Prostate cancer radiotherapy: potential applications of metal nanoparticles for imaging and therapy

Prostate cancer (CaP) is the most commonly diagnosed cancer in males. There have been dramatic technical advances in radiotherapy delivery, enabling higher doses of radiotherapy to primary cancer, involved lymph nodes and oligometastases with acceptable normal tissue toxicity. Despite this, many patients relapse following primary radical therapy, and novel treatment approaches are required. Metal nanoparticles are agents that promise to improve diagnostic imaging and image-guided radiotherapy and to selectively enhance radiotherapy effectiveness in CaP. We summarize current radiotherapy treatment approaches for CaP and consider pre-clinical and clinical evidence for metal nanoparticles in this condition.

Prostate cancer (CaP) is the most commonly diagnosed cancer in males and is responsible for more than 10,000 deaths each year in the UK.1 Technical advances in radiotherapy delivery, including image-guided intensity-modulated radiotherapy (IG-IMRT), have enabled the delivery of higher radiation dose to the prostate, which has led to improved biochemical control. Further improvements in cancer imaging during radiotherapy are being developed with the advent of MRI simulators and MRI linear accelerators.2–4

Nanotechnology promises to deliver significant advancements across numerous disciplines.5 The widest scope of applications are from the biomedical field including exogenous gene/drug delivery systems, advanced biosensors, targeted contrast agents for diagnostic applications and as direct therapeutic agents used in combination with existing treatment modalities.6–11 This diversity of application is especially evident within cancer research, with a myriad of experimental anticancer strategies currently under investigation.

This review will focus specifically on the potential of metal-based nanoparticles to augment the efficacy of radiotherapy in CaP, a disease where radiotherapy constitutes a major curative treatment modality.12 Furthermore, we will also address the clinical state of the art for CaP radiotherapy and consider how these treatments could be best combined with nanotherapeutics to improve cancer outcomes.

Bright Molecules for Sensing, Computing and Imaging: A Tale of Two Once-troubled Cities

The circumstances in Colombo, Sri Lanka, and in Belfast, Northern Ireland, which led to a) the generalization of luminescent PET (photoinduced electron transfer) sensing/switching as a design tool, b) the construction of a market-leading blood electrolyte analyzer and c) the invention of molecular logic-based computation as an experimental field, are delineated. Efforts to extend the philosophy of these approaches into issues of small object identification, nanometric mapping, animal visual perception and visual art are also outlined.

Test-retest variability in structural and functional parameters of glaucoma damage in the glaucoma imaging longitudinal study.

PURPOSE:

To determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma.

PATIENTS AND METHODS:

In this cohort study, the authors analyzed the imaging studies and visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement.

RESULTS:

In this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm for rim area, and 32.8 microm and 31.8 microm for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0, 2.3, 5.7, 3.1, and 3.4, respectively.

CONCLUSIONS:

The variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage.

High-Resolution Microwave Near-Field Imaging Using Resonance Probes

A novel microwave high-resolution near-field imaging technique is proposed and experimentally evaluated in reflectometry imaging scenarios involving planar metal-dielectric structures. Two types of resonance near field probes-a small helix antenna and a loaded subwavelength slot aperture are studied in this paper. These probes enable very tight spatial field localization with the full width at half maximum around one tenth of a wavelength, λ, at λ/100-λ/10 standoff distance. Importantly, the proposed probes permit resonance electromagnetic coupling to dielectric or printed conductive patterns, which leads to the possibility of very high raw image resolution with imaged feature-to-background contrast greater than 10-dB amplitude and 50° phase. In addition, high-resolution characterization of target geometries based on the cross correlation image processing technique is proposed and assessed using experimental data. It is shown that printed elements features with subwavelength size ~λ/15 or smaller can be characterized with at least 10-dB resolution contrast.

Novel precipitated zirconia-based DGT technique for high-resolution imaging of oxyanions in waters and sediments

Water-sediment exchange is a fundamental component of oxyanion cycling in the environment. Yet, many of the (im)mobilization processes overlay complex spatial and temporal redox regimes that occur within millimeters of the interface. Only a few methods exist that can reliably capture these porewater fluxes, with the most popular being high-resolution diffusive gradients in thin films (HR-DGT). However, functionality of HR-DGT is restricted by the availability of suitable analyte binding agents within the sampler, which must be simple to cast and homogeneously distributed in the binding layer, exhibit adequate sorption capacities, be resistive to chemical change, and possess a very fine particle size (≤10 μm). A novel binding layer was synthesized to meet these requirements by in situ precipitation of zirconia into a precast hydrogel. The particle diameter ≤0.2 μm of zirconia in this precipitated gel was uniform and at least 50-times smaller than the conventional molding approach. Further, this gel had superior binding and stability characteristics compared with the commonly used ferrihydrite HR-DGT technique and could be easily fabricated as an ultrathin gel (60 μm) for simultaneous oxygen imaging in conjunction with planar-optodes. Chemical imaging of anion and oxygen fluxes using the new sampler were evaluated on Lake Taihu sediments.

Development of neutron and X-ray imaging detectors based on MHSP

A Micro-Hole & Strip Plate (MHSP) é uma microestrutura desenvolvida recentemente em instituições universitárias portuguesas. Neste trabalho, o seu desempenho como detector para imagiologia é explorado, tendo como objectivo a imagiologia não só de neutrões, mas também de raios X. A aplicação do método da divisão resistiva de carga é aplicada a uma MHSP especialmente desenhada para sensibilidade em posição. Várias abordagens em termos da electrónica de aquisição de sinal são testadas, sem perder de vista a relação desempenho-preço. Resoluções espaciais abaixo de 1 mm foram obtidas com a MHSP a operar em xénon e tetrafluorometano, com um sistema de detecção a um preço modesto quando comparado com as alternativas, e apropriado para inúmeras aplicações em imagiologia de neutrões e de raios X.

Radiological imaging in digital systems: the effect of exposure parameters in diagnostic quality and patient dose

Esta tese pretende contribuir para o estudo e análise dos factores relacionados com as técnicas de aquisição de imagens radiológicas digitais, a qualidade diagnóstica e a gestão da dose de radiação em sistema de radiologia digital. A metodologia encontra-se organizada em duas componentes. A componente observacional, baseada num desenho do estudo de natureza retrospectiva e transversal. Os dados recolhidos a partir de sistemas CR e DR permitiram a avaliação dos parâmetros técnicos de exposição utilizados em radiologia digital, a avaliação da dose absorvida e o índice de exposição no detector. No contexto desta classificação metodológica (retrospectiva e transversal), também foi possível desenvolver estudos da qualidade diagnóstica em sistemas digitais: estudos de observadores a partir de imagens arquivadas no sistema PACS. A componente experimental da tese baseou-se na realização de experiências em fantomas para avaliar a relação entre dose e qualidade de imagem. As experiências efectuadas permitiram caracterizar as propriedades físicas dos sistemas de radiologia digital, através da manipulação das variáveis relacionadas com os parâmetros de exposição e a avaliação da influência destas na dose e na qualidade da imagem. Utilizando um fantoma contrastedetalhe, fantomas antropomórficos e um fantoma de osso animal, foi possível objectivar medidas de quantificação da qualidade diagnóstica e medidas de detectabilidade de objectos. Da investigação efectuada, foi possível salientar algumas conclusões. As medidas quantitativas referentes à performance dos detectores são a base do processo de optimização, permitindo a medição e a determinação dos parâmetros físicos dos sistemas de radiologia digital. Os parâmetros de exposição utilizados na prática clínica mostram que a prática não está em conformidade com o referencial Europeu. Verifica-se a necessidade de avaliar, melhorar e implementar um padrão de referência para o processo de optimização, através de novos referenciais de boa prática ajustados aos sistemas digitais. Os parâmetros de exposição influenciam a dose no paciente, mas a percepção da qualidade de imagem digital não parece afectada com a variação da exposição. Os estudos que se realizaram envolvendo tanto imagens de fantomas como imagens de pacientes mostram que a sobreexposição é um risco potencial em radiologia digital. A avaliação da qualidade diagnóstica das imagens mostrou que com a variação da exposição não se observou degradação substancial da qualidade das imagens quando a redução de dose é efectuada. Propõe-se o estudo e a implementação de novos níveis de referência de diagnóstico ajustados aos sistemas de radiologia digital. Como contributo da tese, é proposto um modelo (STDI) para a optimização de sistemas de radiologia digital.

Multifunctional nanoparticles for MR and fluorescence imaging

In the past few years a new generation of multifunctional nanoparticles (NPs) has been proposed for biomedical applications, whose structure is more complex than the structure of their predecessor monofunctional counterparts. The development of these novel NPs aims at enabling or improving the performance in imaging, diagnosis and therapeutic applications. The structure of such NPs comprises several components exhibiting various functionalities that enable the nanoparticles to perform multiple tasks simultaneously, such as active targeting of certain cells or compartmentalization, imaging and delivery of active drugs. This thesis presents two types of bimodal bio-imaging probes and describes their physical and chemical properties, namely their texture, structure, and 1H dynamics and relaxometry, in order to evaluate their potential as MRI contrast agents. The photoluminescence properties of these probes are studied, aiming at assessing their interest as optical contrast agents. These materials combine the properties of the trivalent lanthanide (Ln3+) complexes and nanoparticles, offering an excellent solution for bimodal imaging. The designed T1- type contrast agent are SiO2@APS/DTPA:Gd:Ln or SiO2@APS/PMN:Gd:Ln (Ln= Eu or Tb) systems, bearing the active magnetic center (Gd3+) and the optically-active ions (Eu3+ and Tb3+) on the surface of silica NPs. Concerning the relaxometry properties, moderate r1 increases and significant r2 increases are observed in the NPs presence, especially at high magnetic fields, due to susceptibility effects on r2. The Eu3+ ions reside in a single low-symmetry site, and the photoluminescence emission is not influenced by the simultaneous presence of Gd3+ and Eu3+. The presence of Tb3+, rather than Eu3+ ion, further increases r1 but decreases r2. The uptake of these NPs by living cells is fast and results in an intensity increase in the T1-weighted MRI images. The optical features of the NPs in cellular pellets are also studied and confirm the potential of these new nanoprobes as bimodal imaging agents. This thesis further reports on a T2 contrast agent consisting of core-shell NPs with a silica shell surrounding an iron oxide core. The thickness of this silica shell has a significant impact on the r2 and r2* relaxivities, and a tentative model is proposed to explain this finding. The cell viability and the mitochondrial dehydrogenase expression given by the microglial cells are also evaluated.

Hole-type gaseous detectors for medical imaging and HEP experiments

This work presents the results on the development of a high pressure Xe gaseous detector envisaging medical imaging. The detector uses two VUV photosensors operating face-to-face, based on the CsI-MHSP with position discrimination capability. The known effect of the charge gain decrease with the gas pressure is compensated with a light gain using the electroluminescence process. Studies of signal amplitude, energy and position resolution are presented. On the second part, gaseous detectors based on THGEM where studied in order to fulfill the requirements of present and future high energy physics experiments. The work is focused on the application of THGEM in RICH detectors elements: a triple THGEM detector using CsI photocathodes in Ne mixtures was suggested. The ion backflow to the photocathode remains a concern and a limitation; to minimize it, the application of a new hole-structure, THCOBRA, was suggested. Preliminary results foresee good perspectives for the successful application of THCOBRA in ion back-flow suppression. This work contains several methods and measurements of the CsI photocathodes behaviour in radiation gaseous detectors. A long discussion on its issues and possible solutions are presented.

MPGDs based radiation imaging devices and applications

Este trabalho descreve o desenvolvimento e aplicação de sistemas baseados em detetores gasosos microestruturados, para imagiologia de fluorescência de raios-X por dispersão em energia (EDXRF). A técnica de imagiologia por fluorescência de raios-X assume-se como uma técnica poderosa, não-destrutiva, em análises da distribuição espacial de elementos em materiais. Os sistemas para imagiologia de EDXRF desenvolvidos são constituídos por: um tubo de raios-X, usado para excitar os elementos da amostra; um detetor gasoso microestruturado; e uma lente pinhole que foca a radiação de fluorescência no plano do detetor formando assim a imagem e permitindo a sua ampliação. Por outro lado é estudada a influência do diâmetro da abertura do pinhole bem como do fator de ampliação obtido para a imagem, na resolução em posição do sistema. Foram usados dois conceitos diferentes de detetores gasosos microestruturados. O primeiro, baseado na microestrutura designada por 2D-Micro-Hole & Strip Plate (2D-MHSP) com uma área ativa de 3 3 cm2, enquanto que o segundo, baseado na estrutura 2D-Thick-COBRA (2D-THCOBRA) apresenta uma área ativa de deteção de 10 10 cm2. Estes detetores de raios-X de baixo custo têm a particularidade de funcionar em regime de fotão único permitindo a determinação da energia e posição de interação de cada fotão que chega ao detetor. Deste modo permitem detetar a energia dos fotões X de fluorescência, bem como obter imagens 2D da distribuição desses fotões X para o intervalo de energias desejado. São por isso adequados a aplicações de imagiologia de EDXRF. Os detetores desenvolvidos mostraram resoluções em energia de 17% e 22% para fotões incidentes com uma energia de 5.9 keV, respectivamente para o detetor 2D-MHSP e 2D-THCOBRA e resoluções em posição adequadas para um vasto número de aplicações. Ao longo deste trabalho é detalhado o desenvolvimento, o estudo das características e do desempenho de cada um dos detetores, e sua influência na performance final de cada sistema proposto. Numa fase mais avançada apresentam-se os resultados correspondentes à aplicação dos dois sistemas a diversas amostras, incluindo algumas do nosso património cultural e também uma amostra biológica.

Lanthanide oxide and phosphate nanoparticles for thermometry and bimodal imaging

Nesta tese relatam-se estudos de fotoluminescência de nanopartículas de óxidos e fosfatos dopados com iões trivalentes de lantanídeos, respectivamente, nanobastonetes de (Gd,Eu)2O3 e (Gd,Yb,Er)2O3 e nanocristais de (Gd,Yb,Tb)PO4, demonstrando-se também aplicações destes materiais em revestimentos inteligentes, sensores de temperatura e bioimagem. Estuda-se a transferência de energia entre os sítios de Eu3+ C2 e S6 dos nanobastonetes Gd2O3. A contribuição dos mecanismos de transferência de energia entre sítios para o tempo de subida 5D0(C2) é descartada a favor da relaxação directa 5D1(C2) 5D0(C2) (i.e., transferência de energia entre níveis). O maior tempo de decaimento do nível 5D0(C2) nos nanobastonetes, relativamente ao valor medido para o mesmo material na forma de microcristais, é atribuído, quer à existência de espaços livres entre nanobastonetes próximos (factor de enchimento ou fracção volúmica), quer à variação do índice de refracção efectivo do meio em torno dos iões Eu3+. A dispersão de nanobastonetes de (Gd,Eu)2O3 em três resinas epoxi comerciais através da cura por UV permite obter nanocompósitos epoxi- (Gd,Eu)2O3. Relatam-se estudos cinéticos e das propriedades térmicas e de fotoluminescência destes nanocompósitos. Estes, preservam as típicas propriedades de emissão do Eu3+, mostrando o potencial do método de cura por UV para obter revistimentos inteligentes e fotoactivos. Considera-se um avanço significativo a realização de uma nanoplataforma óptica, incorporando aquecedor e termómetro e capaz de medir uma ampla gama de temperaturas (300-2000 K) à escala nano, baseada em nanobastonetes de (Gd,Yb,Er)2O3 (termómetros) cuja superfície se encontra revestida com nanopartículas de ouro. A temperature local é calculada usando, quer a distribuição de Boltzmann (300-1050 K) do rácio de intensidades da conversão ascendente 2H11=2!4I15=2/4S3=2!4I15=2, quer a lei de Planck (1200-2000 K) para uma emissão de luz branca atribuída à radiação do corpo negro. Finalmente, estudam-se as propriedades de fotoluminescência correspondentes às conversões ascendente e descendente de energia em nanocristais de (Gd,Yb,Tb)PO4 sintetizados por via hidrotérmica. A relaxividade (ressonância magnética) do 1H destes materiais são investigadas, tendo em vista possíveis aplicações em imagem bimodal (luminescência e ressonância magnética nuclear).

Absorption coefficient of particulate matter on the south-west coast of Europe: a contribution to the validation of the MERIS-Medium Resolution Imaging Spectrometer sensor

Dissolved oxygen (DO) is one of the most important environmental variables of water quality, especially for marine life. Consequently, oxygen is one of the Chemical Quality Elements required for the implementation of European Union Water Framework Directive. This study uses the example of the Ria Formosa, a meso-tidal lagoon on the south coast of Portugal to demonstrate how monitoring of water quality for coastal waters must be well designed to identify symptoms of episodic hypoxia. New data from the western end of the Ria Formosa were compared to values in a database of historical data and in the published literature to identify long-term trends. The dissolved oxygen concentration values in the database and in the literature were generally higher than those found in this study, where episodic hypoxia was observed during the summer. Analysis of the database showed that the discrepancy was probably related with the time and the sites where the samples had been collected, rather than a long-term trend. The most problematic situations were within the inner lagoon near the city of Faro, where episodic hypoxia (<2 mg dm3 DO) occurred regularly in the early morning. These results emphasise the need for a balanced sampling strategy for oxygen monitoring which includes all periods of the day and night, as well as a representative range of sites throughout the lagoon. Such a strategy would provide adequate data to apply management measures to reduce the risk of more persistent hypoxia that would impact on the ecological, important natural resource. economic and leisure uses of this important natural resource.

Radiographers perceptions of magnetic resonance imaging: a study of the causes that lead to the exams repetition

Purpose: To know how often occur the repetitions of MRI exams and sequences in radiology departments. Methods and Materials: A self applied-questionnaire was used as instrument and assigned to 57 radiographers who performed MRI exams to determine which were the causes that lead to the repetition. The questionnaires were interpreted and statistically analyzed through descriptive statistics and Spearman’s rho correlations. Results: At a 95% confidence interval, the major results suggest that the patient’s movement during de MRI exams is the main cause to repeat this exams (mean of 3.88 on a 5 points likert scale). However, there are causes related to the radiographer’s and the results showed that the introduction of wrong imaging parameters by the performer are a major cause too (N=26). Spearman rho correlations between radiographer’s time of experience and frequency of MRI exams repetitions were poor and not significant (r=0.141; p=0.297). The correlations between radiographer’s tiredness and frequency of MRI exams repetitions were negative, weak and not significant (r= -0.151; p=0.263). Conclusion: The patients’ movement may disrupt the examination or degrade the images with artifacts. The level of experience doesn’t influence the repetitions of MRI exams, it seems that seniors radiographers don’t have improvements in performance as it should be expected. It’s recommendable to do training courses regularly to improve the performance and systematically evaluate. Several features will need to be identified which would decrease the MRI exams repetitions.

Diversifying medical imaging of breast lesions

Dissertação de mestrado, Engenharia Informática, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Learner’s satisfaction within a breast imaging eLearning course for radiographers

Background: An asynchronous eLearning system was developed for radiographers in order to promote a better knowledge about senology and mammography. Objectives: to assess the learners’ satisfaction. Methods: Target population included radiographers and radiogr aphy students, in order to assess eLearning satisfaction according to different experience levels in breast imaging. Satisfaction was measured through a questionnaire developed especially for eLearning systems, using a seven - point Likert scale. Main topics related are content, interface, personalization and learning community. Results: Overall, 85% of learners were satisfied with the course and 87,5% considered that the course is successful. Main areas that were evaluated by most learners in a positive way were interface and content (between six and seven - point); on the other hand, learning community presented a wider distribution of answers . Conclusions: The course provides an overall high degree of learner satisfaction, thus providing more effective knowle dge gain on breast imaging for radiographers.