## 1 Introduction
When quantifying tissue components in vivo, these methods usually use near-infrared (NIR) wavelengths, especially in the 650-900 nm range where the absorption of water and fat is rather low. Therefore, spectroscopy-based methods may not be suitable for quantifications of proteins whose absorption peaks do not fall in this range of wavelengths. Fluorescence sensing methods may be used for quantifying the concentration of biological molecules, which may bond to extrinsic fluorophores. However, in most presented methods, the concentration estimation required usage of light propagation models combined with a priori knowledge of the tissue optical properties [8; 9; 10; 11; 12; 13; 14] or the usage of complex tomography systems [15; 16; 17; 18; 19; 20], which are less suitable for endoscopic applications. In addition, most of these methods usually involve an additional calibration process by normalizing the emission against the excitation [21], or normalizing multiple emission wavelengths [22]. Several groups have developed fluorescent probes suitable for the detection of [PERSON]'s disease. Many groups have focused on developing fluorescent probes with high affinity to amyloid-beta protein, which may image the amyloid plaques in the brain. [PERSON] et al. [23] have synthesized and tested a family of dyes (NIAD) that emit a characteristic fluorescence signal only when bound to amyloid-beta protein. They have showed changes in the fluorescence quantum yield, lifetime and emission spectra due to the binding of the probe to amyloid-beta. [PERSON] et al. [24]have described a high quantum yield NIR probe AOI987, penetrating the blood-brain barrier. They demonstrated the interaction of the probe with amyloid plaques in APP23 transgenic mice in vivo and showed increasing fluorescence intensity with increasing plaque load. [PERSON] et al. [25] designed and synthesized curcumin based NIR probes. The CRANAD-58 probe showed significant fluorescence property changes upon mixing with both soluble and insoluble A\(\beta\) species in vitro. They tested it in vivo and revealed that CRANAD-58 was capable of differentiating transgenic and wild-type mice as young as four months old. They have also designed the CRANAD-17 probe, which was capable of inhibiting A\(\beta\)42 cross-linking induced by copper. This raises a possibility for CRANAD-17 to be considered for AD therapy. [PERSON] et al. [26] report the optical profiles of THK-265, which has high binding affinity to amyloid plaques. They demonstrated that amyloid deposits in A\(\beta\)PP transgenic mice could be detected after intravenous administration of THK-265. They reported significantly higher fluorescence intensity in the brain of A\(\beta\)PP transgenic mice than in those of wild-type mice. [PERSON] et al. [27] have also used THK-265 to develop and test a procedure for cerebral amyloid deposits visualization. They demonstrated in vivo the correlation between the intensity of the THK-265 signal and the plaque burden, indicating its utility for direct monitoring of A\(\beta\) aggregation progression. [PERSON] et al. [28] report the synthesis, characteristics, and biological evaluations of a series of donor-acceptor molecules (DANIRs) as smart NIRF imaging probes for A\(\beta\) plaques in AD. These probes were proved to have affinity to A\(\beta\) plaques ex vivo, in vitro, and in vivo, with a significant fluorescence intensity increase and a blue-shift in the emission spectra. Other groups have tried to develop fluorescent probes with affinity to tau proteins. [PERSON] et al. [29] developed a class of tau ligands (PBBs) for optical and PET imaging. These included PBB5, a near-infrared fluorescent probe, which could assess tau accumulation in living mouse models. They demonstrated strong fluorescence of PBB5 in Tg mice expressing a single human four-repeat tau isoform (PS19) relative to non-Tg WT mice in the central nervous system (CNS) suggesting a concentration of this tracer in the PS19 spinal cord. [PERSON] et al.