Optical Probe for Near-Infrared ( NIR ) Fluorescence Signal Detection with High Optical Performance and Thermal Stability

We propose a new optical probe for near-infrared (NIR) fluorescence signal detection with high optical performance and thermal stability. The optical probe is composed of an optical source part for efficient excitation of NIR fluorescence signal, a heat dissipation part for stable operation of the NIR fluorescence probe, and an optical detection part for efficient detection of NIR fluorescence signal. From a simulation by use of an optical simulation tool, Light ToolsTM, we could confirm that the optical probe has optical propagation efficiency of 79.6% in case of using a circular detector with 20 cm in diameter located at 20 cm in distance from the optical source. From a measurement of temperature variation of the optical probe, we could also confirm that the optical probe has thermal stability with a standard deviation of 2.19 ̊C under room temperature condition. Finally, from an evaluation of fluorescence image quality, we could confirm that an optical noise which can bring on by overlapped band between optical spectrum of the optical source for fluorescence excitation and optical spectrum of the emitted fluorescence signal decreased effectively in the optical probe.


Introduction
NIR fluorescence imaging has been used to improve sentinel lymph node (SLN) mapping in breast cancer patients, to assess the extent of colorectal metastases during curative-intended surgery and so on because NIR has relatively low absorption and scattering rates in hemoglobin, water and lipid [1]- [8].LED based light sources have been used in image guided surgery, and in NIR fluorescence-guided surgery because of characteristics of long working distance, computer control, and spectral confinement (typical full width at half maximum, FWHM, 50 µm) and so on.Especially, LEDs come into the spotlight as light sources for medical use because LEDs with high power (more than 1 watt) have been developed recently.Actually, LEDs have been used in NIR fluorescence imaging system such as FLARE TM (Fluorescence-assisted resection and exploration) image guided surgery system and PDE TM (Photodynamic eye, Hamamatsu) [9]- [11].However, although optical power of LEDs has been improved, LEDs still have weaknesses to be considered in medical application such as heat, broad divergence angle, relatively broad spectrum and so on.
In this paper, we propose an optical probe for NIR fluorescence signal detection with high optical performance and thermal stability by making up for the weakness and strengthening the strength of LEDs with high optical power in the optical probe.

An Array of LEDs
Although LEDs with high optical power were developed recently, optical power of single LED is not still sufficient as a light source for medical purposes because of large divergence angle of LEDs.Therefore, an array of LEDs was introduced to overcome insufficient optical power as shown in Figure 1(a).The array of LEDs is composed of 16 LEDs (SP95MR-D2-1W-780, center wavelength: 780 nm, full width at half maximum: 30 nm, Innolight Co.) with each 1 W optical power.780 nm was selected as each LED's wavelength because ICG (Daiichi Sankyo Propharma Co.) which was used to evaluate characteristics of the optical probe has maximum excitation characteristic at 780 nm wavelength.LEDs were not installed in the midmost because the midmost was regarded as a position of a CCD camera (Guppy Pro 031B, Allied Vision Technology Co.) to detect fluorescence signal.power meter with large active area (about 30cm in diameter).So, we replaced the propagation efficiency measurement with optical simulation.In the simulation, a circular detector with 20 cm in diameter was considered as a comparison target of a human breast.Figure 2 shows simulation results of the optical intensity which was radiated from the optical probe.Also, Table 1 shows simulation results of the propagation efficiency of the optical probe system.Figure 3 shows the intensity variation of light to come into the detector according to distance variation from the optical probe.From the Figure 3, we could confirm that 12.73 watt out of total light power, 16 watt can propagate into the circular detector with 20 cm in diameter located at 20 cm in distance from the optical probe by use of the array of LEDs, the mirror and the collimating lenses (about 79.6% optical propagation efficiency).In this case, 20 cm in distance from the optical probe was considered as a minimum distance for efficient fluorescence detection in clinical application.

A Liquid Circulation Module for Heat Dissipation of the Array of LEDs
The array of LEDs generates much heat because the array of LEDs is composed of 16 high-power LEDs.The heat generated from the array of LEDs degrades image quality of the CCD camera because the array of LEDs is in contact with the CCD camera as shown in Figure 4(a).So, a liquid circulation module was introduced to cool down heat generated from the array of LEDs. Figure 5 shows the liquid circulation module.Antifreeze was injected into an inlet through a polymer tube and then antifreeze was released from an outlet after circulation in the liquid circulation module.Under operation of the array of LEDs, temperature on three regions (region 1, 2, and 3 in Figure 4(a)) of the optical probe was measured by an infrared thermometer (TK-307A, Tae Kwang Electronics Co.). Figure 6 shows the temperature variation of the optical probe during operation of the liquid    2 shows temperature variation data of the optical probe during operation of the liquid circulation module and operation of the array of LEDs.From Figure 6 and Table 2, we could confirm the liquid circulation module is very efficient to dissipate the heat generated from the array of LEDs.

A Short-Pass Edge Filter for Optical Noise Elimination of the Array of LEDs
Generally LEDs have broad spectral width (about 50 nm, Full Width at Half Maximum) unlike laser diodes (LDs).Although LED used as a light source for fluorescence excitation has a peak at 780 nm wavelength, it has wavelength components of 800 -830 nm band.The wavelength components can result in optical noise in fluorescence imaging because wavelength components of 800 -830 nm band may be detected by CCD camera after reflection by sample or other objects.To confirm the optical noise problem, ICG fluorescence imaging experiment was conducted with 740 nm LEDs (SP95MR-D2-1W-740, center wavelength: 740 nm, full width at half maximum: 30 nm, Innolight Co.) and 780 nm LEDs (SP95MR-D2-1W-780, center wavelength: 780 nm, full width at half maximum: 30 nm, Innolight Co.).We controlled optical power of 740 nm LEDs and 780 nm LEDs identical, respectively and checked the optical power with the optical power meter (PKIT-07-01, Newport).After check of equality in optical power of 740 nm LEDs and 780 nm LEDs, we put a piece of gauze including a coated part and a control part uncoated with ICG solution (1.25 µg/ml) as shown in Figure 7(a) on the optical power meter.light emitted from 780 nm LEDs was detected by the CCD camera and acted as optical noise in fluorescence imaging.To solve the optical noise problem, a short-pass edge filter (Edge wavelength: 820 nm, Green Optics, Korea) was arranged in front of 780 nm LEDs. Figure 7(d) shows the fluorescence image of ICG when 780 nm LEDs with the short-pass edge filter was used as the excitation light source.From Figure 7(d), we could confirm that 830 nm light emitted from 780 nm LEDs was effectively blocked by the short-pass edge filter and that fluorescence signals of ICG by excitation of 780 nm LEDs improved compared with those by excitation of 740 nm LEDs.In case of use of the short-pass edge filter, contrast (C) which is defined as Equaiton (1) increased from 0 to 0.89 in comparison with case of no use of the short-pass edge filter.
where I FL is intensity of fluorescence signal at the part coated with ICG solution and I BS is intensity of background signal at the control part uncoated with ICG solution in Figure 7.

Conclusion
In this paper, we propose an optical probe for NIR fluorescence signal detection with high optical performance and thermal stability.Propagation efficiency of light in the optical probe was improved by use of an array of LEDs, a mirror, and collimating lenses.Propagation simulation results of the optical probe showed propagation efficiency of 79.6% about a circular detector with 20 cm in diameter located at 20 cm in distance from the optical probe.Heat generated from the optical probe was efficiently dissipated by use of a liquid circulation module.Actually, temperature of the optical probe was maintained below 25˚C.Finally, optical noise of the optical probe which occurs by broad spectral width of LEDs was efficiently eliminated by use of the short-pass edge filter.Therefore, we believe that our optical probe for NIR fluorescence signal detection can provide excellent NIR fluorescence images with high quality in applications of clinical fields.

Figure 1 .
Figure 1.Pictures of (a) the array of LEDs and (b) the mirror for the array of LEDs.

Figure 2 .
Figure 2. Simulation results on propagation of the optical probe system at (a) 0 cm (b) 5 cm (c) 10 cm (d) 20 cm (e) 40 cm and (f) 80 cm distance from the probe.

Figure 3 .
Figure 3.The intensity variation of incident light into the detector.

Figure 4 .
Figure 4. (a) Block diagram and (b) picture of the optical probe for NIR fluorescence.

Figure 5 .
Figure 5. Liquid circulation module for heat dissipation of the array of LEDs.

Figure 6 . 8
Figure 6.Temperature variation of the probe during operation of the liquid circulation module.

Figure 7 (
b) and Figure 7(c) show the fluorescence images of ICG when 740 nm LEDs and 780 nm LEDs were used as the excitation light source, respectively.From Figure 7(b), we could confirm that fluorescence image with less optical noise could be acquired when 740 nm LEDs was used as the excitation light source and that fluorescence signals of ICG by excitation of 740 nm LEDs are very weak because ICG has maximum excitation characteristic at 780 nm wavelength.From Figure 7(c), we could confirm that 830 nm

Figure 7 .
Figure 7. (a) A piece of gauze to test fluorescence signals of ICG (b) fluorescence image by 740 LEDs (c) fluorescence image by 780 LEDs and (d) fluorescence image by 780 LEDs with a short-pass edge filter.
Part coated with ICG solution (10 mm in diameter) Control part uncoated with ICG solution (20 mm in diameter)

Table 1 .
Propagation efficiency of the optical probe system.

Table 2 .
Temperature variation data of the optical probe system during operation of the liquid cooling module under operation of the array of LEDs.