Evaluation of Mouse Models of Colorectal Cancer Using Optical Coherence Tomography and Laser Induced Fluorescence Spectroscopy

Persistent Link:
http://hdl.handle.net/10150/195984
Title:
Evaluation of Mouse Models of Colorectal Cancer Using Optical Coherence Tomography and Laser Induced Fluorescence Spectroscopy
Author:
Hariri, Lida Pamela
Issue Date:
2007
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Colorectal cancer (CRC) is the third leading cause of cancer related deaths. Rodent models of CRC are useful for evaluating diagnostic tools, therapeutics, and disease progression; however, an appropriate imaging tool is needed. Optical coherence tomography (OCT) is a non-destructive imaging modality readily packaged into small diameter endoscopes. Using a near- infrared light source, structural images are generated from index of refraction mismatches with resolutions of 2-15 mm at imaging depths of up to 1.3 mm. In contrast, laser-induced fluorescence (LIF) spectroscopy provides information about biochemical composition, exciting tissues with ultraviolet to green wavelengths of light to measure fluorescence emission from endogenous fluorophores such as NADH, collagen, and porphyrin.We apply OCT and LIF to mouse models of CRC, beginning with a comprehensive ex-vivo evaluation of normal mouse gastrointestinal (GI) tract in various strains and ages and secondarily sampled colorectal neoplasia and inflammatory bowel disease (IBD) using a combined in-air OCT/LIF system. A set of characteristic features of OCT images were developed for normal esophagus, small intestine, and colon; preliminary image feature criteria were also developed for colorectal neoplasia and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin. In the IBD sample, LIF emission displayed potentially diagnostic peaks at 635 and 670 nm, consistent with increased porphyrin production by bacteria associated with IBD.Next, endoscopic OCT/LIF was evaluated in an in-vivo serial study using a prototype 2 mm diameter endoscope to image the lower colon of ApcMin and control mice. Adenoma development over OCT imaging timepoints was characterized as a progressive mucosal thickening to frank mass formation. LIF spectral comparisons revealed decreased 405 nm intensity and the presence of a peak at 680 nm over adenoma.In a final study, ultrahigh resolution OCT (UHR OCT) was used to serially image the lower colon of azoxymethane treated A/J mice to monitor CRC progression and determine OCT's capability of identifying early disease. A panel of blinded mouse colon pathology experts assigned a diagnosis based on the OCT images, which was then compared to a histological diagnosis assigned by a blinded pathologist. At the final imaging timepoint, 95% of adenomas and 23% of gastrointestinal intraepithelial neoplasia (GIN, 38% protruding GIN and 9% non-protruding GIN) were correctly diagnosed. The panel identified 68% of disease foci (95% adenoma, 76% protruding GIN, and 13% non-protruding GIN). Over the OCT imaging timepoints, disease progression followed a typical succession, with normal or GIN preceding adenoma. Endoscopic UHR OCT enabled accurate diagnosis of adenomas, identification of protruding GIN, and non-destructive visualization of CRC progression, providing a tool for cancer research in animal models.
Type:
text; Electronic Dissertation
Keywords:
Biomedical Engineering
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Biomedical Engineering; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Barton, Jennifer K.
Committee Chair:
Barton, Jennifer K.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleEvaluation of Mouse Models of Colorectal Cancer Using Optical Coherence Tomography and Laser Induced Fluorescence Spectroscopyen_US
dc.creatorHariri, Lida Pamelaen_US
dc.contributor.authorHariri, Lida Pamelaen_US
dc.date.issued2007en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractColorectal cancer (CRC) is the third leading cause of cancer related deaths. Rodent models of CRC are useful for evaluating diagnostic tools, therapeutics, and disease progression; however, an appropriate imaging tool is needed. Optical coherence tomography (OCT) is a non-destructive imaging modality readily packaged into small diameter endoscopes. Using a near- infrared light source, structural images are generated from index of refraction mismatches with resolutions of 2-15 mm at imaging depths of up to 1.3 mm. In contrast, laser-induced fluorescence (LIF) spectroscopy provides information about biochemical composition, exciting tissues with ultraviolet to green wavelengths of light to measure fluorescence emission from endogenous fluorophores such as NADH, collagen, and porphyrin.We apply OCT and LIF to mouse models of CRC, beginning with a comprehensive ex-vivo evaluation of normal mouse gastrointestinal (GI) tract in various strains and ages and secondarily sampled colorectal neoplasia and inflammatory bowel disease (IBD) using a combined in-air OCT/LIF system. A set of characteristic features of OCT images were developed for normal esophagus, small intestine, and colon; preliminary image feature criteria were also developed for colorectal neoplasia and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin. In the IBD sample, LIF emission displayed potentially diagnostic peaks at 635 and 670 nm, consistent with increased porphyrin production by bacteria associated with IBD.Next, endoscopic OCT/LIF was evaluated in an in-vivo serial study using a prototype 2 mm diameter endoscope to image the lower colon of ApcMin and control mice. Adenoma development over OCT imaging timepoints was characterized as a progressive mucosal thickening to frank mass formation. LIF spectral comparisons revealed decreased 405 nm intensity and the presence of a peak at 680 nm over adenoma.In a final study, ultrahigh resolution OCT (UHR OCT) was used to serially image the lower colon of azoxymethane treated A/J mice to monitor CRC progression and determine OCT's capability of identifying early disease. A panel of blinded mouse colon pathology experts assigned a diagnosis based on the OCT images, which was then compared to a histological diagnosis assigned by a blinded pathologist. At the final imaging timepoint, 95% of adenomas and 23% of gastrointestinal intraepithelial neoplasia (GIN, 38% protruding GIN and 9% non-protruding GIN) were correctly diagnosed. The panel identified 68% of disease foci (95% adenoma, 76% protruding GIN, and 13% non-protruding GIN). Over the OCT imaging timepoints, disease progression followed a typical succession, with normal or GIN preceding adenoma. Endoscopic UHR OCT enabled accurate diagnosis of adenomas, identification of protruding GIN, and non-destructive visualization of CRC progression, providing a tool for cancer research in animal models.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectBiomedical Engineeringen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineBiomedical Engineeringen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBarton, Jennifer K.en_US
dc.contributor.chairBarton, Jennifer K.en_US
dc.contributor.committeememberUtzinger, Ursen_US
dc.contributor.committeememberBesselsen, Daviden_US
dc.contributor.committeememberGmitro, Arthuren_US
dc.identifier.proquest2090en_US
dc.identifier.oclc659747198en_US
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