Development of an Optical Tissue Clearing Laser Probe System

Abstract

Although low-level laser therapy (LLLT) has been a valuable therapeutic technology in the clinic, its efficacy may be reduced in deep tissue layers due to strong light scattering which limits the photon density. In order to enhance the photon density in deep tissue layers, this study developed an optical tissue clearing (OTC) laser probe (OTCLP) system which can utilize four different OTC methods: 1) tissue temperature control from 40 to 10℃; 2) laser pulse frequency from 5 to 30 Hz; 3) glycerol injection at a local region; and 4) a combination of the aforementioned three methods. The efficacy of the OTC methods was evaluated and compared by investigating laser beam profiles in ex-vivo porcine skin samples. Results demonstrated that total (peak) intensity at full width at half maximum of laser beam profile when compared to control data was increased: 1) 1.21(1.39)-fold at 10℃; 2) 1.22 (1.49)-fold at a laser pulse frequency of 5 Hz; 3) 1.64 (2.41)-fold with 95% glycerol injection; 4) 1.86 (3.4)-fold with the combination method. In conclusion, the OTCLP system successfully improved the laser photon density in deep tissue layers and may be utilized as a useful tool in LLLT by increasing laser photon density.

Low Temperature-Mediated Enhancement of Photoacoustic Imaging Depth

“…The temperature dependency of the Grüneisen parameter has previously been explored in several studies [8,[10][11][12][13][14][15][16][17][18]20]. There are also studies showing the temperature dependency of the scattering coefficient of the tissue [19][20][21][22][23][24]. There is not sufficient evidence about how the absorption coefficient of tissue alters with temperature, particularly in the range of temperature investigated in our study [22][23][24].…”

“…Troy et al reported a positive scattering coefficient change for prostate tissue [22]. Yeo et al studied the porcine and found an increase in the scattering coefficient with the temperature rise [20].…”

“…The temperature dependency of the Grüneisen parameter has previously been explored in several studies [8,[10][11][12][13][14][15][16][17][18]20]. There are also studies showing the temperature dependency of the scattering coefficient of the tissue [19][20][21][22][23][24].…”

Optical clearing based cellular-level 3D visualization of intact lymph node cortex

“…The most frequently used approach is replacing interstitial fluids (RI~1.33) in inter-and intra-cellular space with optical clearing agents (OCAs) which have refractive indices of ~1.46, matched to the average refractive index of most biological samples. It has been demonstrated that several OCAs such as glycerol [26- [30][31][32] and BABB [33] can enhance imaging depth in various organs such as brain [22][23][24][25][26], skin [27][28][29], pancreas [30], colon [31] and heart [32][33][34]. However, optical clearing effect of OCAs on LN has not yet been clearly demonstrated.…”

“…For the last decade, optical clearing technique to improve the imaging depth has been actively investigated [21][22][23][24][25][26][27][28][29][30][31][32][33][34]. As the mismatch in refractive index (RI) between cellular components in tissue is the major cause of light scattering, selective removal of cellular components with relatively low or high refractive index can reduce the light scattering and make the tissue more optically transparent.…”