Reversible hyperosmotic blood-brain barrier disruption (BBBD) has been used in pharmaceutical research as well as human medicine to enhance drug delivery across the blood-brain barrier. However a technique for repeatable BBBD in the canine has not been described. This study describes a repeatable technique for BBBD in the dog and evaluates the clinical and morphological effects of BBBD. Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery in ten dogs. BBBD was achieved in 5 dogs using 25% mannitol while 5 control dogs received only saline. Following recovery, dogs were monitored for clinical signs before a second, non-survival procedure was performed 2-3 weeks later. BBBD was estimated using CT densitometry as well as Evan's blue staining on post-mortem exam. Histopathological evaluation of the brain was performed on all dogs. Seven dogs completed the study. Two treatment dogs were lost after the first infusion with deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost due to vessel wall damage during catheterization. The remaining dogs exhibited only transient neurologic, ocular, and vasculature injury. Successful BBBD was demonstrated in all treatment dogs as evidenced by CT and Evan's blue staining. Histopathological evaluation revealed multifocal areas of infarction in all dogs indicating refinement of the technique is needed. This study shows that repeatable disruption the BBB in the dog is possible and opens the way for further investigations of BBBD using the dog as a model. / Master of Science

Thermoacoustic instabilities in gas turbine operation arise due to unsteady fluctuations in heat release coupled with acoustic oscillations, often caused by varying equivalence ratio perturbations within the flame field. These instabilities can cause irreparable damage to critical turbine components, requiring an understanding of the spatial/temporal variations in equivalence ratio values to predict flame response. The technique of computed tomography for flame chemiluminescence emissions allows for 3D spatially resolved flame measurements to be acquired using a series of integral projections (camera images). High resolution tomography reconstructions require a selection of projection angles around the flame, while captured chemiluminescence of radical species intensity fields can be used to determine local fuel-air ratios. In this work, a tomographic reconstruction algorithm program was developed and utilized to reconstruct the intensity fields of CH* and OH*, and these reconstructions were used to quantify local equivalence ratios in an acoustically forced flame. A known phantom function was used to verify and validate the tomography algorithm, while convergence was determined by subsequent monitoring of selected iterative criteria. A documented method of camera calibration was also reproduced and presented here, with suggestions provided for future calibration improvement. Results are shown to highlight fluctuating equivalence ratio trends while illustrating the effectiveness of the developed tomography technique, providing a firm foundation for future study regarding heat release phenomena. / Master of Science / Acoustic sound amplification occurs in the combustion chamber of a gas turbine due to the machine ramping up in operation. These loud sound oscillations continue to grow larger and can damage the turbine machinery and even threaten the safety of the operator. Because of this, many researchers have attempted to understand and predict this behavior in hopes of ending them altogether. One method of studying these sound amplifications is looking at behaviors in the turbine combustion flame so as to potentially shed light on how these large disturbances form and accumulate. Both heat release rate (the steady release of energy in the form of heat from a combustion flame) and equivalence ratio (the mass ratio of fuel to air burned in a combustion process) have proven viable in illustrating oscillatory flame behavior, and can be visualized using chemiluminescence imaging paired with computed tomography. Chemiluminescence imaging is used to obtain intensity fields of species from high resolution camera imaging, while computed tomography techniques are capable of reconstructing these images into a three-dimensional volume to represent and visualize the combustion flame. These techniques have been shown to function effectively in previous literature and were further implemented in this work. A known calibration technique from previous work was carried out along with reconstructing a defined phantom function to show the functionality of the developed tomography algorithm. Results illustrate the effectiveness of the tomographic reconstruction technique and highlight the amplified acoustic behavior of a combustion flame in a high noise environment.

Optical diagnostics have become indispensable tools for the study of turbulent flows and flames. However, optical diagnostics developed in the past have been primarily limited to measurements at a point, along a line, or across a two-dimensional (2D) plane; while turbulent flows and flames are inherently four-dimensional (three-dimensional in space and transient in time). As a result, diagnostic techniques which can provide 4D measurement have been long desired. The purpose of this dissertation is to investigate two of such 4D diagnostics both for the fundamental study of turbulent flow and combustion processes and also for the applied research of practical devices. These two diagnostics are respectively code named tomographic chemiluminescence (TC) and volumetric laser induced fluorescence (VLIF). For the TC technique, the emission of light as the result of combustion (i.e. chemiluminescence) is firstly recorded by multiple cameras placed at different orientations. A numerical algorithm is then applied on the data recorded to reconstruct the 4D flame structure. For the VLIF technique, a laser is used to excite a specific species in the flow or flame. The excited species then de-excite to emit light at a wavelength longer than the laser wavelength. The emitted light is then captured by optical sensors and again, the numerical algorithm is applied to reconstruct the flow or flame structure. This dissertation describes the numerical and experimental validation of these two techniques, and explores their capabilities and limitations. It is expected that the results obtained in this dissertation lay the groundwork for further development and expanded application of 4D diagnostics for the study of turbulent flows and combustion processes. / Ph. D. / Optical diagnostics have become indispensable tools for the study of turbulent flows and flames. However, optical diagnostics developed in the past have been primarily limited to measurements at a point, along a line, or across a two-dimensional (2D) plane; while turbulent flows and flames are inherently four-dimensional (three-dimensional in space and transient in time). As a result, diagnostic techniques which can provide 4D measurement have been long desired. The purpose of this dissertation is to investigate two of such 4D diagnostics both for the fundamental study of turbulent flow and combustion processes and also for the applied research of practical devices. These two diagnostics are respectively code named tomographic chemiluminescence (TC) and volumetric laser induced fluorescence (VLIF). For the TC technique, the emission of light as the result of combustion (i.e. chemiluminescence) is firstly recorded by multiple cameras placed at different orientations. A numerical algorithm is then applied on the data recorded to reconstruct the 4D flame structure. For the VLIF technique, a laser is used to excite a specific species in the flow or flame. The excited species then de-excite to emit light at a wavelength longer than the laser wavelength. The emitted light is then captured by optical sensors and again, the numerical algorithm is applied to reconstruct the flow or flame structure. This dissertation describes the numerical and experimental validation of these two techniques, and explores their capabilities and limitations. It is expected that the results obtained in this dissertation lay the groundwork for further development and expanded application of 4D diagnostics for the study of turbulent flows and combustion processes.

Yes / Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of highrisk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification.

Yes / Combining information from optical coherence tomography (OCT) imaging and visual field testing is useful in the clinical assessment and monitoring of patients with glaucoma. Measurements of retinal nerve fibre layer thickness or neuroretinal rim width taken around the optic nerve head may be related to the visual field using a structure–function map. In this review, the structure–function mapping methods in clinical use are discussed. Typical clinical maps provide a population average, ‘one size fits all’ representation, but in recent years methods for customising structure–function maps to individual eyes have been developed and these are reviewed here. In the macula, visual field stimuli stimulate photoreceptors for which associated retinal ganglion cells are peripherally displaced. Recently developed methods that relate OCT measurements to visual field test locations in the macula are therefore also reviewed. The use of structure–function maps to relate OCT measurements to localised visual field sensitivity in new applications is also explored. These new applications include the selection of visual field test locations and stimulus intensities based on OCT data, and the formal post‐test combination of results across modalities. Such applications promise to exploit the structure–function relationship in glaucoma to improve disease diagnosis and monitoring of progression. Limitations in the validation and use of current structure–function mapping techniques are discussed. / >Heidelberg Engineering >Australian Research Council. Grant Number: LP130100055 >College of Optometrists. Grant Number: College of Optometrists Research Fellowship

No / Computed tomography (CT) arthrography of the shoulder is an imaging modality of great diagnostic accuracy with regard to glenohumeral instability and in particular labral lesions. Interpretation of the scans is made difficult by the frequent occurrence of normal anatomic variants and the complexity of injuries to the bone and soft tissues. We selected a continuous sample of 50 CT arthrograms of the shoulder and they were reported by two consultant musculoskeletal radiologists. The results were collated and analysed for the level of agreement. Hill¿Sachs showed Kappa (K) statistic to be 0.37 (fair agreement), soft tissue Bankart 0.32 (fair agreement), bony Bankart 0.61 (substantial agreement), anterior capsular laxity 0.41 (moderate agreement) and glenohumeral osteoarthritis 0.20 (slight agreement). All the results were significant with a p value of <0.05. Nine (18%) of the 50 scans were in complete agreement. The results demonstrate that there can be considerable interobserver variation (IOV) in the reports of a CT arthrogram of a shoulder. They highlight the potential difficulties in reporting such images and suggests ways in which the report could be more focussed to provide a clinically reliable report and one which matches the surgical findings accurately.

The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Planar bone scintigraphy is highly sensitive but it may not be sensitive enough to detect subtle lesions in complex bony structures such as the spine. The accurate anatomic localisation of lesions in regions such as this is also limited using planar images. Single Photon Emission Computed Tomography (SPECT) results in a higher lesion contrast resulting in an improved sensitivity for the detection of subtle lesions. SPECT also enables improved lesion localisation, often valuable in distinguishing benign from malignant disease in the spine. A number of previous studies have demonstrated that the addition of SPECT of the spine significantly enhances the value of bone scintigraphy for the detection of bone metastases compared to planar imaging alone. These studies were however not done in the African context where patients typically present with more advanced disease. In a retrospective study of 576 patients with known primary tumors sent to our institution for bone scintigraphy for the diagnosis of bone metastases, we evaluated 119 patients in whom both planar imaging and SPECT were obtained. The studies were graded for the probability of metastatic disease, and the number of spinal lesions was determined with and without SPECT. The influence of adding SPECT on the interpretation of the study was determined in terms of the reported probability of metastatic disease, the exclusion and confirmation of metastatic disease, the decisiveness of interpretation, and the number of spinal lesions. The addition of SPEeT resulted in a statistically significant change in the interpretation of studies, although the actual numbers of patients affected were relatively small. SPEeT resulted in a more decisive interpretation of bone scintigraphy. There was a significant increase in the number of spinal lesions detected after the addition of SPEeT. It was concluded that although the use of SPEeT is ideal, acceptable results could be achieved using planar imaging alone in this patient population. This is particularly relevant in the African context, where SPEeT is often unavailable or scarce and in great demand. / AFRIKAANSE OPSOMMING: Planare beenflikkergrafie is hoogs sensitief, maar moontlik nie sensitief genoeg om subtiele letsels in ingewikkelde beenstrukture soos die werwelkolom aan te toon nie. Akkurate anatomiese lokalisasie van letsels in die genoemde strukture is beperk wanneer slegs planare beelde gebruik word. Enkelfoton-uitstraling Rekenaartomografie (EFERT) lewer 'n hoër letsel kontras, wat 'n verbeterde sensitiwiteit vir die opsporing van subtiele letsels tot gevolg het. EFERT lei ook tot verbeterde letsel lokalisasie, wat dikwels van waarde is om onderskeid tussen benigne en maligne siekte in die werwelkolom te tref. Reeds met 'n aantal vorige studies is aangetoon dat die toevoeging van EFERT van die werwelkolom die waarde van beenflikkergrafie in die opsporing van beenmetastases beduidend verhoog bo dié van planare beelding alleenlik. Hierdie studies is egter nie in omstandighede eie aan Afrika gedoen nie, waar pasiënte kenmerkend met gevorderde siekte voordoen. In In terugskouende studie van 576 pasiënte met bekende primêre tumore, wat na ons instelling verwys is vir beenflikkergrafie om beenmetastases op te spoor, het ons 119 pasiënte, wat beide planare beelding en EFERT ondergaan het, ge-evalueer. Die studies is gegradeer volgens die waarskynlikheid vir metastatiese siekte, en die hoeveelheid werwelkolom letsels, met en sonder EFERT, is bepaal. Die invloed van EFERT op die vertolking van die studie is bepaal in terme van die waarskynlikheid van metastatiese siekte, die bevestiging en uitskakeling daarvan, die beslistheid van vertolking, en die hoeveelheid werwelkolom letsels. Die toevoeging van EFERT het tot 'n statisties beduidende verandering in die vertolking van studies gelei, alhoewel die werklike getal pasiënte wat hierdeur geraak is, relatief min was. EFERT het 'n meer besliste vertolking van beenflikkergrafie tot gevolg gehad. Daar was 'n beduidende toename in die hoeveelheid werwelkolom letsels wat opgespoor is na die toevoeging van EFERT. Daar is tot die slotsom gekom dat, alhoewel die gebruik van EFERT wenslik is, aanvaarbare resultate met slegs die gebruik van planare beelding in hierdie pasiënt bevolkingsgroep verkry kan word. Dit is veral van belang in Afrikaomstandighede, waar EFERT dikwels onbeskikbaar of skaars is, en ook in groot aanvraag is.

published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

Spectral x-ray computed tomography (CT) is an important nascent imaging modality with several exciting potential applications. The research presented in this thesis separates into two primary areas with the common underlying theme of spectral CT; the first area is Compton scatter estimation and the second is interior tomography. First, the research is framed and outputs are identified. Background on the concepts used in the thesis is offered, including x-ray imaging and computed tomography, CT scanner architecture, spectral imaging, interior tomography and x-ray scatter. The mathematical background of techniques for image reconstruction from x-ray transmission measurements are presented. Many of the tools used to perform the research, both hardware and software, are described. An algorithm is developed for estimating the intensity of Compton scattered photons within a spectral CT scan, and a major approximation used by the algorithm is analysed. One proposed interior reconstruction algorithm is briefly evaluated; while this is not directly linked to spectral CT, it is related to the work on a novel hybrid spectral interior micro-CT architecture. Conclusions are summarised and suggestions for future work are offered. Scatter is known to cause artefacts in CT reconstructions, and several methods exist to correct data that has been corrupted by scatter. Compton scatter affects the energy of photons, therefore spectral CT measurements offer the potential to correct for this phenomenon more accurately than conventional measurements. A Compton scatter algorithm is developed and is found to match very well to Monte Carlo validation simulations, with the constraints that the object be at the micro-CT scale and that electron-binding effects are omitted. Development of the algorithm uses an approximation of the post-scatter attenuation to simplify the estimation problem and enable implementation. The consequences of this approximation are analysed, and the error introduced is found to be less than 5% in most biomedical micro-CT situations. Interior tomography refers to the incomplete data situation caused by the truncation of some or all CT projections, and is an active research area. A recently proposed interior reconstruction algorithm is evaluated with regard to its sensitivity to input error, and is found to have mediocre performance in this respect. Published results are not found to be reproducible, suggesting some omission from the published algorithm. A novel hybrid spectral interior architecture is described, along with an iterative reconstruction algorithm for hybrid data sets. The system combines a full field of view conventional imaging chain and an interior field of view spectral imaging chain to enable spectral measurement of a region of interest, and addresses some important limitations of spectral x-ray detectors; promising results are shown. Spectral reconstructions from interior data are shown to have sufficient information to distinguish two k-edge contrast agents (iodine and gadolinium) not only within the interior field of view but also beyond it. The architecture is further explored in the context of radiation exposure reduction, including testing of an analytical hybrid reconstruction algorithm.