Development of Raman Spectroscopy for the Clinical Characterization of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD), comprised of Crohn’s disease and ulcerative colitis, is a complex autoimmune condition characterized by periods of disease flare and remission that seriously impact patient quality of life. Clinical management of IBD involves disease specific therapeutic and surgical treatments, but discrimination between subtypes is challenging due to significant overlap in symptoms and diagnostic test indications. Raman spectroscopy, an optical technique that is sensitive to the biomolecular composition of tissue, has the potential to aid in discrimination and evaluation of these diseases and to serve as a clinically relevant adjunct tool for guiding treatment. In this dissertation, Raman spectroscopy was used to characterize IBD in vivo, ex vivo, and in animal models. A newly developed probabilistic model of light tissue interactions was utilized to evaluate optimal fiber optic probe designs to implement endoscopy-coupled Raman spectral measurements, and instrumentation was physically redesigned to facilitate clinical integration. A cohort of IBD and control patients was recruited from the IBD Center at Vanderbilt University Medical Center and Raman measurements were made in vivo during routine surveillance colonoscopy procedures. Raman spectra were analyzed with multivariate statistical algorithms to identify features that discriminate IBD subtype. Features of disease presentation and anatomical variation were identified as influential factors for further study, and classification achieved 90% sensitivity and 75% specificity to disease subtype. The impact of disease and inter-anatomical variability on Raman spectra was correlated with histopathological scores of active and chronic disease markers associated with IBD to characterize patient tissues removed during surgery. Finally, Raman microspectroscopy was used to collect ex vivo tissue maps from a mouse model of experimental colitis to induce and study the correlation between spectral signatures and the degree of active inflammation, revealing disease markers potentially associated with oxidative stress, energy metabolism, wound healing, and epithelial recovery. Overall, Raman spectroscopy is shown to be a promising tool to understand the underlying disease progression of IBD and discriminate IBD subtype in vivo to enable more comprehensive assessment of patient disease classification and treatment strategy.