## 2 Materials and Method  
### Development of Dual-Scale Fluorescence Endoscopy System  
Figure 1a,b show a schematic diagram and photograph of the developed DSFE system, respectively. First, a rigid-type endoscope probe (HOPKINS II Telescope 27301 AA, [PERSON], Tuttlingen, Germany) was used to build up the WFE system as the guided sheath consisted of two probing paths with inner diameters of 3.0 mm and 1.0 mm, respectively. The larger path was utilized as the laser excitation and florescence-signal detection path of WFE, and the smaller path was used for the insertion of the CFEM probe. The guiding sheath had three channels: Main rigid endoscope (channel 1), air-pump connection for bowel inflation (channel 2), and working channel for an additional probe (channel 3). A high-power light emitting diode (LED) light source (TouchBright X6, Live Cell Instrument, Seoul,  
Republic of Korea) with intensity-adjustable multi LEDs of various wavelengths (405 nm, 480 nm, 525 nm, 630 nm, and white light) was connected to the light post of the endoscopic probe. A single color camera (acA1920-40 uc, Basler AG, Germany) for white-light imaging and a single monochrome camera (Retiga R1, Qimaging, Surrey, BC, Canada) for fluorescence imaging were used to capture white-light and fluorescence image signals, respectively. An achromatic lens (focal length = 50 mm, LA1131-A-ML, Thorlabs, NJ, USA) and a beam splitter (30:70 (Reflection:Transmission)), BS049, Thorlabs, NJ, USA) were assembled between the guiding sheath and detection cameras to simultaneously obtain images from the white-light and fluorescence cameras. The rotating filter wheel contained a green bandpass filter (FF01-540-50-25, Semrock, NY, USA) that was positioned before the fluorescence camera as an emission filter. An air pump (DK-200, DAE-KWANG electronics, Seoul, Republic of Korea) was applied via channel 2 to optimize the colon-imaging condition inside the mouse colon. Using the developed WFE system, we could observe the internal condition of the colon in real time (i.e., 29 frames per second (fps) for white-light imaging and 10 fps for fluorescence imaging), as depicted in Figure 1d. The FOV and spatial resolution at a working distance of 5 mm using the USAF 1951 resolution target (R3L3S1P, Thorlabs, NJ, USA) were 7.5 mm and 57.0 line-pair/mm, respectively.  
After the WFE system was set up, a commercial CFEM system (Cellvizio DualBand(r), Mauna Kea Technologies, Paris, France) with two excitation-wavelength lasers (488 nm and 660 nm, respectively) and two emission filters (502--633 nm and 673--800 nm, respectively) with tunable fluorescence imaging speed (9 to 12 fps) were integrated with the WFE system to generate DSFE by inserting the confocal probe into channel 3 (Figure 1c). Because channel 3 is directly connected to the smaller path of the guiding sheath, the probe of CFEM was able to reach the targeted area easily. Flexible CFEM probes (Mini Z, Mauna Kea Technologies, Paris, France) with a 0.94-mm diameter were used for mouse  
Figure 1: Dual-scale fluorescence endoscopy (DSFE) system. (**a**) Scheme of major component of the DSFE system. (**b**) Corresponding photography of the DSFE system. Inset photography shows three channels of the guiding sheath. (**c**) Magnified endoscopy tip of the fused DSFE probe. The tip diameter of the wide-field fluorescence endoscope (WFE) and confocal fluorescence endomicroscopy (CFEM) probes are 1.9 mm and 0.94 mm, respectively. (**d**,**e**) In vivo white-light WFE endoscopic images of inside the mouse colon with orthotropic mouse colon tumor (T) and the laser emitting from the CFEM probe into the tumoral area.  
-colonic endomicroscopic examination. Moreover, the FOV and spatial resolution of the CFEM probes were 325 \(\upmu\)m and 3.5 \(\upmu\)m, respectively.