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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Imagerie grand champ en anatomopathologie / Wide-field histopathology imaging

Morel, Sophie 28 November 2016 (has links)
L’objectif de cette thèse a été de développer une méthode simple et rapide (35 minutes) d'imagerie afin d’enregistrer des images grand champ (jusqu’à 2,5 cm x 2,5 cm) et multi-échelles (µm-cm) de lames de tissus colorés et non colorés en anatomopathologie.La solution proposée est basée sur l’imagerie sans lentille. C’est une méthode simple, bas coût, qui permet d’enregistrer des images grand champ (10-30 mm²) d’objets épars, comme des virus, des bactéries ou des cellules. Dans ces travaux, nous montrons qu’il est possible d'obtenir en imagerie sans lentille des images d'objets denses tels que des lames de tissus colorés ou non marqués. Pour ce faire, l’échantillon est illuminé sous différentes longueurs d’onde, et un nouvel algorithme de reconstruction holographique multi-longueurs d’onde permet de reconstruire le module et la phase d’objets denses. Chaque image est reconstruite en 1,1 seconde couvrant un champ de 10 mm². Une image totale de la lame de tissu, couvrant un champ de 6,25 cm², est obtenue en 35 minutes en scannant l’échantillon au-dessus du capteur. Les images reconstruites sont multi-échelles, permettant à l’utilisateur d’observer en une seule fois la structure générale du tissu, et de zoomer jusqu’à la cellule individuelle (3-4 µm). La méthode a été testée sur différents échantillons anatomopathologiques colorés et non colorés. Au-delà des lames de tissus, l’imagerie sans lentille multi-longueurs d’onde montre des résultats encourageants pour le diagnostic de la méningite, le suivi au cours du temps d’une population bactérienne pour l’identification et la réalisation d’antibiogrammes, et le suivi au cours du temps de cultures cellulaires. / This PhD project aims to develop a simple, fast (35 minutes), wide-field (up to 2.5 cm x 2.5 cm) multiscale (µm-cm) imaging method for stained and unstained tissue slides for digital pathology application. We present a solution based on lensfree imaging. It is a simple, low-cost technique that enables wide field imaging (10-30 mm²) of sparse objects, like viruses, bacteria or cells. In this project, we adapted lensfree imaging for dense objects observation, like stained or unstained tissue slides. The sample is illuminated under multiple illumination wavelengths, and a new multiwavelength holographic reconstruction algorithm was developed in order to reconstruct the modulus and phase of dense objects. Each image covers 10 mm² field of view, and is reconstructed in 1.1 second. An image of the whole tissue slide covers 6.25 cm². It is recorded in 35 minutes by scanning the sample over the sensor. The reconstructed images are multiscale, allowing the user to observe the overall tissue structure and to zoom down to the single cell level (3-4 µm). The method was tested on various stained and unstained pathology samples. Besides tissue slides, multiwavelength lensfree imaging shows encouraging results for meningitis diagnosis, bacteria population monitoring for identification and antibiotic susceptibility testing, and cell culture monitoring.
42

Recalage de flux de données cinématiques pour l'application à l'imagerie optique / Multi-modal Fusion of Cinematic Flow and Optical Imaging : contributions and applications to small animal imaging.

Savinaud, Mickaël 08 October 2010 (has links)
Parmi les approches d'imagerie préclinique, les techniques optiques sur petit animal fournissent une information fonctionnelle sur un phénomène biologique ainsi que sur sa localisation. De récents développements permettent d'exploiter ces méthodes dans le cadre de l'imagerie sur animal vigile. Les conditions physiologiques se rapprochent alors de celles du fonctionnement normal de l'organisme. Les travaux de cette thèse ont porté sur l'utilisation optimale de cette modalité via des méthodes originales d'analyse et de traitement.Les problèmes soulevés par la fusion des flux cinématiques et de données de bioluminescence nous ont amené à proposer des approches complémentaires d’estimationde mouvement de l’animal. La représentation sous forme implicite des informations issuesde la vidéo de l’animal permettent de construire un critère robuste à minimiser. L’ajout d’uncritère global mesurant la compacité du signal optique permet de considérer dans sa totalité les données multicanaux acquises pour augmenter la précision du recalage. Finalement ces deux modélisations offrent des résultats pertinents et validés expérimentalement.Dans le but de s'affranchir des contraintes de l'observation planaire de nos données nous avons conçu une méthode d’estimation du mouvement 3D de l’animal à partir d’un modèle pré-calculé. Grâce à un système d'acquisition multi-vues et simultanée de la scène, il est possible d’ajouter une contrainte sur l'estimation de la position de la source pour rendre robuste le suivi des poses issues de la vidéo. Les résultats expérimentaux montrent le potentiel de cette méthode pour fournir des mesures 3D précises sur l'animal vigile. / Optical imaging techniques, have taken, since many years, a great part in the preclinicalstudies. The luminescence signal could be now recorded with a short time resolution whichenables studies with freely moving animals. This is an improvement because several studieshighlighted the impact of anesthetics agent and animal handling to perform studies inphysiological conditions. In this thesis, we define the tools, based on computer visionmethods, which offer the possibility to express the potential of this modality.In some cases, animal movement and low signal produce weak localization of the signal.Therefore we propose to improve localization of the optical data for a freely moving animal byusing motion field obtained from the multi-channel data. First, we introduce silhouetteconstraints and landmarks on the mouse skin within a variation framework. To take intoaccount all data in the registration framework, we combine the previously defined criteria,with global ones which measure compactness of signal distribution. Fusion is formulated as adiscrete population framework which produces strong experimental results in comparison topairwise method.In the last part, we propose an original approach to enable 3D optical imaging in case offreely moving animal. Therefore, we present a novel model-based method to animal trackingfrom monocular video which allows the 3D measurement of the signal. The 3D animal poseand the illumination are dynamically estimated through minimization of an objective functionwith constraints on the signal position. Experimental results demonstrate the potential of ourapproach for 3D accurate measurement with freely moving animal.
43

Etude de la dynamique des conséquences fonctionnelles périphériques et centrales de lésions oculaires focales / Dynamic of functional consequences of central and peripheral lesions after focal ocular lesions

Hoffart, Louis 25 June 2010 (has links)
Le cerveau montre d’étonnantes capacités d’adaptation aux modifications des entrées sensorielles, celles-ci pouvant avoir pour origine une modification de l’environnement ou être liées à une pathologie de l’organe récepteur lui-même. Les techniques d’imagerie fonctionnelle permettent d’étudier l’impact d’une atteinte du récepteur sensoriel du système visuel, la rétine, sur le fonctionnement et les capacités de réorganisation du cortex visuel primaire. Le but de ce travail était d’ouvrir des pistes de recherche sur les conséquences fonctionnelles centrales et périphériques de pathologies oculaires se manifestant toute par un scotome visuel important. Dans un premier temps, nous avons étudié l’organisation fonctionnelle du cortex visuel humain en Imagerie par Résonance Magnétique fonctionnelle (IRMf) à haut champ (3T). Le but de cette étude était de cartographier et de délimiter de manière reproductible les aires visuelles de bas niveau (V1, V2 et V3) par la réalisation de cartes corticales rétinotopiques. Nous avons développé un protocole expérimental spécifique afin d’étudier, chez le sujet sain, les modifications de l’organisation rétinotopique corticale en présence d’une interruption locale de stimulation rétinienne (scotome artificiel). Ce protocole a ensuite été appliqué chez un patient présentant une maculopathie en phase aiguë et après récupération fonctionnelle. Cette étude confirme la possibilité de mesurer sur la surface corticale des zones d’activités différentielles correspondant à une modification localisée de la sensibilité rétinienne et permettra, dans le cas d’atteintes rétiniennes évolutives, d’étudier les phénomènes de plasticité corticale au cours de l’évolution de ces pathologies. Dans un second temps, nous avons mis au point un dispositif d’imagerie optique afin de caractériser l’organisation rétinotopique de l’aire V1 chez le rat. Le développement de cette méthode va nous permettre de lancer deux études importantes. Premièrement, nous étudierons la cinétique des modifications de la carte rétinotopique et de l’activité neuronale afin d’évaluer le rôle respectif des phénomènes de plasticité corticale ou de modification du gain neuronal dans la réorganisation fonctionnelle du cortex visuel après lésion rétinienne. Ces résultats 3 seront à comparer aux données acquises en IRMf chez l’homme. Deuxièmement, cette méthode est le préalable à une étude complémentaire qui a pour but de tester l’impact fonctionnel d‘implants rétiniens chez le rat. Les lésions oculaires impliquent aussi des réorganisations locales, en particulier vasculaires dont les conséquences fonctionnelles sont mal connues. Nous avons donc développé en parallèle des modèles de lésions périphérique permettant l’étude des conséquences sur la rétinotopie d’un scotome induit à la suite d’une atteinte sensorielle périphérique. Ce travail ouvre plusieurs perspectives quant à l’exploration fonctionnelle dans des pathologies comme la DMLA. / The brain shows a high ability to reorganize following alteration of sensorial input that may result from modification of the environment or disease of sensorial organs. Modern functional imagery techniques allow to examine the impact on the visual system of such alterations. The aim of this thesis was to develop new approaches for studying at the cortical level, functional consequences of ocular disease associated with a significant visual scotoma. In the first section of this thesis, we used high-field (3T) functional magnetic resonance imaging (fMRI) to study the cortical functional architecture. Our goal was to map the retinotopic organization of human early visual cortical areas (V1, V2, V3). By this method, we identified modifications of retinotopic organization induced by a focal loss of retinal stimulation (artificial scotoma) and we observed the cortical projections of artificial scotoma on healthy subjects by the mean of a specific stimulus. In the following part of the experimentation, this protocol was used on a patient who showed a maculopathy at the acute stage and after recovery. This study confirms the ability to evaluate the cortical representation (size and location) of a focalized modification of the retinal sensibility threshold and could serve as a basis for the future investigation of cortical plasticity in the visual cortex following retinal diseases. The second section of this thesis was directed to the development of optical imaging intrinsic signals on small animals. Our goals were to characterize the retinotopic organization of rat’s visual cortex. With this method, we will investigate the kinetics of cortical remapping and modifications of the neuronal activity level following retinal lesion. These results will be compared to the data previously acquired by fMRI in humans. Another application of our method will be to study the functional impact of retinal prosthesis. Ocular lesions are associated with local modifications of retinal tissue, and especially with neovascular ingrowth, for which functional consequences have not been totally clarified. We therefore developed models of peripheral lesions, which allow to study the effect of scotoma on retinotopic organization of primary visual cortex after peripheral sensory lesion. This thesis gives some new directions in the functional exploration in retinal disease as Age Related Macular Degeneration (ARMD).
44

The role of postsynaptic density (PSD) proteins PSD-95 and PSD-93 for mouse visual cortical plasticity and vision

Stodieck, Sophia Katharina 26 September 2016 (has links)
No description available.
45

Optical Coherence Photoacoustic Microscopy (OC-PAM) for Multimodal Imaging

Liu, Xiaojing 23 November 2016 (has links)
Optical coherence tomography (OCT) and Photoacoustic microscopy (PAM) are two noninvasive, high-resolution, three-dimensional, biomedical imaging modalities based on different contrast mechanisms. OCT detects the light backscattered from a biological sample either in the time or spectral domain using an interferometer to form an image. PAM is sensitive to optical absorption by detecting the light-induced acoustic waves to form an image. Due to their complementary contrast mechanisms, OCT and PAM are suitable for being combined to achieve multimodal imaging. In this dissertation, an optical coherence photoacoustic microscopy (OC-PAM) system was developed for in vivo multimodal retinal imaging with a pulsed broadband NIR light source. To test the capabilities of the system on multimodal ophthalmic imaging, the retina of pigmented rats was imaged. The OCT images showed the retinal structures with quality similar to conventional OCT, while the PAM images revealed the distribution of melanin in the retina since the NIR PAM signals are generated mainly from melanin in the posterior segment of the eye. By using the pulsed broadband light source, the OCT image quality highly depends on the pulse-to-pulse stability of the light source without averaging. In addition, laser safety is always a concern for in vivo applications, especially for eye imaging with a pulsed light source. Therefore, a continuous wave (CW) light source is desired for OC-PAM applications. An OC-PAM system using an intensity-modulated CW superluminescent diode was then developed. The system was tested for multimodal imaging the vasculature of a mouse ear in vivo by using Gold Nanorods (GNRs) as contrast agent for PAM, as well as excised porcine eyes ex vivo. Since the quantitative information of the optical properties extracted from the proposed NIR OC-PAM system is potentially able to provide a unique technique to evaluate the existence of melanin and lipofuscin specifically, a phantom study has been conducted and the relationship between image intensity of OCT and PAM was interpreted to represent the relationship between the optical scattering property and optical absorption property. It will be strong evidence for practical application of the proposed NIR OC-PAM system.
46

Synthesizing Multimodal Imaging Probes and Their Application in Non-Invasive Axonal Tracing by Magnetic Resonance Imaging

Li, Zizhen January 2016 (has links)
Imaging techniques have become much more in demand in modern medicine, especially in fields of disease prognosis, diagnosis and therapeutics. This is because a better understanding of different diseases, characteristics of each patient and further optimizing treatment planning, are all enhanced by advanced imaging techniques. Since each imaging modality has its own merits and intrinsic limitations, combining two or more complementary imaging modalities has become an interesting research area. In this study, gadolinium (Gd3+) doped CdTe quantum dots (QDs) were synthesized and used as multimodal imaging probes of two highly complementary imaging modalities: optical imaging and magnetic resonance imaging. The new imaging probes were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis absorbance spectra, fluorescence spectra (FL) and magnetic resonance imaging (MRI). The optical / MRI imaging probes were further functionalized by conjugating with the axonal tracer dextran amine (10 kDa) for non-invasive axonal tracing observations. Biocompatibility and MRI contrast effect of prepared multimodal imaging probes were investigated by in vitro cell experiments and MRI scanner. Ultimately, it is hoped that this imaging probe will help us better understand the regeneration mechanisms in real time without sacrificing animals at intervening time-points.
47

Investigation of haemodynamic changes and pathophysiology in a remote filament model of stroke

Burrows, Fiona January 2014 (has links)
The initial hours following an ischaemic event in the brain represent a critically important window in which therapeutic interventions to reduce neuronal damage and improve patient outcome can be made. Nevertheless, the dynamics of cerebral blood flow and oxygenation, as well as the local physiological changes, in the first few hours after reperfusion following ischaemic stroke are not well understood. In the first study, a remote filament approach was used to obtain multispectral imaging data before, during and after middle cerebral artery occlusion to investigate early changes in haemodynamic concentration of oxy-/deoxy-haemoglobin and total blood volume, in anaesthetised mice. We use immunohistochemistry to establish the extent of cortical injury and correlate the severity of damage with the change of oxygen perfusion during and after the ischaemic event. Increased numbers of platelets and activated microglia, expression of interleukin-1α, evidence of BBB breakdown and neuronal stress are all seen within the stroked hemisphere of MCAo mice and correlate with the severity of oxy-haemoglobin concentration deficit at experimental but not with the change in oxy-haemoglobin concentration during the acute stroke. In the second study, we used the same remote filament and optical imaging approach to investigate the effects of acute systemic inflammation on haemodynamics pre, during, and after induced cerebral ischaemia. We found that an acute systemic inflammatory challenge exacerbates oxy-haemoglobin deficit after 3 h of reperfusion following an ischaemic event. We investigated known pathophysiological markers to elucidate potential mechanisms that may contribute to this exacerbated oxygenation deficit and found hyper-coagulated platelets within the large and microvessels of the ipsilateral cortex. Our findings demonstrate that despite initial restoration of HbO2 supply after 30 min MCAo there is a delayed compromise that coincides with inflammatory processes that could be a future target for improved stroke outcome after thrombolysis. We also show that acute systemic inflammation exacerbates this oxy-haemoglobin deficit after an ischaemic challenge and increases pathophysiology.
48

Clinical Translation of a Novel Hand-held Optical Imager for Breast Cancer Diagnosis

Erickson, Sarah J. 29 March 2011 (has links)
Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ~2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ~0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo, although the error in probe’s positional information increased to ~0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts.
49

Super-Resolution Imaging and Characterization

Dergan Lin (5929976) 06 December 2019 (has links)
<div>Light in heavily scattering media such as tissue can be modeled with a diffusion equation. A diffusion equation forward model in a computational imaging framework can be used to form images of deep tissue, an approach called diffuse optical tomography, which is important for biomedical studies. However, severe attenuation of high-spatial-frequency information occurs as light propagates through scattering media, and this limits image resolution. Here, we introduce a super-resolution approach based on a point emitter localization method that enables an improvement in spatial resolution of over two orders of magnitude. We demonstrate this experimentally by localizing a small fluorescent inhomogeneity in a highly scattering slab and characterize the localization uncertainty. The approach allows imaging in deep tissue with a spatial resolution of tens of microns, enabling cells to be resolved.</div><div><br></div><div>We also propose a localization-based method that relies on separation in time of the temporal responses of fluorescent signals, as would occur with biological reporters. By localizing each emitter individually, a high-resolution spatial image can be achieved. We develop a statistical detection method for localization based on temporal switching and characterization of multiple fluorescent emitters in a tissue-like domain. By scaling the spatial dimensions of the problem, the scope of applications is widened beyond tissue imaging to other scattering domains. </div><div><br></div><div>Finally, we demonstrate that motion of an object in structured illumination and intensity-based measurements provide sensitivity to material and subwavelength-scale-dimension information. The approach is illustrated as retrieving unknown parameters of interest, such as the refractive index and thickness of a film on a substrate, by utilizing measured power data as a function of object position. </div>
50

Synthèse et évaluation d'agents de contraste destinés à la détection multimodale d'une activité enzymatique / Synthesis and evaluation of molecular probes dedicated to MRI and optical imaging for enzymatic activity detection

Jouclas, Rémy 30 November 2017 (has links)
L’imagerie médicale a permis à l’Homme de mieux connaitre son anatomie, le fonctionnement de son corps, et de diagnostiquer ses pathologies à des stades de plus en plus précoces, à partir de techniques peu invasives. Au cœur de cette discipline, l’imagerie moléculaire permet d’observer les processus biologiques qui participent au fonctionnement du vivant à des fins exploratoires, diagnostiques, thérapeutiques et aujourd’hui théranostiques. L’activité enzymatique étant à l’origine d’une grande part du métabolisme, la plupart des pathologies implique le dérèglement de celle-ci. L’observation par imagerie moléculaire de cette activité constitue alors un outil prépondérant de l’arsenal médical. Parmi les techniques d’imagerie les plus adaptées à cet enjeu, l’Imagerie par Résonnance Magnétique (IRM) permet d’observer les tissus et organes de façon non invasive, en s’appuyant couramment sur l’administration au patient d’agents de contraste. Ces molécules destinées à renforcer la qualité des images acquises peuvent également être utilisées pour réagir à la présence de cibles biologiques d’intérêt, notamment des enzymes, accompagnant ainsi les clichés obtenus d’informations biologiques et physiologiques. Parmi les nombreux outils pharmacologiques destinés à l’IRM, les complexes de lanthanides ont déjà prouvé leur efficacité en imagerie clinique, et peuvent potentiellement être détectés par trois modalités d’imagerie complémentaires : l’IRM à effets T₁ et paraCEST, et l’imagerie optique. Notre équipe travaille à la conception d’une plateforme modulable permettant de détecter une grande variété d’enzymes. Elle est constituée d’un « déclencheur » qui peut être activé par une enzyme ciblée, relié par l’intermédiaire d’un bras « auto-immolable » à un « rapporteur » assurant la détection de la sonde. Ce dernier se compose d’un chélate de lanthanide qui confère à la sonde des propriétés magnétiques détectables par IRM à effets T₁ et paraCEST. Par ailleurs, une antenne de type pyridine assure l’excitation du lanthanide conduisant à sa luminescence, qui peut être détectée par imagerie optique. L’activation enzymatique de l’agent de contraste conduit à la dégradation du bras « auto-immolable », qui s’accompagne d’une modification détectable des propriétés magnétiques et optiques du rapporteur ainsi libéré. Une plateforme de ce type a été conçue lors de travaux précédents ce projet de thèse pour la détection de l’activité de la β-galactosidase. Cependant le processus de dégradation du bras « auto-immolable » déclenché par l’activité de l’enzyme ne permet pas de libérer le rapporteur sous forme activée. En effet, la cascade électronique à l’origine de ce processus est considérablement ralentie par la coordination du bras « auto-immolable » au lanthanide. Aussi, l’objectif de ce projet de thèse consiste à modifier la structure de ces agents de contraste afin de lever ce blocage cinétique, tout en conservant une détectabilité par les trois modalités d’imagerie citées précédemment.Pour ce faire, six nouveaux analogues ont été synthétisés sous forme de modèles de sondes dénués de leur partie déclencheur, afin de s’assurer de la conservation de leurs propriétés magnétiques et optiques tout en s’affranchissant des difficultés synthétiques liées à la présence de celui-ci. A l’issue de la caractérisation physicochimique de ces derniers, deux structures ont été retenues pour la conception de sondes activables par la β-galactosidase. Une première permettant la détection trimodale de l’activation enzymatique, et une seconde dont la détection par IRM à effets T₁ et paraCEST est pH-dépendante. Enfin, à l’issue de leur synthèse, des tests enzymatiques nous ont permis de suivre les cinétiques d’activation des agents de contrastes obtenus par les modalités d’imagerie prévues pour ces composés. / Medical imaging has allowed Mankind to reach a good knowledge in human anatomy, body operation and to diagnose pathologies earlier and earlier, through minimally invasive techniques. Molecular imaging at the heart of this science enables the sight of biological processes standing in the operation of life for both exploratory, diagnostic, therapeutic and even theranostic means. As a wide part of metabolism is provided by enzymatic activity, its imbalance can mean pathological context. Thus, monitoring enzymatic activity through molecular imaging could become a new power weapon in medical arsenal. Among best adapted imaging techniques to this stake, Magnetic Resonance Imaging (MRI) permits to picture tissues and organs non-invasively, widely through contrast agent prescription. These molecules designed to sharpen acquired images quality can also be used for reaction with biological targets of interest, especially enzymes, thus binding those pictures with biological and physiological data. In the many pharmacological tools associated with MRI, lanthanides complexes have already proven efficiency in clinical imaging, and are likely to be detected through three complementary imaging modalities: T₁-MRI, paraCEST-MRI and optical imaging.Our team achieves the design of a tunable platform that can detect a wide range of enzymes. It is composed of a “trigger” that can be activated by a targeted enzyme, bound through a self-immolative linker to a “reporter” moiety that enables the probe to be detected. The latter is endowed with a lanthanide chelate that gives the probe magnetic and optical properties that can be monitored by T₁-MRI or paraCEST-MRI. In addition, a pyridine antenna enables lanthanide sensitization and luminescence, that can be detected by optical imaging. Upon enzymatic activation, self-immolation of the linker causes the release of the reporter moiety, and the modification of its magnetic and optical properties.Previous work in our team has achieved the synthesis of a probe following these concepts and aiming at β-galactosidase activity detection. However, enzyme-triggered self-immolation of the probe did not release the activated reporter moiety, due to the linker’s coordination to the lanthanide. This PhD project is thus intended to modify the chemical structure of this platform to enhance its activation kinetics, while keeping it detectable by MRI and optical imaging. To reach this goal, six novel analogues have been synthetized as models without trigger moiety to check the preservation of magnetic and optical properties while making synthesis easier and faster. Following probes’ magnetic and optical characterization, two structures were selected for the design of a probe aiming at β-galactosidase activity detection. The first one could enable trimodal detection of its activity, and the second one showed pH-dependency of T₁ and paraCEST effects. After synthesis, enzymatic tests allowed us to monitor enzyme activation kinetics for both probes by the previously scheduled imaging modalities.

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