The recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast agent for combined ultrasound and photoacoustic imaging named Photoacoustic nanoDroplets. This agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases. / text

Imaging of biomolecules on the nano-scale is a crucial developing technology with major implications for our understanding of biological systems and for detection and therapy of disease. Plasmonic nanoparticles are a key optical contrast agent whose signal is generated by the collective oscillation of electrons in the metal particle. The resonance behavior of the electrons depends strongly on the arrangement of neighboring nanoparticles in a structure. This property may be exploited in imaging applications to report information on nanoscale morphology of targeted biomolecules. While the effect of plasmon resonance coupling has been studied in dimers and linear arrays of nanoparticles, this phenomenon remains largely unexplored in the case of 2D and 3D assemblies which are important in molecular cell imaging. This dissertation demonstrates how the optical signal from assemblies of gold nanoparticles can be related to nanoscale morphology in cellular imaging systems. First, the scattering spectra from live cells labeled with gold nanoparticles were collected and compared to the nanoscale arrangement of the particles in the same cells as determined by electron micrograph. Then, trends in scattering spectra with respect to nanoparticle arrangement were analyzed using a model system that allowed precise control over arrangement of nanoparticles. Several approaches to creating these model systems are discussed including biochemical linking, capillary assembly of colloidal particles, and direct deposition of gold onto substrates patterned by electron beam lithography. Spectral properties of the assemblies including peak position, width, and intensity are gathered and related to model variables including interparticle gap and overall particle number. It is shown that the redshift in the scattering spectra from nanoparticle assemblies is derived from both the particle number and the gap and is due to near-field coupling of particles as well as phase retardation of the scattered wave. The redshift behavior saturates as the number of particles in the aggregate increases but the saturation point depends strongly on interparticle gap. The drastic dependence of the red-shift saturation on the gap between nanoparticles has not been previously described; this phenomenon can have significant impact on the development of nanoparticle contrast agents and plasmonic sensor arrays. / text

Advanced optical imaging techniques are emerging as useful ways to screen tissues for the presence of cancer. Plasmon resonant nanoparticles have unique optical properties that make them ideal for use as optical contrast agents. The capacity of these particles to serve a multifunctional role dependent on their composition and the intensity of incident light enables them to serve as diagnostic tools and to provide the therapeutic capability of photo-thermal energy conversion or the controlled release of an encapsulated agent. Likewise, the ability to degrade into components of a clearable size may enable the clinical translation of these types of particles.These properties were demonstrated by means of experiments in the support of three specific aims. The first specific aim was to determine whether the unique and tunable optical properties of nanorods lend them to generate signal in advanced optical imaging techniques, and that nanorods can facilitate photo-thermal conversion. The second specific aim was to show that liposomes can serve as a scaffold for the support of an array of gold nanodots to generate a structure that exhibit tunable plasmon resonant characteristics and a resultant ability to generate signal in optical imaging techniques while having the capability to degrade into inert particles of a size that can be readily cleared from the body via the kidney. The final specific aim was to determine whether the gold-coated liposomes of the second specific aim can serve as system for light-based delivery of an encapsulated agent in addition to its role as an optical contrast agent and its biodegradation capacity.Plasmon resonant nanorods and plasmon resonant gold-coated liposomes were generated by reducing free gold from solution onto surfactant coated seed particles and phospholipid liposomes, respectively. Both structures demonstrated the ability to generate signal in optical coherence tomography and in multi-photon confocal microscopy images. Nanorods in high intensity light demonstrate a capacity to mediate photo-thermal energy conversion. While, in similar conditions, gold-coated liposomes are shown to release their contents. Gold-coated liposomes are also shown to degrade to bioinert components of a size reasonable for rapid renal clearance using either surfactant or enzyme.

Computed Tomography is one of the most important image modalities in medical imaging nowadays. Recent developments have led to a new acquisition technique called 'dual-energy', where images are taken with different x-ray spectra. This enables for the first time spectral information in the CT dataset. Our approach was to use an energy resolving detector (Medipix) and investigate its potential in the medical imaging domain. Images are taken in different energy bins. For acquisition of the data, a CT scanner called 'Medipix All Resolution System' (MARS) scanner was constructed. It was upgraded to achieve better image quality as well as faster scan time and a stable operation. In medical imaging, it is important to achieve a high contrast and a good detail recognition at a low dose. Therefore, it is common practice to use contrast agents to highlight certain regions of the body like e.g. the vascular system. But with a broad spectrum acquisition, it is often impossible to distinguish highly absorbing body elements like bones from the contrast agent. We target this problem by a contrast agent study using different energy bins. This so called spectral contrast agent study has been conducted with small animals using the MARS scanner. The data has been processed to create an optimal CT reconstruction. The image enhancement techniques consist of corrections for noisy pixels, intensity fluctuations and eliminating streaks in the sinograms to reduce ring artifacts. In order to evaluate the data, we used two methods of material identification. The material reconstruction method works on projection data and uses a maximum-likelihood estimation to reconstruct images of base materials. The second method, the principal component analysis (PCA), identifies the relevant information from the spectral dataset in a few derived variables that account for most of the variance in the dataset. This resulted in images with enhanced contrast and removed redundancies. It is possible to combine these images in one colour image where anatomical structures are shown in good detail and certain materials show up in different colors. Based on this new information from spectral data, we could show that it is possible to distinguish the spinal bone from contrast agent.

Purpose: To compare hemodynamic of malignant and benign SRMs on CT and CEUS. Method: Seventy biopsy proven SRM underwent CEUS. Sixty-three had CT. After injection of 0.2 ml of Definity, 3min and after 0.9 ml infusion, 30 sec of data were acquires. Lesion hemodynamics relative to the cortex was evaluated both qualitatively and quantitatively. Results: Considering 15 and 20 HU as enhancement threshold, 10% to 13% of patients did not enhance on CT, while all lesions enhanced on CEUS. Papillary RCCs showed hypovascularity with 100% specificity. In other RCCs, PI, WI slope 5 to45%, 50 to100%, 10 to 90%, WO slope 100 to 50%, 100 to 10%, WO intensity at peak+30 seconds were statistically higher than benign SRMs. Conclusion: All solid SRMs enhance on CEUS, while CT does not show vascularity in 10-13% of solid SRMs. CEUS can differentiate malignant from benign SRMs by evaluating their hemodynamics.

Contrast media are commonly used as an enhancement in several diagnostic imaging methods, which in today’s healthcare often are combined with blood works in diagnostics and surgical preparations, as well as to follow up on the patient’s recovery. To save time and money for both the hospital and the patients themselves, the ability to carry out both the radiological examination and the blood works within the same hospital visit would be preferred. However, there have been indications of a potential interference from the contrast media used, and therefore a waiting period is in place. The aim of this study was therefore to see if that waiting period was warranted by testing if contrast media does cause a significant interference in the most common analyses. This was investigated by infusing pooled samples with either iohexol or gadoteric acid, the active components of the most common contrast agents, at either a full dosage or a half dosage. These samples were then run by standard protocol and the results compared to control samples. The results showed that while some analyses proved affected, others proved unaffected or only insignificantly so. Some of the affected analyses were sodium, activated partial thrombin time and hemoglobin. While some analyses such as prostate specific antigen and prothrombin time were unaffected. Analysis of more samples is necessary to confirm the results, but the overall consensus is that while most analyses are unaffected the effects are too large and uncertain to comfortably disregard the waiting time.

abstract: The central theme of this dissertation is to understand the chemical processing science of advanced ceramic materials for biomedicine, including therapy and imaging. The secondary component focuses on the chemical processing of energy materials. Recently, layered double hydroxide (LDH) nanoparticles (NPs) with various intercalated compounds (e.g. fluorescent molecules, radio-labeled ATP, vitamins, DNA, and drugs) have exhibited versatility and promise as a combined therapeutic and diagnostic (i.e. theranostic) vector. However, its eventual acceptance in biomedicine will be contingent on understanding the processing science, reproducibly synthesizing monodispersed NPs with controlled mean particle size (MPS), and ascertaining the efficacy of the NPs for drug delivery and imaging. First, statistical design of experiments were used to optimize the wet chemistry synthesis of (Zn, Al)-LDH NPs. A synthesis model, which allows the synthesis of nearly monodispersed NPs with controlled MPS, was developed and experimentally verified. Also, the evolution of the nanostructure was characterized, from coprecipitation to hydrothermal treatment, to identify the formation mechanisms. Next, the biocompatibility, cellular uptake and drug delivery capability of LDH NPs were studied. In an in vitro study, using cultured pancreatic adenocarcinoma BXPC3 cells, valproate-intercalated LDH NPs showed an improved efficacy (~50 fold) over the sodium valproate alone. Finally, Gd(DTPA)-intercalated LDH NPs were synthesized and characterized by proton (1H) nuclear magnetic resonance. The longitudinal relaxivity (r1) of 28.38 s-1 mM-1, which is over 6 times higher than the clinically approved contrast agent, Gd(DTPA), demonstrated the potential of this vector for use in magnetic resonance imaging. Visible light-transparent single metal-semiconductor junction devices, which convert ultraviolet photon energy into high open circuit voltage (Voc>1.5-2 V), are highly desirable for transparent photovoltaics that can potentially power an electrochromic stack for smart windows. A Schottky junction solar cell, comprised of sputtered ZnO/ZnS heterojunction with Cr/Au contacts, was fabricated and an Voc of <em>f</em>î1.35 V was measured. Also, a low-cost route to form ZnO/ZnS heterojunctions by partial sulfurization of solution-grown ZnO thin films (350 nm-5 <em>f</em>Ým thick; conductivity comparable to phosphorus-doped Si) was demonstrated. A final study was on a cathode material for Li-ion batteries. Phase-pure LiFePO4 powders were synthesized by microwave-assisted sol-gel method and characterized. / Dissertation/Thesis / Doctoral Dissertation Materials Science and Engineering 2014

O uso de agentes de contraste em técnicas de diagnóstico por imagem é uma prática médi-ca rotineira. Certos compostos, presentes em agentes de contraste, possuem propriedades paramagnéticas que podem afetar os sinais da tomografia por ressonância magnética, \"Mag-netic Resonance Imaging\"(MRI). Em estudos aplicados ao trato gastrintestinal (GI), os meios de contraste são amplamente utilizados por via endovenosa, mas também podem ser admi-nistrados oralmente. Porém, a adoção do uso oral é limitada, principalmente, porque os agentes convencionais são caros e causam, geralmente, efeitos colaterais. Desta forma, a-presentamos a caracterização e os resultados preliminares da implementação da polpa do fruto da Euterpe olerácea para um possível uso clínico como agente de contraste oral em MRI do trato GI. A polpa da Euterpe olerácea, conhecida como Açaí, de origem amazônica, apre-senta um aumento de sinal de MRI ponderado em T1 equivalente ao do Gd-DTPA e, tam-bém, um decréscimo de sinal em imagens ponderadas em T2. Investigamos propriedades intrínsecas que possam estar correlacionadas com o aumento de sinal em T1 e à opacidade em T2. O espectro de absorção atômica revelou a presença de íons Fe, Mn e Cu no Açaí, o que contribui para o valor susceptométrico encontrado de -4,83 . 10-6. Essa medida fomen-ta a hipótese de que as mudanças de contraste nas imagens são devido à presença de mate-rial paramagnético, revelando um contraste clinicamente satisfatório nas porções superiores do trato GI. Estudos preliminares indicaram que a homogeneidade e a intensidade do sinal da polpa do Açaí (Euterpe olerácea), no estômago, e duodeno, são próximos daquele encon-trado em agentes convencionais. Além disso, ele não apresentou efeito colateral algum. Devido ao aumento de contraste associado ao Açaí, podemos observar a parede gástrica de forma singular. Ainda, este agente contribuiu para o diagnóstico das vias pancreática e biliar em exames de colangiopancreatografia por ressonância magnética, Magnetic Resonance Colan-giopancreatography (MRCP), com seqüências ponderadas em T2, por reduzir o sinal das alças intestinais. / The use of contrast agents is a common practice in medical imaging protocols. Paramagnetic properties of certain compounds present in contrast agents can affect Magnetic Resonance Imaging (MRI) signals. For abdominal applications, they are usually injected, but may also be administered orally. However, their use as a routine technique is limited, mainly due to the lack of appropriate oral contrast agent. Standard agents are expensive and cause, generally, some kind of side effect. We herein present the preliminary characterization and results for implementation of Euterpe olerácea (popularly named Açaí) as a possible clinical oral contrast agent for MRI of the gastrointestinal (GI) tract. The pulp of Açaí, a fruit from the Amazon area, presented an increase in T1-weighted MRI signal, equivalent to that of Gd-DTPA, and a signal decrease in T2-weighted images. We looked for intrinsic properties that could be responsible for the T1 signal enhancement and T2 opacification. Atomic Absorption spectra revealed the presence of Fe, Mn and Cu ions in Açai. The presence of such ions contribute to the susceptometric value found of -4.83 x 10-6 . This finding assents with the hypothesis that image contrast changes were due to the presence of paramagnetic material. The first measurements in vivo demonstrate a clear increase of contrast due to signal intensity and homogeneity in stomach and bowel walls with the pulp of Açaí, which look like the effects related to standard agents. Consistently, the increase in T1-weighted and the opacification in a T2-weighted acquisition was evident, revealing a biphasic contrast on gastric tissues. Besides, the pulp does not present any side effect. It still has contributed to the diagnostic of pancreatobiliary system at Magnetic Resonance Cholangiopancreatography (MRCP), by reducing overlap of the surround tissues and those structures.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-02-13T14:42:08Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) dissertação para imprimir.pdf: 1944013 bytes, checksum: 446b8ae7597e9bfcfe53826edaa4a028 (MD5) / Made available in DSpace on 2017-02-13T14:42:08Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) dissertação para imprimir.pdf: 1944013 bytes, checksum: 446b8ae7597e9bfcfe53826edaa4a028 (MD5) Previous issue date: 2014-08-20 / FACEPE / Neste trabalho foram sintetizados quantum dots de CdTe e CdTe:Gd3+ tendo o ácido mercapto succínico como estabilizante, visando uma potencial aplicação como agente de contraste bimodal para imagem ótica e magnética. A difração de raios-X evidenciou a formação dos QDs. Após quantificação dos íons dopantes por Espectrometria de Emissão Ótica com Plasma Indutivo Acoplado (ICP-OES), verificou-se 75,7% dos íons Gd3+ adicionados ficaram na nanopartícula. A grande quantidade de íons aderidos à nanopartícula, além da observação do aumento da relaxividade com a diminuição do pH e o deslocamento do estiramento das carbonilas por espectroscopia de infravermelho, são fatores que indicam que os íons Gd3+ aderiram aos QDs pela coordenação com o estabilizante e não por dopagem. A presença do íon gadolínio não alterou o deslocamento do máximo de absorção dos QDs e possivelmente interferiu na cinética de estabilização das superfícies, pois houve a diminuição da intensidade da luminescência dos mesmos. / In this work were synthesized quantum dots of CdTe and CdTe:Gd3+ having mercapto succinic acid (MSA) as a stabilizer, looking forward their use as a bimodal contrast agent for optical and magnetic images. The X-ray diffraction showed the formation of QDs. The quantification of dopants by Optical Emission Spectrometry with Inductive Coupled (ICPOES) Plasma, showed that 75.7% of Gd3+ ions were added in the nanoparticle. The large amount of ions bonded to the nanoparticle and the observation of increased relaxivity with decreasing pH and the observed shift of the stretching of carbonyls by infrared spectroscopy, are factors that indicated that Gd3+ ions were adhered to the QDs by coordinating with the stabilizer and not by doping. The presence of gadolinium ions did not change the absorption maximum band of the QDs, but probably changed the stabilization kinetics at the QD surface, due to the observed luminescence intensity decreasing.

O ferro é essencial para a vida do ser humano, desempenhando um papel fundamental no metabolismo. Contudo, quando não armazenado em compartimentos biológicos adequados, o metal apresenta um potencial tóxico ao organismo, uma vez que contribui para a formação de espécies reativas de oxigênio. A sobrecarga de ferro é uma condição desfavorável para portadores de algumas disfunções genéticas, como a hemocromatose, ou de anemias crônicas que requeiram transfusões de sangue periódicas, como é o caso da talassemia. Os fármacos atuais que controlam a patologia, como a desferrioxamina (DFO), requerem infusão subcutânea lenta, causando desconforto em pacientes e podendo trazer um série de complicações, como insuficiência hepática e renal. A modificação dessas moléculas com biopolímeros é uma proposta para minimizar efeitos colaterais e aumentar a biodisponibilidade do fármaco no organismo. Dentre esses biopolímeros, destacam-se as albuminas proveniente do soro bovino (BSA) e do ovo (OVA), que têm baixa toxicidade, baixo custo e abundância de sítios reativos, que quando modificados, favorecem reação com a desferrioxamina. Como resultado, houve a reação dos biopolímeros com a desferrioxamina, com mudanças em suas estruturas secundárias e possível dimerização, resultando na formação de conjugados possuem afinidade com íon ferro e capacidade antioxidante semelhante ao fármaco original, características que tornam os compostos bons candidatos a uma alternativa à terapia de quelação. Os conjugados BSA-DFO e OVA-DFO podem reagir, além do ferro, com gadolínio, fazendo com o que os complexos tenham uma potencial aplicação como agentes de contraste em ressonância magnética de imagem (MRI). Neste trabalho, vimos que o complexo entre Gd(III) e BSA-DFO apresentou uma relaxatividade de 52,92 s-1 mM-1 para T2 e 45,37 s-1 mM-1 para T1 , um valor bem superior aos fármacos disponíveis no mercado, que apre-sentam relaxatividade entre 4 e 5 s-1 mM-1, o que foi explicado por sua elevada massa molecular, indicando que poderia ter bons efeitos na qualidade de MRI, com menores doses. / Iron is essential for human life, playing a fundamental role in metabolism. However, when not stored in appropriate biological compartments, the metal presents a toxic potential to the body, contributing to the formation of reactive oxygen species (ROS). Iron overload is an unfavorable condition for people with certain genetic disorders, such as hemochromatosis, or chronic anemias that require periodic blood transfusions, as thalassemia. Current drugs that control the pathology, as desferrioxamine, require slow subcutaneous infusion, causing discomfort in patients and may lead to a number of complications, such as hepatic and renal failures. As a result, the biopolymers were reacted with desferrioxamine, with changes in their secondary structures and possible dimerization, resulting in the formation of conjugates with iron ion affinity and antioxidant capacity similar to the original drug, characteristics that make the compounds good candidates for an alternative chelation therapy As a result, the reaction of the biopolymers with desferrioxamine caused a change in the secondary structure, with possible formation of dimers and showing different mobility when exposed to an electric potential difference. Not all polymer chains have reacted with DFO, however BSA-DFO complex has antioxidant capacity similar to the original drug. The BSA-DFO and OVA-DFO conjugates can react, in addition to iron, with gadolinium, making the complexes potential contrast agents for magnetic resonance imaging (MRI). In this work, the complex between Gd(III) and BSA-DFO presented a relaxativity of 52,92 s-1 mM-1 for T2 and 45,37 s-1 mM-1 for T1, values higher than the available drugs in the market (4 - 5 s-1 mM-1) which was explained by the high molecular weight, indicating a good effects on the quality of MRI, with lower doses.