<p>Small animal imaging is a valuable tool in preclinical biomedical research which relies on the use of animal models to understand human disease. Newly emerging optical imaging techniques such as bioluminescence tomography offer an inexpensive and sensitive alternative to more established imaging technologies. These techniques are capable of non-invasively imaging a variety of cellular and molecular processes <em>in vivo</em>. As an emerging technology, current bioluminescence imaging methods suffer from several limitations, preventing them from reaching their full potential.</p> <p>In this work, we describe the design and characterization of an integrated imaging system capable of multispectral bioluminescence tomography (BLT), diffuse optical tomography (DOT), and X-ray computed tomography (CT). The system addresses many of the inherent problems encountered in planar bioluminescence imaging techniques, allowing for the recovery of more accurate and quantitative bioluminescence data. The integrated X-ray CT scanner provides anatomical information which aids in the visualization and localization of the recovered bioluminescence distributions and also helps to constrain the inverse reconstruction in the diffuse optical tomography system. It was found that the inclusion of spatial priors from X-ray CT improved the reconstructed image quality dramatically. Four image reconstruction algorithms were evaluated for their ability to recover the effective attenuation coefficients of a series of test phantoms. Two of the algorithms (a modified Levenberg-Marquardt method, and a single-step Tikhonov method) did not use any <em>a priori</em> spatial information. Two other algorithms (hard priors and soft priors) used <em>a priori </em>structural information from X-ray CT to constrain the reconstruction process. The two methods incorporating spatial prior information resulted in recovered optical property distributions with RMS errors ranging from 8 % to 15 % in a series of test phantoms versus errors of 11 % to 26 % for non-spatial methods. The soft priors method was shown to be more resilient to imperfect <em>a priori</em> information.</p> <p>The multispectral BLT component was used to recover accurate bioluminescence distributions in test phantoms using <em>a priori</em> background optical properties recovered from the DOT system. Multispectral measurements were shown to provide an accurate method for estimating the position of a bioluminescence source due to the wavelength dependent attenuation of tissue. Experimental measurements are presented which explore the importance of accurate estimates of background optical properties in BLT. The hard spatial prior method was found to provide the best overall recovery of total source strength, position, and fidelity at all source depths up to 12.5 mm. The total source strength was recovered to within 8 %, while the source position was recovered to within 0.16 mm in all cases. Errors in recovered power and position showed no dependence on depth up to the maximum of 12.5 mm.</p> / Doctor of Philosophy (PhD)

<p>The typical High Dose Rate (HDR) lung brachytherapy procedure involves inserting treatment catheters into the bronchi next to the tumour location using a bronchoscope. The anterior-posterior and lateral fluoroscopy images are acquired in order to localize the catheters prior to treatment. Although, these images enable accurate reconstruction of the catheter location, they do not allow for the visualization of the tumour or organs-at-risk due to poor soft tissue contrast. Although CT images offer an improved soft tissue contrast, moving the patient with catheters in place prior to each treatment is impractical.</p> <p>An alternative option is to use prior diagnostic or external beam radiation treatment planning CT images. These images cannot be used for treatment planning directly because of the variation in patient positioning between the CT and orthogonal images acquisition. In order to account for positioning differences, a 2D/3D registration algorithm that registers the orthogonal images with a previously acquired CT data was developed. The algorithm utilizes a rigid registration model based on a pixel/voxel intensity matching approach. A similarity measure combining normalized mutual information (NMI), image gradient, and intensity difference was developed. Evaluation of the algorithm was performed using tissue equivalent phantoms, and, in the clinical setting using data from six patients. The mean registration error was 2.1 mm and 3.2 mm for phantoms and patients respectively.</p> <p>External objects such as the treatment table and ECG leads are often in CT images, affecting the above mentioned 2D/3D registration. To address this, an algorithm for automatic removal of external objects from CT images was developed. This was applied to automatic contouring and removal of the fiducial markers in CT images used for external beam radiation therapy treatment planning for breast cancer. The algorithm was further modified to compute the girth of patients as part of a diagnostic radiology clinical trial.</p> / Doctor of Philosophy (PhD)

Biliary diseases are uncommon, potentially fatal causes of acute abdomen in dogs. Little information is present comparing the performance of computed tomography (CT) to ultrasound in identifying canine biliary pathology. Thirty-five client-owned dogs presenting for acute abdomen signs received an abdominal ultrasound and contrast-enhanced abdominal CT. Two authors reviewed the randomized, anonymized CT and ultrasound studies. Twenty-eight dogs had biliary pathology and seven dogs serving as controls had no evidence of biliary disease. The final diagnoses of patients with biliary pathology included cholelithiasis, gallbladder mucoceles, cholangiohepatitis/cholangitis, extrahepatic biliary obstruction, gallbladder wall edema, gallbladder wall mass, and cystic mucosal hyperplasia. Computed tomography was more accurate in identifying cholelithiasis than ultrasound. No statistical difference in the odds to identify other biliary pathology was identified between ultrasound and CT. Findings from this study suggest CT may be used in place of ultrasound in canine patients presenting for acute abdominal signs of biliary origin.

Introduction: We argue, for studies of growth or treatment changes, superimposed CBCT images ought to be employed routinely. The location of 3D landmarks on curved structures, however, has been complex. In this study, a reliable method of CBCT superimposition was developed with the aid of AMIRA XImage® software. The specific focus was to develop a practical method for cranial base superimpositions at sella turcica in serial CBCT images. Subsequently, evaluations of the anterior curvature of hypophyseal fossa during growth were completed to confirm the stability. Comparisons of surface changes in the superimposed images in different regions were also made. Methods: Samples of pre- and post-orthodontic CBCT data were procured from Case Western Reserve University. Cranial base changes in 10 adolescent patients of Class I and II hypodivergent, normodivergent, and hyperdivergent malocclusions, were observed over an average interval of 2 years and 5 months. Cranial base models were superimposed using a rigid registration technique, and 3D models constructed from manual segmentation in the AMIRA software. Surface distance changes of the entire cranial base were compared to that of the anterior portion of sella turcica. Results: Mean surface distance changes for the entire cranial base and anterior sella were 0.73-1.57 ± 0.71-1.30 mm and 0.37-0.63 ± 0.29-0.43 mm, respectively. The area above a threshold of 0.5 mm was 61.02-74.11% (cranial base) and 40.70-50.94% (anterior sella) as well. Paired t-tests were applied to compare differences between the mean distance and area above the threshold for data of cranial base versus anterior sella. Both illustrated p-values less than 0.0001 and were statistically significant. Intra-rater reliability was evaluated by completing segmentation and registration three consecutive times on each CBCT volume. Mean surface differences were within 0.01 mm with the exception of one patient. In addition, all subjects exhibited less than 1.00% deviation except three patients, which deviated by 1.03%, 1.46%, and 1.64%, respectively. Conclusions: A practical method of superimposition of serial CBCT images was developed. Through production of color maps, the surface distance of the anterior portion of sella turcica was shown to change much less than the clivus and remaining cranial base structures in pre- and post-treatment scans of growing children. Lastly, the method of superimposition developed here may assist future studies of skeletal changes with accuracy. / Oral Biology

Accurate attenuation correction is essential for quantitative positron emission tomography. Typically, this correction is based on a coincidence transmission measurement using an external source of positron emitter, which is positioned close to the detectors. This technique suffers from poor statistical quality and high dead time losses, especially with a high transmission source strength. We have proposed and tested the use of single photon transmission measurement with a rotating rod source, to measure the attenuation correction factors (ACFs). The singles projections are resampled into the coincidence geometry using the detector positions and the r,)d source location. A nonparalyzable dead time correction algorithm was developed for the block detectors used in the McMaster PET scanner. Transaxial resolution is approximately 6 mm, which is comparable to emission scanning performance. Axial resolution is about 25 mm, with only crude source collimation. ACFs are underestimated by approximately 10% due to increased crossplane scatter, compared to coincidence transmission scanning. Effective source collimation is necessary to obtain suitable axial resolution and improved accuracy. The response of the correction factors to object density is linear to within 15%, when comparing singles transmission measurement to current coincidence transmission measurement. The major advantage of using singles transmission measurement IS a dramatically increased count rate. A factor of seven increase in count rate over coincidence scanning is possible with a 2 mCi transmission rod source. There are no randoms counted in singles transmission scans, which makes the measured count rate nearly linearly proportional with source activity. Singles detector dead time is approximately 6% in the detectors opposite a 2 mCi rod source. Present hardware and software precludes the application of this technique in a clinical environment. We anticipate that real time acquisition of detector singles can reduce the transmission scanning time to under 2 minutes, and produce attenuation coefficient images with under 2% noise. This is a significant improvement compared to the current coincidence transmission technique. / Thesis / Master of Science (MS)

This study attempts to develop a method for absolute quantitation in Positron Emission Tomography. This includes the definition of the dimension and the position of a tumour in the brain as well as the evaluation of the amount of drug delivered to the tumour and to surrounding tissues in a pixel-by-pixel way, from the image. The defined objectives can be achieved using the calibrated FWHM values of the distribution of events in the tumour image, versus distance, to determine the dimension and the position of the tumour. The concentration activity in the tumour and the tumour-to-nontumour activity ratios can be obtained from the image, using a modified filter and the calibration of the tomograph. The colour scale of the image can be expressed in absolute units (μCi/ml) and the concentration activity can be evaluated in each pixel of the image or in each volume element of the body. / Thesis / Master of Science (MS)

京都大学 / 新制・課程博士 / 博士(情報学) / 甲第24745号 / 情博第833号 / 新制||情||139(附属図書館) / 京都大学大学院情報学研究科通信情報システム専攻 / (主査)教授 山本 衛, 教授 橋口 浩之, 教授 梅野 健 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

Simulative tests, such as asphalt pavement analyzer (APA), Hamberg rut tester etc. have been widely used to evaluate the performance of asphalt mixtures. However, simulative tests to evaluate the performance of the mixtures cannot give fundamental properties of Asphalt Concrete (AC) due to the complex stress and strain fields. On the other hand, due to the availability of high-performance computing systems and software, numerical techniques are gaining popularity. This dissertation presents a computational simulation method of the APA tests in order to evaluate the rutting potential of asphalt mixtures based on actual microstructure reconstructed from X-ray tomography images. In the study, the microstructure of AC is obtained through the analysis of X-ray images, which included the digital information of the microstructure for the scanned specimen. In the simulations the three phases, mastic (asphalt binder with mineral filler), aggregates, and voids are assigned with different material properties. Aggregates are modeled as an elastic material, and air voids are removed during the loading steps. The adopted two-layer model is only used to represent the rate and temperature dependent behavior of the mastics. The parameters are obtained with inverse methods. Based on the sensitivity analysis of the parameters, an iterative procedure is performed to optimize the parameters using the experimental measurement and results of the model simulations. A parametric study is also conducted to study the effect of major parameters such as the stiffness ratio of the networks on the macro response of the model. The simulation results obtained shows a good agreement with the experimental results. The dissertation also presents a method to measure micro strains in asphalt mixture. An automated procedure using tomography images to reconstruct three-dimensional particles is developed. The translations of the particles are obtained from the coordinate differences of particles' mass centers before and after the APA testing. The micro and macro strains in the mixture are calculated based on the particle translations. A good correlation is found between measured strains and experimental result. / Ph. D.

In this thesis, a finite-frequency theory is developed to calculate Born sensitivity kernels for Rayleigh-wave phase and amplitude measurements that are valid in regions near seismic stations. Calculations of sensitivity kernels for inter-station measurements show that exact travelling-wave representation of Green tensor is necessary when station spacing is close to or smaller than the seismic wavelength. This finite-frequency theory will allow us to take advantage of dense seismic arrays to obtain high-resolution surface-wave tomography using inter-station measurements. The non-linear dependence of surface wave phase upon large perturbations in crustal thickness as well as finite-frequency effects in global surface-wave tomography are investigated using wave propagation simulations. Calculations show that non-linearity as well as finite-frequency effects can be accounted for by using 2D phase-velocity kernels for boundary perturbations. A 3D-reference tomographic approach is developed for iterative inversions of global crustal structure where Frechet kernels are calculated in 3D reference models. A global dataset of minor-arc and major-arc Rayleigh wave dispersion measurements at periods between 25 seconds and 100 seconds are built and global phase velocity maps based on the dataset are obtained using diffractional tomography. The phase velocity model confirms many general features associated with surface tectonics including the ocean-continent dichotomy and the signature of lithospheric cooling in oceanic plates. There are significant differences between the phase velocity model and calculations based on a current global model CRUST2.0+S20RTS in oceanic regions, Archean and Proterozoic cratons as well as orogenic belts. In addition, the high resolution phase velocity maps reveal a major change in the distribution of small scale anomalies in the Pacific at different wave periods. / Ph. D.

Characterization of composite materials, such as Asphalt Concrete (AC) and other engineering materials is required to provide data for design and construction. This is usually carried out through various performance tests, which are always time consuming for specimen preparation, equipment calibration and test setting up. For materials with time- and temperature-dependent properties, this procedure requires fabrication of a large number of specimens in order to get reasonably comprehensive results. Furthermore, for materials that consist of phases with significant differences in properties, macroscopic homogeneous assumption or microscopic statistic approximation will lead to complex correction schemes. This will add complexity in material characterization. On the other hand, the homogeneity based interpretation of test results makes it difficult to understand the interaction between different components. The objective of this research is to develop a numerical testing method for material characterization based on x-ray tomography and finite element method. The introduction of tomography technology, such as x-ray tomography into engineering field makes it possible to obtain material microstructure without disturbing the phase configuration. Along with the development of image analysis technology, image data can be manipulated to obtain digitalized sample reconstruction and to build finite element geometric model. Based on well developed material models that sufficiently capture the essential behavior of individual material component, we developed a framework of numerical tests for characterization of composite material. The geometric model imports the microstructural data of the sample, the configuration of aggregates, voids and flakes, through x-ray tomography and image processing. The voids distribution as well as density variation was quantified to verify the model microscopic characteristics. FORTRAN programs were developed to automatically achieve data transfer and model generation, e.g. boundary identification and ABAQUS simulation model generation. Material model was studied and selected for different material components. Viscoplastic material models were evaluated and calibrated in ABAQUS. Monotonic loading and repeated loading were considered in the study to validate the model for most characterization needs. The digital model was validated through small sample tests and was implemented and used in various material characterizations. For the wood panel characterization, the anisotropic elastic properties were studied while the viscous and plastic responses were studied for asphalt concrete. Factors affecting the accuracy and the limitations of the application were determined. It is worth noting that further advance and data collection will make the calibration of material model more accurate. Nevertheless, the work can be extended to other regimes, such as high speed impact especially where the actual testing is complicated to setup. / Ph. D.