The advent of both powerful small animal imaging techniques and a diverse array of genetically defined mouse models of human cancer have provided a unique opportunity to establish novel preclinical protocols for monitoring tumor growth in vivo. Numerous reports now document the use of magnetic resonance imaging (MRI) to image spontaneous tumors of the colon, brain, prostate, stomach and breast.1–5
Although a number of additional image-based techniques have been established for the detection of colorectal adenomas and cancers in humans, including virtual colonoscopy, double-contrast barium enemas, computed tomography (CT) and positron emission tomography (PET), their routine use in rodents has been hindered by the need for the miniaturization of complex equipment, lack of portability and cost. Colonoscopy remains the most widely used tool for screening patients at increased risk for colorectal cancer,6
providing high sensitivity and specificity for lesion detection and surveillance. In addition, the procedure is well tolerated, low risk, relatively inexpensive and, unlike PET and CT, does not require highly specialized, automated instrumentation.
For more than a decade, the Apc+/Min
mouse model has been used extensively to evaluate the efficacy of chemopreventive agents against colon cancer.7
However, only a limited number of groups have demonstrated their success in obtaining images of the mouse colon using microendoscopes2,4,8
and microcomputed tomography colonography.9
Following early efforts by Huang et al,8
Becker and colleagues2
published a detailed protocol for capturing high-resolution images of the mouse colon using a rigid endoscope. In parallel with this development, Funovics and colleagues3,4
have developed a multichannel fluorescence endoscope for the detection of exogenous fluorophores in lesions of the mouse colon. Use of the conventional Apc+/Min
mouse for the majority of these studies has been problematic due to the predominance of small intestinal adenomas and few if any colorectal adenomas in these animals.10
This deficiency has precluded the establishment of a reliable method for quantifying lesion size in vivo.
A unique strain of mice (Apc+/Min-FCCC
) has been established by this group, which spontaneously develops multiple colorectal adenomas;11
thus representing an ideal system in which to establish endoscopic protocols for the detection of colorectal lesions. Use of the Apc+/Min-FCCC
mouse strain facilitated the first detection of colon adenomas by MRI.12
MRI represents a noninvasive method for adenoma detection, the acquisition of high-resolution images of anatomical structures, and a means for accurate serial measurement of solid tumor volumes in animal models.12–14
Although attempts have been made to grade colon adenomas based on their size relative to the circumference of the colon,2
accurate measurement of the area/volume of colon lesions in vivo has not been reported to date.
The goal of the present study was to develop an endoscopy-based protocol for the accurate estimation of adenoma size in vivo from images obtained during colonoscopic examinations. While the methods are similar in principle to those currently in use for human colonoscopy, such as open biopsy forceps or linear probe methods,15–18
the highly restricted geometry of the mouse colon and the large size of the adenomas relative to the diameter of even the fully insufflated lumen of the colon make it necessary to employ a modified technique involving a geometrical construction of the measuring probe. A strong correlation of the resulting size estimates with those obtained by MRI and at necropsy supports the future use of endoscopy to monitor adenoma growth and response to therapeutic intervention in animal models over time.