## 1 Introduction  
Colorectal cancer is the second leading cause of cancer-related death in the United States, and the American Cancer Society (ACS) estimates that 51,020 people will die in 2019 [1]. Various drugs have been evaluated to treat patients with advanced-stage cancer with conventional chemotherapeutic agents, such as monoclonal antibodies [2, 3], receptor tyrosine kinase inhibitors [3], and immune checkpoint inhibitors [4, 5]. However, despite these efforts, the five-year survival rate of stage IV colorectal cancer remains 14% [1], and resistance to chemotherapy, radiotherapy, and immunotherapy causes cancer treatment to fail [6]. Bacteria is a potential anti-tumor drug that can be used to overcome conventional therapeutic limitations [7]. Many types of bacteria species have the unique ability to invade and colonize solid tumors, resulting in the retardation of tumor growth and even tumor clearance in preclinical studies [8; 9; 10; 11]. In addition, bacterial infection activates host immunity and promotes a therapeutic effect [12; 13]. Salmonella is bacteria with multiple anti-tumor functions, including tumor targeting, intratumoral penetration, direct tumor killing, anti-angiogenic, and immune activation [14; 15; 16; 17]. Phase I clinical trials using salmonella have been allowed by the United State Food and Drug Administration (FDA) for advanced cancer patients [18; 19; 20]. The visualization of the bacteria is important to understand the biodistribution of the bacteria in vivo. Therefore, the fluorescence imaging techniques, which have characteristics including high-sensitivity, real-time imaging, and easy accessibility, are introduced. Fluorescence imaging enables the monitoring of the bacteria without euthanization of the animal tumor model. However, owing to the limited tissue penetration of light, the tumor needs to be located in a superficial area of the body [21; 22]. The majority of the preclinical bacterial therapies for colon cancer have used mouse models with subcutaneous xenograft tumors [23; 24]. It is convenient to evaluate tumor response by measuring the tumor size. However, the subcutaneous tumor model is less relevant to clinical cancer and has a limitation in representing both primary and metastatic sites [25; 26]. The orthotopic colon tumor model, in which the colon tumor locates on the mouse colon, is better in terms of understanding the biological features of cancer. Therefore, the fluorescence endoscopic approach may be an optimal tool to directly evaluate bacterial cancer therapy in the orthotopic colon tumor model. Fluorescence endoscopic systems have been widely used in colon cancer research. Wide-field fluorescence endoscopy (WFE) enables the early detection of small tumors with tumor-specific fluorescence materials in vivo [27]. WFE specialized for near-infrared fluorescence dye has demonstrated the early detection of dysplastic lesions with high efficiency [28]. Liquid-crystal tunable filter (LCTF)-equipped WFE has demonstrated multispectral fluorescence imaging with various target fluorescent materials in vivo [29]. However, these WFE systems only show gross, tissue-scaled images, rather than cellular-scaled images. The confocal fluorescence endomicroscopy (CFEM) system was introduced to obtain cellular-scaled colon imaging [30]. The CFEM has provided a detailed cellular structure of colon cancer [31; 32; 33; 34]. CFEM has demonstrated colonic mucosa in vivo with high resolution [35]. However, the CFEM system has a small field of view (FOV) and a short working distance. The tip of the CFEM probe should be in contact with the colonic mucosa. It is impossible to image the whole surface of the colon using CFEM. Therefore, it is important to identify suspicious colonic lesions prior to locating the CFEM probe. However, it is extremely difficult to identify suspicious small lesions with a wide-field endoscope under white-light imaging, especially in the early-stage tumors.