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.

O sucesso do tratamento endodôntico está associado não só com a limpeza e a instrumentação do sistema de canais radiculares (SCR), mas com a capacidade de selamento do material obturador principalmente do terço apical. O objetivo do presente estudo in vitro foi analisar o volume de guta-percha e de cimento endodôntico no milímetro apical das obturações, utilizando diferentes cimentos e técnicas de condensação. Para tanto, 64 incisivos centrais superiores foram preparados com instrumentos rotatórios de NiTi até o diâmetro cirúrgico #60.02, e então distribuídos aleatoriamente em quatro grupos. Para cada um usou-se um cimento diferente, a saber: Endofill, Sealer 26, AH Plus e Sealapex. E para cada cimento utilizado, metade dos dentes foi obturada pela técnica de condensação lateral ativa (n=8), e a outra metade, pela técnica da condensação lateral passiva (n=8). Feitas as obturações, os dentes foram submetidos ao exame tomográfico com o uso do microtomógrafo SkyScan 1174 v2. As imagens foram reconstruídas pelo programa NRecon e em seguida foi avaliado o parâmetro tridimensional do volume de cimento e guta-percha no milímetro apical, por meio do programa CTan. A análise de variância a dois critérios para o volume de guta-percha demonstrou haver diferença estatisticamente significante para o fator de variação Cimento endodôntico (p>0,05). Por meio do teste Tukey, observou-se que o grupo obturado com o Sealer 26 apresentou maior volume de guta-percha no milímetro apical do comprimento de trabalho quando comparado ao Endofill que se apresentou com menor volume. Já a análise de variância para o volume de cimento endodôntico demonstrou haver diferença estatisticamente significante para o fator de variação Cimento endodôntico (p<0,05), Técnica obturadora (p<0,05) e pelas interações dos fatores (p<0,05). O teste Tukey para o fator de variação Cimento endodôntico demonstrou que o grupo obturado com o Sealapex apresentou menor volume de cimento no milímetro estudado quando comparado ao grupo obturado com AH Plus e Sealer 26, que evidenciaram maior volume de cimento. Em relação ao fator de variação Técnica obturadora, a condensação lateral ativa apresentou menor volume de cimento comparada técnica passiva. Pode-se concluir que o maior volume de guta-percha foi encontrado nos dentes obturados com o cimento endodôntico Sealer 26, semelhantes aos obturados com Sealapex e AH Plus, independentemente da técnica de condensação. O menor volume de cimento endodôntico foi encontrado no grupo obturado com Sealapex, semelhante ao grupo obturado com o Endofill. Em relação à técnica obturadora, a condensação lateral ativa apresentou menor volume de cimento quando comparada à passiva. / The success of endodontic treatment is associated not only with the cleaning and the instrumentation of the root canal system (RCS) but also with the sealing ability mainly in the apical third of the filling material. The aim of this in vitro study was to analyze the volume of gutta-percha and sealer in the apical millimeter of the fillings, using different obturation technique and sealers. For that purpose, 64 maxillary central incisors were prepared with NiTi rotary instruments until the surgical diameter of #60.02, and then divided randomly into four groups. For each group, different sealers were used, such as Endofill, Sealer 26, AH Plus and Sealapex. And for each sealer used, half the teeth were obturated using an active lateral condensation technique (n=8), and the other half by passive lateral condensation technique (n=8). After the fillings procedures, samples were examined by SkyScan 1174 v2 micro-CT. Images were reconstructed by NRecon software, and then the dimensional parameter of the volume of sealer and gutta-percha at the apical millimeter was evaluated through the CTan program. The ANOVA Two-Way results for the analysis of the volume of guttapercha showed a statistically significant difference for endodontic sealer factor (p>0,05). The Tukey test showed that the group filled with Sealer 26 had higher volume of gutta-percha at the apical millimeter of working length when compared to that of the Endofill, which presented lower volumes. However, the ANOVA Two-Way analysis for the volume of sealer, showed a statistically significant difference for the endodontic sealer factor (p<0.05), obturation technique (p<0.05) and between the interactions of the factors (p<0.05). The Tukey test for the Sealer endodontic variation factor showed that the group filled with Sealapex had the lowest volume of sealer in the studied millimeter when compared to the group filled by AH Plus and Sealer 26, which had the highest volume of sealer. Regarding the filling technique variation factor, the active lateral condensation technique showed lower sealer volume than passive. It can be concluded that the higher volume of gutta-percha was found in teeth filled with sealer Sealer 26, similar to Sealapex and AH Plus, regardless of the technique of condensation. The lowest volume of sealer was found in the group filled with Sealapex, similar to the group filled with Endofill. Regarding the obturation technique, the active lateral condensation technique showed lowest volume of sealer than the passive.

OBJECTIVE: Breast cancer represents a significant risk in women's health, affecting many women worldwide. Current treatment options in the U.S involve a multidisciplinary approach, most often beginning with surgery to remove cancerous tissue. Evaluation of margins for cancer on excised tissue is an important part of surgery, an important predictor of survival. As a result, there has been a great deal of research interest in intraoperative margin assessment, with a focus on fast and accurate results. Micro-computed Tomography (micro-CT) has emerged as a promising avenue to this end. We hypothesize that micro-CT scans will show a statistically significant difference in radiodensity between cancerous and non-cancerous tissue at intraoperative scan times. METHODS: 15 breast lumpectomy specimens were collected from patients undergoing surgery at Massachusetts General Hospital (MGH). Lumpectomies were scanned with a Nikon XTH225 Micro-CT scanner. Corresponding histology slides were scanned with a whole slide scanner, and matched with micro-CT scans. Representative areas of cancerous and non-cancerous tissues were segmented from micro-CT scans, and their respective radiodensity differences were tested for statistical significance. RESULTS: 9 of 15 lumpectomy cases were successfully matched with histology sections. Of the 9 cases matched, 8 showed a statistically significant difference in mean radiodensity. CONCLUSION: Due to potential confounds in the study, the results are difficult to deem conclusive. However, micro-CT remains a promising tool in margin assessment, and could be fit for clinical use with further study.

Bone quality influences bone strength with important consequences for osteoporosis, fracture risk and dental implant success. Whilst imaging that is capable of capturing bone structure in 3D is becoming more common, quantitative clinical measures of bone quality rely on bone quantity, not structure. If bone quality could be more accurately measured, and the influence of bone architecture better understood, strength may be better predicted. This thesis presents methods for making structural comparisons between successive micro-CT images of loaded bone and explores the limitations of these. I present a novel method to detect where damage occurs in loaded rat vertebrae based on multiscale rigid registration and difference measures. Together these methods represent a quantitative approach to image guided failure analysis. Time-lapsed micro-CT images of 14 successively loaded rat vertebrae were acquired and damaged regions found using these. Using a random forest classifier I tested whether the damaged regions could be predicted by several commonly used structural measures (bone area and volume), three-dimensional texture measures (co-occurrence matrices and fractal dimension) and a more novel type of architectural measure (based on the structure tensor). A combination of parameters was able to predict damage regions with specificities in the range 70-90% and sensitivities of 60-70%.Using ovariectomised rats as a model of osteoporosis I have performed a pilot experiment to investigate how changes in bone quality might effect our results. The wider applicability of my methods are demonstrated by applying them to dental cone beam images of healthy and osteoporotic patients.

Various configurations of unidirectional carbon/epoxy composite rods were impacted radially, inspected using micro-CT scanning equipment, and tested in axial compression to measure the residual strength after impact. This data was used to correlate the relationship between impact energy, residual strength, and the peak crack area and total crack volume along the length of the specimens. These specimens represent local members of open three-dimensional composite lattice structures (e.g., based on isogrid or IsoTruss® geometries) that are continuously fabricated using advanced three-dimensional braiding techniques. The specimens were radially impacted with 2.5 J (1.9 ft-lbs), 5.0 J (3.7 ft-lbs), 7.5 J (5.6 ft-lbs), 10 J (7.4 ft-lb), 15 J (11 ft-lbs), and 20 J (15 ft-lbs) of energy, and compared to undamaged control specimens. The unidirectional core specimens were 8 mm (5/16") in diameter and were consolidated with various sleeve configurations and materials. Sleeves differed in types (bi-directional braided sleeves or unidirectional spiral wraps), nominal sleeve coverage of the core fibers (full or half), and sleeve material (Nomex Thread or Dunstone Hi-Shrink Tape). The unsupported length of the specimens used in this research was 50.8 mm (2") to ensure a strength-controlled compression failure rather than a failure due to buckling. After impact, the specimens were scanned using a micro-CT scanner at resolutions of 50 and 35 microns and subsequently tested in axial compression. The micro-CT scan images were analyzed to measure the crack areas along the specimen. From this analysis, the peak crack area and total crack volume along the length of the specimen was calculated. Similar to past research, as the impact energy increases, the residual compression-strength-after-impact decreases. As the impact energy increases, specimens with shrink tape sleeves had the largest increase in peak crack area and overall crack volume while specimens with full spiral sleeves had the lowest increase in peak crack area and overall crack volume. A bimodal increase is evident in the peak crack area and total crack volume over the length of the specimen where specimens impacted at 15 J (11 ft-lbs) showed the highest peak crack area across all sleeve types. There is a slight correlation between the increase in peak crack area and overall crack volume and the decrease in residual compression strength after impact. Shrink Tape, while yielding a higher quality specimen with greater compression strength prior to impact, did not protect the specimens against damage due to impact as well as other sleeve types. This was shown by the large decrease in residual compression strength after impact and increase in peak crack area and overall crack volume as the impact energy increased.

Research involved in modeling human lung disease conditions has provided insight into disease development, progression, and treatment. In particular, mouse models of human pulmonary disease are increasingly utilized to characterize lung disease conditions. With advancements in small animal imaging it is now possible to investigate the phenotypic differences expressed in inbred mouse strains in vivo to investigate specific disease conditions that affect the lung. In this thesis our aim was to generate a comprehensive characterization of the normative mouse lung phenotypes in three of the most utilized strains of mice, C57BL/6, A/J, and BALB/c, through imaging techniques. The imaging techniques that we utilized in this research included micro-CT, a custom Large Image Microscope Array (LIMA) system for 3D microscopy, and classical histology. Micro-CT provided a non-destructive technique for acquiring in vivo and fixed lung images. The LIMA 3D microscopy system was utilized for direct correspondence of the gold standard histology images as well as to validate the anatomical structures and measurements that were extracted from the micro-CT images. Finally, complete lung histology slices were utilized for assessment of the peripheral airspace structures that were not resolvable using the micro-CT imaging system. Through our developed imaging acquisition and processing strategies we have been able to successful characterize important phenotypes in the mouse lung that have not previously been known as well as identify strain variations. These findings will provide the scientific community with valuable information to be better equipped and capable of pursuing new avenues of research in investigating pulmonary disease conditions that can be modeled in the mouse.

Proopiomelanocortin (POMC) is a polypeptide precursor with 241 amino acid residues which undergoes extensive post-translational modification to yield a range of smaller, biological active peptides including £\-, £] -, £^-melanocyte-stimulating hormone (£\-MSH, £]-MSH, £^-MSH )¡A£]-endorphin (£]-EP) and adrenocorticotrophic hormone (ACTH). POMC-derived peptides play important roles in appetite and energy homeostasis. Recently, the peripheral POMC system is under active investigation to delineate their pathogenic roles in metabolic diseases such as Cushing¡¦s syndrome and obesity. In the present study, we utilized adenovirus gene delivery system to achieve systemic POMC overexpression in adult C57/BL6 mice for at least 30 days. Subsequently, the plasma and abdominal adipose tissue of mice were collected and analyzed by biochemical assays and weight determination respectively. POMC overexpression did not increase in the food uptake and body weight. These results imply that local POMC gene delivery induced the visceral fat accumulation and altered the metabolism in mice. It was observed that systemic POMC overexpression significantly elevated the triglyceride and the cholesterol levels in mice. However, POMC gene delivery also induced elevated plasma glucose concentration at weeks 1-4 and evoked glucose tolerance in mice at week 4. Interestingly, insulin resistance was readily detected in POMC-transduced in mice at as early as week 1. Besides, Micro-CT scanning and histological studies demonstrated that the visceral fat was significantly increased in POMC over-expressing mice compared with control animals. These data indicate that hepatic POMC gene delivery causes systemic ACTH rise and insulin resistance, which recapitulates the clinical features of Cushing¡¦s syndrome. In summary, POMC gene delivery induces systemic POMC overexpression and results in visceral fat accumulation and insulin resistance, which may facilitates a mice model for Cushing¡¦s-like metabolic syndrome.

Craniosynostosis is the premature fusion of one or more cranial sutures in the developing skull. If left untreated, craniosynostosis can result in developmental delays, blindness, deafness, and other impairments resulting from an increase in the intracranial pressure. In many cases, the treatment consists of complex calvarial vault reconstruction with the hope of restoring a normal skull appearance and volume. Re-synostosis, the premature re-closure following surgery, occurs in up to 40% children who undergo surgery. If this occurs, a second surgery is needed to remove portions of the fused skull in an attempt to correct the deformities and/or relieve an increase in intracranial pressure. These subsequent surgeries are associated with an incredibly high incidence of life threatening complications. To address this unmet clinical need we have developed strategies to delay the post-operative bone growth in a clinically relevant murine model of re-synostosis. The overall objective of this thesis was to develop a hydrogel based therapy to delay rapid bone regeneration in a murine model of re-synostosis. The overall hypothesis was that delivery of key BMP inhibitors involved in regulating normal suture development and regeneration will delay the rapid bone growth that in seen in a pediatric murine model of re-synostosis. The overall approach is to use micro-computed tomography (µCT) to determine the time course of suture fusion and to identify genes associated with key developmental time points, to develop a pediatric specific mouse model that displays rapid re-synostosis, and lastly to develop a hydrogel based therapy to delay the re-synostosis of this cranial defect.

Data can be acquired from tissue's vascular structure and used for modeling and visualization. To acquire data from a vascular tree, we make its structure available for the gathering of data by separating it from the structures of surrounding tissues, which includes the capillary structure. The capillary structure contains important information, but, because of its size, is the most difficult to acquire data from. In this work, we look at methods for contrasting the vascular structure from surrounding tissues, and focus on the use of corrosion casting for this procedure. We collected image data using micro-computer tomography (micro-CT) and converted data into stereolithography models. Models were imported into computer aided design (CAD) software, which was used to further process the models in order to ensure that the necessary structures were in place for the recreation of the capillary structures' relationship to targeted cell systems. Recreating the cell system-capillary system relationship is the reason building this model is so important. It is this relationship that we seek to model so that, in the future, we can create designs that guide the fabrication of three-dimensional (3D) scaffolding, which mimic capillary patterns with supportive structure that serve as an extracellular matrix for 3D tissue engineering. This method had been designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy.

This study looks at improving reduced platen compression (RPC) specimen preparation procedures by developing a better method for locating the ideal RPC specimen on each bone. These improvements are aimed at decreasing the amount of time required to complete an RPC analysis and improving the quality of the obtained results. High-resolution micro-CT scans are used to gain a better understanding of rat long bone anatomy by quantifying the location, shape, and orientation of the growth plate, primary spongiosa, and secondary spongiosa. Micro-CT analysis shows that there are easily identifiable external landmarks on the anterior side of both tibias and femurs that identify the end of the growth plate and the point at which the top of an ideal RPC specimen should be located. The landmarks are the most proximal tip of the patellar surface for the femur and the base of the tibial tuberosity for the tibia. This study also analyzes the effect of variations in the actual RPC specimen location from the ideal location and the effect of different platen sizes on test results using BMD as a surrogate for mechanical properties. The analysis shows that the BMD increases as the target RPC specimen location approaches the growth plate and decreases on moving away from the growth plate. The study also indicates that consistency is necessary when obtaining RPC specimens to avoid error due to variation from the specified landmark. Additionally, the BMD decreased as the diameter of the platen is reduced. Choosing platen size then becomes a trade off between testing the greatest amount of cancellous bone possible and potentially higher load sharing by the cortical shell with larger platen sizes as well as the risk of compressing cortical bone during the test.