This thesis evaluates a particular ultrasonic nondestructive testing (NDT) system in order to determine its capabilities and limitations in locating defects in concrete structures; specifically tunnel linings, bridge decks, and pavements. The device, a phased-array ultrasonic tomography (UST) system that utilizes shear waves, is a significant advancement in NDT systems. Consequently, there is a need in structural engineering to verify new technologies by assessing their flaw-detecting capabilities in a variety of structural applications. The UST technique does not currently have a testing methodology that is field-ready. In order to develop a methodology, the system was evaluated based on its ability to detect simulated defects, then taken to the field to evaluate natural structural defects on public tunnels, pavements, and airport runways. Types of concrete defects the system is used to detect and localize include air- and water-filled voids, vertical cracks, horizontal delaminations, and abnormalities such as clay lumps. The device is also used to determine reinforcement depth and spacing as well as concrete thickness measurements. This research concludes that the UST system is exceptional at locating horizontal delaminations ranging from 0.05-2.0 mm (0.002-0.079 in.), and is able to differentiate between fully debonded and partially-bonded areas. Vertical cracks could only be detected once they begin to form parallel to the testing surface; however, omission of surface details was found to be a strong indicator of crack presence. Backwall surfaces up to a depth of 762 mm (30 in.) were successfully and accurately determined. Air- and water-filled voids as well as reinforcement details such as layout and depth were also successfully determined and located. With the exception of some medium-sized clay lumps (with a diameter of approximately 102 mm, or 4 in.) surrounding reinforcement, all clay lumps tested were also highly successful.

Positron Emission Tomography (PET) has gained an important roll in clinical for diagnosis, staging and prognosis of a range of cancer types. Utilization of PET for monitoring and evaluation of cancer treatment is an attractive but almost new concept. The proper choice of PET-tracer as a biomarker for treatment follow-up is crucial. The important characteristic for a suitable tracer is its ability to reflect the response to a treatment at an early stage, before any morphologically changes occurs. It would be an advantage to screen a battery of PET tracers in a preclinical model and introduce a few potential tracers in clinical trial. The most conventional pre-clinical approach in PET-oncology utilizes xenografts in mice or rats and requires a large number of subjects. It would be a great advantage to introduce a less demanding but still reliable preclinical method for a more efficient planning of studies in animal model and then in human trials. The Multicellular Tumour Spheroid (MTS) system represents an intermediary level between cells growing as monolayer and solid tumours in experimental animals or patients. It mimics the growth of naturally occurring human tumours before neovascularization and appears to be more informative than monolayer and more economical and more ethical than animal models. The aim of this work was to establish, refine and evaluate the application of MTS model as a preclinical approach in PET oncology. The vision was to introduce a preclinical method to probe and select PET tracer for treatment monitoring of anticancer drugs, which can hopefully be applied for optimization in breast cancer treatment. In this thesis, a number of basic experiments were performed to explore the character of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) uptake in MTS. FDG as the most established PET tracer was an obvious initial option for the evaluation of the model. For further assess-ment, we studied effects on FDG uptake in MTS treated with five routinely used chemother-apy agents. For association of PET tracer uptake to size change of MTS, we developed a reliable and user-friendly method for size determination of MTS. The next step was to apply the MTS model to screen PET tracers for analysis of early response of chemotherapy in breast cancer. Finally the method was utilized for translational imaging exemplified with a new chemotherapy agent. The results were encouraging and the MTS model was introduced and evaluated as a preclini-cal tool in PET oncology. The method was implicated to in vitro quickly assess a therapy profile of existing and newly developed anticancer drugs in order to investigate the effects of candidate drugs on tumour-growth, selection of appropriate PET tracer for treatment monitor-ing and finally understanding relation between growth inhibition and biomarkers as part of translational imaging activities.

No description available.

No description available.

Larger and stronger muscles are positively associated with bone strength in the growing skeleton; however, less is known about the role of muscle properties on bone strength later in life. The primary objective of this study was to examine the relationship between muscle cross sectional area (MCSA), muscle force and rate of torque development (RTD) with bone strength indices (bone strength index (BSI) and strength strain index (SSI)) in the radius of healthy middle-aged adults. All bone and muscle measurements were determined in the non-dominant forearm in a sample of 40 healthy adults (23 men, 17 women: mean age 49.5, SD 2.3 yrs). Peripheral quantitative computer tomography (pQCT) was used to scan the distal and shaft sites of the radius bone in the forearm. MCSA was determined from the forearm shaft scan. Forearm muscle force was measured by hand grip dynamometry and RTD was obtained from isometric wrist flexion from an isokinetic dynamometry protocol. Hierarchical regression analyses were used to identify whether muscle properties (MCSA, grip force, and RTD) independently predicted radius bone strength indices (BSI and SSI), after adjusting for the confounders of sex, height and weight. Steps of the regression models that included sex, height, weight and a muscle property explained between 66% and 71% of variance in distal radius BSI and between 74% and 78% variance of estimated bone strength (SSI) at the shaft site (all steps p<0.001). MCSA explained a significant amount of variance in BSI (R2=0.08; p<0.01) and SSI (R2=0.04; p<0.05) at the radius. Grip force was also a significant predictor of SSI (R2=0.05; p<0.01) but not distal radius BSI (R2=0.03; p=0.07). Conversely, RTD explained a significant amount of variance in bone strength at the distal radius (R2=0.04; p<0.05), but not at the shaft (R2=0.01; p=0.17). These cross sectional findings support the theory that regional muscle size, force, and rate of torque development are related to estimated bone strength in the forearm at midlife. Further research should focus on targeted interventions to help determine which muscle property elicits a greater osteogenic response to optimize bone strength at distal and shaft sites of the radius.

This project initiated with the aim for improving the ultrahigh resolution optical coherence tomography (UHR-OCT) system performance by considering the limitations to the axial OCT resolution for in vivo imaging of human and animal retina. To this end, a computational model was developed to simulate the effect of wavelength-dependant water absorption on the detected spectral shape of the broad-bandwidth light source used in UHR-OCT at 1060nm wavelength region, which effectively determines the axial OCT resolution in the retina. For experimental verification of the computational model, a custom built light source with a re-shaped spectrum (Superlum Inc.) was interfaced to the state-of-the-art UHR-OCT system. About 30% improvement of the axial OCT resolution in the rat retina and ~12% improvement of the axial OCT resolution in the human retina was achieved compared to the case of the almost Gaussian shaped spectrum of the standard, commercially available SLD. Although water absorption in the 1060nm spectral region strongly affects the sample beam, selecting a suitable light source with specific spectral shape can compensate for the undesired water absorption effect and thus result in significantly improved axial resolution in in vivo OCT retinal images. To demonstrate the advantages of the state-of-the-art OCT technology for non invasive retinal imaging, an established animal model of outer retina degeneration (sodium iodate (NaIO3)-induced retina degeneration) was employed for longitudinal monitoring of the degeneration and investigation of possible early and dynamic signs of damage undetected by other imaging modalities. The long-term (up to 3 months) and short-term (up to 12 hours) effect of sodium iodate toxicity on the layered structure of retina was monitored longitudinally and in vivo for the first time using OCT. An initial acute swelling of the retina, followed by progressive disruption and degeneration of outer retina was observed as a result of sodium iodate-induced damage. Changes in the thickness and optical reflectivity of individual retinal layers were extracted from the OCT images to quantify the changes occurring at different stages of the disease model. Results from this project present the theoretical and practical limits to the highest axial OCT resolution achievable for retina imaging in the 1060nm spectral range both in small animals and humans, and provided a framework for future development of novel light sources. Furthermore, UHR-OCT imaging was shown to be an effective and valuable modality for in vivo, non invasive investigation of retina degenerative disease.

Dual Energy Computed Tomography (DECT) is an emerging technique that offers new possibilities to determine composition of tissues in clinical applications. Accurate knowledge of tissue composition is important for instance for brachytherapy (BT) treatment planning. However, the accuracy of CT numbers measured with contemporary clinical CT scanners is relatively low since CT numbers are affected by image artifacts. The aim of this work was to estimate the accuracy of CT numbers measured with the Siemens SOMATOM Definition Flash DECT scanner and the accuracy of the resulting volume or mass fractions calculated via the three material decomposition method. CT numbers of water, gelatin and a 3rd component (salt, hydroxyapatite or protein powder) mixtures were measured using Siemens SOMATOM Definition Flash DECT scanner. The accuracy of CT numbers was determined by (i) a comparison with theoretical (true) values and (ii) using different measurement conditions (configurations) and assessing the resulting variations in CT numbers. The accuracy of mass fractions determined via the three material decomposition method was estimated by a comparison with mass fractions measured with calibrated scales. The latter method was assumed to provide highly accurate results. It was found that (i) axial scanning biased CT numbers for some detector rows. (ii) large volume of air surrounding the measured region shifted CT numbers compared to a configuration where the region was surrounded by water. (iii) highly attenuating object shifted CT numbers of surrounding voxels. (iv) some image kernels caused overshooting and undershooting of CT numbers close to edges. The three material decomposition method produced mass fractions differing from true values by 8% and 15% for the salt and hydroxyapatite mixtures respectively. In this case, the analyzed CT numbers were averaged over a volumetric region. For individual voxels, the volume fractions were affected by statistical noise. The method failed when statistical noise was high or CT numbers of the decomposition triplet were similar. Contemporary clinical DECT scanners produced image artifacts that strongly affected the accuracy of the three material decomposition method; the Siemens’ image reconstruction algorithm is not well suited for quantitative CT. The three material decomposition method worked relatively well for averages of CT numbers taken from volumetric regions as these averages lowered statistical noise in the analyzed data.

Human exposure to reduced weightbearing results in bone loss. The rate of bone loss during microgravity exposure is similar to that of a post-menopausal women. In fact, the maintenance of bone mass is intimately dependent on exercise. Therefore, exercise associated mechanical loads to bone tissue are an important countermeasure to prevent disuse-induced bone loss. However, the types of exercise modalities required to prevent such bone loss are unclear. Moreover, how mechanical loading to bone translates into molecular osteogenic signals in bone cells is unknown. Radiation exposure is another potent inducer of bone loss, namely observed on Earth in the clinical setting following radiotherapy procedures. It is expected that long duration space missions outside the protection of Earth’s magnetosphere will result in significant galactic cosmic radiation exposure. However, the magnitude of bone loss resulting from this galactic cosmic radiation exposure is unclear. Moreover, it is unknown if radiation exposure will exacerbate disuse-induced bone loss. Therefore, a series of experiments were designed to determine: 1) Will simulated galactic cosmic radiation exacerbate reduced weightbearing-induced bone loss? 2) Will pharmacological activation of the putative mechanosensing Wnt pathway enhance exercise-induced bone mass gain? To address these questions the experimental study series employed two animal models of reduced weightbearing, hindlimb unloading and partial weightbearing. These model test-beds enabled the evaluation of two novel countermeasures (simulated resistance exercise and glycogen synthase kinase-3 (GSK-3) therapeutic) and simulated exposure to space radiation environments. To test the impact of simulated space radiation (28Si) one study of the series was conducted at Brookhaven National Laboratory. To quantify the impact of the abovementioned countermeasures and space radiation on bone, mechanical testing, peripheral quantitative computed tomography, micro-computed tomography, histomorphometry, and immunohistochemistry served as primary outcome measures. The primary findings are: 1) Low-dose high-LET radiation negativity impacts maintenance of bone mass by lowering bone formation and increasing bone resorption. This impaired bone formation response is in part due to sclerostin induced suppression of Wnt signaling. 2) Combining GSK-3 inhibition with high intensity exercise mitigates cancellous bone loss and restores cortical periosteal growth during disuse.

Iterative CT reconstruction algorithms are superior to the standard convolution backpropagation (CBP) methods when reconstructing from a small number of views (hence less radiation), but are computationally costly. To reduce the execution time, this work implements and tests a parallel approach to iterative algorithms using a cluster of workstations, which is a low cost system found in many offices and non-academic sites. A previous implementation showed little speedup because of the significant cost of inter-processor communication. In this thesis, several data partitioning methods are examined, including some image tiling methods that exploit the spatial locality demonstrated by local CT. Using these methods, computation can proceed locally, without the need for inter-processor communication during every iteration. A relative speedup of up to 17 times is obtained using 25 processors, demonstrating that good performance can be obtained running computationally intensive CT reconstruction algorithms on distributed memory hardware. / October 2007

Abstract Both in the closed and open eye state the superior limbus is covered by the upper lid. This region is of physiological interest and clinical importance because in chronic hypoxia, neovascularization of the cornea commonly occurs here. The limbal region in general is additionally of importance as the stem cells which are the source of the new corneal cells are located in the epithelium of the limbus and these are vital for normal functioning and are affected under certain adverse conditions. Purpose: In this experiment I examined corneal morphology in the limbal area and in particular under the upper lid in order to primarily examine the variation in the corneal limbal epithelial and total thickness as well as epithelial and endothelial cell density. Methods: I measured 30 eyes OD/OS (chosen randomly) of thirty healthy subjects aged from 18 to 55 years in the first study and twelve participants in the second study, with refractive error ≤ ±4 D and astigmatism ≤ 2 D. The thickness and cell density of five positions: superior, inferior, temporal, nasal limbal and central cornea was determined with optical coherence tomography (OCT) and confocal microscopy. At least three scans of each position were taken in both studies with OCT. At least 40 of 100 adjacent sagittal scans of each image were measured using OCT software program. In the confocal study, image J software was used to determine cell densities. Results: The epithelial and corneal limbal thickness were significantly thicker than the epithelial and central corneal thickness (p<0.05). The limbal, inferior cornea is thinner than the three other positions and the temporal region of the cornea is the thickest both in epithelial and total cornea. Epithelial cell density was significantly lower in the superior cornea than the four other positions. There was no significant difference in the endothelial cell density. Conclusions: Using OCT with high resolution and cross-sectional imaging capability and confocal microscope with high magnification, I found that the limbal cornea is significantly thicker than the central cornea both in total and in epithelial thickness. In the limbus, one might expect the superior cornea (under the lid) to be thickest (because of the expected hypoxia) whereas I found the temporal cornea was thickest. The epithelial cell density was lower in the superior cornea but there was no significant difference in cell densities in the endothelium. Further morphological investigation is of interest.