A avaliação da presença de destruição óssea provocada por neoplasias malignas de boca e orofaringe é um fator de fundamental importância no estabelecimento da terapêutica adequada para o caso, como também, para a determinação do prognóstico do paciente. O presente estudo teve por objetivo determinar os aspectos clínicos (localização, forma de apresentação e estadiamento) que podem estar associadas com o potencial de infiltração do osso subjacente a lesão, como também determinar a sensibilidade e especificidade do exame físico. A população de estudo consistio de vinte e cinco pacientes (17 homens e 8 mulheres, média de idade de 57,88 anos) portadores de neoplasias malignas de boca e orofaringe atendidos no Ambulatório de Semiologia da Faculdade de Odontologia da Universidade de São Paulo – campus São Paulo, no período de agosto de 2003 a agosto de 2004, os quais foram submetidos ao exame clínico e a tomografia computadorizada (TC). A TC foi considerada o padrão ouro para a avaliação da presença de destruição óssea. Foi observada a presença de infiltração neoplásica para o tecido ósseo adjacente em 68% dos casos (17 pacientes). O exame físico dos pacientes revelou uma sensibilidade de 80% e especificidade de 87,50% na análise de comprometimento do osso, além de uma acurácia de 84%. As lesões que se apresentavam clinicamente como uma úlcera do tipo infiltrativa e lesões do tipo nodulares, não ulceradas, foram as que apresentaram maior potencial de infiltrar-se para o osso, 68,75% e 100% respectivamente. A localização do tumor em determinados sítios, também influenciou diretamente na presença de invasão óssea,principalmente lesões localizadas em região de gengiva, trígono retromolar, palato duro e orofaringe. O estadiamento das lesões revelou relação existente entre o tamanho do tumor e a presença de metástases à distância com a presença de infiltração da neoplasia para o tecido ósseo. Concluindo, observou-se que a identificação de determinados parâmetros clínicos como localização, forma de apresentação clinica, tamanho da lesão e a presença de metástases à distância, associado a um criterioso exame físico regional podem servir como valiosas ferramentas para a análise de envolvimento ósseo por neoplasias malignas de boca e orofaringe. / The assessment of bone destruction by oral and oropharynx malignant neoplasms is a critical factor in the therapeutic planning and to determine the patient prognostic. The aim of this study was to determine the clinical aspects (localization, clinical manifestation and stage) that can be associated with the potential of bone infiltration, and also determine the physical exam sensibility and specificity. The study population consisted of twenty five patients (17 men and 8 women, mean age 57.88 years-old), with malignant neoplasms of the mouth and oropharynx, of the Stomatology Clinic of the College of Dentistry at the Sao Paulo University - campus Sao Paulo, in the period of august 2003 to august 2004, who were submitted to a clinical and computed tomography (CT) examinations. CT was considered the gold standard to evaluate the presence of bone involvement. The presence of bone destruction by the tumor was observed in 68% of the cases (17 patients). The physical examination of the patients revealed 82% of sensibility, 87.50% of specificity, and 84% of accuracy in the assessment of bone invasion by these diseases. The lesions that were clinical considered to be infiltrative ulcer and nodular lesions, non-ulcerated, presented the highest potential to cause bone destruction, 68.75% and 100% respectively. The tumor localization in specific sites also influenced the presence of bone invasion, meanly with the lesions localized in the gingival, retromolar trigone, hard palate and oropharynx. The stage of the lesions revealed a relation between the size and the presence of distant metastasis, with the presence of invasion by the neoplasm. In conclusion, it was determined that the identification of some clinical parameters such localization, clinical presentation, lesion size and the presence of distant metastasis, associated with a perceptive regional physical exam must be use as a value tool is the assessment of bone destruction by oral and oropharynx malignant neoplasms.

O presente projeto consistiu no estudo e aplicação do algoritmo FDK (Feldkamp-Davis-Kress) para a reconstrução de imagens tomográficas utilizando a geometria de feixe cônico, resultando na implementação de um sistema adaptado de tomografia computadorizada multicortes (TCMC). Para a aquisição das projeções, utilizou-se uma plataforma giratória com goniômetro acoplado, um equipamento de raios X e um detector digital, tipo CCD. Para processar a reconstrução das imagens, foi utilizado um PC, no qual foi implementado o algoritmo FDK. Inicialmente foi aplicado o algoritmo FDK original, no qual se assume o caso físico ideal no processo de medições. Em seguida, foram incorporadas ao algoritmo, algumas correções de artefatos relacionados ao processo de medição das projeções. Para testar o funcionamento do algoritmo implementado, foram feitas reconstruções a partir de projeções simuladas computacionalmente. Foram montados e testados três sistemas de aquisição de projeções, nos quais foram usados diferentes equipamentos de raios X, detectores, metodologias e técnicas radiográficas, a fim de garantir que fossem coletados os melhores conjuntos possíveis de projeções. Realizou-se a calibração do sistema de TCMC implementado. Para isso, utilizou-se um objeto com uma distribuição de coeficientes de atenuação linear conhecida, que foi projetado e fabricado especificamente para isto. Por fim, o sistema de TCMC implementado foi utilizado na reconstrução tomográfica de um objeto não homogêneo, cuja distribuição volumétrica do coeficiente de atenuação linear é desconhecida. As imagens reconstruídas foram analisadas a fim de avaliar o desempenho do sistema de TCMC implementado. / This work consisted on the study and application of the FDK (Feldkamp-Davis-Kress) algorithm for tomographic image reconstruction using cone-beam geometry, resulting on the implementation of an adapted multi-slice computed tomography (MSCT) system. For the acquisition of the projections, a rotating platform coupled to a goniometer, an x-ray equipment and a CCD type digital detector were used. The FDK algorithm was implemented on a PC which was used for the reconstruction process. Initially, the original FDK algorithm was applied considering only the ideal physical conditions in the measurement process. Then some artifacts corrections related to the projections measurement process were incorporated. Computational simulations were performed to test the functioning of the implemented algorithm. Three projections acquisition systems, which used different x-ray equipments, detectors, methodologies and radiographic techniques, were assembled and tested in order to ensure that the best possible set of data was collected. The implemented MSCT system was calibrated. A specially designed and manufactured object with a known linear attenuation coefficient distribution was used for this purpose. Finally, the implemented MSCT system was used for multi-slice tomographic reconstruction of an inhomogeneous object, whose attenuation coefficient distribution was unknown. The reconstructed images were analyzed to assess the performance of the TCMC system that was implemented.

INTRODUÇÃO: A doença de Chagas (DCh) representa um grave problema de saúde pública na maioria dos países da América Latina. Sintomatologia frequente, a dor torácica ou precordial em pacientes com DCh pode assemelhar-se àquela observada na doença arterial coronária (DAC), constituindo-se, dessa forma, em desafio diagnóstico para os clínicos. A frequência da DAC em pacientes com DCh continua indefinida na literatura, permanecendo a hipótese de que pacientes com DCh possam apresentar menor proporção de DAC. A angiografia coronária por tomografia computadorizada (ATC), em aparelho de múltiplas colunas de detectores, é um método não invasivo de alta acurácia que permite o diagnóstico precoce de placas ateromatosas, obstrutivas ou não, e que poderia detectar a frequência de DAC neste grupo de pacientes. OBJETIVO: Investigar a presença de aterosclerose coronária em pacientes com DCh, comparando com um grupo controle de indivíduos assintomáticos e sem doença coronária conhecida, utilizando a angiografia coronária por tomografia computadorizada. MÉTODOS: Foram estudados 43 pacientes portadores da DCh, sendo 16 (37,2%) homens. O grupo controle foi composto por 66 indivíduos não portadores da DCh, sendo 28 (42,4%) homens. Os grupos foram pareados pelo escore de risco de Framingham, respeitando-se a mesma faixa de risco (baixo, intermediário e alto), além do pareamento por sexo e faixa etária. Os exames foram realizados em tomografia computadorizada de 320 colunas de detectores e o diagnóstico de DAC foi definido pela presença de placa aterosclerótica, mesmo sem causar obstrução luminal. DAC obstrutiva significativa foi considerada pela presença de ao menos uma placa causando redução maior do que 50% do diâmetro da luz arterial. RESULTADOS: Foram observadas diferenças significativas nos parâmetros relacionados à DAC, sendo sua frequência significativamente menor nos pacientes portadores da DCh. A presença de DAC foi observada em 9 indivíduos (20,9%) portadores da DCh e em 32 indivíduos do grupo controle (48,5%), com p=0,004. A magnitude da estenose coronária foi significativamente menor nos pacientes com DCh que nos controles na análise por paciente, por território e por segmentos coronários (p<0,001, p=0,012 e p=0,045, respectivamente). CONCLUSÕES: Os pacientes portadores da DCh apresentam baixa frequência de DAC definida pela tomografia computadorizada de artérias coronárias. A frequência de DAC, obstrutiva ou não, em pacientes com DCh foi significativamente menor que a observada no grupo controle de pacientes sem DAC prévia conhecida / INTRODUCTION: Chagas disease (CD) is a serious public health problem in most of Latin American countries. Precordial or chest pain in patients with CD is a frequent symptom and can be similar to that observed in coronary artery disease (CAD), what represents a diagnostic challenge to the physicians. The frequency of CAD in patients with CD continues undefined in the literature, remaining the hypothesis that patients with CD could present a lower proportion of CAD. Computed tomography angiography (CTA) is a high accuracy and non-invasive method that allows an early diagnostic of atherosclerotic plaque, obstructive or not, and that could detect the frequency of CAD in this group of patients. OBJECTIVE: Investigate coronary atherosclerosis by CTA in patients with CD, comparing with an asymptomatic control group without known CAD. METHODS: 43 patients with CD were studied and 16 (37.2%) were men. The control group was composed by 66 non-carriers of CD and 28 (42.4%) were men. The groups were matched for Framingham risk score (low, medium and high) as well as sex and age. The exams were performed in 320-multidetector rows CT and the CAD diagnostic was defined as the presence of atherosclerotic plaques, even without luminal obstruction. Significant obstructive CAD was considered if at least one plaque was present causing more than 50% of reduction in the arterial lumen diameter. RESULTS: Significant differences were observed in parameters related to CAD, showing lower frequency of CAD in patients with CD. The presence of CAD was observed in 9 patients (20.9%) with CD and in 32 patients (48.5%) from the control group, with p=0.004. The magnitude of coronary stenosis was significantly lower in patients with CD than in controls, in a per patient, per territory and per segment coronary analyses (p<0.001, p=0.012 e p=0.045, respectively). CONCLUSIONS: Patients with CD have a low frequency of CAD defined by coronary CTA. The CAD frequency, obstructive or not, in patients with CD was significantly lower than the observed in the control group without known CAD

O objetivo deste estudo foi comparar, por meio de tomografia computadorizada de feixe cônico, a inclinação axial dos dentes posteriores e a morfologia óssea alveolar mandibular entre indivíduos com diferentes padrões faciais. Para isso, foram utilizadas 58 tomografias de indivíduos maiores de 14 anos de idade não tratados ortodonticamente. Os indivíduos foram divididos em 3 grupos de acordo com o padrão facial avaliado pelo índice VERT de Ricketts: Grupo 1: composto por 18 indivíduos com padrão braquifacial, com idade média de 21,58 anos (d.p.=7,43); Grupo 2: composto por 23 indivíduos com padrão mesofacial, com idade média de 19,14 anos (d.p.=5,19); e Grupo 3: composto por 17 indivíduos com padrão dolicofacial, com idade média de 19,09 anos (d.p.=6,89). Foi realizada uma avaliação quantitativa das tábuas ósseas vestibular e lingual dos dentes pósteroinferiores, em tomografias de feixe cônico. As medidas utilizadas foram: altura do osso mandibular vestibular e lingual, largura mandibular cervical e média, inclinação mandibular, inclinação da face vestibular, largura do molar, angulação do molar e ângulo dente/osso. A comparação intergrupos foi realizada com a utilização do teste ANOVA a um critério de seleção e teste de Tukey quando necessário. Para verificar se existe correlação entre o padrão facial e as variáveis estudadas foi utilizado o teste de correlação de Pearson. Os resultados demonstraram que os indivíduos braquifaciais apresentaram uma menor inclinação mandibular quando comparados aos indivíduos mesofaciais e dolicofaciais. Houve diferença significante da altura mandibular vestibular entre os três grupos avaliados, sendo que esta foi menor no grupo braquifacial, intermediária no grupo mesofacial e maior no grupo dolicofacial. A altura mandibular lingual foi menor no grupo braquifacial em comparação aos grupos mesofacial e dolicofacial. A largura mandibular média foi maior nos indivíduos braquifaciais em relação aos mesofaciais. / The aim of this study was to compare, with cone beam computed tomography, the axial inclination of posterior teeth and mandibular alveolar bone morphology among individuals with different facial patterns. For this, 58 CT scans of untreated individuals orthodontically aged more than 14 years were used. The subjects were divided into 3 groups according to the facial pattern evaluated by the VERT index by Ricketts: Group 1 comprised 18 individuals with brachyfacial pattern, with a mean age of 21.58 years (s.d.=7.43); Group 2 comprised 23 individuals with mesofacial pattern, with a mean age of 19.14 years (s.d.=5.19); and Group 3 comprised 17 individuals with dolichofacial pattern, with a mean age of 19.09 years (s.d.=6.89). A quantitative assessment of the buccal and lingual bone plates of the mandibular posterior teeth were made in cone beam CT scans. The variables measured were: buccal and lingual mandibular height, cervical and middle mandibular width, mandibular inclination, inclination of the buccal surface, molar width, molar angle and tooth/bone angle. The intergroup comparison was performed by one-way ANOVA and Tukey test when necessary. To check whether there is a correlation between facial pattern and the variables studied, the Pearson correlation test was used. The results showed that the brachyfacial subjects had a smaller mandibular angle when compared to mesofacial and dolichofacial individuals. There was significant difference in the buccal mandibular height between the three groups, and this was smaller in the brachyfacial group, intermediate in the mesofacial group and larger in the dolichofacial group. Lingual mandibular height was smaller in brachyfacial group when compared to mesofacial and dolichofacial groups. The mean mandibular width was greater in brachyfacial than in mesofacial subjects.

O objetivo deste estudo foi comparar, por meio de tomografia computadorizada de feixe cônico, a inclinação axial dos dentes posteriores e a morfologia óssea alveolar mandibular entre indivíduos com diferentes padrões faciais. Para isso, foram utilizadas 58 tomografias de indivíduos maiores de 14 anos de idade não tratados ortodonticamente. Os indivíduos foram divididos em 3 grupos de acordo com o padrão facial avaliado pelo índice VERT de Ricketts: Grupo 1: composto por 18 indivíduos com padrão braquifacial, com idade média de 21,58 anos (d.p.=7,43); Grupo 2: composto por 23 indivíduos com padrão mesofacial, com idade média de 19,14 anos (d.p.=5,19); e Grupo 3: composto por 17 indivíduos com padrão dolicofacial, com idade média de 19,09 anos (d.p.=6,89). Foi realizada uma avaliação quantitativa das tábuas ósseas vestibular e lingual dos dentes pósteroinferiores, em tomografias de feixe cônico. As medidas utilizadas foram: altura do osso mandibular vestibular e lingual, largura mandibular cervical e média, inclinação mandibular, inclinação da face vestibular, largura do molar, angulação do molar e ângulo dente/osso. A comparação intergrupos foi realizada com a utilização do teste ANOVA a um critério de seleção e teste de Tukey quando necessário. Para verificar se existe correlação entre o padrão facial e as variáveis estudadas foi utilizado o teste de correlação de Pearson. Os resultados demonstraram que os indivíduos braquifaciais apresentaram uma menor inclinação mandibular quando comparados aos indivíduos mesofaciais e dolicofaciais. Houve diferença significante da altura mandibular vestibular entre os três grupos avaliados, sendo que esta foi menor no grupo braquifacial, intermediária no grupo mesofacial e maior no grupo dolicofacial. A altura mandibular lingual foi menor no grupo braquifacial em comparação aos grupos mesofacial e dolicofacial. A largura mandibular média foi maior nos indivíduos braquifaciais em relação aos mesofaciais. / The aim of this study was to compare, with cone beam computed tomography, the axial inclination of posterior teeth and mandibular alveolar bone morphology among individuals with different facial patterns. For this, 58 CT scans of untreated individuals orthodontically aged more than 14 years were used. The subjects were divided into 3 groups according to the facial pattern evaluated by the VERT index by Ricketts: Group 1 comprised 18 individuals with brachyfacial pattern, with a mean age of 21.58 years (s.d.=7.43); Group 2 comprised 23 individuals with mesofacial pattern, with a mean age of 19.14 years (s.d.=5.19); and Group 3 comprised 17 individuals with dolichofacial pattern, with a mean age of 19.09 years (s.d.=6.89). A quantitative assessment of the buccal and lingual bone plates of the mandibular posterior teeth were made in cone beam CT scans. The variables measured were: buccal and lingual mandibular height, cervical and middle mandibular width, mandibular inclination, inclination of the buccal surface, molar width, molar angle and tooth/bone angle. The intergroup comparison was performed by one-way ANOVA and Tukey test when necessary. To check whether there is a correlation between facial pattern and the variables studied, the Pearson correlation test was used. The results showed that the brachyfacial subjects had a smaller mandibular angle when compared to mesofacial and dolichofacial individuals. There was significant difference in the buccal mandibular height between the three groups, and this was smaller in the brachyfacial group, intermediate in the mesofacial group and larger in the dolichofacial group. Lingual mandibular height was smaller in brachyfacial group when compared to mesofacial and dolichofacial groups. The mean mandibular width was greater in brachyfacial than in mesofacial subjects.

Desde a invenção da tomografia computadorizada (CT) nos anos 70, toda década trouxe novas tecnologias para esta modalidade. Com estes avanços, também surgiu a necessidade de novas e melhores técnicas de avaliação de desempenho e segurança dos equipamentos de CT. Hoje, o controle de qualidade de equipamentos de CT é, em grande parte, feito manualmente. Portanto, é lento e, em parte, subjetivo. Neste trabalho, um software foi escrito em MatLab® para processar imagens do phantom de CT Catphan500®, aperfeiçoando a rotina do programa de controle de qualidade de CT. Com pouca interferência do usuário, o software mede a espessura de corte, incremento entre cortes e tamanho de pixel, avalia a linearidade do número CT, estima a Função Transferência de Modulação (MTF), o ruído e o Espectro de Potência do Ruído (NPS). Para a validação do software, conjuntos de imagens do phantom foram obtidas em 10 equipamentos de CT diferentes, com 27 protocolos diferentes. Cada conjunto foi analisado pelo software, e os resultados obtidos foram comparados aos resultados previamente obtidos pela rotina normal do programa controle de qualidade. Para essa comparação, dois testes de hipótese foram empregados: o teste t de Student (para os valores de espessura de corte, incremento entre cortes, tamanho de pixel e os coeficientes da avaliação de linearidade do número CT, adotando um valor-p de 0,01) e o teste F de Fisher (para o ruído, valor-p de 0,05). As funções MTF e NPS atualmente não são medidas na rotina do controle de qualidade, portanto não há resultado prévio para fazer esta comparação. Ao invés disso, o NPS foi ajustado em função da MTF (através da relação teórica que há entre os dois) e a qualidade do ajuste foi avaliada pelo teste de qui-quadrado. Dos 101 valores de t e 25 valores de F calculados, 2 e 1 respectivamente estavam fora do intervalo de aceitação. Este resultado está de acordo com os valores-p escolhidos e, portanto, os resultados obtidos pelo software estão de acordo com os resultados da rotina de controle de qualidade convencional. Os ajustes de NPS e MTF obtiveram incertezas grandes nos parâmetros de ajuste (incertezas da mesma ordem de grandeza dos próprios parâmetros). Porém, a avaliação do qui-quadrado reduzido indica que os ajustes foram aceitáveis (com exceção de um, que mostrou uma anomalia no NPS medido e foi desconsiderado). Portanto, o NPS e MTF obtidos estão de acordo com a expectativa teórica. / Since the introduction of the CT scanner as a diagnostic imaging modality, the scientific community has seen new and more complex CT technologies. These improvements brought the need for new and improved techniques to evaluate the safety and performance of these scanners. Nowadays, the interpretation of images generated during the implementation of CT quality control procedures are done visually in much of the cases. Therefore, it is slow and partially subjective. In this work, a software was written in MatLab to process images of the Catphan500 CT phantom, in order to improve the CT quality control workflow and its accuracy. The software evaluate the slice thickness, slice increment, and pixel size, calculates the CT number linearity, and assesses the Modulation Transfer Function (MTF), the noise and the Noise Power Spectrum (NPS). Image sets of the phantom were obtained from 10 different scanners using 27 different protocols in order to validate the software. Comparative results correlating the software output and corresponding data previously obtained by the current quality control program routine were used to conduct this validation. For this comparison, two statistical tests were employed: the Students t-test (for slice thickness, slice increment, pixel size, and the coefficients of the CT number linearity evaluation, with a chosen p-value of 0.01) and the Fisher F-test (for the noise, with chosen p-value of 0.05).The functions MTF and NPS are not currently measured by the quality control routine, so there was no previous result for comparison. Instead, the NPS was fitted as a function of the MTF (using the theoretical relationship between both functions) and the quality of the fit was evaluated using the reduced chi-square. From 101 t values and 25 F values calculated, 2 and 1 were outside the acceptance interval, respectively. This result agrees with the chosen p-values, and therefore the software results are in good agreement with the traditional quality control routine results. The fits of NPS and MTF presented large uncertainties in the fitting parameters (uncertainties of the same order of magnitude as the parameters themselves). However, the reduced chi-square evaluation indicates a good fit (with the exception of one fit, which showed an anomaly on the measured NPS and was unconsidered). Therefore, the obtained MTF and NPS were in agreement with the theoretical expectations.

Radiotherapy planning involves the calculation of dose deposition throughout the patient, based upon quantitative electron density images from computed tomography (CT) scans taken before treatment. Cone beam CT (CBCT), consisting of a point source and flat panel detector, is often built onto radiotherapy delivery machines and used during a treatment session to ensure alignment of the patient to the plan. If the plan could be recalculated throughout the course of treatment, then margins of uncertainty and toxicity to healthy tissues could be reduced. CBCT reconstructions are normally too poor to be used as the basis of planning however, due to their insufficient sampling, beam hardening and high level of scatter. In this work, we investigate reconstruction techniques to enable dose calculation from CBCT. Firstly, we develop an iterative method for directly inferring electron density from the raw X-ray measurements, which is robust to both low doses and polyenergetic artefacts from hard bone and metallic implants. Secondly, we supplement this with a fast integrated scatter model, also able to take into account the polyenergetic nature of the diagnostic X-ray source. Finally, we demonstrate the ability to provide accurate dose calculation using our methodology from numerical and physical experiments. Not only does this unlock the capability to perform CBCT radiotherapy planning, offering more targeted and less toxic treatment, but the developed techniques are also applicable and beneficial for many other CT applications.

Computed tomography (CT) is routinely used for diagnosing lung disease and developing treatment plans using images of intricate lung structure with submillimeter resolution. Automated segmentation of anatomical structures in such images is important to enable efficient processing in clinical and research settings. Convolution neural networks (ConvNets) are largely successful at performing image segmentation with the ability to learn discriminative abstract features that yield generalizable predictions. However, constraints in hardware memory do not allow deep networks to be trained with high-resolution volumetric CT images. Restricted by memory constraints, current applications of ConvNets on volumetric medical images use a subset of the full image; limiting the capacity of the network to learn informative global patterns. Local patterns, such as edges, are necessary for precise boundary localization, however, they suffer from low specificity. Global information can disambiguate structures that are locally similar. The central thesis of this doctoral work is that both local and global information is important for segmentation of anatomical structures in medical images. A novel multi-scale ConvNet is proposed that divides the learning task across multiple networks; each network learns features over different ranges of scales. It is hypothesized that multi-scale ConvNets will lead to improved segmentation performance, as no compromise needs to be made between image resolution, image extent, and network depth. Three multi-scale models were designed to specifically target segmentation of three pulmonary structures: lungs, fissures, and lobes. The proposed models were evaluated on a diverse datasets and compared to architectures that do not use both local and global features. The lung model was evaluated on humans and three animal species; the results demonstrated the multi-scale model outperformed single scale models at different resolutions. The fissure model showed superior performance compared to both a traditional Hessian filter and a standard U-Net architecture that is limited in global extent. The results demonstrated that multi-scale ConvNets improved pulmonary CT segmentation by incorporating both local and global features using multiple ConvNets within a constrained-memory system. Overall, the proposed pipeline achieved high accuracy and was robust to variations resulting from different imaging protocols, reconstruction kernels, scanners, lung volumes, and pathological alterations; demonstrating its potential for enabling high-throughput image analysis in clinical and research settings.

Despite affecting many organ systems, the leading cause of morbidity and mortality in the cystic fibrosis (CF) population is lung disease. For the current studies we investigated elements of CF lung disease in a porcine model of CF and in people with CF. Our primary analysis tool was chest computed tomography (CT). To investigate early CF lung disease we examined three week old CF and non-CF pigs. We found three week old CF pigs to have large, irregular tracheal smooth muscle bundles, airways of reduced size, airways of irregular shape, and airways of abnormal distensibility. Three week old CF pig lung parenchyma was more heterogenous in density than three week non-CF pigs, especially in the right cephalad lung. The degree of lung tissue heterogeneity in CF pigs correlated with the degree of lung infection. Three week old CF pigs also had significantly more air trapping upon exhalation, evidence of airflow obstruction, than non-CF pigs. The degree of air trapping correlated with the degree of mucus accumulation in the airways. These data show that CF pigs spontaneously develop hallmark features of CF lung disease within weeks of birth, and that abnormal airway growth and development in CF may contribute to lung disease. This study helped set the foundation for future comparative studies involving CF therapeutics, for example, antibiotics and mucolytics. In adults with CF we performed a before drug, after drug study. The drug was ivacaftor, and it restores the basic underlying defect in a subset of people with CF: impaired function of a particular anion channel. We hypothesized that abnormal airway smooth muscle behavior in people with CF, known as “CF asthma,” is, in part, a primary pathogenic mechanism of CF lung disease. We tested our hypothesis by assaying smooth muscle tone before and after administration of ivacaftor. We limited the time duration to two days. We reasoned two days was long enough for ivacaftor to become effective, but not long enough to reverse long standing lung infection and inflammation which could affect smooth muscle function independently. The implication being, that observed changes would be directly due to restoration of the CF defect. We found evidence suggesting relaxation of airway and vascular smooth muscle tone. And, the change in airway smooth muscle tone correlated with the change in vascular smooth muscle tone. These data suggest that impaired smooth muscle function is a primary element of CF lung disease. Many of the people in our two day ivacaftor study returned for follow up after one year of ivacaftor therapy. We hypothesized that radiographic features of lung disease would improve following one year of ivacaftor therapy. We observed no change in lung volume upon inspiration, but a reduction in expiratory lung volume, approximately half of which occurred within two days. Our airway measurements were confounded by errors in scan reconstruction, however, other published studies report airway wall thinning over long term ivacaftor administration. Taken together, these studies of pigs with CF and people with CF, help us understand this disease.

The use of computed tomography (CT) in the care of patients has grown dramatically since its introduction over 30 years ago. The vast majority of the utilization research has focused on factors associated with the variable use in the outpatient and emergency department settings. This has left much of the inpatient use and variation understudied. This study has multiple aims. The first is to characterize the inpatient variation across multiple states and markets. The second is to evaluate the relationship between inpatient CT use and commercial payers across these areas. The third is to develop a model to evaluate the relationship between inpatient CT use and the characteristics of markets, hospitals, and patients. The study uses a four-state convenience sample of cross-sectional data for hospitals. It included non-Federal, acute care hospitals that reported the performance of inpatient CT exams during 2015 (N=181). The literature review was used to justify the inclusion of variables in the study. The descriptive analyses were used to justify the appropriateness of the variables and methodology for testing. A comparison of means demonstrated the significant differences for inpatient utilization between states. A univariate general linear model demonstrated a negative relationship with a hospital’s proportion of commercially insured patients and the inpatient utilization rate. An ordinary least squares multivariate linear regression was used to test for variable significance within each of three constructs: markets, hospitals, and patients. The results indicated that inpatient CT rates were positively associated with higher level of insurer concentration (market), positively associated with system centralization (hospitals), and negatively associated with a hospital’s increasing proportion of minority patient discharges (patients). The study serves an important function in identifying varying patterns of CT utilization across the full spectrum of inpatients across multiple states, regardless of payer. It also creates new knowledge about how the characteristics of these markets, hospitals, and patients are related to inpatient use. It also provides implications for administrators, researchers, and policy makers. The additional knowledge and understanding provided by this research have the potential to lead to improvements in the appropriate and equitable use of inpatient CT exams.