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.

Study of gene expression in thyrotropin-stimulated thyroid cells by cDNA expression array: ID3 transcription modulating factor as an early response protein and tumor marker in thyroid carcinomas.

Induction of cell proliferation by mitogen or growth factor stimulation leads to the specific induction or repression of a large number of genes. To identify genes differentially regulated by the cAMP-dependent transduction pathway, which is poorly characterized so far, we used the cDNA expression array technology. Hybridizations of Atlas human cDNA expression arrays with (32)P-labeled cDNA probes derived from control or thyrotropin (TSH)-stimulated dog thyrocytes in primary culture generated expression profiles of hundreds of genes simultaneously. Among the genes that displayed modified expression, we selected the transcription factor ID3, whose expression was increased by a cAMP-dependent stimulus. ID3 overexpression after TSH stimulation was first verified by Northern blotting analysis, and its mRNA regulation was then investigated in response to a variety of agents acting on thyrocyte proliferation and/or differentiation. We show that: (1) ID3 mRNA induction was stronger after stimulation of the cAMP cascade, but was not restricted to this signaling pathway, as phorbol myristate ester (TPA) and insulin also stimulated mRNA accumulation; (2) in contrast, powerful mitogens for thyroid cells, epidermal growth factor and hepatocyte growth factor, did not significantly modify ID3 mRNA levels; (3) ID3 protein levels closely parallelled mRNA levels, as revealed by immunofluorescence experiments showing a nuclear signal regulated by TSH; (4) in papillary thyroid carcinomas, ID3 mRNA was downregulated. Our results suggest that ID3 expression might be more related to the differentiating process induced by TSH than to the proliferative action of this hormone.

Immediate early gene expression in dog thyrocytes in response to growth, proliferation, and differentiation stimuli.

In dog thyroid cells, insulin or IGF-1 induces cell growth and is required for the mitogenic action of TSH through cyclic AMP, of EGF, and of phorbol esters. HGF per se stimulates cell proliferation and is thus the only full mitogenic agent. TSH and cAMP enhance, whereas EGF phorbol esters and HGF repress differentiation expression. In this study, we have investigated for each factor and regulatory cascade of the intermediate step of immediate early gene induction, that is, c-myc, c-jun, jun D, jun B, c-fos, fos B, fra-1, fra-2, and egr1; fra-1 and fra-2 expressions were very low. TSH or forskolin increased the levels of c-myc, jun B, jun D, c-fos, and fos B while decreasing those of c-jun and egr1. Phorbol myristate ester stimulated the expression of all the genes. EGF and HGF stimulated the expression of all the genes except jun D and for EGF fos B. All these effects were obtained in the presence and in the absence of insulin, which shows that insulin is not necessary for the effects of the mitogens on immediate early gene expression. The definition of the repertoire of early immediate genes inductible by the various growth cascades provides a framework for the analysis of gene expression in tumors. (1) Insulin was able to induce all the protooncogenes investigated except fos B. This suggests that fos B could be the factor missing for insulin to induce mitogenesis. (2) No characteristic pattern of immediate early gene expression has been observed for insulin, which induces cell hypertrophy and is permissive for the action of the other growth factors. These effects are therefore not accounted for by a specific immediate early gene expression. On the other hand, insulin clearly enhances the effects of TSH, phorbol ester, and EGF on c-myc, junB, and c-fos expression. This suggests that the effect of insulin on mitogenesis might result from quantitative differences in the transcription complexes formed. (3) c-myc, c-fos, and jun B mRNA induction by all stimulating agents, whether inducing cell hypertrophy, or growth and dedifferentiation, or growth and differentiation, suggests that, although these expressions are not sufficient, they may be necessary for the various growth responses of thyroid cells. (4) The inhibition of c-jun and egr1 mRNA expression, and the marked induction of jun D mRNA appear to be specific features of the TSH cAMP pathway. They might be related to its differentiating action. (5) fos B, which is induced by TSH, forskolin, phorbol ester, and HGF but not by insulin, could be involved in the mitogenic action of the former factors.

A robust tri-state election algorithm for scalable applications

Existing election algorithms suffer limited scalability. This limit stems from the communication design which in turn stems from their fundamentally two-state behaviour. This paper presents a new election algorithm specifically designed to be highly scalable in broadcast networks whilst allowing any processing node to become coordinator with initially equal probability. To achieve this, careful attention has been paid to the communication design, and an additional state has been introduced. The design of the tri-state election algorithm has been motivated by the requirements analysis of a major research project to deliver robust scalable distributed applications, including load sharing, in hostile computing environments in which it is common for processing nodes to be rebooted frequently without notice. The new election algorithm is based in-part on a simple 'emergent' design. The science of emergence is of great relevance to developers of distributed applications because it describes how higher-level self-regulatory behaviour can arise from many participants following a small set of simple rules. The tri-state election algorithm is shown to have very low communication complexity in which the number of messages generated remains loosely-bounded regardless of scale for large systems; is highly scalable because nodes in the idle state do not transmit any messages; and because of its self-organising characteristics, is very stable.

Estoppel and the interests of the prospective beneficiary

Reviews case law concerning proprietary and testamentary estoppel. Examines two cases in which an elderly person made certain comments and encouraged an understanding between themselves and the claimants, that on death properties would be left to them, but where the requisite legal formalities were not undertaken. Illustrates the contrasting courts' approach, once estoppel has been established, in finding the appropriate remedy to satisfy and considers the challenges faced by the courts in differentiating between constructive trust and proprietary estoppel. [From Legal Journals Index]

Condition assessment of a 63-year old reinforced concrete structure exposed to the North Sea

This paper describes the condition of a reinforced concrete balustrade consisting of some 1000 individual beam elements all exposed similarly to the hostile marine environment of the North Sea at Arbroath, Scotland since 1943. A comparison is made of the condition of the original construction with the condition of repairs carried out in 1968 and in 1993. It is shown that the 1943 construction shows very little corrosion-induced cracking and little rust staining even though it does not appear to be of high construction quality. Only a very low percentage of the balustrade beams have been replaced. In contrast the beam installed in 1968 and later in 1993 show very considerable and large concrete cracks directly attributable to the corrosion of the longitudinal reinforcement, even though the concrete is of a higher quality and density. A detailed condition survey and statistics of crack sizes are presented in the paper. It is found that the higher corrosion resistance of the 1943 concrete is generally consistent with the concrete electrical resistivity measurements but the degree of corrosion of the reinforcing bars is inconsistent with chloride penetration measurements. The results are compared with the very few observations available in the literature for ageing concrete structures in marine environments. The results cast doubt on the conventional wisdom that chloride content at the reinforcement correlates well with reinforcement corrosion.

The Islay wave power project: an engineering prospective

The design, construction and subsequent operation of the 75 kW oscillating water column wave power plant on the Isle of Islay has provided a significant insight into the practicality of wave power conversion. The development of wave power plant poses a significant design and construction challenge for not only civil but also mechanical and electrical engineers. The plant must withstand the immense forces imposed during storms, yet efficiently convert the slow cyclic motion of waves into a useful energy source such as electricity and do so at a price competitive with other forms of generation. In addition, the hostile marine environment hampers the construction process and the variability of the wave resource poses problems for electrical control and grid integration. Many sceptics consider wave power conversion to be too difficult, too expensive and too variable to justify the effort and expense necessary to develop this technology. However, the authors contend that with modular wave power systems developed from the practical experience gained with the Islay plant, wave power is a viable technology with a considerable world market potential. However, this technology is still at the early stages of development and will require the construction of a number of different prototypes before there is extensive commercial exploitation.

An operant determination of the behavioural mechanism of benzodiazepine enhancement of food intake

Rationale A recent review paper by Cooper (Appetite 44:133–150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper’s review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability). Objectives The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration. Materials and methods The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455–458, 1982 and Behav Neurosci 97:639–653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes. Results The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant. Conclusions These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

Multi-potent mesenchymal stromal cells in blood.

Peripheral blood-derived multi-potent mesenchymal stromal cells circulate in low number. They share, though not all, but most of the surface markers with bone marrow-derived multi-potent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the filed of adult stem cell biology, such as systemic migration of bone marrow-derived multi-potent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multi-potent mesenchymal stromal cells is summarized and the above-mentioned topics are discussed.

Cooperativism, entrepreneurship and economic development: a linking theoretical model

Cooperatives, as a kind of firms, are considered by many scholars as an remarkable alternative for overcoming the economic crisis started in 2008. Besides, there are other scholars which pointed out the important role that these firms play in the regional economic development. Nevertheless, when one examines the economic literature on cooperatives, it is detected that this kind of firms is mainly studied starting from the point of view of their own characteristics and particularities of participation and solidarity. In this sense, following a different analysis framework, this article proposes a theoretical model in order to explain the behavior of cooperatives based on the entrepreneurship theory with the aim of increasing the knowledge about this kind of firms and, more specifically, their contribution to regional economic development.

Analysis of malts by capillary electrophoresis

A range of malts, as well as their high- and low-molecular-mass fractions, has been examined by capillary electrophoresis in phosphate buffer, pH 2.5, and in carbonate buffer, pH 9.5, and the results have been compared with those for roasted barley and for caramels. The malts fall into two categories: (i) the lightly roasted malts, where the high-molecular-mass coloured fraction is negatively charged at pH 9.5 and positively charged at pH 2.5; and (ii) the highly roasted malts (and the roasted barley), where the high-molecular-mass fraction migrates close to the electro-osmotic flow at both pH 9.5 and 2.5, implying that it carries little or no charge. The former category shows migration patterns similar to Class III caramels, whereas the latter migrates differently from Class I, III and IV caramels as well as from the former. Capillary electrophoresis therefore has considerable potential for differentiating between malts and between malts and caramels and roasted barley. (C) 2002 Society of Chemical Industry.

Conflict, Regulation and Marginalisation in the North of Ireland: The Experiences of Children and Young People

Based on primary research and consultations conducted over the last four years in the north of Ireland, this article considers the lives and experiences of children and young people in communities where the legacy of conflict and economic deprivation are most marked. It explores the reality of differential policing in communities where paramilitaries filled the policing deficit during the Conflict through informal 'justice' and punishment beatings. Finally, it considers the potential for change in a climate increasingly hostile towards children and young people, and the realisation of their rights.

The Impact of Disrespect on Prisoners’ Aggression: Outcomes of Experimentally Inducing Violence Supportive Cognitions

Self-report research suggests that much violence is triggered by perceived insults and disrespect. This may be particularly true in the context of a prison or another environment of acute deprivation, whereby individuals have little other recourse to means of reputation enhancement. This paper presents the findings of two studies conducted with prisoner volunteers inside a Category C (minimum security) prison in England. In the first study, the authors randomly assigned a sample of 89 prisoners to one of two conditions: the experimental group were asked to discuss times they have been disrespected by authority figures inside and outside the prison; the control group were asked more neutral questions. Both groups then completed several measures of cognitive beliefs, distortions, and hostile attribution biases. None of the measures differed across the two groups except the measure of excuse and justification acceptance. Controlling for other factors, the experimental group endorsed these rationalisations at a significantly higher rate than the control group. This finding suggests that raising the salience of disrespect - reminding prisoners of times they have been made to feel unworthy of consideration - may raise the risk that prisoners will engage in violence by providing prisoners with justifications or excuses for actions they might not otherwise endorse. These findings received some additional validation in the second study, a qualitative analysis of offender accounts of violence and aggression within the prison. Implications for reducing violence within prisons are discussed.

Social exclusion and social capital: A comparison and critique

Social exclusion and social capital are widely used concepts with multiple and ambiguous definitions. Their meanings and indicators partially overlap, and thus they are sometimes used interchangeably to refer to the inter-relations of economy and society. Both ideas could benefit from further specification and differentiation. The causes of social exclusion and the consequences of social capital have received the fullest elaboration, to the relative neglect of the outcomes of social exclusion and the genesis of social capital. This article identifies the similarities and differences between social exclusion and social capital. We compare the intellectual histories and theoretical orientations of each term, their empirical manifestations and their place in public policy. The article then moves on to elucidate further each set of ideas. A central argument is that the conflation of these notions partly emerges from a shared theoretical tradition, but also from insufficient theorizing of the processes in which each phenomenon is implicated. A number of suggestions are made for sharpening their explanatory focus, in particular better differentiating between cause and consequence, contextualizing social relations and social networks, and subjecting the policy 'solutions' that follow from each perspective to critical scrutiny. Placing the two in dialogue is beneficial for the further development of each.

Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis

Adult neural stem cells (aNSCs) derived from the subventricular zone of the brain show therapeutic effects in EAE, an animal model of the chronic inflammatory neurodegenerative disease MS; however, the beneficial effects are modest. One critical weakness of aNSC therapy may be an insufficient antiinflammatory effect. Here, we demonstrate that i.v. or i.c.v. injection of aNSCs engineered to secrete IL-10 (IL-10–aNSCs), a potent immunoregulatory cytokine, induced more profound functional and pathological recovery from ongoing EAE than that with control aNSCs. IL-10–aNSCs exhibited enhanced antiinflammatory effects in the periphery and inflammatory foci in the CNS compared with control aNSCs, more effectively reducing myelin damage, a hallmark of MS. When compared with mice treated with control aNSCs, those treated with IL-10–aNSCs demonstrated differentiation of transplanted cells into greater numbers of oligodendrocytes and neurons but fewer astrocytes, thus enhancing exogenous remyelination and neuron/axonal growth. Finally, IL-10–aNSCs converted a hostile environment to one supportive of neurons/oligodendrocytes, thereby promoting endogenous remyelination. Thus, aNSCs engineered to express IL-10 show enhanced ability to induce immune suppression, remyelination, and neuronal repair and may represent a novel approach that can substantially improve the efficacy of neural stem cell–based therapy in EAE/MS.