As materials get reduced in size down to the nanoscale it becomes more complex to characterize them. In this regard transmission electron microscopy has been extensively used to better characterize and understand the mechanical behavior of materials at the nanoscale, although there are various contrast mechanisms that can be used in a TEM micrograph. Focusing in particular on diffraction contrast, we know that dislocation lines are interpreted based on how the displacement field of a dislocation in an infinite crystal influences contrast. However, from a practical standpoint most of the samples that are used in microscopy are of a finite size. Thus, it is important to understand the change in contrast of a screw dislocation by taking into account the effect of crystal size. A MATLAB program has been written to simulate contrast in the TEM of a screw dislocation, taking into account the modified displacement fields for finite size crystals. The effect of reducing crystal size and the effect of microscopic parameters, such as the deviation parameter and g.b diffraction conditions have been also analyzed. / text

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

No description available.

Enzymes are important biomarkers for determining tumor growth and progression. We have developed two molecules to image enzyme response by catalyCEST MRI. This technology allows for non-invasive detection of enzymes. A background of importance of measuring enzyme activity and MRI agents developed for this purpose have been covered in Chapter 1. We have synthesized a responsive paramagnetic Chemical Exchange Saturation Transfer (CEST) agent, called Tm-DO3A-cadaverine. This contrast agents has been successfully cross-linked to the protein albumin by the enzyme transglutaminase leading to the appearance of CEST at -9.2 ppm. The enzyme catalysis has been validated by measuring chemical exchange rates. We have shown that the position of the CEST peak is influenced by the conformation of the molecule depending on the neighboring amino acids to glutamine. This is the first example to show the appearance of CEST due to formation of a covalent bond. We have also synthesized a diamagnetic CEST agent with a large chemical shift dispersion to detect cathespin B activity. Upon enzyme mediated cleavage of PheArgSal, the aryl amide CEST peak at 5.3 ppm disappears. Taking a ratio of the CEST effects from salicylic acid at 9.5 ppm and aryl amide at 5.3 ppm we can detect enzyme activity. The salicylic acid moiety also undergoes some slow response due to enzyme action, as evident by the disappearance of CEST at 9.5 ppm. However, this proof of concept study is the first example of a DIACEST agent designed to measure enzyme activity using a ratio of two CEST effects from the same substrate. The last chapter highlights suggests improvements to the catalyCEST research. The appendix shows the use of bulk magnetic susceptibility measurements by NMR to determine bio-distribution of lanthanides in ex-vivo tissue.

Purpose: To examine the relationship between visual acuity (VA) and radial deformation acuity (RDA) in children 6 to 12 years of age with amblyopia. Methods: RDA was measured in 35 participants with the Manchester RDA charts. VA was measured with the Early Treatment Diabetic Retinopathy Research Study (ETDRS) chart. Results: Median VA in non-amblyopic and amblyopic eyes was 0.04 logMAR (IQF -0.06 – 0.12) and 0.24 (IQF 0.12 – 0.04), respectively (Wilcoxon Signed Ranks test, z = -5.07, p < 0.001). Median RDA in non-amblyopic and amblyopic eyes was 2.73 log (IQF 2.53 – 2.87) and 2.63 log (IQF 2.53 – 2.77), respectively (Wilcoxon, z = -2.56, p < 0.05). Spearman correlation suggested that the amblyopic deficits in VA and RDA were related, r = -0.42, p < 0.05. Conclusion: A deficit in RDA was present in most children with amblyopia. A moderate relationship was noted between the amblyopic deficits found in VA and RDA.

The gadolinium ((^153)Gd) complexes of 21 aza-phosphinic and aza-carboxylic acid macrocycles based on 1,4,7,10- tetraazacyclododecane were studied as possible contrast agents for magnetic resonance imaging. The acid dissociation rates and partition coefficients of gadolinium complexes were measured and related to their in vivo stability and route of elimination in mice. The anionic aza-phosphinic acids had low acid dissociation rates (24-78 x l0(^6) sec (^-1) at pH 1) which correlated with high in vivo stability (<0.025% dose in the skeleton at 24 hours). [Gd.l2N4P4Bz4]" shows potential as a gall bladder, bile duct contrast imaging agent at doses of 0.1 to 10 µmol/kg , and for tumour detection within the hepatobiliary system at doses of 100 to 200 µmol /kg .Macrocycles based on l,4,7,10-tetraazacyclododecane can be used to complex yttrium (90y) for tumour therapy. 90y complexes of aza-phosphinic and aza-carboxylic acid derivatives showed slow acid catalysed dissociation rates of 1-14 X 10"6 sec'l at pH 1, and rapid association kinetics of greater than 80% yttrium uptake within 30 minutes at 5 µM ligand. A tetraaza-carboxylic acid and a tri-phosphinic acid derivative modified with maleimide were linked to monoclonal antibodies and labelled with 90y. Both were highly stable in vivo with <0.0l% 90y dose in the mouse femur shaft at 48 hours.Seven aza-phosphinic and aza-carboxylic acid macrocycles based on i,4,7,-triazacyclononane were labelled with radioactive gallium or indium. Gallium complexes were generally more stable in vivo than the corresponding indium complexes. Three 67Ga and two min complexes showed potential as imaging agents and one gallium complex as a hepatobiliary imaging agent. Several complexes were examined as possible tumour localisation agents, [Ga.9N3] giving a tumour to blood ratio of 22:1 at 4 hours after injection.

The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanoparticles is important in drug development and imaging-guided therapy. The current study reports the use of combined micro-CT and optical imaging FMT to quantitatively assess the whole body and intratumoural distribution of a nano-sized liposome-based CT/optical imaging probe carrying iohexol and Cy5.5. Micro-CT was used to guide the FMT tumour delineation and signal correction. This investigation demonstrates the critical role micro-CT can play in guiding FMT-based quantification of distribution. As well the combination of CT and optical imaging enable visualization of the liposomes at the whole body, tumor and cellular levels with high sensitivity and excellent anatomical background. Such non-invasive assessment of therapeutic distribution at the macro and micro scale is necessary for implementation of personalized medicine including image-guided patient stratification and real-time adjustment of therapeutic dose.

This thesis deals with the nature and definition of phonological similarity and shows that, when similarity plays a role in the motivation of phonological processes, it is evaluated over abstract, phonological features and not purely phonetic properties. Empirical evidence for this position is drawn from the domain of consonant harmony. Typological studies of consonant harmony (Hansson 2001, Rose and Walker 2004) have argued that segments which interact in consonant harmony processes must be highly similar to one another. This thesis provides analyses of a range of consonant harmony processes and demonstrates that, in each case, the notion of similarity needed in order to determine participating segments is evaluated over contrastive feature specifications. Contrastive specifications are established according to language-specific feature hierarchies (Jackobson and Halle 1956, Dresher 2003, forthcoming) with some features taking scope over others. Languages analyzed in some detail include Bumo Izon, Kalabari Ijo, Hausa, Dholuo, Anywa, Tzutujil and Aymara. Two definitions of similarity are proposed in order to account for two sets of cases. In one set of consonant harmony processes, interacting segments are similar in the sense that they constitute the natural class of segments contrastively specified in the harmonic feature. In another set of cases, participating segments must be similar according to the following definition; they must differ in only a single marked and contrastive feature specification.

The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanoparticles is important in drug development and imaging-guided therapy. The current study reports the use of combined micro-CT and optical imaging FMT to quantitatively assess the whole body and intratumoural distribution of a nano-sized liposome-based CT/optical imaging probe carrying iohexol and Cy5.5. Micro-CT was used to guide the FMT tumour delineation and signal correction. This investigation demonstrates the critical role micro-CT can play in guiding FMT-based quantification of distribution. As well the combination of CT and optical imaging enable visualization of the liposomes at the whole body, tumor and cellular levels with high sensitivity and excellent anatomical background. Such non-invasive assessment of therapeutic distribution at the macro and micro scale is necessary for implementation of personalized medicine including image-guided patient stratification and real-time adjustment of therapeutic dose.

This manuscript presents an investigation and application of the medical radiographic technique of Dynamic Contrast-enhanced Computed Tomography with an emphasis on its application to the measurement of tissue perfusion using the techniques of CT Perfusion. CT Perfusion was used in association with Fluoro- Deoxy Glucose Positron Emission Tomography (FDG PET) to investigate altered blood flow due to the angiogenic effects of tumour in the clinical setting of medical imaging for cancer diagnosis and staging. CT perfusion, CT enhancement and Doppler ultrasound studies were compared in a series of patient studies performed for the assessment of metastatic liver disease. There was good correlation between all techniques for the arterial phase but not between Doppler measurements of the portal phase and any CT measurement. A new method was developed for quantifying CT perfusion and enhancement values, the Standardised Perfusion Value (SPV) and the Standardised Enhancement Value (SEV). The SPV was shown to correlate with FDG uptake in a series of 16 patient studies of lung nodules, an unexpected and potentially important finding that if confirmed in a larger study may provide an additional diagnostic role for CT in the assessment of lung nodules. Investigation of a commercially available package for the determination of CT Perfusion, CT Perfusion GE Medical Systems, was undertaken in a small series of brain studies for assessment of acute stroke. This data set showed the technique to positively identify patients with non-hemorrhagic stroke in the presence of a normal conventional CT, to select those cases where thrombolysis is appropriate, and to provide an indication for prognosis. An investigation of the accuracy and cost-effectiveness of FDG PET in solitary pulmonary nodules using Australian data was carried out. FDG PET was found to be accurate, cost saving and cost effective for the characterisation of indeterminate solitary pulmonary nodules in Australia. This work was expanded to include the impact of quantitative contrast enhancement CT (QECT) on the cost-effectiveness of FDG PET. The addition of QECT is a cost effective approach, however whether QECT is used alone or in combination with FDG PET will depend on local availability of PET, the cost of PET with respect to surgery and the prior probability of malignancy. A published review of CT perfusion, clinical applications and techniques, is included in the body of the work. Dynamic contrast-enhanced CT and FDG PET were used to investigate blood flow, expressed as SPV, and metabolic relationships in non-small cell lung cancers (NSCLC) of varying size and stage. A significant correlation between SPV and FDG uptake was only found for tumours smaller than 4.5 cm2. Blood flow-metabolic relationships are not consistent in NSCLC but depend on tumour size and stage. Dynamic contrast-enhanced CT as an adjunct to an FDG study undertaken using integrated PET-CT offers an efficient way to augment the assessment of tumour biology with possible future application as part of clinical care. In summary the work has developed a method for standardizing the results of dynamic contrast-enhanced CT and investigated its potential when applied with FDG PET to improve the diagnosis and staging of cancers.