Estimation of intra and inter strain variation in breast density of rats

Ratna Swathi Kanamaluru

doi:10.17918/etd-4242

Breast cancer is one of the major causes of female mortality. Based upon incidence rates between 2007 and 2009, it is estimated that 12.4 % of women born in the United States are at risk of developing breast cancer during their lives. Therefore, it is essential to assess and understand the various factors that increase the risk of breast cancer in women. Among the known risk factors of breast cancer, breast density has been shown to be a strong and independent factor of breast cancer risk. Animal models are widely used in research and have led to a better understanding of many human diseases. However, no animal model for breast density currently exists. This thesis details the development of a new image-based assessment for breast density in an animal model. The work described in this thesis is part of a larger study to determine the intra- and inter-strain variability of breast density in rats. Ex vivo micro-CT imaging of rat mammary glands is being investigated to determine the breast density of various rat strains. The excised glands were imaged in a custom designed tissue holder. The holder consists of a plastic histology slide, upon which the tissue is mounted, held in a microarray slide tube; the tube contains a calibration device made of adipose and glandular tissue equivalent tissue-equivalent plastics and a damp sponge to maintain humidity in the tube. A total of 96 mammary glands were imaged from five different inbred rat strains. A subset of these samples was subject to procedural changes in terms of sample preparation, orientation of the glands, and preparatory procedures of the glands. As a consequence, 33 cases were eliminated from further analysis. Of the 63 remaining cases, 54 mammary glands were analyzed to determine breast density. The development of the imaging methodology was followed by longitudinal and reproducibility studies in order to assess the stability of the acquisition technique. The data obtained from the 54 mammary glands were analyzed to examine the effect of various acquisition factors including scan date, sample position, and positioning of the calibration device. Variations in the bright and dark mean values of the calibration device were observed with time and repositioning. A significant difference was noted with respect to both orientation of the phantom and phantom tilt. Analysis revealed that these differences were due to variations in the selection of the regions of interest (ROI) of the calibration device, together with the homogeneity of the calibration device. In spite of these technical limitations, preliminary results indicate a significant inter-strain difference in the means of gland intensities. In addition, a statistical correlation exists between left and right gland intensities that is consistent with prior human results. The histogram of the normalized gland mean intensities, representing the breast density, was concordant with the volumetric breast density histogram obtained from human breast CT and mammography data. These results suggest that this novel image acquisition method is suitable for the assessment of breast density of rat models using a micro-CT scanner, and that it may have utility for research in novel diagnostic and therapeutic procedures.

Estimation of intra and inter strain variation in breast density of rats

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Estimation of intra and inter strain variation in breast density of rats

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