Dissertations / Theses: 'Molecular imaging applications'

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GAMBINO, GIUSEPPE. "High-relaxivity systems and molecular imaging probes for Magnetic Resonance Imaging applications." Doctoral thesis, Università del Piemonte Orientale, 2014. http://hdl.handle.net/11579/46171.

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Chow, Mei-kwan April, and 周美君. "Cellular, molecular and metabolic magnetic resonance imaging: techniques and applications." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44901148.

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Bottrill, Melanie Clare. "New routes to biocompatible nanoparticles and their applications in molecular imaging." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506114.

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Tang, Mei-yee, and 鄧美宜. "Characterizations and applications of carbon nanotubes contrast agentsin magnetic resonance molecular imaging." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44701391.

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Ma, Yun. "Photofunctional molecular materials for chemical sensing, bioimaging and electrochromic applications." HKBU Institutional Repository, 2015. https://repository.hkbu.edu.hk/etd_oa/206.

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This thesis is dedicated to developing novel photofunctional molecular materials for the applications in chemical sensing, bioimaging and electrochromic. To begin with, a brief introduction of photofunctional molecular materials and an overview of their applications in chemical sensing, bioimaging and electrochromic were presented in Chapter 1. In chapter 2, we have synthesized a series of water-soluble phosphorescent cationic iridium(III) solvato complexes (1-7) as multicolor cellular probes for imaging in living cells. All of these complexes can be dissolved in PBS. The emission of complexes can be tuned from green to red by changing the chemical structure of cyclomedtalating ligands. All complexes exhibit low cytotoxicity to living cells and exhibit cell membrane permeability and specific staining of cytoplasm. They enter the cells by the mechanism of energy-independent passive diffusion mechanisms. More importantly, complex 7 can act as a two-photon phosphorescent cellular probe, and fluorescence lifetime imaging microscopy is successfully applied for bioimaging in the presence of short-lived background fluorescence. We developed two excellent optical probes for CO2 detection in Chapter 3. The first one for the CO2 detection is a phosphorescent probe based on an iridium(III) complex with 2-phenylimidazo-[4,5-f][1,10]phenanthroline. After bubbling CO2 into the detection solution, the quenched phosphorescence by the addition of CH3COO can be recovered. Photobleaching experiment demonstrates that this phosphorescent CO2 probe shows higher photostability than some of the reported organic probes. More importantly, the time-resolved PL experiment demonstrates that this probe can be used to detect CO2 in the presence of strong background fluorescence, which improves the sensitivity and signal-to-noise ratio of the sensor in complicated media. The second one is a water-soluble fluorescent probe based on tetraphenylethene derivative. After bubbling CO2 into the detection solution, remarkable color change and fluorescence enhancement could be observed. The response of this probe to CO2 in aqueous solution is fast and the detection limit is about 2.4 × 106 M. To emphasize the practical application of this probe, a porous film was successfully fabricated by mixing the dye with sodium carboxymethyl cellulose in water, which can serve as an efficient CO2 gas sensor. More importantly, this probe exhibits low cytotoxicity towards live cells and has the ability to monitor the external CO2 concentration changes of living cells. Chapter 4 focused on the development of novel soft salt based phosphorescent probe. This type of probe consists of two oppositely charged ionic complexes with two distinguishable emission colors, which makes it a perfect candidate as a ratiometric probe. The emission color of 10 changes from blue to red with increasing pH value. 10 is cell-permeable and exhibits low cytotoxicity, and it has been successfully applied for ratiometric pH imaging with the use of confocal microscopy, demonstrating its great potential for intracellular environment monitoring. Furthermore, phosphorescence lifetime imaging experiments can detect intracellular pH variations by photoluminescence lifetime measurements, which allowed for eliminating background fluorescence and selecting long-lived phosphorescence images. Quantitative measurement of intracellular pH fluctuations caused by oxidative stress has been successfully carried out for 10 based on the pH-dependent calibration curve. A series of cationic Zn(II) complexes has been designed and synthesized in chapter 5. The photophysical properties of these Zn(II) complexes are affected by the counterions. By altering the counterions, the emission peak can be changed from 549 nm to 622 nm. Interestingly, the CIE coordinate and the emission colors can be simply tuned by adjusting the concentration of 11d in the polyether. Under an electric field of about 15 V applied onto the electrodes, the emission color of the solution of 11b-11d near the cathode changed its original emission color to sky blue. Based on this interesting electrochromic fluorescence of 11d, a quasi-solid information recording device has been successfully designed. Furthermore, data encryption has been realized by combining 1d with BODIPY, and information decoding processed has been accomplished, for the first time, by employing TPA excitation techniques, in which the large TPA cross section of 11d is differentiated from small TPA cross section of common organic dyes. Finally, Chapters 6 and 7 present the concluding remarksand the experimental details of the work described in Chapters 25

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Favicchio, Rosy. "Fluorescence molecular tomography evaluation and applications for in vivo imaging of tumour proliferation." Thesis, University of Portsmouth, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516877.

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Persson, Gustav. "Temporal Modulation in Fluorescence Spectroscopy and Imaging for Biological Applications." Doctoral thesis, KTH, Experimentell biomolekylär fysik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-10243.

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This thesis explores the benefits of intensity modulation for the purpose of extending the range of applications of fluorescence spectroscopy and imaging in cellular and molecular biology and medicine. Long-lived transient states of fluorescent molecules can, because of their long lifetimes, be used to detect subtle changes in the microenvironment of the molecule. A method for determining the kinetic rates for transitions to and from such states by registration of changes in the average fluorescence intensity related to different modulation of the excitation source is introduced. It combines the detection sensitivity of fluorescence with the environmental sensitivity of the long-lived transient states and allows the use of slow detectors such as CCD cameras, making parallelization and wide-field imaging possible developments. An extension of this method, generating image contrast based on triplet state population using a standard laser scanning microscope, is also shown. A strategy to combine fluorescence correlation spectroscopy (FCS) with modulated excitation, in a way that allows extraction of correlation data for all correlation times, is presented. This enables the use of modulation to optimize measurement conditions with respect to photophysical properties of the dyes used. FCS with modulated excitation will probably prove useful in future studies involving multiple kinetic processes occurring in overlapping time ranges. One of the ideas from this project also constitutes a powerful method for generating artifact free correlation curves from data sets where sections have been removed. This is potentially very useful in biological studies where spikes in the measurements often cause problems. In the final project, cross-correlation and alternating excitation are combined in measurements on a pH-sensitive ratiometric dye to clearly distinguish the protonation–deprotonation dynamics from other processes. The presented approach makes the protonation related fluctuations manifest themselves as a very distinct anti-correlating component in the correlation curve. This enables robust data analysis using a simple model.
QC 20100805

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Friedman, Mikaela. "Affibody molecules targeting the epidermal growth factor receptor for tumor imaging applications." Doctoral thesis, Stockholm : School of Biotechnology, Royal Institute of Technology (KTH), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4710.

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Daryaei, Iman, and Iman Daryaei. "Study, Evaluation, and Applications of MRI Contrast Agents that Work Based on CEST and T2-EX Mechanisms." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/625366.

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MRI is a powerful imaging method that offers several advantages including non-ionizing radiation, significant depth of penetration, and great spatial resolution. Current demand for precision medicine and the movement toward personalized medicine have encouraged researchers in the field of medical imaging to develop MRI-based techniques. Various techniques are now available for molecular imaging by MRI. MRI started by utilizing T1 relaxation properties of molecules but soon after other relaxation mechanisms such as T2 and recently Chemical Exchange Saturation Transfer (CEST) were developed. Each of those MRI techniques offers advantages and disadvantages such as differences in experimental procedures, complexity of the method, selectivity and specificity of signals, and translation into clinical applications. We have been developing MRI techniques and responsive contrast agents for CEST MRI in the Pagel laboratory (Contrast Agent and Molecular Imaging Laboratory, also called CAMEL) for the past decade. We have mainly utilized MRI techniques and responsive contrast agents to detect and measure cancer biomarkers. Detection of the activity of enzymes and measurement of pH have been our main focus, and we have developed catalyCEST MRI probes and techniques for the detection of the activity of enzymes and acidoCEST for the measurement of pH. My research started with investigation on paramagnetic agents as potential CEST MRI probes (paraCEST) and continued with an investigation on diamagnetic agents (diaCEST). I completed several projects in which I prepared and evaluated paraCEST and diaCEST contrast agents for the detection of DT-diaphorase, and alkaline phosphatase enzymes, respectively. Although CEST MRI was my main activity in CAMEL, I started a new direction in CAMEL after encountering a series of observations that were unexplainable with CEST MRI. Through my research, I introduced a new class of responsive contrast agents based on the T2-Exchange (T2-Ex) relaxation mechanism. I employed the T2-Ex mechanism to evaluate responsive contrast agents for the detection of nitric oxide biomolecule and nitroreductase enzyme. My research activities in the CAMEL group resulted in one review paper, one book chapter, two published research articles, and two submitted research manuscripts at the time of preparing my PhD dissertation. In addition to my projects, I was involved in another project that focused on nanocapsule drug delivery, which resulted in a second author publication.

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Wilson, Neil. "Studies on the reactivity of copper complexes with NO and CO, and their applications in molecular imaging." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9490.

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This thesis is concerned with the development of metal complexes capable of selectively trapping and releasing nitric oxide and carbon monoxide. In the case of the former, we have utilised copper(II) complexes containing a nitrobenzofurazan (NBD) fluorophore which exhibit a restoration of fluorescence in the presence of nitric oxide. These complexes have shown to be water soluble, cell permeable, non toxic and selective towards nitric oxide over several other reactive oxygen and nitrogen species of biological relevance. For this reason these complexes have been used for the cellular imaging of nitric oxide. We have shown that our complexes can be localised within the cell membrane and can be used to image NO with a detection limit of 1μM. The second part of this thesis deals with the synthesis of copper(I) complexes of tris(2- pyridylmethyl)amine (tmpa) and their reactivity towards carbon monoxide. The aim of these studies was to develop pre-concentrating reagents capable of trapping 11CO for radiolabelling applications (more specifically for Positron Emission Tomography (PET) labelling). Indeed, these copper(I) complexes have been shown to trap near quantitative amounts of 11CO from nitrogen-rich gas streams without the need for elevated pressure or low temperature. To be useful, the trapping/release system must be compatible with some means of incorporating the CO into the desired target molecule. It has been demonstrated that [Cu(tmpa)(CO)]+ can be used as the CO source when performing palladium-catalysed carbonylations between amines and aryl halides to form amides.

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Teeling-Smith, Richelle Marie. "Single Molecule Electron Paramagnetic Resonance and Other Sensing and Imaging Applications with Nitrogen-Vacancy Nanodiamond." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1424779811.

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Pliquett, Jacques. "Development of fluorescent platforms for the design of multifunctional compounds for in vitro and in vivo applications in molecular imaging." Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCK067.

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Cette thèse s’inscrit dans le développement et l’évaluation de nouvelles plateformesmoléculaires pour une application en imagerie optique par fluorescence. Nous avons cherché àdévelopper de nouveaux outils multifonctionnels et modifiables à façon. Cette approche estnécessaire car l’introduction d’un fluorophore peut fortement influencer les propriétés ducomposé final. Cela signifie que l’introduction du fluorophore sur l’agent sélectionné doit avoirêtre réalisé dès le départ. Pour cela deux axes principaux ont été étudiés; le premier consiste àutiliser des BODIPY pour le développement d’agents thérapeutiques traçables pour uneapplication principalement in vitro; le deuxième cible sur la conception de plateformes à based’AzaBODIPY compatibles avec l’imagerie in vivo.Dans la première partie deux fluorophores à base de 3,5-dichloro-BODIPY ont été identifiéscomme plateformes prometteurs. Ils ont été fonctionnalisés sélectivement par un agent or(I)-phosphine, un thiosucre et un phosphonium afin de pouvoir étudier l’influence du positionnementde chaque substituant sur les propriétés finales. Nous avons pu démontrer qu’unefonctionnalisation sélective et spécifique est possible avec ces substituants fragiles ; cela nous apermis de développer 12 agents théranostiques à base d’or(I). Les propriétés photophysiques etbiologiques ont ensuite été évaluées; pour cela nous avons déterminé leurs propriétés antiprolifératives (3 lignés cellulaires), la balance hydrophile, l’accumulation d’or dans les cellules etla localisation des composés des composés par microscopie confocale. Cette stratégie deplateforme multifonctionnelle nous a permis de développer un panel de composés traçables ayantdes activités mixtes ainsi que des distributions cellulaires distinctes. Cette étude a permisl’identification et la sélection de trois ou quatre composés qui feront l’objet d’une étudeapprofondie.Dans la deuxième partie de cette thèse nous avons développé des plateformes multifonctionnellescompatibles avec l’imagerie in vivo; pour cela nous avons poursuivi deux approches différentes.La première était l’utilisation de 1,7-di(phenol)3,5-di(phenyl)-azaBODIPY, suivi par safonctionnalisation sur les groupements OH afin de développer un traceur bioconjugablefluorescent dans le proche infrarouge (NIR-I). Malheureusement ce traceur possède despropriétés optiques très défavorables. Nous avons alors développé une approche innovante baséesur la fonctionnalisation de l’atome de bore. En s’appuyant sur cette approche deux traceursfortement fluorescents dans le proche infrarouge et solubles dans l’eau ont été développés. Cesfluorophores ont été conjugués sur un anticorps innovateur afin de permettre l’imagerie optiquedu ligand PD-L1. Les traceurs se sont montrés stables pour au moins 48h dans le plasma murin etpossèdent de très bonnes propriétés optiques. Comme preuve de concept nous avons conduitune étude préclinique in vivo. Cette étude a montré que les traceurs sont fortement fluorescents(NIR-I) et ne possèdent pas de toxicité imminente.La méthodologie développée pendant cette thèse présente un grand potentiel pour des étudesallant plus loin et des futures applications ; il est possible d’appliquer les principes et outilsdéveloppés sur d’autre fluorophores ; la méthodologie permet une fonctionnalisation très richeavec une grande variété de substituants d’intérêt. Son utilisation n’est pas limitée aux applicationsbiologiques, biochimiques et médicinales
The objective of this thesis was the development and evaluation of new molecular platformsfor optical fluorescence imaging applications. This work sought to develop new tools that caneasily be modified and adapted to the specific needs of the intended use. This is required asthe fluorophore will influence the final properties and should thus be incorporated beforestructural optimization of the selected agent rather than at the very end. Two main axes wereexplored; the use of BODIPYs for the development of trackable therapeutic agents that areprimarily intended for in vitro applications and the use of azaBODIPYs for the design of an invivo compatible fluorescent platform.In the first part two fluorophores on the basis of a 3,5-dichloro-BODIPY were identified aspromising platforms. These platform molecules were selectively functionalized using a gold(I)-phosphine moiety, a thiosugar and a phosphonium to explore their selective functionalizationand investigate the influence of each substitutents position on the final properties. Weshowed that a site-specific, selective functionalization with these fragile substituents ispossible and developed 12 gold(I)-bearing therapeutic agents. We evaluated thephotophysical properties of all obtained compounds which was followed by a characterizationof their biological properties (antiproliferative properties on 3 cancer cell lines, lipophilicbalance and cellular gold accumulation as well as fluorescence imaging on 3 cell lines for upto 24h). We succeeded in developing a panel of closely related trackable compounds thatdisplay mixed activity in cells and distinct cellular localization. This investigation permitted theselection of three to four hits that will be studied further.In the second part we developed an in vivo-compatible multifunctional platform following twostrategies: the first was the use of 1,7-di(phenol)-3,5-di(phenyl)-azaBODIPY and thefunctionalization of the hydroxy groups for the development of a bioconjugable NIR-I probe.Unfortunately the developed probe displayed very unfavourable optical properties; wetherefore developed a new strategy that is entirely based on the functionalization of the boronatom. Using this approach we successfully synthesized 2 watersoluble, strongly fluorescent(NIR-I) molecular platforms that were conjugated to an innovative antibody to image the PD-L1 ligand. The developed probes displayed excellent optical properties, are stable for at least48h in mice plasma and were validated in a preclinical study on mice. The developed probesdisplayed strong fluorescence in vivo and showed no acute toxicity.The developed methodology shows great potential for further investigations and futurestudies; it can be transposed onto other closely related fluorophores and permits versatilefunctionalization with a large variety of compounds of interest. Its use is thus not limited tobiological, biochemical and medical applications

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Hernandez, Christopher. "Stabilized Nanobubbles for Diagnostic Applications." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1521123706295258.

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Garbin, Valeria. "Optical tweezers for the study of microbubble dynamics in ultrasound." Doctoral thesis, Università degli studi di Trieste, 2007. http://hdl.handle.net/10077/3220.

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2005/2006
Optical tweezers enable for non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. Understanding the dynamics of ultrasound-driven contrast agent microbubbles from a fundamental physical standpoint is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. However, experiments on bubble dynamics presently suffer from a lack of control on bubble position, because of buoyancy, microstreaming and bubble clustering. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, an ultra-high speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this thesis, optical tweezers and an ultra-high speed camera are integrated into an experimental setup to control the boundary conditions and record the oscillations of the microbubbles. Optical tweezers are commonly obtained by focusing a laser beam through a microscope objective, as the high intensity gradient in the focal region causes dielectric microparticles to be attracted in the focus. In the special case of microbubbles, which exhibit a lower refractive index than the surrounding liquid, the opposite situation arises: they are pushed away from the region of maximum intensity. Nevertheless, microbubbles can be trapped in the dark core of a donut-shaped trap, which can be obtained e.g. by focusing a Laguerre-Gaussian beam. In our setup, a Gaussian beam is converted to a Laguerre-Gaussian mode by using diffractive optical elements implemented on a spatial light modulator. This allows to trap and manipulate single or multiple microbubbles, and to control the distance from interfaces as well as the bubbleto- bubble distance. The “Brandaris 128” ultra-high speed camera is used, in combination with the optical tweezers, to recorded the bubble oscillations at a frame rate of 15 million frames per second. The influence of a rigid wall on the resonance frequency and oscillation amplitude was experimentally investigated. An experimental phospholipid-coated agent (BR-14, Bracco Research S.A., Geneva, Switzerland) was used throughout the experiments. A resonance frequency curve was recorded for the same bubble positioned at the wall and at controlled distance from the wall. The experiments show a drop in the resonance frequency for the bubble close to the ii Abstract wall, as expected from the theoretical models. These results are highly relevant for molecular imaging applications, where the response of targeted microbubbles needs to be discriminated from that of freely flowing ones. We also quantify the bubble-to-bubble interaction, in two ways: first, we compare the change of the radial oscillations of one bubble with and without a neighboring bubble. Second, we resolve the change in distance between two bubbles during ultrasonic insonation. This results from an acoustical, generally attractive, interaction force between the bubbles, termed secondary Bjerknes force. To understand this rich two-bubble dynamics, we couple a recent single-bubble model, accounting for both gas and monolayer properties with a model quantifying the mutual interaction of bubbles in their translation and oscillations. Experiments where optical tweezers are used as a force sensor to measure the binding force in an antigen-antibody complex at the single molecule level are also presented. In the future, the possibility of combining optical micromanipulation with the force-sensing capabilities of optical tweezers will open the way to a new class of experiments which will give us a deeper insight into fundamental bubble phenomena and find direct application to new ultrasound-assisted targeting strategies.
XIX Ciclo
1979

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Nord, Christoffer. "The Colours of Diabetes : advances and novel applications of molecular optical techniques for studies of the pancreas." Doctoral thesis, Umeå universitet, Umeå centrum för molekylär medicin (UCMM), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119845.

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Diabetes is a rapidly increasing health problem. In a global perspective,approximately 415 million people suffered from diabetes in 2015 and this number ispredicted to increase to 640 million by 2040. To tackle this pandemic there is a needfor better analytical tools by which we can increase our understanding of the disease.One discipline that has already provided much needed insight to diabetes etiology isoptical molecular imaging. Using various forms of light it is possible to create animage of the analysed sample that can provide information about molecularmechanistic aspects of the disease and to follow spatial and temporal dynamics. The overall aim of this thesis is to improve and adapt existing andnovel optical imaging approaches for their specific use in diabetes research. Hereby,we have focused on three techniques: (I) Optical projection tomography (OPT),which can be described as the optical equivalent of x-ray computed tomography(CT), and two vibrational microspectroscopic (VMS) techniques, which records theunique vibrational signatures of molecules building up the sample: (II) Fouriertransforminfrared vibrational microspectroscopy (FT-IR) and (III) Ramanvibrational microspectroscopy (Raman). The computational tools and hardware applications presented here generallyimprove OPT data quality, processing speed, sample size and channel capacity.Jointly, these developments enable OPT as a routine tool in diabetes research,facilitating aspects of e.g. pancreatic β-cell generation, proliferation,reprogramming, destruction and preservation to be studied throughout the pancreaticvolume and in large cohorts of experimental animals. Further, a novel application ofmultivariate analysis of VMS data derived from pancreatic tissues is introduced.This approach enables detection of novel biochemical alterations in the pancreasduring diabetes disease progression and can be used to confirm previously reportedbiochemical alterations, but at an earlier stage. Finally, our studies indicate thatRaman imaging is applicable to in vivo studies of grafted islets of Langerhans,allowing for longitudinal studies of pancreatic islet biochemistry.viIn summary, presented here are new and improved methods by which opticalimaging techniques can be utilised to study 3D-spatial, quantitative andmolecular/biochemical alterations of the normal and diseased pancreas.

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Grandclaude, Virgile. "Synthèse de sondes chémiluminescentes et profluorescentes pour des applications en imagerie in vivo." Thesis, Rouen, INSA, 2011. http://www.theses.fr/2011ISAM0009.

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L’imagerie moléculaire optique joue maintenant un rôle essentiel dans le diagnostic pré-clinique et le développement de médicaments. En effet, c’est un outil précieux dans la détection et le suivi de cellules vivantes que ce soit en utilisant de simples agents de marquage ou des sondes plus développées, dites « intelligentes » et activées uniquement par une interaction spécifique avec le bio-analyte ciblé. Ce travail de thèse a consisté à développer des outils synthétiques innovants afin d’optimiser les paramètres physico-chimiques et les propriétés optiques des sondes luminescentes. Ceci dans le but de répondre à la problématique complexe de l’imagerie dans le contexte in vivo. Nous avons notamment travaillé sur des aspects de pro-fluorescence et de chémiluminescence. De nouveaux pro-fluorophores à phénol basés sur une architecture originale de type bis-coumarinique ont été développés. De plus, nous avons mis en place une méthode d’hydrosolubilisation généralisable aux fluorophores à phénol de type coumarine et xanthène. Nos recherches en chémiluminescence ont permis la synthèse de nouveaux chémiluminophores couplés à des fluorophores organiques afin d‘augmenter l’efficacité d’émission de chémiluminescence dans le rouge. Enfin, nos travaux ont permis de mettre en place les premières « cassettes » chémiluminescentes basées sur une architecture de type 1,2-dioxétane
Optical molecular imaging is now playing a pivotal role both in pre-clinical diagnosis and drug development. Indeed, this is a valuable tool for the real time detection and monitoring of living cells either through the use of structurally simple labels or more recently by means of sophisticated fluorescent probes, called “smart” probes and only activatable upon specific interaction with the targeted bio-analyte. The aim of this PhD work was the design of new synthetic tools aimed at optimizing physico-chemical and optical properties of fluorescent probes intended for challenging in vivo imaging applications. We have focused on the pro-fluorescence and chemiluminescence approaches. New phenol-based pro-fluorophores have been developed by using an original bis-coumarinic scaffold. In the context of the chemistry of fluorophores, we have also investigated a general method for the water-solubilisation of phenol-based fluorophore belonging to the coumarin and xanthene families. Our research in chemiluminescence has led the synthesis of new chemiluminophores covalently linked to fluorescent organic dyes aimed at increasing the emission efficiency in the red region of such chemiluminophores. Thus, the first chemiluminescent “energy transfer cassettes” based on a 1,2-dioxetane scaffold have been obtained

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Fournier, I. "Développements en Imagerie par Spectrométrie de Masse MALDI et Applications aux Problématiques Biologiques." Habilitation à diriger des recherches, Université des Sciences et Technologie de Lille - Lille I, 2005. http://tel.archives-ouvertes.fr/tel-00167305.

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L'imagerie par spectrométrie de masse MALDI est une technologie actuellement en plein essor. Elle permet d'obtenir rapidement en une seule étape d'acquisition la répartition moléculaire de différents composés (en particulier protéines) présents dans un tissu ; en s'affranchissant des étapes longues et coûteuses en échantillons que sont les extractions et séparations habituellement nécessaires par des techniques plus classiques.
Cependant, afin d'augmenter encore la potentialité de cette technologie, des développements restent encore à effectuer. Les recherches menées ont donc plus particulièrement portées sur ces développements.
En particulier, la recherche et l'étude de nouvelles matrices plus adaptées à l'analyse directe de tissu en MALDI sont particulièrement importantes. Dans ce contexte, certaines matrices ioniques se sont révélées particulièrement adaptées aux tissus en permettant d'obtenir une plus grande intensité du signal, un plus grand nombre de composés détectés, de bonnes performances en mode négatif, une grande homogénéité de cristallisation, une grande stabilité sous vide et une faible ablation de matériel consécutivement à l'irradiation laser. Dans un autre aspect, le traitement préalable des tissus permet également une amélioration de la qualité spectrale et des performances d'études structurales en mode MS/MS. Se sont révélés particulièrement intéressants les traitements des tissus aux solvants organiques et les digestions enzymatiques et en particulier pour les tissus conservés en blocs de paraffine après fixation.
D'autre part l'étude de la répartition des ARNm au sein des tissus est un développement crucial afin d'obtenir des images de colocalisation transcriptome/protéome. Est proposé dans ce travail un nouveau concept permettant de réaliser ces images, basé sur une analyse indirecte des ARNm, au travers de l'utilisation d'un groupement photoclivable relié à un peptide marqueur de séquence connue qui sera détecté.
Enfin, l'ensemble de ces développements trouve de nombreuses applications dans le domaine de la biologie et notamment dans le cadre de pathologies tel que le cancer de l'ovaire.

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Gavrilovic, Milan. "Spectral Image Processing with Applications in Biotechnology and Pathology." Doctoral thesis, Uppsala universitet, Centrum för bildanalys, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-160574.

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Color theory was first formalized in the seventeenth century by Isaac Newton just a couple of decades after the first microscope was built. But it was not until the twentieth century that technological advances led to the integration of color theory, optical spectroscopy and light microscopy through spectral image processing. However, while the focus of image processing often concerns modeling of how images are perceived by humans, the goal of image processing in natural sciences and medicine is the objective analysis. This thesis is focused on color theory that promotes quantitative analysis rather than modeling how images are perceived by humans. Color and fluorescent dyes are routinely added to biological specimens visualizing features of interest. By applying spectral image processing to histopathology, subjectivity in diagnosis can be minimized, leading to a more objective basis for a course of treatment planning. Also, mathematical models for spectral image processing can be used in biotechnology research increasing accuracy and throughput, and decreasing bias. This thesis presents a model for spectral image formation that applies to both fluorescence and transmission light microscopy. The inverse model provides estimates of the relative concentration of each individual component in the observed mixture of dyes. Parameter estimation for the model is based on decoupling light intensity and spectral information. This novel spectral decomposition method consists of three steps: (1) photon and semiconductor noise modeling providing smoothing parameters, (2) image data transformation to a chromaticity plane removing intensity variation while maintaining chromaticity differences, and (3) a piecewise linear decomposition combining advantages of spectral angle mapping and linear decomposition yielding relative dye concentrations. The methods described herein were used for evaluation of molecular biology techniques as well as for quantification and interpretation of image-based measurements. Examples of successful applications comprise quantification of colocalization, autofluorescence removal, classification of multicolor rolling circle products, and color decomposition of histological images.

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Ben, Azzouna Rana. "Le gallium : applications en vue d'une utilisation en imagerie moléculaire." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCD053.

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La tomographie par émission de positons (TEP) est une technique d’imagerie moléculaire avec de meilleures performances que la tomographie par émission monophotonique. Son utilisation contribue à l’amélioration des prises en charge des patients. Dans les centres dépourvus de cyclotrons, le 68Ga disponible à partir d’un générateur constitue une alternative pour le développement de traceurs TEP. Pour pouvoir développer des 68Ga-traceurs, un travail de caractérisation de la qualité des éluats a été effectué. Des méthodes de marquage adaptées ont été mises en place et validées. Nous nous sommes intéressés à trois cibles moléculaires particulièrement intéressantes dans les pathologies cardiovasculaires: les récepteurs de la somatostatine (SSTR) surexprimés dans les tumeurs neuroendocrines (TNE) mais constituant aussi une cible d’intérêt dans les pathologies cardiovasculaires à composante inflammatoire ; la phosphatidylsérine (PS), un marqueur de l’apoptose cellulaire et de l’activation plaquettaire ; la P-sélectine, un marqueur des activations plaquettaire et endothéliale. Les traceurs suivants ont été développés: 1) Analogues de la somatostatine ciblant les SSTR: a)68Ga-DOTANOC validé pour l’imagerie des TNE-Gastroentéropancréatiques dans le cadre d’un essai clinique multicentrique. b) 68Ga-NODAGANOC testé in vitro sur des cellules d’adénocarcinome pancréatique. Cette validation initiale dans l’application la plus fréquente(oncologie) a pour objectif de faciliter le passage vers des applications cardiovasculaires futures (athérosclérose, myocardite...) ; 2) Un peptide ciblant la PS : le 68Ga-P04087 ; 3) Un polysaccharide ciblant la P-sélectine: 68Ga-NODAGA-Asphy. Les deux derniers traceurs ont été testés sur un modèle d’endocardite infectieuse chez le rat
The Positron emission tomography (PET) is a molecular imaging technique with usually better performances than Single-Photon Emission Computed Tomography. Consequently, the use of PET and appropriate tracers could enable clinicians to make a better therapeutic decision, thus improving the management of patients. In centers without cyclotrons, 68Ga available from a generator is an alternative for the development of PET tracers. In order to develop 68Ga labeled-molecules, a characterization of the quality of the eluates was performed. Radiolabeling techniques adapted to the quality of the starting material were developed and validated. In this thesis we focused on three particularly interesting molecular targets in cardiovascular pathologies: somatostatin receptors (SSTR), overexpressed in neuroendocrine tumors (NETs) but also constituting a target of interest in cardiovascular diseases with an inflammatory component; phosphatidylserine (PS), a marker of cell apoptosis and platelet activation; P-selectin, a marker of platelet and endothelial activation.The following tracers have been developed: 1) Somatostatin analogues which target SSTR: a) 68Ga-DOTANOC validated for Gastroenteropancreatic-NETs imaging and used in a multicenter clinical trial. b) 68Ga-NODAGANOC tested in vitro on pancreatic adenocarcinoma cells. This initial validation in the most common application (oncology) aims to facilitate the transition to future cardiovascular applications (atherosclerosis, myocarditis ...) 2) A peptide for PS targeting: 68Ga-P04087; 3) A polysaccharide for P-selectin targeting: 68Ga-NODAGA-Asphy. The last two radiolabeled molecules were tested in a rat model of infective endocarditis

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Castelló, Serrano Iván. "Design and applications for quantum-onion-multicode nanospheres and other luminescent semiconductor-derived nanocomposites." Doctoral thesis, Universitat Rovira i Virgili, 2013. http://hdl.handle.net/10803/119655.

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Los puntos cuánticos son nanopartículas semiconductoras que exhiben unas propiedades ópticas y electrónicas dependientes del tamaño. Debido a sus dimensiones en el rango de 1-100 nm, la relación superficie-volumen de estos materiales llega a ser enorme y sus estados electrónicos se vuelven discretos. Además, por el hecho de que el tamaño del nanocristal es más pequeño que el de un excitón, las cargas están espacialmente confinadas y esto eleva sus energías en lo que se conoce como confinamiento cuántico. Así, las propiedades optoelectrónicas están atribuidas a este efecto de confinamiento y esto permite calibrar la emisión. Los puntos cuánticos tienen una fluorescencia muy estable en comparación con los fluoróforos orgánicos que la pierden en cuestión de minutos. Además, y contrariamente a los fluoróforosogánicos, estos nanocristales tienen una amplia excitación y una emisión estrecha lo que los hace extremadamente aplicables para visualización multicolor. Calibrar la longitud de onda de emisión de los puntos cuánticos es simplemente una cuestión de calibrar su tamaño. Por todo estas razones, explicadas en el capítulo 1, los puntos cuánticos han desplazado a los fluoróforos convencionales como método para visualización en los últimos 5 años. Estos puntos cuánticos son tóxicos y necesitan ser encapsulados para prevenir envenenamiento por metales pesados cuando son usados en bioaplicaciones. Un trabajo previo en nuestro laboratorio, detallado en el capítulo 2, encontró un método de síntesis capa-a-capa para obtener nanocebollas, que consisten en varias capas de sílica rellenas con diferentes puntos cuánticos. Esta disposición es muy útil para tener diferentes colores, como si fuesen viales diferentes, confinados en unos pocos nanómetros. La matriz de sílica juega un papel importante para hacer a los puntos cuánticos solubles en agua y proteger su fotoluminiscencia del efecto de apagado, al menos en el rago de pH útil para las aplicaciones viológicas. Cuanto mayor es el grosor de la capa de sílica o mayor el número de capas, mayor es la protección ofrecida a los puntos cuánticos del interior. Basándonos en este principio, mostramos que estas nanocebollas, que nosotros llamamos nanocebollasmulticódigo (Quantum-onion-multicode, QOM), pueden ser usadas como sensor de pH, como se detalla en el capítulo 3. Se ha demostrado que la relación entre la intensidad de fotoluminiscencia entre dos poblaciones de puntos cuánticos se corresponde con el valor de pH del medio, haciendo que nuestro sistema confiera un carácter potencialmente aplicable como sensor ratiométrico de pH. Además, el desarrollo de puntos cuánticos dentro de espferas de sílica como sondas biomoleculares puede dar nuevas percepciones para paliar algunas limitaciones que tienen los puntos cuánticos por sí mismos de forma individual como marcadores biológicos, por ejemplo: mejor fotostabilidad si están dentro de la matriz, mayor superficie disponible para reacciones químicas, mejor capacidad de unión de las esferas, menor toxicidad, y mejor manipulación. Sin embargo, la mayoría de las nanopartículas orgánicas requieren de una funcionalización química con silano, tiol, amino, carboxilo u otros grupos con el fin de otorgarles propiedades aplicables para ser suministradas a células, como son: buena compatibilidad, gran afinidad entre el transportador y la carga, marcaje celular, estabilidad y mayor tiempo de circulación. En el pasado, los hidróxidos de doble capa, también conocidos como materiales tipo hidrotalcita o arcillas aniónicas, han sido la excepción a esta regla. Estos materiales consisten en capas de nanoláminas cargadas positivamente en estructura tipo brucita neutralizada por aniones en el espacio interlaminar. Desde un punto de vista médico, se han publicado muchos cambios interesantes con estos materiales para albergar fármacos y biomoléculas ya sea por intercambio aniónico o por proceso de delaminación-relapilamiento. Este tipo de material has sido usado para transportar puntos cuánticos solubles en agua hechos de teulro de cadmio (capítulo 4) o nanopalos (capítulo 5). Por una parte, las hidrotalcitas intercalan a los puntos cuánticos de teluro de cadmio muy rápido y no se necesitan delaminarse previamente. El material híbrido muestra una alta estabilidad en medio fisiológico a diferentes pH, convirtiéndolo en una herramienta de visualización aplicable para el diagnóstico en nanomedicina. Notoriamente, las propiedades ópticas de los puntos cuánticos sufrieron un salto hacia el azul, atribuido a diferentes factores, como se detalla en el capítulo 4. Sin embargo, este efecto es reversible tras la disolución de la transportador sólido, la hidrotalcita. Con lo que podemos decir que los puntos cuánticos de teluro de cadmio muestran un efecto de memoria óptica. Estas transiciones ópticas se detienen cuando rodeamos los puntos cuánticos de una capa de sílica, preparando puntos cuánticos@silica/hidrotalcita, siendo la capa de sílica una barrera entre las nanopartículas y las arcillas. Esta combinación conduce a una barrera eficiente para los procesos de liberación de puntos cuánticos al medio biológico, tratándose por tanto de un andamiaje inorgánico nanoestructurado que evita toxicidad a la vez que permite una visualización múltiple y un diagnóstico simultáneo en sistemas terapéuticos avanzados. Por otro lado, se prepararon hidrotalcitas cargadas con partículas elongadas luminiscentes de CdSe@CdS, siendo la delaminación el mejor proceso para la carga debido al mayor tamaño de las nanopartículas, como se detalla en el capítulo 5. Este material híbrido resultó tener más luminiscencia y mayor tiempo de vida que cuando estaba cargado con puntos cuánticos, lo que supone una ventaja y un requisito para observaciones in vitro de tiempos prolongados. En consecuencia, se requieren una menor cantidad de nanopartículas y una menor excitación, lo que implica una menor toxicidad o daño a las células. Con estos resultados remarcamos que la combinación de dos campos como son el óptico y el de los nanomateriales, puede crear herramientos potentes para bioaplicaciones. En el capítulo 6, se usan cultivos celulares incubados con los materiales híbridos detallados en los capítulos 4 y 5 para demostrar la utilidad de esta clase de materiales como agentes de visualización. Observamos una dependencia respecto al diámetro de las nanopartículas y la calidad de los resultados, pero se necesitan más pruebas para esclarecer si esta correlación es verdadera o otros factores como la estructura del material transportador están implicados. Finalmente, en el capítulo 7, detallo como, combinando la especificidad de interacciones biomoleculares y la capacidad de calibrado de las propiedades ópticas de puntos cuánticos y fluoróforos, hemos desarrollado por primera vez un sistema in vitro para detectar fibrosis quística tanto de forma cualitativa (1nanoSi) como cuantitativa (2nanoSi). La novedad de nuestro sistema es el uso de procesos de transferencia de energía (FRET), cuyo mecanismo describe como se produce transferencia de energía de un dador (inicialmente en su estado electrónico excitado) y un aceptor a través de un emparejamiento dipolo-dipolo no radiativo. Para que se dé este proceso debe de haber un buen solapamiento entre la emisión del dador y la absorción del aceptor. Además, es un proceso muy dependiente y limitado por la distancia. Hemos anclado un péptido corto previamente marcado con un derivado de rodamina llamado TAMRA a la superficie de las nanoesferas rellenas de un tipo (1nanoSi, rellenas con CdSe540) o dos tipos (2nanoSi, rellanas con CdSe540 y CdSe660, siendo los números las longitudes de emisión) puntos cuánticos. Estas esferas se funcionalizaron con grupos amino para unir los péptidos marcados con TAMRA. Las secuencias de los péptidos diferían en un solo aminoácido: uno tiene prolina y el otro arginina en su lugar. La gente con fibrosis quística tiene mala digestión de péptidos porque los enzimas proteolíticos tienen problemas para llegar al duodeno, que es donde estos enzimas son activos. Elegimos la tripsina como enzima proteolítico por su especificidad de corte, ya que solo corta tras lisina y arginina pero no si estos van seguidos por prolina. Por tanto, en condiciones sanas, la secuencia peptídica sufrirá corte y no se observará FRET en el péptido que no tiene prolina. Al observar los espectros de emisión de los sistemas 1nanoSi vimso que había FRET debido a un buen solapamiento entre la emisión de los puntos cuánticos verdes (CdSe540) y la absorción del fluoróforo TAMRA. Cuando se produce el corte del péptido por la acción de la tripsina, se rompe este proceso de transferencia de energía y la relación entre la fluorescencia entre el dador y el aceptor cambia: el pico del TAMRA decrece mientras que el de los puntos cuánticos verdes aumenta durante la digestión. Pero estos es solo cualitativo, el sistema necesita un tercer componente que no se vea afectado por el FRET para ser cuantitativo. Decidimos usar puntos cuánticos rojos (CdSe660). Ahora nuestro sistema tenia dos capas (2nanoSi), la más interna rellena con puntos cuánticos rojos y la más externa con puntos cuánticos verdes. Tras observar los espectros de emisión vimos que solo cambiaban los picos de los puntos cuánticos verdes y fluoróforo, en cambio el pico de los puntos cuánticos rojos no variaba, lo que significa que solo se producía FRET entre los CdSe540 y el TAMRA. A pesar del pequeño solapamiento entre la emisión del TAMRA y la absorción de los puntos cuánticos rojos, la distancia entre ellos es demasiado grande y no se produce el FRET. Observamos diferentes comportamientos dependiendo de la concentración de tripsina. Usamos la relación entre la intensidad de fluorescencia entre las dos poblaciones de puntos cuánticos como sensor ratiométrico. Dibujando los valores de esta relación de intensidades a través del tiempo obtuvimos las cinéticas de la digestión para diferentes concentraciones de tripsina. A mayor concentración, más rápida era la digestión. La recta patrón resultante de dibujar los valores experimentales de la relación de intensidades I540/I660 para un tiempo de digestión de 10 minutos demostró una buena linearidad que permite determinar la concetración de enzima a niveles clínicamente relevantes para poder diagnosticar la fibrosis quística. En global, estos resultados nos permiten proponer el sistema 2nanoSi como un sensor ratiométrico de fluorescencia y herramienta para calcular la concentración de tripsina, siendo además un método para detectar la fibrosis quítica y otras enfermedades relacionadas con el páncreas fácil de usar, rápido y no invasivo.

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Koonjoo, Neha. "Development of Overhauser-enhanced magnetic resonance imaging in vivo : application to molecular imaging of proteolysis." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0157/document.

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Ce travail fait l’objet d’une avancée scientifique dans le développement de la technique d’IRM rehaussée par l’effet Overhauser dans la souris à 0,2 T. Cette dernière repose sur le transfert de polarisation des spins électroniques saturés d’un radical libre vers les spins des protons (généralement de l’eau) voisins pour rehausser le signal RMN du proton. Notre équipe a développé cette technique pour détecter une activité protéolytique au travers de deux stratégies. La première partie de la thèse a été de détecter pour la première fois une activité protéolytique in situ dans des souris saines et in vitro sur cellules vivantes. L’efficacité du rehaussement par effet Overhauser repose sur le temps de corrélation des spins des électrons non-appariés. Un radical nitroxyde greffé à l’élastine a été utilisé comme substrat. La protéolyse de ce dernier par des élastases pancréatiques a conduit l’observation en 3D d’un rehaussement du signal RMN de plus de 10 fois dans le tube digestif de souris vivantes. De plus, des développements méthodologiques, tels que l’implémentation de la séquence TrueFISP, le sous-échantillonnage par la méthode “Keyhole”, et la reconstruction des données en 3D ont été faits. La deuxième stratégie repose sur des molécules de nitroxyde ayant l’unique propriété de pouvoir décaler leurs pics de résonance après hydrolyse. Un nitroxyde phosphorylé en position Béta pouvant être détecté à deux fréquences spécifiques différentes avant et après hydrolyse d’un groupement chimique a été synthétisé par des chimistes à Marseille. L’hydrolyse de cette macromolécule a été observée in vivo dans l’estomac de souris saines avec des rehaussements de plus de 400% et imagée en 3D avec une bonne résolution spatio-temporelle. Ainsi, une prochaine étape serait de poursuivre ce travail sur un modèle pathologique et développer cette technique à un champ magnétique plus bas
This work relates the continuity and advances in the implementation of the Overhauser-enhanced Magnetic Resonance Imaging technique on a 0.2 T scanner. Briefly, OMRI technique is based on polarization transfer of saturated electronic spins from free nitroxide radicals to proton spins of surrounding water molecules in the aim to drastically enhance proton NMR signal. To this technique, our research team has merged specific strategies for proteolytic activity detection. The first strategy relies on a 3D visualization of proteolytic activity happening in intact living cells or in vivo in healthy mice. With an Overhauser switch based upon changes in molecular tumbling time, high Overhauser enhancements of 10-fold were observed in the intestinal tract of mice after that elastolytic activity of our probe: the nitroxide-labeled elastin macromolecule took place. In addition, MRI developments - TrueFISP sequence implementation, undersampling Keyhole method and data reconstruction were carried out for imaging these rapid biological processes. A second exquisite strategy is also described using nitroxides with shifting resonant peaks. Here, a Beta-phosphorylated nitroxide molecule was specifically detected at two distinct frequencies: one for its substrate and the other for its product once hydrolysis took place. This hydrolysis was imaged in 3D in the stomach of living mice with Overhauser enhancements of more than 400% and with a good spatiotemporal resolution. The perspectives of this work lie on a future detection of a pathological proteolytic activity in vivo and eventually and development of very low magnetic field OMRI

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Glendenning, Jennifer Louise. "Application of molecular imaging to address current clinical challenges in breast cancer." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/application-of-molecular-imaging-to-address-current-clinical-challenges-in-breast-cancer(1d0b4ee4-bbce-43a1-8e01-4241cf667034).html.

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Breast cancer has multiple sub-types, designated in clinical practice by the presence or absence of prognostic and predictive biomarkers: oestrogen receptor, progesterone receptor and the human epidermal growth receptor 2 (HER2). Molecular imaging offers the opportunity firstly to non-invasively and dynamically interrogate in vivo tumour sites to provide prognostic and predictive evaluation at clinically meaningful on-treatment time points. Secondly, it may address diagnostic challenges in the metastatic setting by enabling assessment of inter- and intra-lesion heterogeneity without requirement for tissue acquisition from multiple sites. This thesis describes pre-clinical evaluation of a novel HER2 targeted DARPin radiotracer as an in vivo diagnostic across multiple tumour sites in murine models. Metastatic breast xenograft models were developed and validated using bioluminescence imaging and definitive histology for in vivo evaluation of a novel HER2 targeted DARPin radiotracer. In subsequent preclinical testing the DARPin radio-tracer failed to differentiate HER2 status of pre-clinical tumour xenografts models and this data raises significant questions regarding suitability of the DARPin radiotracer for clinical evaluation as a HER2 diagnostic. Additionally this work reports the set-up of a Phase 2 imaging feasibility study designed in two parts to evaluate post-cycle 1 PET response using the FLT- and FDG-PET imaging tracers to address clinical questions concerning tracer selection, scan acquisition and interpretation for validation of Positron Emission Tomography (PET) response as a predictive biomarker of neoadjuvant response in the triple negative breast cancer (TNBC) phenotype. Part A (participant recruitment completed) delivers the first phenotype specific repeatability constraints for the most commonly reported standardised uptake parameters (SUV); maximum (SUVmax), mean (SUVmean), peak (SUVpeak) and lean body mass corrected peak (SULpeak), assessed at conventional (90 minutes) and exploratory (120 and 180 minute) acquisition time points. The TNBC SUV intrinsic variability was 12-24% in both tracers and is dependent on scan acquisition time and SUV parameter. The FDG tracer has progressed to the second phase, Part B, to provide the first TNBC phenotype specific response data at a post-cycle 1 time point. The data suggests SUV change can predict later residual cancer burden and that >40% threshold change will be required to differentiate RCB 0-1 vs 2-3 response, a change that exceeds current EORTC/PERCIST recommendations for solid tumour chemotherapy response prediction. The study will inform future use of early FDG-PET as an exploratory biomarker in window of opportunity and novel therapy neo-adjuvant trials in TNBC.

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Wu, Changfeng. "Fluorescent conjugated polymer dots for single molecule imaging and sensing applications." Connect to this title online, 2008. http://etd.lib.clemson.edu/documents/1239895063/.

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24

Gyngell, M. L. "The application of steady-state free precession (SSFP) in 2d-Ft NMR imaging." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376522.

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Wild, D. "Glucagon-like peptide-1 receptor imaging probes translation of molecular biology into clinical application including insulinoma and islet cell imaging." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1325641/.

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Strong over-expression of Glucagon-like Peptide-1 receptors (GLP-1-R) in human pancreatic β cells and in insulinoma provide an attractive target for imaging. This is relevant since the preoperative localisation of insulinomas remains a challenge whilst serial measurements of functional β cell mass (BCM) may improve monitoring of novel diabetes therapies such as islet cell replacement. The aim of the thesis was to develop and evaluate GLP-1-R imaging probes and translate these into clinical applications, including insulinoma and β cell imaging. After extensive preclinical evaluation (internalization, externalization, biodistribution, pharmacokinetic, imaging and detailed dosimetry studies) of different GLP-1-R imaging tracers, the most promising probe, [Lys40(Ahx-DOTA-111In)NH2]-exendin-4, was selected for a first in man study. This novel probe was then prospectively evaluated in the management setting of benign and malignant insulinoma. An additional proof of concept study was performed in a patient after intramuscular transplantation of islet cells. The GLP-1-R planar imaging study showed focally raised tracer uptake in functional β cells transplanted into the brachioradialis muscle of a 48 years old woman. In patients with benign insulinomas GLP-1-R imaging was superior to conventional imaging (CT, MRI, somatostatin receptor imaging and endoscopic ultrasound) and detected the insulinoma in all 6 patients pre- and intra-operatively. This is in contrast to patients with malignant insulinoma where conventional imaging (CT and somatostatin receptor imaging) was superior to GLP-1-R imaging, which detected the primary tumour and metastases in only 4/11 patients. In conclusion, these data, based on the development and evaluation of a novel probe, strongly suggest that GLP-1-R imaging offers a new approach to localise benign insulinomas. With further refinements of the labelling agent and the imaging methodology, it is expected that GLP-1-R imaging may have the potential for non-invasive imaging of pancreatic islets and the early diagnosis of β cell graft rejection. This thesis has led to six original publications and one review article. These are listed at the end of each chapter. For a full list please see appendix.

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Norouzi, Neil. "Synthesis and application of novel near infrared cyanine dyes and optical imaging agents." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10002.

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The use of fluorescent imaging probes for the real time detection of cellular malfunctions, such as enzyme over expression has shown promise. Fluorescent dyes with absorption and emission values below 600 nm are limited in their in vivo applications due to high background auto-fluorescence and low resolution images. Employing near infrared (NIR) fluorophores such as cyanine dyes can overcome this disadvantage. Cyanine dyes can be synthesised using solution or solid-phase techniques with the use of solution phase chemistry allowing for larger scale and higher yielding reactions. Utilising a selection of functional groups and varying polymethine chain lengths a cyanine dye library with tuneable absorption and emission wavelengths was synthesised. This thesis gives the first detailed examples of how modifications on heptamethine cyanine dyes alter their cellular uptake and cellular toxicity. Furthermore, a NIR fluorescent microsphere is reported as well as NIR functionalised microspheres with the ability to be tracked within cells. Additional lines of work involved the synthesis of a fluorescent sensor for the visualisation of bacteria. Aminopeptidases are present within the peptidoglycan cell wall of Gram negative bacteria and therefore can be targeted for real time detection of bacteria to aid in the detection of infectious diseases. A coumarin based probe is reported which detects aminopeptidase in gram negative bacteria in vitro.

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Sinharay, Sanhita. "Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/612945.

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The in vivo detection of enzyme activity is a significant biomarker in tumorigenesis. Assessment of enzyme activity relative to enzyme concentration can serve as quite an accurate measurement of several disease states. Chemical Exchange Saturation Transfer (CEST) MRI is a non-invasive imaging technique that can be used to evaluate enzyme activity. Compared to other contrast agents CEST MRI agents have a slower chemical exchange rate and thus have greater specificity for detecting the intended biomarker. Chapter 1 provides an overview of the advances made in the field of molecular imaging for detection of cancer biomarkers. The molecular mechanism of each technique is explained with specific examples and advantages as well as disadvantages of each technique. Chapter 2 investigates the specific example of detection of an enzyme, γ-glutamyl transferase (GGT) in ovarian cancer tumor models using a catalyCEST MRI contrast agent. This chapter discusses the step-by step evaluation of the non-metallic contrast agent, from synthesis to evaluation of its catalytic efficiency with Michaelis Menten kinetics studies and finally in vivo GGT detection in ovarian tumor models of OVCAR-8 and OVCAR-3. Chapter 3 investigates the enzyme, Kallikrein-6 and its detection in HCT116 colon cancer tumor model. In addition to enzyme detection, enzyme inhibition using Antithrombin III inhibitor has also been explored within in vitro media and in vivo HCT116 tumor model. Chapter 4 introduces the catalyCEST agent for detection of sulfatase enzyme. This chapter discusses the synthesis of this agent and its ability to detect sulfatase in bacterial cell suspension and mammalian cell suspension. These examples portray catalyCEST MRI as a platform technology for enzyme activity detection. Finally in Chapter 5 future ideas have been proposed to improve the in vivo detection and broaden the applications of catalyCEST MRI in the field of enzyme studies.

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Fernández-Cuervo, Velasco Gabriela, and Velasco Gabriela Fernández-Cuervo. "Design, Synthesis and Application of catalyCEST MRI Agents for Enzyme Detection." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/626152.

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A notable need exists for noninvasive tools to increase our mechanistic understanding of disease progression at a cellular and molecular level. Studying the functions of proteins in their innate in vivo tissue environment can provide useful information about pathology enabling appropriate treatment and early diagnosis. Chemical exchange saturation transfer MRI contrast provides real-time functional characterization of the biological landscape and can be used to detect multiple enzyme biomarker activities. A dual-enzyme catalyCEST contrast agent was developed as a proof-of-concept to demonstrate the potential of using a salicylic acid scaffold and control the CEST signal through enzyme activation. In addition, a straightforward route was designed to synthesize a diamagnetic catalyCEST MRI agent that is a substrate for β-galactosidase and β-glucuronidase enzymes. The synthesized agents generated two peaks in the CEST spectrum, at 4.25 ppm corresponding to a carbamate moiety and at 9.25 ppm corresponding to the salicylic acid moiety. Chemical exchange rates of liable protons were determined from a QUESP Hanes-Woolf plot. In the presence of the corresponding enzymes, the catalyCEST agent was activated via saccharide hydrolysis followed by a spontaneous disassembly to produce 4-aminosalicylic acid. This reaction converted the carbamate moiety into a free primary amine, and caused a loss of CEST signal at 4.25 ppm. The CEST signal at 9.25 ppm was unaffected by the enzyme catalysis, and therefore used as an internal control signal. Michaelis-Menten enzyme kinetics studies were performed with CEST MRI to verify that catalyCEST MRI could truly detect enzyme activity. The Michaelis-Menten kinetics constants from MRI studies were compared to the kinetics constants measured with UVvis results from the same contrast agent, demonstrating the quantitative potential of catalyCEST MRI with both contrast agents. These findings demonstrate that the newly synthesized modular agents have the potential to become reliable catalyCEST MRI imaging probes. In addition, the modular design of these agents facilitates the conjugation of other enzyme substrates to the carbamate spacer, so that this approach constitutes a platform technology for the detection of enzyme activity.

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Shi, Fengjian. "LASER ELECTROSPRAY MASS SPECTROMETRY: INSTRUMENTATION AND APPLICATION FOR DIRECT ANALYSIS AND MOLECULAR IMAGING OF BIOLOGICAL TISSUE." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/445496.

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Chemistry
Ph.D.
This dissertation elucidates the instrumentation and application of a hybrid ambient ionization source, laser electrospray mass spectrometry (LEMS), for the direct analysis and molecular imaging of biological tissue without matrix deposition. In LEMS, laser pulses from a Ti:Sapphire laser amplifier (60 fs, 800 nm, and 1 mJ) interact with surface analytes and transfer them from the condensed phase into the gas phase without the requirement of either exogenous matrix or endogenous water in the sample. The laser vaporized analytes are captured and ionized by an electrospray source, and finally detected by a mass analyzer. It was found that a turn-key, robust femtosecond fiber laser with longer wavelength, longer duration, and lower pulse energy at 1042 nm, 425 fs, and 50 µJ, respectively, provided comparable results with the Ti:Sapphire laser. Vaporization of intact, dried or aqueous cytochrome c and lysozyme samples was demonstrated by the fiber laser. A charge states distribution at lower charge states indicating folded conformation of proteins and the hemoglobin α subunit-heme complex from whole blood was observed. Endogenous anthocyanins, sugars, and other metabolites were detected and revealed the anticipated metabolite profile for the flower petal and leaf samples by the fiber laser. Phospholipids, especially phosphatidylcholine, were identified from a fresh mouse brain section sample. These lipid features were suppressed in both the fiber laser and Ti:Sapphire LEMS measurement in the presence of optimal cutting temperature compounds which are commonly used in animal tissue cryosectioning. This dissertation also details the design of an automated mass spectrometry imaging source based on the Ti:Sapphire LEMS. The laser, translation stage, and mass analyzer are synchronized and controlled using a customized user interface to enable step-by-step scanning of the area of interest on a given tissue sample. The imaging source is coupled with a high resolution accurate mass quadrupole time-of-flight (QTOF) mass analyzer with tandem mass analysis capability. A lateral resolution of 60 µm was demonstrated on a patterned ink film by LEMS imaging. Plant metabolites including sugar and anthocyanins were directly imaged from a leaf sample. Small metabolites, lipids and proteins were simultaneously imaged from a single tissue section of a pig liver sample. Biomarkers of blood-brain barrier damage and traumatic brain injury (TBI) that occurred during the injury were detected and imaged from a TBI mouse brain. The loading values from principal component analysis (PCA) were shown to be useful for identification of features of interest from the large LEMS imaging dataset.
Temple University--Theses

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Tan, Han-Min. "High resolution angle-scanning widefield surface plasmon resonance imaging and its application to bio-molecular interactions." Thesis, University of Nottingham, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556099.

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The work described in this thesis is to develop a microscope into a high resolution bio-molecular interaction sensor. A "prism less" widefield surface plasmon microscope has been constructed and applied to imaging of interactions of protein and its antibody in aqueous media through a high NA objective. There are two main parts in this thesis: (1) design and layout of a high resolution angle scanning widefield surface plasmon resonance microscope; and (2) the application to bio-molecular interactions. In the first part, an angle-scanning widefield surface plasmon imaging (AW-SPRI) system consisting of an optical system, a liquid handling system and a data processing system is described. In the optical system, surface plasmons are excited by objective coupling. A spatial light modulator in a conjugate back focal plane of the objective lens allows dynamic control of illumination angle. The reflected bright-field widefield images, encoded with SPR signals, are detected by a CCD. The SPR signals in the images are decoded by a signal processing algorithm. AW-SPRI also combines well-controlled liquid handling units in order to monitor bio-molecular interactions or detect analytes in water-based solvent. The system shows high sensor resolution ( 5 x 10-5 RIU) as a biosensor. In addition, the edge response of A W -SPRI images with the BSA grating vector parallel to the incident polarization direction is 6.5 flm in air and 7.6 urn in water and the edge response with the BSA grating vector perpendicular to the incident polarization direction is 4.3 urn in air and 4.8 urn in water. The system presents high spatial resolution, too. The second part introduces sensor chip preparation and bio-molecular interactions. The sensor chip is where the bio-molecular interaction takes place and where the biochemical binding event is transduced into SPR signals. There are three types of sensor chips mentioned in this thesis which are bare gold-coated coverslips, protein grating patterns on a gold surface created by micro-contact printing, and protein grating patterns covalently immobilised on a gold surface created by photolithography. The patterned proteins on gold surfaces as our sensor chips are used to perform bio-molecular interactions. The results show our system can be used for comparison or determination of the concentration of ligands on the sensor chip or the affinities of the analyte with different samples on sensor chips. In addition, the measurement of affinity and rate constants show that the AW-SPRI can be used to measuring binding processes and carry out kinetic analysis of macromolecular interactions with standard interaction cycle method. Although the errors are larger than with the commercial SPR machines (SR 7000DC), they are nevertheless of similar order of magnitudes. To the authors' knowledge, this is the first demonstration of such high spatial resolution for quantitative, label-free, real-time detection of bio-molecule interaction cycles.

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Bird-Lieberman, Elizabeth Louise. "Potential application of lectins as molecular imaging tools to detect dysplasia in Barrett's oesophagus during endoscopy." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609520.

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Ghosh, Arindam [Verfasser]. "Single Molecule Fluorescence Spectroscopy and Imaging: Advanced Methods and Applications in Life Sciences / Arindam Ghosh." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1235222748/34.

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Ramos-Ortiz, Gabriel. "Frequency conversion in conjugated organic molecules and its applications to ultra-fast pulse diagnostic and imaging." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/289952.

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This dissertation is devoted to the study of third-harmonic generation (THG) in push-pull chromophore-doped polymer films. This kind of films, with amorphous structure, exhibit null second harmonic generation but strong THG when pumped at the fundamental wavelengths within the telecommunication range (1.4-1.6 μm). It is demonstrated that at 1550 nm, micrometer-thick samples generate up to 17 muW of green light with an input power of 250 mW delivered by an optical parametric oscillator. This high conversion efficiency is achieved without the use of phase matching or cascading of quadratic nonlinear effects and it is due to high values of the third-order nonlinear susceptibility combined with weak film absorption at the third harmonic wavelength. The efficient THG process opens the doors to low cost and sensitive third-order optical autocorrelation and cross-correlation applications. So, in addition to the basic research performed about the characterization of the THG in push-pull chromophore-doped polymer films, two applications are demonstrated. The first is the complete diagnostic of femtosecond pulses by THG-Interferometric Autocorrelation and by THG Frequency-Resolved Optical Gating. The second is the THG-Cross-correlation Time-Gated Imaging of objects embedded in highly scattering conditions.

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Ledesch, Ralph [Verfasser]. "Simultaneous dual-color imaging on single-molecule level on a Widefield microscope and applications / Ralph Ledesch." Jülich : Forschungszentrum Jülich GmbH, Zentralbibliothek, 2018. http://d-nb.info/1168026903/34.

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Fontana, Cristiano Lino. "An Imaging Camera for Biomedical Application Based on Compton Scattering of Gamma Rays." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423412.

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In this thesis we present the R&D of a Compton Camera (CC) for small object imaging. The CC concept requires two detectors to obtain the incoming direction of the gamma ray. This approach, sometimes named ``Electronic Collimation,'' differs from the usual technique that employs collimators for physically selecting gamma-rays of a given direction. This solution offers the advantage of much greater sensitivity and hence smaller doses. We propose a novel design, which uses two similar Position Sensitive Photomultipliers (Hamamatsu 8500) coupled to different scintillators (one plastic and one inorganic). Assets of just one kind of detector are the simplicity of design and operation. Along the experimental apparatus we present our original algorithm for image reconstruction, that was tested with a Geant4 Monte Carlo code. Employed on experimental data, we obtained a resolution of 6 mm, which is suitable for small animal imaging (such as rats or rabbits) and for small human organs imaging (thyroid and prostate). The prototype was designed to be a compact modular element that can be extended placing more similar detectors side by side
In questa tesi presentiamo il lavoro di ricerca e sviluppo di una Camera Compton (CC) per imaging di piccoli oggetti. Le CC richiedono l'utilizzo di due rivelatori per ottenere la direzione d'incidenza di raggi gamma. Questo approccio, talvolta chiamato ``Collimazione Elettronica,'' si differenzia dalle tecniche usuali che utilizzano collimatori per selezionare fisicamente i raggi gamma di una certa direzione. Questa soluzione offre il vantaggio di una sensibilità maggiore e quindi di dosi inferiori. Proponiamo qui un nuovo sistema, che usa due similari Fotomoltiplicatori sensibili alla posizione (Hamamatsu 8500) accoppiati a differenti scintillatori (uno in plastica ed uno inorganico). Avere un solo tipo di rivelatore comporta una maggiore semplicità di progettazione ed utilizzo. Assieme all'apparato sperimentale, presentiamo il nostro algoritmo originale per la ricostruzione d'immagini, che è stato testato con un codice Monte Carlo scritto con Geant4. Applicando l'algoritmo ai dati sperimentali, abbiamo ottenuto una risoluzione di 6 mm, che è adatta all'imaging di piccoli animali (quali ratti e conigli) e per piccoli organi umani (tiroide e prostata). Il prototipo è stato sviluppato per per essere un elemento modulare compatto, che può essere esteso affiancando altri rivelatori simili

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Lamprou, Efthymios. "Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners." Doctoral thesis, Universitat Politècnica de València, 2021. http://hdl.handle.net/10251/162991.

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[ES] La Tomografía por Emisión de Positrones (PET) es una de las técnicas más importantes en la medicina de diagnóstico actual y la más representativa en el campo de la Imagen Molecular. Esta modalidad de imagen es capaz de producir información funcional única, que permite la visualización en detalle, cuantificación y conocimiento de una variedad de enfermedades y patologías. Áreas como la oncología, neurología o la cardiología, entre otras, se han beneficiado en gran medida de esta técnica. A pesar de que un elevado número de avances han ocurrido durante el desarrollo del PET, existen otros que son de gran interés para futuras investigaciones. Uno de los principales pilares actualmente en PET, tanto en investigación como en desarrollo, es la obtención de la información del tiempo de vuelo (TOF) de los rayos gamma detectados. Cuando esto ocurre, aumenta la sensibilidad efectiva del PET, mejorando la calidad señal-ruido de las imágenes. Sin embargo, la obtención precisa de la marca temporal de los rayos gamma es un reto que requiere, además de técnicas y métodos específicos, compromisos entre coste y rendimiento. Una de las características que siempre se ve afectada es la resolución espacial. Como discutiremos, la resolución espacial está directamente relacionada con el tipo de centellador y, por lo tanto, con el coste del sistema y su complejidad. En esta tesis, motivada por los conocidos beneficios en imagen clínica de una medida precisa del tiempo y de la posición de los rayos gamma, proponemos configuraciones de detectores TOF- PET novedosos capaces de proveer de ambas características. Sugerimos el uso de lo que se conoce como métodos de "light-sharing", tanto basado en cristales monolíticos como pixelados de tamaño diferente al del fotosensor. Estas propuestas hacen que la resolución espacial sea muy alta. Sin embargo, sus capacidades temporales han sido muy poco abordadas hasta ahora. En esta tesis, a través de varios artículos revisados, pretendemos mostrar los retos encontrados en esta dirección, proponer determinadas configuraciones y, además, indagar en los límites temporales de éstas. Hemos puesto un gran énfasis en estudiar y analizar las distribuciones de la luz centellante, así como su impacto en la determinación temporal. Hasta nuestro conocimiento, este es el primer trabajo en el que se estudia la relación de la determinación temporal y la distribución de luz de centelleo, en particular usando SiPM analógicos y ASICs. Esperamos que esta tesis motive y permita otros muchos trabajos orientados en nuevos diseños, útiles para instrumentación PET, así como referencia para otros trabajos. Esta tesis esta organizada como se describe a continuación. Hay una introducción compuesta por tres capítulos donde se resumen los conocimientos sobre imagen PET, y especialmente aquellos relacionados con la técnica TOF-PET. Algunos trabajos recientes, pero aún no publicados se muestran también, con el objetivo de corroborar ciertas ideas. En la segunda parte se incluyen las cuatro contribuciones que el candidato sugiere para el compendio de artículos.
[CA] La Tomografia per Emissió de Positrons (PET) és una de les tècniques més importants en la medicina de diagnòstic actual i la més representativa en el camp de la Imatge Molecular. Esta modalitat d'imatge és capaç de produir informació funcional única, que permet la visualització en detall, quantificació i coneixement d'una varietat de malalties i patologies. Àrees com l'oncologia, neurologia o la cardiologia, entre altres, s'han beneficiat en gran manera d'aquesta tècnica. Tot i que un elevat nombre d'avanços han ocorregut durant el desenvolupament del PET, hi ha altres que són de gran interés per a futures investigacions. Un dels principals pilars actuals en PET, tant en investigació com en desenvolupament, és l'obtenció de la informació del temps de vol (TOF en anglès) dels raigs gamma detectats. Quan açò ocorre, augmenta la sensibilitat efectiva del PET, millorant la qualitat senyal-soroll de les imatges. No obstant això, l'obtenció precisa de la marca temporal dels raigs gamma és un repte que requerix, a més de tècniques i mètodes específics, compromisos entre cost i rendiment. Una de les característiques que sempre es veu afectada és la resolució espacial. Com discutirem, la resolució espacial està directament relacionada amb el tipus de centellador, i per tant, amb el cost del sistema i la seua complexitat. En aquesta tesi, motivada pels coneguts beneficis en imatge clínica d'una mesura precisa del temps i de la posició dels raigs gamma, proposem nouves configuracions de detectors TOF-PET capaços de proveir d'ambduess característiques. Suggerim l'ús del que es coneix com a mètodes de "light-sharing", tant basat en cristalls monolítics com pixelats de diferent tamany del fotosensor. Aquestes propostes fan que la resolució espacial siga molt alta. No obstant això, les seues capacitats temporals han sigut molt poc abordades fins ara. En aquesta tesi, a través de diversos articles revisats, pretenem mostrar els reptes trobats en aquesta direcció, proposar determinades configuracions i, a més, indagar en els límits temporals d'aquestes. Hem posat un gran èmfasi a estudiar i analitzar les distribucions de la llum centellejant, així com el seu impacte en la determinació temporal. Fins al nostre coneixement, aquest és el primer treball en què s'estudia la relació de la determinació temporal i la distribució de llum de centelleig, en particular utilitzant SiPM analògics i ASICs. Esperem que aquesta tesi motive i permeta molts altres treballs orientats en nous dissenys, útils per a instrumentació PET, així com referència per a altres treballs. Aquesta tesi esta organitzada com es descriu a continuació. Hi ha una introducció composta per tres capítols on es resumeixen els coneixements sobre imatge PET i, especialmente, aquells relacionats amb la tècnica TOF-PET. Alguns treballs recents, però encara no publicats es mostren també, amb l'objectiu de corroborar certes idees. La segona part de la tesi conté els quatre articles revisats que el candidat suggereix.
[EN] Positron Emission Tomography (PET) is one of the greatest tools of modern diagnostic medicine and the most representative in the field of molecular imaging. This imaging modality, is capable of providing a unique type of functional information which permits a deep visualization, quantification and understanding of a variety of diseases and pathologies. Areas like oncology, neurology, or cardiology, among others, have been well benefited by this technique. Although numerous important advances have already been achieved in PET, some other individual aspects still seem to have a great potential for further investigation. One of the main trends in modern PET research and development, is based in the extrapolation of the Time- Of-Flight (TOF) information from the gamma-ray detectors. In such case, an increase in the effective sensitivity of PET is accomplished, resulting in an improved image signal-to-noise ratio. However, the direction towards a precise decoding of the photons time arrival is a challenging task that requires, besides specific approaches and techniques, tradeoffs between cost and performance. A performance characteristic very habitually compromised in TOF-PET detector configurations is the spatial resolution. As it will be discussed, this feature is directly related to the scintillation materials and types, and consequently, with system cost and complexity. In this thesis, motivated by the well-known benefits in clinical imaging of a precise time and spatial resolution, we propose novel TOF-PET detector configurations capable of inferring both characteristics. Our suggestions are based in light sharing approaches, either using monolithic detectors or crystal arrays with different pixel-to-photosensor sizes. These approaches, make it possible to reach a precise impact position determination. However, their TOF capabilities have not yet been explored in depth. In the present thesis, through a series of peer-reviewed publications we attempt to demonstrate the challenges encountered in these kinds of configurations, propose specific approaches improving their performance and eventually reveal their limits in terms of timing. High emphasis is given in analyzing and studying the scintillation light distributions and their impact to the timing determination. To the best of our knowledge, this is one of the first works in which such detailed study of the relation between light distribution and timing capabilities is carried out, especially when using analog SiPMs and ASICs. Hopefully, this thesis will motivate and enable many other novel design concepts, useful in PET instrumentation as well as it will serve as a helpful reference for similar attempts. The present PhD thesis is organized as follows. There is an introduction part composed by three detailed sections. We attempt to summarize here some of the knowledge related to PET imaging and especially with the technique of TOF-PET. Some very recent but still unpublished results are also presented and included in this part, aiming to support statements and theories. The second part of this thesis lists the four peer-reviewed papers that the candidate is including.
This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the Spanish Ministerio de Economía, Industria y Competitividad under Grants No. FIS2014-62341-EXP and TEC2016-79884-C2-1-R. Efthymios Lamprou has also been supported by Generalitat Valenciana under grant agreement GRISOLIAP-2018-026.
Lamprou, E. (2021). Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/162991
TESIS

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Parlanti, Paola. "Neurodegenerative disorders: overcoming single-method limits through the application of a new correlative imaging approach." Doctoral thesis, Scuola Normale Superiore, 2018. http://hdl.handle.net/11384/85907.

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Pinaud, Fabien Floren. "Peptide-coated semiconductor quantum dots and their applications in biological imaging of single molecules in live cells and organisms." Diss., Restricted to subscribing institutions, 2007. http://proquest.umi.com/pqdweb?did=1383485011&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.

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Pauff, Steven M. "Advancements in the Synthesis and Application of Near-Infrared Imaging Reagents: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/751.

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Fluorescence-based imaging techniques provide a simple, highly sensitive method of studying live cells and whole organisms in real time. Without question, fluorophores such as GFP, fluorescein, and rhodamines have contributed vastly to our understanding of both cell biology and biochemistry. However, most of the fluorescent molecules currently utilized suffer from one major drawback, the use of visible light. Due to cellular autofluorescence and the absorbance of incident light by cellular components, fluorescence imaging with visible wavelength fluorophores often results in high background noise and thus a low signal-to-noise ratio. Fortunately, this situation can be ameliorated by altering the wavelength of light used during imaging. Near-infrared (NIR) light (650-900 nm) is poorly absorbed by cells; therefore, fluorophores excited by this light provide a high signal-to-noise ratio and low background in cellular systems. While these properties make NIR fluorophores ideal for cellular imaging, most currently available NIR molecules cannot be used in live cells. The first half of this thesis addresses the synthetic difficulties associated with preparing NIR fluorophores that can be used within living systems. Small molecule NIR fluorophores are inherently hydrophobic which makes them unsuitable for use in the aqueous environment of the cell. Water-solubility is imparted to these dyes through highly polar sulfonates, which subsequently prevents the dyes from entering the cell. The novel work presented here details vii synthetic routes to aid in the development of sulfonated NIR fluorophores, which can be delivered into live cells through the inclusion of an esterase-labile sulfonate protecting group. Application of these synthetic techniques should allow for the development of novel NIR fluorophores with intracellular applications. The second half of this thesis addresses the need for novel NIR imaging reagents. Although several classes of NIR scaffolds do exist, most NIR probes are derivatives of a single class, heptamethine indocyanines. The work described here increases this palette by displaying the ability of NIR oxazines to function as an imaging reagent in live cells and in vivo and as a molecular sensor of biologically-relevant environmental conditions. Combined, the work contained herein has the capacity to not only advance the current NIR toolkit, but to expand it so that fluorescence imaging can move out of the dark and into the NIR light.

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Pauff, Steven M. "Advancements in the Synthesis and Application of Near-Infrared Imaging Reagents: A Dissertation." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/751.

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Fluorescence-based imaging techniques provide a simple, highly sensitive method of studying live cells and whole organisms in real time. Without question, fluorophores such as GFP, fluorescein, and rhodamines have contributed vastly to our understanding of both cell biology and biochemistry. However, most of the fluorescent molecules currently utilized suffer from one major drawback, the use of visible light. Due to cellular autofluorescence and the absorbance of incident light by cellular components, fluorescence imaging with visible wavelength fluorophores often results in high background noise and thus a low signal-to-noise ratio. Fortunately, this situation can be ameliorated by altering the wavelength of light used during imaging. Near-infrared (NIR) light (650-900 nm) is poorly absorbed by cells; therefore, fluorophores excited by this light provide a high signal-to-noise ratio and low background in cellular systems. While these properties make NIR fluorophores ideal for cellular imaging, most currently available NIR molecules cannot be used in live cells. The first half of this thesis addresses the synthetic difficulties associated with preparing NIR fluorophores that can be used within living systems. Small molecule NIR fluorophores are inherently hydrophobic which makes them unsuitable for use in the aqueous environment of the cell. Water-solubility is imparted to these dyes through highly polar sulfonates, which subsequently prevents the dyes from entering the cell. The novel work presented here details vii synthetic routes to aid in the development of sulfonated NIR fluorophores, which can be delivered into live cells through the inclusion of an esterase-labile sulfonate protecting group. Application of these synthetic techniques should allow for the development of novel NIR fluorophores with intracellular applications. The second half of this thesis addresses the need for novel NIR imaging reagents. Although several classes of NIR scaffolds do exist, most NIR probes are derivatives of a single class, heptamethine indocyanines. The work described here increases this palette by displaying the ability of NIR oxazines to function as an imaging reagent in live cells and in vivo and as a molecular sensor of biologically-relevant environmental conditions. Combined, the work contained herein has the capacity to not only advance the current NIR toolkit, but to expand it so that fluorescence imaging can move out of the dark and into the NIR light.

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Lau, Khim Heng. "Development and application of high-resolution secondary ion mass spectrometry analysis of therapeutic and imaging molecules in cells and tissue sections." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543023.

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Martinage, Olivier. "Elaboration d’une nouvelle plateforme de développement de traceurs in vivo : application à l’imagerie de la néoangiogenèse tumorale." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA114841/document.

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L’imagerie moléculaire est aujourd’hui un outil non-invasif essentiel pour le diagnostic de nombreuses pathologies. Les traceurs technétiés sont actuellement les plus répandus car le 99mTc est facilement disponible, abordable et présente des caractéristiques idéales pour l’imagerie. Néanmoins, le développement de traceurs efficaces nécessite un long et coûteux processus d’optimisation souvent empirique. Dans ce contexte, nous avons entrepris le développement d’une plateforme technétiée conçue pour présenter au sein de sa structure de nombreux sites potentiels de fonctionnalisation et compatible avec une approche combinatoire.Dans un premier temps, un ensemble de 12 ligands N3X (X = N, O, S) a été préparé. Chacun d’entre eux présente dans sa structure un motif triazole introduit par chimie-click et intervenant dans la complexation du métal par un de ses atomes d’azote. Nous avons ensuite évalué l’aptitude de ces ligands à chélater le cœur oxotechnétium dans des conditions douces (5 min, température ambiante) compatible avec une utilisation en milieu hospitalier. Le complexe TriaS-99mTc a été formé quantitativement et sa stabilité en plasma murin a été étudiée. Il s’est révélé stable à plus de 90% dans le plasma murin après 6h d’incubation. L’étude in vivo de ce complexe a par la suite révélé une élimination efficace du milieu circulant par la voie urinaire avec une dégradation minoritaire.A titre d’illustration, nous avons ensuite engagé la structure TriaS dans deux approches distinctes pour le développement de traceurs de la néoangiogenèse tumorale en ciblant l’intégrine αvβ3. D’une part, dans le cadre d’une approche intégrée, plusieurs complexes fonctionnalisés, mimes de RGD, ont été obtenus. Dans chaque cas, l’adjonction de groupements fonctionnels n’a pas affecté l’efficacité de la chélation. En outre la stabilité en plasma est maintenue à un niveau très correct. D’autre part, nous avons développé une approche bifonctionnelle dans laquelle le motif c(RGDfK) joue le rôle de molécule ciblante. Dans ce cas, un motif variable (ici un PEG) peut être introduit par chimie combinatoire pour moduler la solubilité, la biodistribution, et l’excrétion des traceurs
Molecular imaging is an essential non-invasive tool usable for diagnosis and characterisation of many diseases. Technetium-based tracers are the most popular ones due to disponibility, cost and radiochemical properties of 99mTc. Nevertheless, effective tracers development requires a long, expensive, and mainly empirical optimisation process. This context prompted us tu carry on the development of a new technetium structure which exhibits lots of potential functionalisation spots compatible with a combinatorial approach. We synthesised 12 N3X (X = N, O, S) different ligands. Each of them includes a triazole moiety, (formed via a click-chemistry reaction), which is involved in the metal complexation that implies one of its nitrogen atoms. Then we evaluated their ability to readily form oxotechnetium complexes in conditions that are compatible with medical use in hospital. One complex was formed in quantitative yields and its stability in mice plasma was investigated. A complex called TriaS-99mTc, stable to more than 90% after 6h incubation, was selected. In vivo study of TriaS-99mTc revealed an efficient blood clearance via the urinary excretion pathway with very low degradation. As an application, we used this structure for the development of tracers that target integrin αvβ3, a known biomarker of tumor neoangiogenesis. First, we synthesised functionnalised TriaS-based integrated complexes. Fonctionnal modification of TriaS by addition of side chains and substituents did not affect its ability to chelate oxotechnetium quantitatively. In addition, its stability in mice plasma was satisfactory. We also developped a bifonctionnal approach using c(RGDfK) peptide as the targeting biomolecule. In this way, a variable moiety (herein a PEG moiety) can be inserted in the structure through click-chemistry in order to modulate tracers solubility, biodistribution and excretion

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Bouvier-Müller, Alix. "Identification de nouvelles sondes moléculaires contre des biomarqueurs des maladies neurodégénératives Application of aptamers for in vivo molecular imaging and theranostics Nucleic acid aptamers for neurodegenerative diseases." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL011.

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Les aptamères sont des oligonucléotides dont la structure tridimensionnelle leur permet d’interagir avec une molécule-cible. Ils sont isolés par une méthode d’évolution dirigée appelée « SELEX » permettant de sélectionner un oligonucléotide capable de se lier à la molécule-cible, parmi une banque comportant un grand nombre de séquences différentes. Les protéine α-synucléine (α-syn) sous forme agrégées sont retrouvées accumulées au sein d’agrégats dans le cerveau des patients pour plusieurs maladies neurodégénératives regroupées sous le nom de « synucléinopathies ». Le but de ma thèse était de sélectionner des aptamères reconnaissant de manière spécifique différentes isoformes de la protéine α-syn. Nous avons, en utilisant la technique du SELEX, réussi à isoler plusieurs aptamères capables de reconnaitre une isoforme de la protéine α-syn avec une bonne affinité et une bonne spécificité. Ce travail est une preuve de concept qu’il est bien possible d’isoler des aptamères reconnaissant spécifiquement une isoforme particulière de la protéine α-syn. Ces aptamères « spécifiques » pourraient être utilisés au sein de biocapteurs pour la détection d’isoformes particulières d’α-syn. Ceux-ci pourraient alors permettre à la communauté scientifique de mieux étudier et comprendre le rôle des différentes isoformes de la protéine α-syn dans les synucléinopathies. Ces biocapteurs pourraient également être utilisés comme outil de diagnostic, en permettant la détection des différentes isoformes d’α-syn dans des échantillons de patients
Aptamers are oligonucleotides whose three-dimensional structure allows them to interact with a target molecule. They are isolated by a directed evolution method named "SELEX" making possible to select an oligonucleotide able to bind to a target molecule, from a library comprising a large number of different sequences. Aggregated α-synuclein (α-syn) proteins are found accumulated inside aggregates in the brains of patients for several neurodegenerative diseases grouped under the name "synucleinopathies". The aim of my thesis was to select aptamers that specifically recognize different isoforms of the α-syn protein. Using the SELEX technique, we have succeeded in isolating several aptamers capable of recognizing a particular isoform of the α-syn protein with good affinity and good specificity. This work is a proof of concept that it is indeed possible to isolate aptamers that specifically recognize a particular isoform of the α-syn protein. These "specific" aptamers could be used in biosensors for the detection of particular α-syn isoforms. These could then allow the scientific community to better study and understand the role of the different α-syn protein isoforms in synucleinopathies. These biosensors could also be used as a diagnostic tool, allowing the detection of different α-syn isoforms in patient samples

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Yu, Tingting. "Solid state luminescent molecules, macromolecules and materials, their response to stimuli and their applications in devices." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSEN061.

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Au cours de cette thèse, nous avons développé de nouveaux chromophores conjugués luminescents présentant une alternance de groupements donneurs et accepteurs, avec une attention particulière quant à leurs propriétés d’émission dans le rouge et proche infra-rouge à l’état solide ou agrégats. Nous avons étudié l’influence de la longueur de chaine et de la nature de la substitution donneur/accepteur non seulement sur les propriétés optiques en solution mais aussi (et surtout) sur le matériau agrégé. Enfin, en utilisant les propriétés spécifiques de certains des composés développés selon cette approche, nous avons exploré leur potentiel pour des applications allant de matériaux fluorochrome stimuli-responsifs (sous forme de films) à l’élaboration de sondes à deux photons émettant dans le proche infra rouge pour l’imagerie biologique. Les principaux accomplissements de cette thèse sont les suivant: 1/ de nouveaux polymères alternant des motifs triarylamine (ou carbazole)/ tetraphenylethylene (TPE) dans leur chaine principale ont été synthétisés. Leurs propriétés d’émission à l’état solide présentent des caractéristiques d’agrégats-J, peu courant dans les dérivés TPE, ce que nous attribuons à l’arrangement linéaire des chaînes polymères; 2/ Une nouvelle famille de colorants diphenylamine/benzobisthiazole et leurs dérivés oligomères ont été synthétisés. Leurs propriétés de luminescence présentent une sensibilité marquée à la protonation, que nous avons utilisée dans la conceptions de dispositifs luminescents commutables par stimuli acide/base; 3/Nous avons exploré la possibilité d’introduire des modifications chimiques complémentaires sur cette nouvelle famille de chromophores, afin d’obtenir des composés luminescents à l’état solide dans le proche infrarouge, en particulier par un changement de la nature de la transition électronique à transfert de charge intramoléculaire vers une transition cyanine, par le biais d’une quaternarisation des fonction benzobisthiazole. D’autres modifications ont conduit à une amélioration de la biocompatibilté des molécules, de leurs propriétés AIE, ou encore de leur spécificité de marquage cellulaire; 4/ Ces nouveaux composés présentent une luminescence photo-commutable (de type allumé/éteint), qui pourrait présenter un intérêt dans l’élaboration d’agents de contraste pour l’imagerie de microscopie super-résolue
In this thesis, we developed new luminescent conjugated chromophores presenting an alternation of electron donor and acceptor groups, with a specific focus on their emission properties in aggregates or solid states in far-red or near infrared region. We studied the influence of chain length and donor/acceptor substitution not only on the optical properties of the isolated compounds, but also (and especially) on the material in its aggregated state. Finally, taking advantages of these specific properties of some of the as-designed candidates, we explored their potential applications ranging from fluorochromic stimuli-responsive sensors (in film form) to red and NIR luminescent two-photon probes for biological imaging. The main achievements of this thesis are the following: 1) new alternating triarylamine or carbazole / tetraphenylethylene (TPE) polymers were synthesized. Their solid state luminescence poseeses typical J-aggregates emission features in solid state, unusual in TPE derivatives that we relate to the linear polymeric nature of the object; 2) A new family of diphenylamine / benzobisthiazole chromophores and derived oligomers were synthesized . Their luminescence properties present a marked sensitivity to protonation, which we took advantage of in the making of acid-base responsive luminescent devices; 3) we explored the possibility of additional chemical transformations of the newly designed chromophore, in order to achieve solid state NIR emission, in particular by means of a change in the character of the electronic transition from Intra-Molecular Charge Tranfer (ICT) to Cyanine transition owing to benzothiazole quaternarization. Other modifications resulted in improvement of their AIE properties, bioavailability and selectivity of their cellular compartments staining ability; 4) These new compounds present a reversible photoinduced “on-off” switching of their luminescence properties, which might present an interest in the design of contrast-agents for super resolution imaging

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Bernhard, Claire. "Synthèse d'agents chélatants bifonctionnels macrocycliques pour le marquage de molécules biologiques par des métaux : application en imagerie médicale." Thesis, Dijon, 2011. http://www.theses.fr/2011DIJOS024/document.

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L’imagerie moléculaire est devenue incontournable pour le diagnostic et le traitement de cancers. Cette discipline regroupe un ensemble de techniques telles que la tomodensitométrie (CT), l’Imagerie par Résonance Magnétique (IRM), l’imagerie optique ou encore l’imagerie nucléaire (tomographie par émission de positons TEP, tomographie d’émission monophotonique TEMP). Chacune de ces techniques possède ses propres avantages et inconvénients et ne peut apporter à elle seule des informations anatomiques et fonctionnelles suffisantes. Les travaux actuels sont portés sur la conception de systèmes dits multimodaux afin de combiner les avantages de différentes techniques, voire de bénéficier d’un effet synergique. De par leur sensibilité comparable et leur complémentarité, coupler l’imagerie nucléaire à l’imagerie optique devient alors avantageux. La conception des systèmes monomoléculaires (MOMIA) contenant deux fonctions détectables par imagerie nucléaire (complexe de radiométaux) et imagerie optique (sonde fluorescente) nécessite en amont la mise au point d’outils de synthèses performants. La première partie de ce travail de thèse est consacrée à la synthèse d’agents chélatants bifonctionnels à base de polyamines macrocycliques, destinés à une utilisation en imagerie médicale. Ces agents doivent présenter d’excellentes propriétés de coordination vis-à-vis du métal visé, et posséder une fonction de greffage pour assurer le couplage avec une biomolécule vectrice. L’accès à de tels systèmes a nécessité le développement d’outils de synthèse efficaces de précurseurs macrocycliques dérivés du cyclène et du 13aneN4. L’introduction sélective de diverses fonctions de greffage visant principalement les résidus de type lysine a permis la préparation de plusieurs familles de composés, dont certains ont pu être « bioconjugués» à des peptides ou anticorps au sein du laboratoire ou dans le cadre de diverses collaborations. Plus particulièrement, la facilité d’utilisation du système « DOTAGA anhydride » a permis l’introduction aisée d’unités DOTA sur des nanoparticules ou des anticorps monoclonaux. Egalement, l’introduction d’une fonction alcyne a permis l’accès à de nouvelles briques moléculaires préparées par « click chemistry ». Dans une seconde partie sont présentés les travaux relatifs à la synthèse d’agents bimodaux originaux. Pour accéder à de tels systèmes, l’introduction d’un fluorophore de la famille des bodipys a été envisagée. L’absence de travaux antérieurs relatifs au couplage d’une polyamine cyclique et une entité bodipy a nécessité la préparation préalable d’un système modèle « DOTA bodipy », permettant de s’assurer par des études photophysiques que la présence des complexes métalliques macrocycliques ne va pas, ou peu, interférer avec les propriétés de fluorescence du bodipy. L’utilisation d’un espaceur « acide aminé » a alors permis d’accéder à de nouveaux bodipys porteurs de deux groupes fonctionnels en position méso. La fonctionnalisation a posteriori de ces briques de construction a permis l’introduction en dernier lieu d’unités macrocycliques N- et/ou C- fonctionnalisés. La préparation de système émettant dans le proche I.R. a été également envisagée
Molecular imaging became a major tool for the diagnosis and the treatment of cancers. This research field includes different techniques, such as Tomography (CT), Magnetic Resonance Imaging (MRI), Optical Imaging or nuclear Imaging (PET Positron Emission Tomography, SPECT Single Photon Emission Computed Tomography). Each imaging modality has its own strengths and weaknesses, and thus, combining different and complementary systems can overcome inherent limitations associated with any one individual techniques and improve the accuracy of disease diagnosis and enhancing patient management. In particular dual-modality Optical/Nuclear imaging may find important preclinical and clinical applications. One possible approach seeks to fuse the two imaging systems into one molecule (MonOmolecular Multimodality Imaging Agent [MOMIA]) in order to ensure the same biodistribution of the two probes. Our strategy consists in combining a DOTA-like compound allowing complexation of radiometal for nuclear imaging (SPECT or PET) with a bodipy moiety, valuable probe those fluorescent properties can be finely adjusted. The first part of this work is dedicated to the synthesis of bifunctional chelating agents based on macrocyclic polyamines for medical imaging application. These compounds must show excellent coordination properties towards the aimed radiometal and possess a grafting function to allow the coupling with a biomolecule. Powerful and general routes for the synthesis of a wide range of N- and C-functionalized macrocycles derived from cyclen and 13aneN4 are described, which enable to access to a wide range of new BFCs by introduction of different functional groups reactive towards primary amines, such as carboxylic acid, isothiocyanate or anhydride function. Some compounds were conjugated to different biomolecules, such as peptides or antibodies. Morever, the introduction of an alkyne function yields a novel family of bifunctional agents allowing chemoselective attachment to functionalized biomolecules or to modified amino acids using « click chemistry ». In a second part, we focused on the introduction of a bodipy moeity to obtain new bimodal agents for dual Optical/Nuclear imaging. Interestingly, the attachment of the polyaminocarboxylate (DOTA derivative) to the bodipy makes it soluble in water and complexation of different metal cations of interest in the macrocyclic cavity does not significantly alter the luminescence properties of the whole system. In addition, the functionalization of the meso position by using an appropriate linker between the bodipy and DOTA-like units, i.e. a 4-nitrophenylalanine derivative, could provide a new bimodal tag for labeling antibodies or peptides. Optimisation of the second generation bodipy-DOTA, i.e. derivatization reaction to reach the near-IR range or introduction of C-functionalised macrocycles was also investigated

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Grimault, Stephan. "Détermination des propriétés du signal RMN par une approche numérique : application aux expériences de diffusion et d'imagerie fonctionnelle." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10157.

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Ce travail etaient est centre sur l'etude et la quantification du signal rmn dans certaines conditions in vivo. Une approche numerique de type monte carlo a ete utilisee. Une premiere etude porte sur la mesure in vivo du coefficient apparent de diffusion (cad) de lipides mobiles detectes dans des tumeurs cerebrales et confines dans des micro-domaines. Le modele numerique permet d'estimer la taille des micro-domaines sur la base du cad mesure. Un diametre de 10 a 12 m a ete trouve, valeur qui concorde avec les etudes par microscopie. Une seconde etudes porte sur la quantification des effets de la desoxygenation du sang sur la baisse du cad observee experimentalement lors de l'etude de l'ischemie. Une double etude numerique et experimentale nous a permis de conclure que la desoxygenation du sang n'est pas la principale cause de la baisse du cad. L'approche numerique est basee sur un modelisation du tissu cerebral prenant en compte la diffusion des molecules d'eau, le reseau vasculaire et les gradients internes generes autour ce dernier. Une troisieme etude porte sur la quantification du contraste bold (blood oxygenation level dependent) utilise en imagerie fonctionnelle. Differents parametres lies au secteur vasculaire, a la diffusion des molecules d'eau, et a la sequence d'impulsions ont ete considere. A partir de simulations basees sur une modelisation du tissu cerebral, des equations analytiques de la vitesse de relaxation de l'aimantation transversale en fonction des differents parametres d'interets ont ete. Dans ce travail, nous avons developpe un outil numerique aidant a la quantification du signal rmn et facilement adaptable aux diverses problematiques rencontrees dans differents secteurs de la rmn (diffusion, imagerie fonctionnelle).

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Miloudi, Lynda. "Application des techniques spectroscopiques vibrationnelles couplées aux analyses statistiques multivariées pour la caractérisation et l'objectivation des produits de soins comestiques." Thesis, Tours, 2018. http://www.theses.fr/2018TOUR3801/document.

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La fonction barrière de la peau, qui protège l’organisme contre les molécules exogènes, limite la pénétration des actifs cosmétiques, ce qui réduit l’efficacité des molécules actives dans les couches profondes de l’épiderme. Il est alors apparu essentiel d'optimiser l'administration des actifs cosmétiques déjà existants afin d’en tirer tout le bénéfice escompté. Certaines innovations sont développées pour répondre à ce défi, notamment l’encapsulation des actifs cosmétiques dans des nanosystemes. En parallèle, il est nécessaire de s’intéresser aux méthodes analytiques capables de fournir une information qualitative et quantitative sur ces systèmes dispersés dans un produit fini complexe et de permettre une évaluation biologique à différents stades de développement des formulations
The barrier function of the skin, which protects the body against exogenous molecules, limits the penetration of active cosmetic ingredients (ACI), thus reduce the effectiveness of molecules with a deep cellular target. Therefore, it appeared crucial to optimize the administration of existing active cosmetic in order to get the full benefits expected. Some innovations are explored to bypass this issue, including the encapsulation of existing active cosmetic in nanocarriers. In parallel, it is important to also focus on the development of analytical methodologies that could provide qualitative and quantitative information, in particular the determination of ACI contents and potentially excipients incorporated in a final form, and biological evaluation at different stages of formulation

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Houzet, Julien. "Alignement moléculaire : caractérisation et application à la mesure de thermalisation ultra-rapide et au contrôle de génération d'harmoniques." Phd thesis, Université de Bourgogne, 2013. http://tel.archives-ouvertes.fr/tel-01005137.

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La thématique de cette thèse est l'alignement moléculaire. Celui-ci est un sujet très important qui ouvre la voie sur un contrôle beaucoup plus fin de nombreux phénomènes. Ainsi, nous avons développé une nouvelle technique de mesure de l'alignement moléculaire suivant un axe et permettant d'en conserver le signe. Celle-ci est, à l'instar des techniques de mesure de l'alignement moléculaire développées dans l'équipe, basée sur la mesure de variation d'indice de réfraction induite par l'alignement moléculaire. La technique développée ensuite permet également la mesure de l'alignement moléculaire, tout en étant aussi une application de celui-ci puisqu'il permet ici la génération de troisième harmonique. L'alignement moléculaire est également mis en oeuvre dans la dernière étude puisque nous montrons qu'il apporte la résolution nécessaire à l'étude de la thermalisation d'un échantillon moléculaire excité

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Maigné, Alan. "Caractérisation et modélisation par microscopie électronique en transmission à balayage (STEM) et spectroscopie de perte d’énergie d’électrons (EELS) de « nanohorns » de carbone monofeuillet fonctionnalisés pour des applications pharmaceutiques Review of recent advances in spectrum imaging and its extension to reciprocal space Revealing the Secret of Water-Assisted Carbon Nanotube Synthesis by Microscopic Observation of the Interaction of Water on the Catalysts Role of Subsurface Diffusion and Ostwald Ripening in Catalyst Formation for Single-Walled Carbon Nanotube Forest Growth Effect of hole size on the incorporation of C60 molecules inside single-wall carbon nanohorns and their release Adsorption Phenomena of Tetracyano-p-quinodimethane on Single-Wall Carbon Nanohorns Carbon Nanohorns as Anticancer Drug Carriers Effect of Functional Groups at Hole Edges on Cisplatin Release from Inside Single-Wall Carbon Nanohorns Optimum Hole-Opening Condition for Cisplatin Incorporation in Single-Wall Carbon Nanohorns and Its Release Functionalization of Carbon Nanohorns with Azomethine Ylides: Towards Solubility Enhancement and Electron-Transfer Processes Aqueous carbon nanohorn–pyrene–porphyrin nanoensembles: Controlling charge-transfer interactions Photoinduced Electron Transfer on Aqueous Carbon Nanohorn–Pyrene– Tetrathiafulvalene Architectures Soluble Functionalized Carbon Nanohorns." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS600.

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La caractérisation et modélisation de « nanohorns » monofeuillets (SWNH) et de forêts de nanotubes par microscopie analytique sont présentées ainsi que leurs applications pour le traitement du cancer. Dans une première partie, nous introduirons les méthodes de microscopie et de spectroscopie utilisées dans nos expériences. Nous étudierons ensuite le processus de croissance de forêts de nanotubes de carbone monofeuillets (dans le contexte d’une collaboration avec l'AIST au Japon). Les SWNH, leur structure, propriétés de remplissage et de fonctionnarisation seront analysés et une nouvelle méthode sera présentée pour l'étude de la porosité de matériaux inorganique en EELS. Des calculs ab-initio seront aussi utilisés pour étudier l'effet des défauts dans les parois des SWNH sur les phénomènes d'oxydation et de remplissage des SWNH. Finalement, nous étudierons les possibles applications de SWNH dans le domaine pharmaceutique, et en particulier pour les traitements cancéreux
In this manuscript, we will expose the characterization and modelling of Single Wall Nanohorns (SWNH) and Nanotube Forests by analytical microscopy and the functionalization of SWNH for drug delivery applications. Firstly, we will introduce the microscopy and spectroscopy methods used for our experiments. We will then study the growth process of Single Wall Carbon Nanotubes (SWCNT) forests (within the framework of a collaboration with AIST, Japan). SWCH, their structure, modifications and filling properties will be analysed in details. An original method will be presented to study the porosity of inorganic material with EELS. Ab initio calculation will also be used to explore the effect of the defects present in the SWNH wall on the oxidation and filling process. We will study the potentialities of Single Wall Carbon nanohorns as Drug Delivery Systems and particularly as anticancer drug carriers

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Lu, Ja-Yu, and 呂佳諭. "Terahertz Molecular Imaging and Sensing Applications." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/73770036528057148700.

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博士
國立臺灣大學
光電工程學研究所
95
Recently THz imaging and sensing techniques become focusing in THz technology and the main driven force of THz generation and detection. Due to the unique capability of direct molecular identification differed from other EM waves (optical waves and microwaves), it enables noninvasive and label-free molecular imaging and sensing based on THz waves. In order to develop THz imaging and sensing technique or system with high sensitivity, low loss, ease of control and high flexibility for various practical applications, many researchers have made lots effort on it. In this thesis, we provide other alternatives for THz imaging and sensing application. Based on an optoelectronic THz photonic transmitter with ultra high conversion efficiency, we demonstrate a compact THz molecular imaging system with extremely low driven power (<5mW optical pump, 15V bias). Based on the micron-sized photonic transmitter operating at room temperature, an improved signal-to-noise ratio with a reasonable spatial resolution and high penetration depth (>3cm) can be achieved. Biomedical THz imaging has been demonstrated by scanning a dried seahorse and a fresh flower, which were hidden in plastic sample holders and were invisible. Tissue and water distributions of distinct regions of the bio-samples were clearly resolved, showing the high imaging contrasts of the demonstrated system. These results reveal the possibility to construct a compact and high-sensitivity THz imaging system with less than 1-mW optical excitation which is promising in the future clinical application and sensing of hidden objects such as explosives and viruses. By planar integrating a THz micro-source into a glass-substrated microchip within a THz near-field distance, we demonstrate a compact, label-free, noninvasive, and sensitive micro-biosensing system with low-power consumption. The demonstrated THz microchip allows us to locally specify various illicit drug powders with weights on the order of nanograms. Our demonstration shows the possibility to integrate optoelectronic photonic transmitters with the current biochip technology for various biosensing applications, including DNA sequencing, explosive and virus detections, and rapid identification of the static status or even the dynamics of various biomolecules. To efficiently transmit THz waves for achieving THz imaging and sensing with high SNR, is another important issue in THz technology. In this thesis, we develop an air-core microstructure fiber (AMF) for THz transmission. The novel THz-AMF has advantages of with extremely low loss and tunable guiding wavelength by scaling the size of MF. In addition, most THz field is concentrated inside the central hollow air-core and guided without outside interference. We will introduce the design and fabrication of THz-AMF and discuss the waveguiding mechanism. The demonstrated THz-AMF is ideal for various THz applications, including low-dispersion high THz power transmission for nonlinear applications, THz sensing, and THz optical communication for avoiding the interference from surroundings. A THz subwavelength plastic fiber has been previously developed by our labs for low loss waveguiding. Due to most THz field guided outside the fiber core which is different from the traditional optical fiber, resulting in great decrease of dielectric absorption and thus could guide for a long distance (more than one meter). In this thesis, we further explore the feasibility on imaging by using THz subwavelength fiber on which THz wave is loosely guided. We study its bending loss, energy transfer ratio, and modal spot quality. Furthermore, we also construct a compact room-temperature transmitted fiber scanning THz imaging system based on a low-loss subwavelength plastic fiber. Various biological images have been acquired by direct scanning of a THz subwavelength fiber in a large area, and it reveals that the subwavelength plastic fiber enables high SNR imaging with reasonable spatial resolution (close to diffraction limit). Finally, we first ever demonstrate a THz endoscope based on the subwavelength THz fiber, and apply it for imaging of biological specimen and metal pattern without focusing system. The measured images not only reflected the 2D molecular distribution, but revealed the depth variation and thus showed the surface profile or morphology of imaged object. This novel THz endoscope is especially suitable for water-rich biological specimen, because it overcomes the limitation of water absorption which becomes restriction in the conventional transmitted THz imaging system.

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Dissertations / Theses on the topic 'Molecular imaging applications'

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