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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. NAFLD is closely linked with obesity, and can progress to cirrhosis and liver failure. Despite its prevalence, there is a limited understanding of NAFLD in the context of obesity and bariatric surgery, with few guidelines on clinical management and limited understanding of its pathophysiology. Bariatric surgery presents an ideal platform for NAFLD research. This thesis addresses key knowledge gaps in a range of clinical and pathophysiological areas encompassing the full spectrum of NAFLD, with the primary aim of improving management of this pervasive disease in obesity.

Fourier transform infrared (FTIR) microspectroscopic imaging and small angle x-ray scattering (SAXS) were combined to investigate the supramolecular structure of collagen from 27 tissue sections from patients undergoing mastectomy, excisional biopsy, or mammoplasty. Both techniques were correlated by matching the scattering profile from the SAXS data with the integrated area of the infrared collagen region ( 1300 – 1180 cm − 1 ) . The FTIRspectral profiles and multivariate analysis of various tissue components showed consistent differences between all major tissue components, particularly between cancer and normal tissue cells. Analysis of the SAXS data revealed broad differences between cancer and normal tissue, but were inconclusive due to the small sample size. Parameters were extracted from each technique in relation to their characterization of collagen to reveal a good correlation between the two techniques, which diagnostically parallels with gold-standard Hematoxylin and Eosin (H&E) stained sections. The results show that the integrated area of collagen region in the FTIRspectrum for cancerous samples is greater than that for noncancerous samples indicating collagen disorder. This supports the notion that collagen is structurally disrupted in cancertissue consistent with the interpretation of the SAXS data. Overall, both these techniques successfully distinguished cancer from normal breast tissue. Integration of these two techniques was able to better segregate cancer as well as provide a more complete understanding of the differences in collagen on all structural levels during breast cancer development.