. Microbubbles cavitation activity was studied in vitro to better understand its effect on BBB disruption. The uncertainty on the amplitudes of cavitation signals recorded with a passive single-element detector (PCD) through the skull was quantified. A position-based correction of the PCD signal was assessed and validated. The effect of the volume of a cavitation cloud in the unfocused ultrasound field on the signal amplitude recorded by the PCD during the clinical treatment was discussed. Two methods for localizing and discriminating cavitation sources in a transcranial context were evaluated by simulations and in vitro
Sbeity, Fatima. "Identification et modélisation de systèmes non linéaires générant des sous et ultra-harmoniques : Application à l'imagerie ultrasonore sous et ultra-harmonique". Phd thesis, Université François Rabelais - Tours, 2013. http://tel.archives-ouvertes.fr/tel-01062555.
Pełny tekst źródłaShi, Da. "Préparation et caractérisation de microbulles fonctionnelles stabilisées par des fluorocarbures et décorées de nanoparticules dendronisées : évaluation comme agents du contraste bimodaux pour l'IRM et l'imagerie par ultrasons". Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAF053.
Pełny tekst źródłaThis Thesis focuses on the preparation and characterization of microbubbles stabilized with a fluorocarbon gas and decorated with dendronized magnetic nanoparticles. The impacts of perfluorohexane exposure mode on Langmuir monolayers formed by phospholipids and on the properties of microbubbles were evaluated. The behaviours of Langmuir monolayers formed by dendrons and of the mixtures of dendrons and phospholipids were investigated. The attractive fluorine-fluorine interactions that develop between the fluorocarbon gas and the fluorinated terminal group prompt the adsorption of nanoparticles grafted with dendrons to the air/water interface. Small and stable microbubbles decorated with dendronized iron oxide nanoparticles were prepared. The magnetic microbubbles were examined as bimodal contrast agents for MRI and ultrasound imaging on a murine model in collaboration with the Universitätklinikum in Freiburg. This work was supported by the INTERREG V (Nanotransmed)
Lin, Fanglue. "Ultrasound contrast imaging with multi-pulse transmission". Phd thesis, INSA de Lyon, 2013. http://tel.archives-ouvertes.fr/tel-01018646.
Pełny tekst źródłaWischhusen, Jennifer. "Ultrasound Microbubbles for Molecular Imaging and Drug Delivery : detection of Netrin-1 in Breast Cancer & Immunomodulation in Hepatocellular Carcinoma". Electronic Thesis or Diss., Lyon, 2017. http://www.theses.fr/2017LYSE1317.
Pełny tekst źródłaUltrasound molecular imaging uses microbubbles as ultrasound contrast agents which are functionalized with targeting ligands. Upon intravenous injection, targeted microbubbles bind to molecular markers presented on the tumor endothelium and enable the non-invasive assessment cancer-related biomarkers. In the present thesis, ultrasound molecular imaging was developed for detection of netrin-1, which is upregulated in 70% of metastatic breast cancer and promotes cell survival. A newly developed netrin-1 interference therapy requires the identification of patients who overexpress the target protein and, could benefit from anti-netrin-1 therapy. In vivo imaging of netrin-1 showed a significantly increased imaging signal in netrin-1-positive breast tumors compared to netrin-1-negative breast tumors and normal mammary glands. The results suggest that ultrasound molecular imaging allows accurate detection of netrin-1 on the endothelium of netrin-1-positive tumors and has the potential to become a companion diagnostic for netrin-1 interference therapy in breast cancer patients.Ultrasound-targeted microbubble destruction triggers cavitation and sonoporation thereby permeabilizing the tissue and facilitating local drug delivery. Further, immune cell infiltration and tumor antigen release are induced and trigger anti-tumor immune responses. In the present thesis, ultrasound-targeted microbubble destruction-mediated delivery of anti-cancer microRNA-122 and anti-microRNA-21 is studied for immune response activation in hepatocellular carcinoma, in which the immune microenvironment is deregulated. Tumor lymph nodes showed pro-tumor cytokine downregulation and anti-tumor cytokine upregulation, suggesting an overall positive therapy response with regard to the tumor immunology. The results identified ultrasound-targeted microbubble destruction-mediated miRNA delivery as a potent immuno-modulatory therapeutic approach
Wischhusen, Jennifer. "Ultrasound Microbubbles for Molecular Imaging and Drug Delivery : detection of Netrin-1 in Breast Cancer & Immunomodulation in Hepatocellular Carcinoma". Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1317/document.
Pełny tekst źródłaUltrasound molecular imaging uses microbubbles as ultrasound contrast agents which are functionalized with targeting ligands. Upon intravenous injection, targeted microbubbles bind to molecular markers presented on the tumor endothelium and enable the non-invasive assessment cancer-related biomarkers. In the present thesis, ultrasound molecular imaging was developed for detection of netrin-1, which is upregulated in 70% of metastatic breast cancer and promotes cell survival. A newly developed netrin-1 interference therapy requires the identification of patients who overexpress the target protein and, could benefit from anti-netrin-1 therapy. In vivo imaging of netrin-1 showed a significantly increased imaging signal in netrin-1-positive breast tumors compared to netrin-1-negative breast tumors and normal mammary glands. The results suggest that ultrasound molecular imaging allows accurate detection of netrin-1 on the endothelium of netrin-1-positive tumors and has the potential to become a companion diagnostic for netrin-1 interference therapy in breast cancer patients.Ultrasound-targeted microbubble destruction triggers cavitation and sonoporation thereby permeabilizing the tissue and facilitating local drug delivery. Further, immune cell infiltration and tumor antigen release are induced and trigger anti-tumor immune responses. In the present thesis, ultrasound-targeted microbubble destruction-mediated delivery of anti-cancer microRNA-122 and anti-microRNA-21 is studied for immune response activation in hepatocellular carcinoma, in which the immune microenvironment is deregulated. Tumor lymph nodes showed pro-tumor cytokine downregulation and anti-tumor cytokine upregulation, suggesting an overall positive therapy response with regard to the tumor immunology. The results identified ultrasound-targeted microbubble destruction-mediated miRNA delivery as a potent immuno-modulatory therapeutic approach
Larivière, Mélusine. "Nanoparticles functionalized with human antibodies for multimodal molecular imaging of atherosclerosis". Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0389/document.
Pełny tekst źródłaBecause cardiovascular diseases are the leading cause of death in the world, providing clinicians with reliable and straightforward imaging techniques to identify "vulnerable" patients from the general population appears like the Holy Grail of the cardiovascular field. Atherosclerosis, identified as the underlying condition for most acute cardiovascular events, is characterized by the constitution of a lipidrich atheroma plaque, driven both by excess cholesterol and inflammation, which eventual rupture triggers clotting into the blood flow. It involves a wealth of cellular and molecular actors, which are so many potential markers for molecular imaging, aiming at deciphering how to warn clinicians about the possible occurrence of myocardial infarction or stroke. Here, human antibodies (HuAbs) selected by phage-display for their recognition of over-expressed biomarkers of the pathology are proposed as targeting ligands. They were further engineered for site-specific grafting, either by introducing Cysteine or Sortase recognition tags, and used to target contrast agents for MRI, fluorescence, or PET imaging. In vitro and ex vivo validation studies were carried out on atheroma sections of animal models. In vivo studies in the ApoE-/- mouse model were realized with the anti-platelet TEG4 HuAb using MRI, which provided insights on the biological relevance and feasibility to detect platelets-rich, high-risk atheroma plaques. The development of contrast agents useful in multi-modality imaging, and multi-functionalized with HuAbs is underway. It should serve as an accurate molecular imaging method for atherosclerosis, further more easily translated into the clinical arena
Pašović, Mirza. "Tissue harmonic reduction : application to ultrasound contrast harmonic imaging". Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10060.
Pełny tekst źródłaUltrasound contrast agents are small micro bubbles that respond nonlinearly when exposed to ultrasound wave. The nonlinear response gives possibility of harmonic ultrasound images which has many advantages over fundamental imaging. However, to increase ultrasound contrast harmonic imaging performance we must first understand nonlinear propagation of ultrasound wave. Nonlinear propagation distorts the propagating wave such that higher harmonics appear as the wave is propagating. The theory that was laid down, was allowed implementing a new method of modelling nonlinear ultrasound propagation. The knowledge obtained during this process was used to construct a multiple component second harmonic reduction signal for reduction of their harmonics generated due to the tissue nonlinearities. As a consequence detection of ultrasound contrast agents at higher harmonics was increased. Further more, a powerful ultrasound imaging technique called Pulse Inversion, was further enhanced with multiple component second harmonic reduction signal. What was learned during investigation of the Pulse Inversion, technique lead to a new phase coded ultrasound contrast harmonic method called second harmonic inversion;. Also it was noted that for different type of media the level of distortion of ultrasound pulse is different. It depends largely on the nonlinear parameter B / A. Although the work on this parameter has not been finished it is very important to continue in this direction since B / A imaging with ultrasound contrast agents has a lot of potential
Beauvineau, Claire. "Conception et synthese de nouvelles sondes ciblees pour l'imagerie moleculaire". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2011. http://pastel.archives-ouvertes.fr/pastel-00644998.
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