Task-based imaging of colon cancer in the Apc(Min/+) mouse model

The University of Arizona, Tucson, Arizona, United States
Applied Optics (Impact Factor: 1.78). 06/2006; 45(13):3049-62. DOI: 10.1364/AO.45.003049
Source: PubMed


Optical coherence tomography (OCT), laser-induced fluorescence (LIF), and laser-scanning confocal microscopy (LSCM) were used for the task of multimodal study of healthy and adenomatous mouse colon. The results from each modality were compared with histology, which served as the gold standard. The Apc(Min/+) genetic mouse model of colon cancer was compared with wild-type mice. In addition, a special diet was used for the task of studying the origins of a 680 nm autofluorescent signal that was previously observed in colon. The study found close agreement among each of the modalities and with histology. All four modalities were capable of identifying diseased tissue accurately. The OCT and LSCM images provided complementary structural information about the tissue, while the autofluorescence signal measured by LIF and LSCM provided biochemical information. OCT and LIF were performed in vivo and nondestructively, while the LSCM and histology required extraction of the tissue. The magnitude of the 680 nm signal correlates with chlorophyll content in the mouse diet, suggesting that the autofluorescent compound is a dietary metabolite.

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    • "Autofluorescence of skin, fur, and tissue, due to several cellular components, including NADPH, flavin coenzymes, elastin, and collagen, can interfere significantly with signal from fluorescent reporters if emission wavelengths overlap (Figure 2) [6]. Additionally, chlorophyll present in standard mouse food autofluoresces thus interfering with many common reporters [7]. To compensate for autofluorescence, software has been developed with advanced mathematical modeling to separate the sources of different wavelengths. "
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    ABSTRACT: The detection and subsequent quantification of photons emitted from living tissues, using highly sensitive charged-couple device (CCD) cameras, have enabled investigators to noninvasively examine the intricate dynamics of molecular reactions in wide assortment of experimental animals under basal and pathophysiological conditions. Nevertheless, extrapolation of this in vivo optical imaging technology to the study of the mammalian brain and related neurodegenerative conditions is still in its infancy. In this review, we introduce the reader to the emerging use of in vivo optical imaging in the study of neurodegenerative diseases. We highlight the current instrumentation that is available and reporter molecules (fluorescent and bioluminescent) that are commonly used. Moreover, we examine how in vivo optical imaging using transgenic reporter mice has provided new insights into Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Prion disease, and neuronal damage arising from excitotoxicity and inflammation. Furthermore, we also touch upon studies that have utilized these technologies for the development of therapeutic strategies for neurodegenerative conditions that afflict humans.
    Full-text · Article · Jul 2014 · BioMed Research International
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    • "Specifically, studies have investigated the interaction of fat content in the diet and genetic susceptibility to colon cancer in the Apc Min/+ mouse model. Because mutations in Adenomatous Polyposis Coli (APC) was observed in over 80% of sporadic human colon cancer cases [44-46], Apc Min/+ mice carrying a dominant mutation in the Apc gene commonly serve as the mouse model of choice for the human Familial Adenomatous Polyposis (FAP) syndrome. Apc Min/+ mice spontaneously develop multiple intestinal neoplasia (Min) and numerous intestinal polyps, which increase in number and accelerate in development in response to a high fat diet [47]. "
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    ABSTRACT: BackgroundTo determine how diets high in saturated fat could increase polyp formation in the mouse model of intestinal neoplasia, Apc Min/+ , we conducted large-scale metabolome analysis and association study of colon and small intestine polyp formation from plasma and liver samples of Apc Min/+ vs. wild-type littermates, kept on low vs. high-fat diet. Label-free mass spectrometry was used to quantify untargeted plasma and acyl-CoA liver compounds, respectively. Differences in contrasts of interest were analyzed statistically by unsupervised and supervised modeling approaches, namely Principal Component Analysis and Linear Model of analysis of variance. Correlation between plasma metabolite concentrations and polyp numbers was analyzed with a zero-inflated Generalized Linear Model.ResultsPlasma metabolome in parallel to promotion of tumor development comprises a clearly distinct profile in Apc Min/+ mice vs. wild type littermates, which is further altered by high-fat diet. Further, functional metabolomics pathway and network analyses in Apc Min/+ mice on high-fat diet revealed associations between polyp formation and plasma metabolic compounds including those involved in amino-acids metabolism as well as nicotinamide and hippuric acid metabolic pathways. Finally, we also show changes in liver acyl-CoA profiles, which may result from a combination of Apc Min/+ -mediated tumor progression and high fat diet. The biological significance of these findings is discussed in the context of intestinal cancer progression.ConclusionsThese studies show that high-throughput metabolomics combined with appropriate statistical modeling and large scale functional approaches can be used to monitor and infer changes and interactions in the metabolome and genome of the host under controlled experimental conditions. Further these studies demonstrate the impact of diet on metabolic pathways and its relation to intestinal cancer progression. Based on our results, metabolic signatures and metabolic pathways of polyposis and intestinal carcinoma have been identified, which may serve as useful targets for the development of therapeutic interventions.
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    • "However, a fasting time of about 6 hours is suggested as an effective way to ensure uniformity in some studies such as positron emission tomography with F-FGD (Hildebrandt et al. 2008). In addition, when optical imaging is performed, it is necessary to consider dietary composition because food components such as chlorophyll can be a source of background autofluorescence (McNally et al. 2006). Mice should always have free access to water, even shortly before general anesthesia. "

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