Multi-Modality Study of Mouse Colon Cancer

Introduction

Colorectal cancer (CRC) is the third most common form of cancer in both men and women in the United States. CRC will account for an estimated 11% of new cancer cases and 10% of cancer fatalities in 2004. Early detection is essential as CRC has a 5 year survival rate of 90% when detected at an early stage. The survival rate drops to less than 10% after metastasis. Unfortunately, only 38% of CRC cases are discovered in the early stagei.

New tools that minimize the invasiveness of screening, aid early detection and enable the serial monitoring of disease progression and therapies for CRC are needed. There are multiple scenarios under which these tools must function. In vivo, minimally invasive imaging tools are needed for both human patients and the mouse models that are used to develop and test therapies. Ex vivo, non-destructive imaging is needed to determine tissue function and structure with minimal artifacts. Ex vivo, histology, a destructive imaging technique, provide the gold standard for diagnosis and tissue evaluation.

Multi-Modality Study of Mouse Colon Cancer

Optical coherence tomography (OCT), laser induced fluorescence (LIF) and laser scanning confocal microscopy (LSCM) are used to study healthy and adenomatous mouse colon. The results from each modality are then compared to histology, which serves as the gold standard. The ApcMin strain of mice is used as a model of colon cancer. This is the same genetic mutation that causes familial adenomatous polyposis, an inherited CRC condition, in humans. In addition, special diets are used to study the origins of autofluorescent signals that have previously been observed in colon.

Our studies have found close agreement among each of the modalities and with the histology. All four modalities were accurately able to identify diseased tissue state. The OCT and LSCM images provided complementary structural information about the tissue sample. The autofluorescence signal measured by LIF and LSCM provided biochemical information about the tissue sample. In the current study, OCT and LIF were performed in vivo and non-destructively using our dual modality OCT-LIF endoscope, while the LSCM and histology analysis required the extraction of the tissue. The origin of a 680nm signal appears to correlate with mouse diet, suggesting that the autofluorescent source is a dietary byproduct.


Figure 1.OCT image and corresponding LIF spectra of healthy colon taken from a high chlorophyll diet mouse. The LIF emission peaks at 390nm and 450nm with an absorption dip at 420nm is typical of healthy tissue. The presence of a distinct peak at 680nm is visible throughout the colon as well. External to the colon, other tissues, such as adipose tissue and pancreas, are visible.


Figure 2. Average and standard deviation of absolute intensity of LIF signal at 680nm in normal diet mice (#1-#9) and high chlorophyll diet mice (#10-#18). The 680nm autofluorescent emission appears to correlate with mouse diet. A student t-test confirms that he means of the 680nm signal in each group are statistically significant at p << 0.01.

Technological Developments

A new, higher resolution OCT system is being developed for use in the study of mouse colon cancer. The current system is not able to resolve the crypt structures in the colon. It is our hope that with the new system, we will be better able to resolve early disease state in the structure of the colon. Combined with the biochemical information from LIF (also being integrated into the new system), we hope to further demonstrate the diagnostic potential of OCT and LIF.

Researchers

Primary: James McNally and Jennifer Barton

Additional: Alex Tumlinson, Lida Hariri, Ned Kirkpatrick, Urs Utzinger, Eugene Gerner

Funding

This work was supported in part by grants from the National Institutes of Health (CA109385) and the Specialized Program of Research Excellence (CA095060).

For additional information contact James McNally.

iCancer Facts and Figures 2004 (American Cancer Society, Atlanta, GA, 2004). http://www.cancer.org/downloads/STT/CAFF_finalPWSecured.pdf
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