The way in which the myocardium responds to its mechanical environment must be understood in order to develop reasonable treatments for congestive heart failure. The first step toward this understanding is to characterize and quantify the cardiac microstructure in healthy and diseased hearts. Myocardium has a laminar architecture made up of myolaminae, which are sheets of myocytes surrounded by a collagen weave. By enhancing the contrast between the myocytes and the surrounding collagen, the myocardium can be investigated and its laminar structure can be quantified. Many of the techniques that have been used to view the microstructure of the heart require the use of toxic or caustic chemicals for fixation or staining. An efficient imaging method that uses polarization microscopy and enhances the contrast between the collagen and myocytes while minimizing the use of harmful chemicals was developed in this research. Collagen is birefringent; therefore its visibility should be enhanced through polarization microscopy and image processing. The sheet angles were viewed directly by cutting slices of a rat septum perpendicular to the fiber angle. Images of different polarization combinations were taken and a region of interest was selected on the sample. Image processing techniques were used to reduce the intensity variation on the images and account for the variable gain of the camera. The contrast between the collagen and myocytes was enhanced by comparing adjusted images to the background and looking at a single image this comparison produced. Although the contrast was enhanced, the embedding media reduced the collagen signal and the enhancement was not as striking as expected.

The way in which the myocardium responds to its mechanical environment must be understood in order to develop reasonable treatments for congestive heart failure. The first step toward this understanding is to characterize and quantify the cardiac microstructure in healthy and diseased hearts. Myocardium has a laminar architecture made up of myolaminae, which are sheets of myocytes surrounded by a collagen weave. By enhancing the contrast between the myocytes and the surrounding collagen, the myocardium can be investigated and its laminar structure can be quantified. Many of the techniques that have been used to view the microstructure of the heart require the use of toxic or caustic chemicals for fixation or staining. An efficient imaging method that uses polarization microscopy and enhances the contrast between the collagen and myocytes while minimizing the use of harmful chemicals was developed in this research. Collagen is birefringent; therefore its visibility should be enhanced through polarization microscopy and image processing. The sheet angles were viewed directly by cutting slices of a rat septum perpendicular to the fiber angle. Images of different polarization combinations were taken and a region of interest was selected on the sample. Image processing techniques were used to reduce the intensity variation on the images and account for the variable gain of the camera. The contrast between the collagen and myocytes was enhanced by comparing adjusted images to the background and looking at a single image this comparison produced. Although the contrast was enhanced, the embedding media reduced the collagen signal and the enhancement was not as striking as expected.

<p>Pre-clinical imaging has provided pulmonary researchers with a number of valuable tools for studying both the lung and lung disease. A greater understanding of the structure/function relationships within the rodent lung would help to bridge the gap between functional images of the lung and its underlying anatomy.</p> <p>The objectives of this work were to visualize and measure the components of rodent lung anatomy. Contrast-enhanced microCT images were used to visualize the airways and major blood vessels from both the Sprague-Dawley rat and the BALB/c mouse. These observations and measurements were used in the development of a pulmonary lung model containing both the conducting airways and blood vessels. The model can be applied to unenhanced images of the rodent lung to facilitate the regionalization of functional imaging data (SPECT/PET). The model has been used to simulate bronchoconstriction and deposition patterns of inhaled particles. Extensive validation revealed that the model was unable to fully reproduce the rodent lung and that further refinement is necessary.</p> <p>The finer structure of the rodent lung, which could not be resolved using our microCT system, was measured using histological sections of the rodent lung. Software was developed and validated to automatically quantify the increases in airspace size that are associated with several respiratory conditions.</p> <p>Together, this work sheds light on the underlying anatomy of the rodent lung that is present in both anatomical and functional images. The knowledge will help researchers to understand some of the structural changes that are occurring with the development of lung disease.</p> / Doctor of Philosophy (PhD)

<p>Allergic asthma is a disease involving airway inflammation, commonly linked to allergen exposure. Computed tomography (CT) is used to quantitatively assess changes in density, hence inflammation, in the lung. CT imaging provides the ability to non-invasively and longitudinally study disease progression and evaluate treatment efficacy. The objective of this study was to determine the sensitivity of CT to detect the anti-inflammatory effects of budesonide (BUD) by measuring airway tissue density in a rat model of allergic airway disease.</p> <p>Female<strong> </strong>Brown Norway rats were exposed intratracheally to house dust mite (HDM) extract (250 µg in 100µL saline) or saline control every other day for a total of five administrations (inflammatory phase). ABUD dose and temporal response study was performed usingBUD 0, 10, 100, and 300 µg/kg administered concurrently with HDM for three and six treatments (treatment phase). CT scanning was performed at baseline, post inflammatory phase, and after three and six BUD treatments. From the CT, density was measured in a defined volume of interest surrounding the major airways. Bronchoalveolar lavage (BAL) and histological samples were collected at the same time points.</p> <p>After the inflammatory phase, a significant increase in peribronchial density was found in the HDM group compared to controls. This corresponded to a significant increase in inflammation by histology andBALtotal cell count (TCC), specifically eosinophils. Within the treatment phase after three treatments,BUD100 and 300 µg/kg led to a significant shift in lung density compared to HDM exposure alone, to a state similar to baseline. All BUD treated groups expressed a significant reduction in peribronchial density after six treatments. However, histology andBALTCC only showed a significant decrease in inflammation after six treatments for all three BUD doses.</p> <p>CT densitometry is a sensitive, non-invasive method of evaluating the anti-inflammatory effects of budesonide and can be used for future screening of therapies in allergic lung models. Airway segmentation of CT permits the localized assessment of peribronchial inflammation, while other outcome measurements, such as BAL cytology, provide whole lung assessment which may not accurately reflect important regional changes.</p> / Master of Science (MSc)

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