Investigation and Development of a Fully 3D Tilt Capable Hybrid SPECT - CT System for Dedicated Breast Imaging

X-ray mammography has been the gold standard for breast imaging for decades, despite the significant limitations posed by the two dimensional (2D) image acquisitions. Difficulty in diagnosing lesions close to the chest wall and axilla, high amount of structural overlap and patient discomfort due to compression are only some of these limitations. To overcome these drawbacks, three dimensional (3D) breast imaging modalities have been developed including dual modality single photon emission computed tomography (SPECT) and computed tomography (CT) systems. This thesis focuses on the development and integration of the next generation of such a device for dedicated breast imaging. The goals of this dissertation work are to: [1] understand and characterize any effects of fully 3-D trajectories on reconstructed image scatter correction, absorbed dose and Hounsifeld Unit accuracy, and [2] design, develop and implement the fully flexible, third generation hybrid SPECT-CT system capable of traversing complex 3D orbits about a pendant breast volume, without interference from the other. Such a system would overcome artifacts resulting from incompletely sampled divergent cone beam imaging schemes and allow imaging closer to the chest wall, which other systems currently under research and development elsewhere cannot achieve.

The dependence of x-ray scatter radiation on object shape, size, material composition and the CT acquisition trajectory, was investigated with a well-established beam stop array (BSA) scatter correction method. While the 2D scatter to primary ratio (SPR) was the main metric used to characterize total system scatter, a new metric called ‘normalized scatter contribution’ was developed to compare the results of scatter correction on 3D reconstructed volumes. Scatter estimation studies were undertaken with a sinusoidal saddle (±15° polar tilt) orbit and a traditional circular (AZOR) orbit. Clinical studies to acquire data for scatter correction were used to evaluate the 2D SPR on a small set of patients scanned with the AZOR orbit. Clinical SPR results showed clear dependence of scatter on breast composition and glandular tissue distribution, otherwise consistent with the overall phantom-based size and density measurements. Additionally, SPR dependence was also observed on the acquisition trajectory where 2D scatter increased with an increase in the polar tilt angle of the system.

The dose delivered by any imaging system is of primary importance from the patient’s point of view, and therefore trajectory related differences in the dose distribution in a target volume were evaluated. Monte Carlo simulations as well as physical measurements using radiochromic film were undertaken using saddle and AZOR orbits. Results illustrated that both orbits deliver comparable dose to the target volume, and only slightly differ in distribution within the volume. Simulations and measurements showed similar results, and all measured dose values were within the standard screening mammography-specific, 6 mGy dose limit, which is used as a benchmark for dose comparisons.

Hounsfield Units (HU) are used clinically in differentiating tissue types in a reconstructed CT image, and therefore the HU accuracy of a system is very important, especially when using non-traditional trajectories. Uniform phantoms filled with various uniform density fluids were used to investigate differences in HU accuracy between saddle and AZOR orbits. Results illustrate the considerably better performance of the saddle orbit, especially close to the chest and nipple region of what would clinically be a pedant breast volume. The AZOR orbit causes shading artifacts near the nipple, due to insufficient sampling, rendering a major portion of the scanned phantom unusable, whereas the saddle orbit performs exceptionally well and provides a tighter distribution of HU values in reconstructed volumes.

Finally, the third generation, fully-suspended SPECT-CT system was designed in and developed in our lab. A novel mechanical method using a linear motor was developed for tilting the CT system. A new x-ray source and a custom made 40 x 30 cm2 detector were integrated on to this system. The SPECT system was nested, in the center of the gantry, orthogonal to the CT source-detector pair. The SPECT system tilts on a goniometer, and the newly developed CT tilting mechanism allows ±15° maximum polar tilting of the CT system. The entire gantry is mounted on a rotation stage, allowing complex arbitrary trajectories for each system, without interference from the other, while having a common field of view. This hybrid system shows potential to be used clinically as a diagnostic tool for dedicated breast imaging.

Single- and multiphoton detachment of K

Single- and multiphoton detachment rates have been calculated for K- using the R-matrix Floquet approach. Single-photon detachment rates, obtained at a laser field peak intensity of 10(9) W cm(-2), are discussed and compared with other theoretical work. Two-photon detachment rates at the same intensity have also been obtained, and similarities with results from earlier calculations for Li- and Na- are discussed. Three-photon rates are also presented at this laser intensity, and are compared and contrasted with those arising in the single-photon case, since both involve resonance structure with P-1(o) symmetry. The influence of resonances such as the 5s(2) S-1(e) doubly excited state and excitations of the residual atom are also considered.

Strong erbium luminescence in the near-infrared telecommunication window

A new type of near-infrared emitting rare-earth complex has been synthesised, consisting of three bis(perfluoroalkylsulfonyl)imide ligands and one 1,10-phenanthroline molecule. The chelate rings formed by the rare-earth ion and the bidentate ligands do not contain any carbon atoms and can hence be considered as 'inorganic' chelate rings. The absence of C-H stretching vibration modes in the first coordination sphere of the rare-earth ion and the presence of a light-harvesting moiety (1,10-phenanthroline) bound to the rare-earth ion result in a complex that can be efficiently excited and exhibits intense near-infrared luminescence. (C) 2004 Elsevier B.V. All rights reserved.

Photo-double detachment from the F- ion

The correlated process of photodetaching two electrons from the F- ion following the absorption of a single photon has been investigated over an energy range 20-62 eV. In the experiment, a beam of photons from the Advanced Light Source was collinearly merged with a counter-propagating beam of F- ions from a sputter ion source. The F+ ions produced in the interaction region were detected, and the normalized signal was used to monitor the relative cross section for the double-detachment reaction. An absolute scale for the cross section was established by measuring the spatial overlap of the two beams and by determining the efficiency for collection and detection of the F+ ions. The measured cross section is compared with R-matrix and random phase approximation calculations. These calculations show that the Auger decay of the 2s2p(6) core-excited state of the F atom plays a minor role in the production of F+ ions and that double detachment is likely to be dominated by simultaneous correlated ejection of two valence electrons at energies well above threshold.

The Ectocarpus genome and the independent evolution of multicellularity in brown algae

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related(1). These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae(2-5), closely related to the kelps(6,7) (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic(2) approaches to explore these and other(4,5) aspects of brown algal biology further.

A comprehensive aerosol spray method for the rapid photocatalytic grid area analysis of semiconductor photocatalyst thin films

Indicator inks, previously shown to be capable of rapidly assessing photocatalytic activity via a novel photo-reductive mechanism, were simply applied via an aerosol spray onto commercially available pieces of Activ (TM) self-cleaning glass. Ink layers could be applied with high evenness of spread, with as little deviation as 5% upon UV-visible spectroscopic assessment of 25 equally distributed positions over a 10 cm x 10 cm glass cut. The inks were comprised of either a resazurin (Rz) or dichloroindophenol (DCIP) redox dye with a glycerol sacrificial electron donor in an aqueous hydroxyethyl cellulose (HEC) polymer media. The photo-reduction reaction under UVA light of a single spot was monitored by UV-vis spectroscopy and digital images attained from a flat-bed scanner in tandem for both inks. The photo-reduction of Rz ink underwent a two-step kinetic process, whereby the blue redox dye was initially reduced to a pink intermediate resorufin (Rf) and subsequently reduced to a bleached form of the dye. In contrast, a simple one-step kinetic process was observed for the reduction of the light blue redox dye DCIP to its bleached intermediates. Changes in red-green-blue colour extracted from digital images of the inks were inversely proportional to the changes seen at corresponding wavelengths via UV-visible absorption spectroscopy and wholly indicative of the reaction kinetics. The photocatalytic activity areas of cuts of Activ (TM) glass, 10 cm x 10 cm in size, were assessed using both Rz and DCIP indicator inks evenly sprayed over the films: firstly using UVA lamp light to activate the underlying Activ (TM) film (1.75 mW cm(-2)) and secondly under solar conditions (2.06 +/- 0.14 mW cm(-2)). The photo-reduction reactions were monitored solely by flat-bed digital scanning. Red-green-blue values of a generated 14 x 14 grid (196 positions) that covered the entire area of each film image were extracted using a Custom-built program entitled RGB Extractor(C). A homogenous degradation over the 196 positions analysed for both Rz (Red colour deviation = 19% UVA, 8% Solar: Green colour deviation = 17% UVA, 12% Solar) and DCIP (Red colour deviation = 22% UVA, 16% Solar) inks was seen in both UVA and solar experiments, demonstrating the consistency of the self-cleaning titania layer on Activ (TM). The method presented provides a good solution for the high-throughput photocatalytic screening of a number of homogenous photocatalytically active materials simultaneously or numerous positions on a single film; both useful in assessing the homogeneity of a film or determining the best combination of reaction components to produce the optimum performance photocatalytic film. (C) 2010 Elsevier B.V. All rights reserved.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage ( European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

Strong Coupling and Long-Range Collective Interactions in Optomechanical Arrays

We investigate the collective optomechanics of an ensemble of scatterers inside a Fabry-Pérot resonator and identify an optimized configuration where the ensemble is transmissive, in contrast to the usual reflective optomechanics approach. In this configuration, the optomechanical coupling of a specific collective mechanical mode can be several orders of magnitude larger than the single-element case, and long-range interactions can be generated between the different elements since light permeates throughout the array. This new regime should realistically allow for achieving strong single-photon optomechanical coupling with massive resonators, realizing hybrid quantum interfaces, and exploiting collective long-range interactions in arrays of atoms or mechanical oscillators.

Substrate Clamping Effects on Irreversible Domain Wall Dynamics in Lead Zirconate Titanate Thin Films

The role of long-range strain interactions on domain wall dynamics is explored through macroscopic and local measurements of nonlinear behavior in mechanically clamped and released polycrystalline lead zirconate-titanate (PZT) films. Released films show a dramatic change in the global dielectric nonlinearity and its frequency dependence as a function of mechanical clamping. Furthermore, we observe a transition from strong clustering of the nonlinear response for the clamped case to almost uniform nonlinearity for the released film. This behavior is ascribed to increased mobility of domain walls. These results suggest the dominant role of collective strain interactions mediated by the local and global mechanical boundary conditions on the domain wall dynamics. The work presented in this Letter demonstrates that measurements on clamped films may considerably underestimate the piezoelectric coefficients and coupling constants of released structures used in microelectromechanical systems, energy harvesting systems, and microrobots.

Quantum state storage and processing for polarization qubits in an inhomogeneously broadened Λ-type three-level medium

We address the propagation of a single photon pulse with two polarization components, i.e., a polarization qubit, in an inhomogeneously broadened "phaseonium" \Lambda-type three-level medium. We combine some of the non-trivial propagation effects characteristic for this kind of coherently prepared systems and the controlled reversible inhomogeneous broadening technique to propose several quantum information processing applications, such as a protocol for polarization qubit filtering and sieving as well as a tunable polarization beam splitter. Moreover, we show that, by imposing a spatial variation of the atomic coherence phase, an effcient quantum memory for the incident polarization qubit can be also implemented in \Lambda-type three-level systems.

Optical quantum memory for polarization qubits with V-type three-level atoms

We investigate an optical quantum memory scheme with V-type three-level atoms based on the controlled reversible inhomogeneous broadening (CRIB) technique. We theoretically show the possibility to store and retrieve a weak light pulse interacting with the two optical transitions of the system. This scheme implements a quantum memory for a polarization qubit - a single photon in an arbitrary polarization state - without the need of two spatially separated two-level media, thus offering the advantage of experimental compactness overcoming the limitations due to mismatching and unequal efficiencies that can arise in spatially separated memories. The effects of a relative phase change between the atomic levels, as well as of phase noise due to, for example, the presence of spurious electric and magnetic fields are analyzed.

Robust nonadiabatic molecular dynamics for metals and insulators

We present a new formulation of the correlated electron-ion dynamics (CEID) scheme, which systematically improves Ehrenfest dynamics by including quantum fluctuations around the mean-field atomic trajectories. We show that the method can simulate models of nonadiabatic electronic transitions and test it against exact integration of the time-dependent Schrodinger equation. Unlike previous formulations of CEID, the accuracy of this scheme depends on a single tunable parameter which sets the level of atomic fluctuations included. The convergence to the exact dynamics by increasing the tunable parameter is demonstrated for a model two level system. This algorithm provides a smooth description of the nonadiabatic electronic transitions which satisfies the kinematic constraints (energy and momentum conservation) and preserves quantum coherence. The applicability of this algorithm to more complex atomic systems is discussed.

Multiphoton inner-shell ionization of the carbon atom

We apply time-dependent R-matrix theory to study inner-shell ionization of C atoms in ultra-short high-frequency light fields with a photon energy between 170 and 245 eV. At an intensity of 10¹⁷ W/cm², ionization is dominated by single-photon emission of a 2l electron, with two-photon emission of a 1s electron accounting for about 2-3% of all emission processes, and two-photon emission of 2l contributing about 0.5-1%. Three-photon emission of a 1s electron is estimated to contribute about 0.01-0.03%. Around a photon energy of 225 eV, two-photon emission of a 1s electron, leaving C⁺ in either 1s2s2p³ or 1s2p⁴ is resonantly enhanced by intermediate 1s2s²2p³ states. The results demonstrate the capability of time-dependent R-matrix theory to describe inner-shell ionization processes including rearrangement of the outer electrons.

Hydrogel-forming microneedle arrays made from light-responsive materials for on-demand transdermal drug delivery

We describe, for the first time, stimuli-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 hours). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in ?on-demand? delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

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.