Open Access
Add to BibSonomy
Abstract
Picosecond Nd:YAG lasers using diffractive optical elements (DOE) and micro-lens arrays (MLA) have widely been used in dermatology for the treatment of pigmented lesions and skin rejuvenation. This study designed and developed a new optical element of diffractive micro-lens array (DLA) by combing the features of DOE and MLA in order to achieve uniform and selective laser treatment. Both optical simulation and beam profile measurement demonstrated that DLA created a square macro-beam consisting of multiple micro-beams in a uniform distribution. Histological analysis confirmed that the DLA-assisted laser treatment generated micro-injuries at various skin depths from the epidermal layer to the deep dermal layer (up to 1200 µm) by adjusting the focal depths while DOE showed shallow penetration depths and MLA created non-uniform micro-injury zones. The DLA-assisted picosecond Nd:YAG laser irradiation can provide a potential benefit for pigment removal and skin rejuvenation via uniform and selective laser treatment.
© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
1. Introduction
Picosecond Nd:YAG laser with a very short pulse duration (several hundred picoseconds) and a high peak power has widely been used in dermatology for treatment of pigmented lesions, resurfacing, and skin rejuvenation [1,2]. The laser can deliver optical energy to target chromophores with no or minimal damage to the surrounding tissue because of selective photopyrolysis. To achieve the selective photothermolysis, the wavelength of laser should be preferentially absorbed by the target chromophores. The picosecond Nd:YAG laser can irradiate 1064 nm light on the skin to target the specific chromophores, such as melanin, hemoglobin, and water [3,4]. In addition, the laser pulse duration is as important as the wavelength for the target chromophores to prevent the diffusion of thermal energy into the surrounding tissue. In order to minimize collateral damage to the surrounding tissue and to deliver light energy intensively to the target chromophore, the pulse duration should be equal to or shorter than the thermal relaxation time (TRT) of the target chromophores [5]. Thus, the pulse duration of several hundred picoseconds is 100-fold shorter than TRT of the skin chromophores (∼50 ns), leading to effective ablation and no or minimal thermal injury in the skin.
For effective skin treatment, picosecond Nd:YAG laser light is often used with optical elements, such as diffractive optical element (DOE) and micro lens array (MLA) [6–8]. The purpose of using DOE or MLA is the application of multiple micro-beams with high power density on skin. The multiple micro-beams induce cavitation (or vacuoles) in the epidermis and dermis [9–11]. The laser-induced vacuolization can generate micro-injury in the skin, and clinical evidences have reported skin rejuvenation resulting from the application of the micro-injury [12,13]. However, the picosecond Nd:YAG laser treatment using DOE and MLA still suffers from a difficulty of treating the deeper regions of the skin (DOE) or entailing a uniform distribution of the vacuolization (MLA). Our previous study reported that DOE induced uniform vacuolization merely up to 400 µm below skin surface (near the basal membrane), which corresponds to the target depth for pigment removal. DOE homogenizes the incident laser light as a holographic beam splitter and thus achieves the uniform distribution of the micro-beams. However, the homogenization process diminishes the applied laser energy, which eventually limits the optical penetration in the skin tissue. In the case of MLA, the vacuoles were formed deeper in the skin (around 700 µm), which is the target depth for skin rejuvenation, but their spatial distribution was non-uniform (Gaussian-like) in the treated region [14,15]. Typically, the uniform distribution can attribute to selective skin treatment with minimal injury as well as better wound healing.
The goal of the current research was to develop a new optical element, diffractive micro-lens array (DLA), that enables deep and uniform laser treatment of pigments in a multi-layered skin tissue. As aforementioned, DOE and MLA suffer from shallow treatment depth and less uniform treatment, respectively. It is thus hypothesized that the combined features from DOE and MLA may obtain uniform and deep laser treatment of subcutaneous pigments at various depths in the skin to improve clinical outcomes. Figure 1 illustrates the schematics of handpiece designs with three optical elements: (a) DOE, (b) MLA, and (c) DLA (combination of DOE and MLA). The performance of the three optical elements was analyzed in terms of optical simulations, macro-beam patterns, and micro-beam distributions. Ex vivo skin tissue was tested with picosecond Nd:YAG laser light by using the three optical elements, and histological analysis was conducted to elucidate the optical and thermal responses of the tissue to the three optical elements.
Fig. 1. Schematic handpiece designs with three optical elements: (a) DOE, (b) MLA, and (c) DLA. Picosecond Nd:YAG laser light (red arrows) was perpendicularly incident on the skin tissue surface. Note that each tissue demonstrates the corresponding beam profile (DOE = diffractive optical elements; MLA = micro-lens array; DLA = diffractive micro-leans array; FL = focal lens; BP = beam profile).
2. Materials and methods
2.1 Light source
For experiments, picosecond Nd:YAG laser (wavelength = 1064 nm, pulse duration = 450 ps at full width at half maximum (FWHM); Picore, Bluecore Company, Busan, Republic of Korea) was used with three different handpieces: diffractive optical element (DOE; fused silica, macro-beam size = 4 mm in rectangular shape, micro-beam diameter (at image plane) = 165 µm, 49 micro-beams, focal length = 40 mm; Bluecore Company, Busan, Republic of Korea), micro-lens array (MLA; fused silica, macro-beam diameter = 4 mm in circular shape, micro-beam diameter (at image plane) = 220 µm, 37 micro-beams, focal length = 38.6 mm; Bluecore Company, Busan, Republic of Korea) handpiece, and diffractive micro-lens array (DLA). The DLA handpiece consisted of a combination of DOE and MLA and had variable focal depths (FDs) from the tip of the handpiece ranging from 0 (direct contact) to 6 mm. The picosecond laser system component had an articulated arm that delivered laser beam to a target tissue. Each hand-piece was mounted on the end of the articulated arm. The applied irradiances were 5.6 GW/cm2 for DOE and DLA and 7.1 GW/cm2 for MLA (single pulse energy = 400 mJ with stability of ≥ 90%). The corresponding fluences were 2.5 J/cm2 for DOE and DLA and 3.1 J/cm2 for MLA. It should be noted that MLA yielded a slightly higher fluence than DOE and DLA because of the smaller beam area (i.e., circle). A pyroelectric energy sensor (PE50BF-DIF-C, Ophir, Jerusalem, Israel) in conjunction with an energy meter (Vega, Ophir, Jerusalem, Israel) was used for energy calibration prior to each experiment in order to minimize any experimental errors. Figure 1 presents schematic handpiece designs using three optical elements: (a) DOE, (b) MLA, and (c) DLA. The red regions in tissue represent the corresponding beam profiles from the handpieces.
2.2 Laser beam simulation
A spatial distribution of the laser beam from each handpiece was simulated by using an optical design program (ZEMAX 13 release 2/premium, Non-Sequential Mode, Kirkland, WA, USA). The optical simulation was performed to estimate the laser beam profiles observed at the distance corresponding to the length of the handpiece. In the simulation, the wavelength of the light source was 1064 nm. The arrangement and specifications of an optical system were set based on focal lengths and the measured distance between optical elements (DOE and MLA; fused silica) and a focal lens (N-BK7). The parameters for DOE were calculated by following the HOLO/OR LTD’s tutorial on the Design and integration of 1D and 2D diffractive beam splitters (multi-spot) into optical systems in sequential and non-sequential modes of ZEMAX. A MS-219-I-Y-A (HOLO/OR) product was used to have a grating period (Λ) of 86.902 µm and a line/µm (1/Λ) of 0.012. For MLA, a spherical lens (focal length = 38.6 mm) with Extruded in Object Type section of Non-Sequential Mode was used to make a hexagonal micro-lens. The hexagonal lens was thus combined with both Boolean and Array functions to create the micro-lens array. DLA was constructed by arranging DOE and MLA in line on the optical pathway. DOE was positioned first in the optical pathway, the focal length was corrected with a plano-convex lens, and MLA was positioned last. Finally, a rectangular detector was employed in the simulated system in order to acquire the laser beam profiles through the Detector Viewer window.
2.3 Detection of beam profiles
To verify optical simulation results, laser beam profile was detected with three handpieces. Each handpiece was horizontally positioned, and both a neutral density filter (LBP2-ND3, 0.05-2% Transmission, Newport Corporation, CA, USA) and a laser beam profiler (LBP2-HR-VIS3, 190-1100 nm Silicon CCD, 1624 × 1224 Pixels, Newport Corporation, CA, USA) were situated at the end of the handpiece. The applied pulse energy was set at 1 mJ (fluence = 8 mJ/cm2) to prevent any color saturation in the acquired beam images.
2.4 Ex vivo experiments
Dark pigmented porcine skin samples (Minipig; age = 4 months; weight = 16-20 kg) were procured from CRONEX Corp. (Hwaseong, Republic of Korea) to evaluate tissue responses to picosecond laser with three handpieces (DOE, MLA and DLA) in ex vivo model. The flesh skin samples were prepared by storing in an insulated box with ice the day after euthanasia. The tissue samples were sectioned in 25 × 25 mm2 with 7 to 10 mm in thickness. Prior to laser irradiation, each handpiece was positioned vertically to the sectioned tissue surface. The macro-beam size was 4 × 4 mm2 in a square shape (DOE and DLA) and 4 mm in diameter (MLA). The applied laser fluences were 2.5 J/cm2 for DOE and DLA and 3.1 J/cm2 for MLA, and a single shot was applied for the laser treatment. The laser irradiation with each handpiece was repeated five times (N = 5). The effect of FD on the tissue was evaluated by applying four different FDs (0, 2, 4, and 6 mm) under the same irradiation condition.
Laser-irradiated skin tissues were harvested and fixed in a 10% neutral formalin solution (Sigma Aldrich, St. Louis, Missouri) for seven days according to a pathologist’s recommendation. The tissues were embedded in paraffin blocks and sliced in ∼6 µm thickness. For histological analysis, the tissues were stained with hematoxylin and eosin (HE). The stained tissue slides were evaluated by using an optical microscope (Leica DM500, Leica, Wetzlar, Germany) to observe various tissue responses to picosecond laser light with three handpieces qualitatively and quantitatively. The extent of irreversible thermal injury (vacuole or thermal disruption) in the tissue was quantified in terms of size and depth for comparison by using Image J (National Institute of Health, Bethesda, MD, USA).
3. Results
3.1 Beam profile simulation
Figure 2(a) demonstrates the beam profiles emitted from three different handpieces (DOE, MLA, and DLA) acquired by optical simulations. Each beam profile was formed on the plane of the distal end of the handpiece. The beam profile of the DOE handpiece consisted of 49 micro-beams (7 × 7 dots) in a macro-beam (4 × 4 mm2). Each micro-beam size was 100 µm in diameter and uniformly distributed. Unlike DOE, the MLA handpiece showed a total of 127 micro-beams (including all energy levels) in a circular macro-beam (diameter = 6.8 mm). The highest intensity of the micro-beams occurred at the center, but the micro-beam intensity gradually decreased and became the lowest at the margin of the MLA macro-beam. It was noted that the micro-beam size varied from 198 µm (center) to 149 µm (margin). The DLA handpiece showed a square macro-beam (4.6 × 4.6 mm2) consisting of 49 micro-beams (7 × 7 dots) in a uniform distribution, similar to the DOE handpiece. However, each micro-beam size was 502 µm in diameter, which was larger than that from the DOE handpiece.
Fig. 2. Numerical simulations (a and b) and corresponding beam profiles (c and d) of DOE, MLA, and DLA: (a) simulated beam patterns at focal plane, (b) cross-sectional view of irradiance along line (á-á´) in (a), (c) measured beam profiles at focal plane, and (d) cross-sectional view of irradiance along line (ć-ć´) in (c).
Figure 2(b) exhibits cross-sectional views of the beam profiles acquired from the lines (á-á´) in Fig. 2(a). Both DOE and DLA handpieces showed a uniform distribution of micro-beams in an equivalent macro-beam size. However, the DOE micro-beams yielded two-fold higher irradiances (I in W/cm2) in a narrower intensity distribution whereas the DLA micro-beams had lower irradiances in a wider distribution (i.e., larger micro-beam size with lower irradiance). The MLA handpiece demonstrated a Gaussian distribution of the micro-beams, of which the maximum intensity occurred at the center. Although the micro-beam intensities were comparable between DOE and MLA (center), the MLA micro-beam size (center) was two-fold larger than the DOE micro-beam size. It should be noted that the red dashed lines in Fig. 2(b) represent the contours of the micro-beam irradiances.
3.2 Beam profile detection
Figures 2(c) and 2(d) present the actual beam profiles measured from three handpieces. Similar to Fig. 2(a), DOE handpiece showed a rectangular beam profile (4 × 4 mm2) with 49 micro-beams (7 × 7 dots; size = 50 µm). MLA handpiece yielded a total of 37 micro-beams (size = 100 µm) in a circular macro-beam with a dimeter of 4.8 mm. Compared to the simulation results, the smaller micro-beam size could result from application of low laser energy to prevent light saturation for the beam profile measurements. The difference between the number of micro-beams and the macro-beam size in the simulation occurred as the laser beams with low energy were hardly detected by the beam profiler. The DLA handpiece showed a square macro-beam pattern (4.3 × 4.3 mm2) with a total of 48 micro-beams, and each micro-beam size was 500 µm. Both the simulations and the experimental measurements showed a good agreement on the spatial distributions of macro- and micro-beams (Figs. 2(b) and 2(d)).
3.3 Histological analysis
Figure 3 shows HE-stained images of ex vivo porcine skin tissue after picosecond Nd:YAG laser irradiation with DOE, MLA and DLA. Both DOE and MLA handpieces induced vacuoles in the treated tissue. In the case of the DOE handpiece, the vacuoles were mainly created near the basal membrane in the epidermal layer without damage to the stratum corneum. The MLA handpiece presented noticeable thermal damage to the stratum corneum (partial surface ablation), but the formation of the vacuoles was deeply and widely distributed in the dermal layer. On the other hand, the DLA handpiece showed that the dermis was partially torn and discolored (dark purple regions) with no vacuolization. These histological features evidenced a result of laser-induced mechanical and thermal damage in the tissue, which was called as thermal disruption (TD) in the current study. It should be noted that the formation of the vacuoles (DOE and MLA) or TD (DLA) well corresponded to the spatial distributions of the incident laser beam, which is shown at the top of the images (red areas) in Fig. 3.
Fig. 3. Histological analysis of porcine skin tissue after picosecond Nd:YAG laser irradiation with DOE, MLA, and DLA: Picosecond Nd:YAG laser light was incident perpendicularly on the skin tissue surface with each optical element beam profile (red in top images; 40X). Note that the yellow solid lines in H&E-stained histological images (bottom; 200X) represent laser-induced vacuoles (V) by DOE and MLA) and thermal decomposition (TD) by DLA, respectively.
Figure 4 quantitatively compares the maximum penetration depths (MPDs) of irreversible thermal injury (vacuoles for DOE and MLA and TD for DLA) in porcine skin tissue after picosecond laser treatment. The DOE handpiece created the smallest MPD in the skin (406 ± 106 µm) while the MLA handpiece yielded a two-fold larger MPD than the DOE handpiece (793 ± 271 µm; p < 0.001). On the other hand, the DLA handpiece (FD = 6 mm) generated the largest MPD of 1113 ± 130 µm (p < 0.05 vs. DOE and MLA).
Fig. 4. Quantitative comparison of maximum penetration depth (MPD in µm) in porcine skin tissue after picosecond laser treatment with DOE, MLA, and DLA (***p < 0.001 DOE vs. MLA; ***p < 0.05 DLA vs. DOE and MLA).
3.4 DLA evaluations
Figure 5(a) shows HE-stained histological images (10×) of skin tissue after DLA-assisted laser treatment at various FDs. Yellow dashed lines represent the formation of TD in the tissue, which corresponded to the discolored region with the directional tissue disruption. Overall, the depth of the TD increased with FDs. FD = 0 mm created the shallowest TD solely in the epidermis (E) while FD = 6 mm induced the deepest TD distributed in the intermediate region of the dermis (ID) and reticular dermis (RD). Figure 5(b) quantifies the penetration depth of the TD at various FDs (N = 20 per FD). FD = 0 mm yielded the shallowest penetration of the TD (57 ± 21 µm) with the minimal distribution in the epidermal layer. Similar to Fig. 5(a), the penetration depth gradually increased with FDs. When FD = 2 mm, the TD primarily occurred between papillary dermis (PD) and ID (371 ± 230 µm). FDs of 4 mm and 6 mm entailed the TD in the ID (587 ± 261 µm) and RD (763 ± 356 µm), respectively. It was noted that FD = 6 mm created the deepest TD in a wider distribution in the tissue. Table 1 summaries tissue responses and the extent of irreversible thermal injury after picosecond laser treatment with DOE, MLA, and DLA.
Fig. 5. Quantitative analysis of porcine skin tissues after DLA-assisted laser irradiation at various focal depths (FD): (a) H&E-stained histological images (40X) captured at various FDs (0, 2, 4, and 6 mm). Yellow dotted areas represent laser-induced thermal decomposition (TD) in tissue. (b) Quantitative analysis on penetration depth of TD for each FD measured from histological images (N = 20). Note that different background colors in (b) represent various skin layers (E = epidermis; PD = papillary dermis; ID = intermediate region of the dermis; RD = reticular dermis).
Table 1. Summary of tissue response and treatment depth after laser treatment with DOE, MLA, and DLA
Figure 6 shows a quantitative comparison of TD area as a function of TD depth at four different FDs. Evidently, the TD area increased with the TD depth. When FD = 0 mm, the TD with an average area of 269 µm2 was formed limitedly in the epidermal layer. FD = 2 mm distributed the TD with an average area of 284 µm2 over PD and ID. When FD = 4 mm, the TD with an average area of 436 µm2 was mostly generated in ID, and the partial TD was formed at the interface between ID and RD. FD = 6 mm created the largest TD area (4,980 µm2), covering from PD to deep RD.
Fig. 6. Quantitative comparison of thermal decomposition (TD) area as function of TD penetration depth: (a) Focal depth (FD) = 0 mm, (b) FD = 2 mm, (c) FD = 4 mm, and (d) FD = 6 mm. Note that different background colors represent various skin layers (E = epidermis; PD = papillary dermis; ID = Intermediate region of the dermis; RD = reticular dermis).
4. Discussion
The current study designed a new DLA optical element to achieve multiple micro-beams in a uniform manner and to induce uniform micro-injury zones at various depths in multi-layered skin tissue. Both optical simulation and beam profile measurements validated that DLA formed multiple micro-beams, of which size was ten- and five-fold larger than those of DOE and MLA, respectively (Fig. 2). According to our previous study, DOE created vacuoles in a uniform manner at three FDs (0, 5, and 10 mm). The vacuoles were hardly formed in the skin layer deeper than 400 µm possibly due to the limited beam collimation. In fact, the preliminary optical simulation confirmed that the beam distribution became diverging significantly beyond the focal plane, implicating that the optical breakdown was solely limited within the skin surface. Although MLA generated the vacuoles in the deeper skin layer (∼1064 µm), the distribution of the vacuoles was inherently Gaussian-like and no significant change in the penetration depth was observed with varying FDs. On the other hand, the current study demonstrated that DLA was able to create a uniform distribution of TD in the ex vivo skin and to control the TD location in a FD-dependent manner (0∼6 mm; Table 1). In addition, DLA could target the chromophores located in the deep skin layers by forming the extent of TD up to 1,115 µm in spite of a different type of micro-injury, compared to those of DOE and MLA. Therefore, DLA-assisted picosecond laser treatment can provide the combined features from DOE and MLA and may help obtain deep and uniform laser treatment at various depths in the skin for enhancing clinical outcomes.
DLA entailed TD with skin tissue partially ripped and discolored whereas both DOE and MLA created evident vacuolization in the upper epidermal basal membrane (Fig. 3). In spite of a uniform distribution of micro-beams (Fig. 2), both mechanical and thermal micro-injury (i.e., TD) after DLA-assisted laser treatment could be associated with a large coverage of the DLA micro-beams. The current pulse duration (450 ps) is considerably shorter than TRT of skin chromophores (∼50 ns), satisfying thermal confinements for laser treatment [16]. However, the larger DLA micro-beams could have decreased the incident irradiance inside the tissue, possibly mitigating the immediate development of laser-induced plasma with high pressure and temperature upon volumetric energy deposition. Instead, the targeted tissue volume could have undergone both partial pressure elevation (mechanical injury) and heat accumulation as well as conduction (thermal injury), resulting in the axial tissue rupture surrounded by irreversible thermal coagulation (Figs. 3 and 5) at various tissue depths. In fact, it was observed during the experiments that DLA-assisted laser irradiation formed plasma with noticeably weaker luminescence and lower pressure transient (less audible sound), compared to DOE- and MLA-assisted laser irradiation. However, the potential benefits of the combined micro-injury by generated by the DLA-assisted laser treatment still needs to be explored for clinical translations. Therefore, further studies will design and optimize the optical layouts for DLA in order to have a smaller micro-beam size for inducing vacuolization instead of TD inside the tissue during picosecond laser irradiation. In addition, the delayed response of the skin tissue to TD will be investigated to elucidate the effect of the combined (mechanical and thermal) micro-injury after the DLA-assisted laser treatment on chronic inflammation, wound healing and repair, and collagen remodeling, compared with that of the skin to the vacuolization.
DLA-assisted picosecond laser irradiation could provide multiple treatment options, such as pigment removal, skin rejuvenation, and collagen remodeling, selectively at various skin layers and depths. Figure 5 shows that the location of the micro-injury (vacuoles or TD) formation seemed to be contingent upon FDs. Thus, it is conceived that the selective laser treatment of various skin layers could broaden clinical benefits. For instance, the DLA-assisted laser irradiation at FD = 0 mm yielded the vacuoles solely within the epidermal layer (∼100 µm; Fig. 5), implicating selective pigment destruction as a result of light absorption [17] by pigment-laden cells (melanocytes, keratinocytes, and naevus cells [18]) in E. Hence, the selective destruction of the pigment-laden cells can be instrumental in treating pigmented skin disease. On the other hand, the deeper FDs of 2 and 6 mm were able to generate micro-injury (TD) in PD (100∼300 µm) and RD (700 µm ∼), respectively (Fig. 5). The occurrence of the micro-injury could stimulate papillary and reticular fibroblasts in PD and RD, respectively, further activating collagen formation and remodeling in the skin [19,20]. For clinical translations, further in vivo studies should be pursued in in vivo porcine models to evaluate the collagen remodeling and to validate the potential effects of the proposed treatment on PD and RD by means of visualization with polarized light microscopy, western blot analysis, and real-time PCR analysis.
Although DLA could provide uniform micro-beam distributions at various depths in skin, experimental limitations still remain. It was noted that the current optical simulation showed a 40% smaller DOE micro-beam diameter that the actual one (100 µm for simulation vs. 165 µm for measurement). A potential explanation for the discrepancy can be the application of the HOLO/OR LTD’s tutorial using different DOE specifications, such as raw material data, optical properties, and surface pattern, for the current simulation. In particular, scanning electron microscopy should be employed to identify both pattern and physical dimension of the DOF surface for more accurate prediction on the DOE micro-beam diameter. Therefore, the new optical design for the actual DOE and MLA specifications will be developed in order to further evaluate and optimize the performance of the proposed optical elements with the optical simulations. In spite of the uniform micro-beam array for DLA (7 × 7), the rotational alignment of DOE and MLA in the same handpiece could still induce interference patterns (e.g., Moire pattern) because of different optical features. Thus, the alignment of the optical elements should be further optimized to minimize the interference patterns and to attain the uniform micro-beam array for DLA with smaller micro-beam diameters. Unlike DOE and MLA, DLA generated larger micro-beams with lower intensities (Fig. 2), which led to TD in the skin rather than vacuolization (Fig. 3). In spite of the uniform distribution of the micro-beams, DLA was a combination of DOE and MLA by increasing a DC component in the beam profile, which led to TD with the increased micro-beam diameter. Thus, further investigations will be followed to optimize the optical configurations of DLA to generate a smaller micro-beam size in a uniform micro-beam array with a capacity for variable focal depths. Thus, the smaller micro-beams could yield the uniformly localized vacuoles or micro-injury zones at various skin depths, improving clinical efficacy and safety. In addition, in the case of the DOE and MLA handpieces, the focus of the micro-beams was close to the skin surface or superficial layer of the skin. If optical breakdown were dominant in E or PD, cavitation dynamics consumed most of the laser energy and worked as a shield against any further migration of photons into the deeper layer of the skin. In the case of picosecond laser, it can be conceived that all the energy was virtually expended in the optical breakdown and photoacoustic coupling (i.e. shockwave and cavitation) with minimal direct thermal contribution. Any subsequent thermal effects could be secondary to acoustic-thermal coupling. In order to deliver the incident laser energy deeper with more spatial control, these superficial disruptive events need to be minimized. Although the proposed method was to move FD of the DLA handpiece into ID and RD, the optical breakdown was minimized but photothermal coupling became more effective instead to produce the deeper lesions (Figs. 3 and 4). Alternatively, the position of the plano-convex lens focus in the DOE handpiece can also be adjusted to provide similar phenomena (i.e., dominant photothermal effect with deeper TD) to the DLA performance although the current study evaluated the feasibility of a combination of DOE and MLA. Thus, instead of the proposed combination, further design and quality of DOE should be performed to enhance a therapeutic capacity of selective picosecond laser treatment and its treatment outcomes in the skin. The current study used ex vivo porcine skin to compare the performance of three optical elements. In spite of quantitative validations, the ex vivo tissue hardly reflects human tissue because of different optical/thermal properties, no blood perfusion with convective heat transfer, no metabolic heat generation [21]. In addition, the current findings merely demonstrated the acute response of the laser-treated tissue to the picosecond laser irradiation with DOE, MLA, and DLA. However, for clinical translations, the delayed tissue response should be investigated to confirm the development of micro-lesions, the degree of inflammation, wound healing, and collagen remodeling. Therefore, further in vivo large animal studies will be performed to validate the current ex vivo findings and to substantiate the potential clinical benefit of DLA in terms of acute/chronic tissue response, degree of pigment removal, and skin rejuvenation.
5. Conclusion
The current study designed and developed a new optical element of DLA by combing the features of DOE and MLA in order to achieve uniform and selective laser treatment of skin. Both a uniform distribution of micro-beams and a constant beam collimation from DLA could help generate TD in a uniform manner and at various skin depths. Further in vivo studies will be performed to validate the potential benefits of DLA-assisted picosecond laser treatment on skin in a large animal model in terms of acute/chronic tissue response, the degree of pigment removal, and skin rejuvenation for clinical translations.
Funding
Korea Medical Device Development Fund (202016B01); National Research Foundation of Korea (2021R1A6A1A03039211).
Acknowledgments
This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: 202016B01) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2021R1A6A1A03039211).
Disclosures
The authors declare that there are no conflicts of interest related to this article.
Data availability
Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon reasonable request.
References
1. Y. X. Dai, Y. Y. Chuang, P. Y. Chen, and C. C. Chen, “Efficacy and safety of ablative resurfacing with a high-energy 1,064 Nd-YAG picosecond-domain laser for the treatment of facial acne scars in Asians,” Lasers Surg. Med. 52(5), 389–395 (2020). [CrossRef]
2. D. G. Kim, S. M. Nam, J. S. Shin, and E. S. Park, “Effectiveness of the pico-toning technique for the treatment of melasma with a low fluence 1,064-nm Nd: YAG laser in Asian patients,” Medical Lasers 9, 166–171 (2020). [CrossRef]
3. L. Carroll and T. R. Humphreys, “LASER-tissue interactions,” Clin. Dermatol. 24(1), 2–7 (2006). [CrossRef]
4. N. Stewart, A. C. Lim, P. M. Lowe, and G. Goodman, “Lasers and laser-like devices: Part one,” Australas. J. Dermatol. 54(3), 173–183 (2013). [CrossRef]
5. R. R. Anderson and J. A. Parrish, “Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation,” Science 220(4596), 524–527 (1983). [CrossRef]
6. T. H. S. Wong, “Picosecond laser treatment for acquired bilateral nevus of ota–like macules,” JAMA Dermatol. 154(10), 1226–1228 (2018). [CrossRef]
7. C. H. Lee, E. M. Jin, H. S. Seo, T.-U. Ryu, and S. P. Hong, “Efficacy and safety of treatment with fractional 1,064-nm picosecond laser with diffractive optic element for wrinkles and acne scars: A clinical study,” Ann. Dermatol. 33(3), 254 (2021). [CrossRef]
8. S. Palawisuth, W. Manuskiatti, C. Apinuntham, R. Wanitphakdeedecha, and K. A. G. Cembrano, “Quantitative assessment of the long-term efficacy and safety of a 1064-nm picosecond laser with fractionated microlens array in the treatment of enlarged pores in Asians: A case-control study,” Lasers Surg. Med. 54(3), 348–354 (2022). [CrossRef]
9. H. J. Chung, H. C. Lee, J. Park, J. Childs, J. Hong, H. Kim, and S. B. Cho, “Pattern analysis of 532-and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin,” Lasers Med. Sci. 34(6), 1207–1215 (2019). [CrossRef]
10. H.-J. Ahn, D. H. Suh, I.-H. Kang, S. J. Lee, M. K. Shin, and K. Y. Song, “Interaction of skin with fractional picosecond laser in Asian patients,” The Journal of Clinical and Aesthetic Dermatology 14, 14 (2021).
11. M. Zhang, Y. Guan, Y. Huang, E. Zhang, T. Lin, and Q. Wu, “Histological Characteristics of Skin Treated With a Fractionated 1064-nm Nd: YAG Picosecond Laser With Holographic Optics,” Lasers Surg. Med. 53(8), 1073–1079 (2021). [CrossRef]
12. L. Kirsanova, E. Araviiskaia, M. Rybakova, E. Sokolovsky, A. Bogantenkov, and F. Al-Niaimi, “Histological characterization of age-related skin changes following the use of picosecond laser: low vs high energy,” Dermatologic Therapy 33, e13635 (2020). [CrossRef]
13. C. S. M. Wong, M. W. M. Chan, S. Y. N. Shek, C. K. Yeung, and H. H. L. Chan, “Fractional 1064 nm picosecond laser in treatment of melasma and skin rejuvenation in Asians, a prospective study,” Lasers Surg. Med. 53, 1032–1042 (2021). [CrossRef]
14. H. Kim, J. K. Hwang, M. Jung, J. Choi, and H. W. Kang, “Laser-induced optical breakdown effects of micro-lens arrays and diffractive optical elements on ex vivo porcine skin after 1064 nm picosecond laser irradiation,” Biomed. Opt. Express 11(12), 7286–7298 (2020). [CrossRef]
15. H. Kim, J. K. Hwang, J. Choi, and H. W. Kang, “Dependence of laser-induced optical breakdown on skin type during 1064 nm picosecond laser treatment,” J. Biophotonics 14, e202100129 (2021). [CrossRef]
16. M. F. Yang, V. V. Tuchin, and A. N. Yaroslavsky, “Principles of light-skin interactions,” in Light-Based Therapies for Skin of Color (Springer, 2009), pp. 1–44.
17. D. J. Goldberg, “Laser treatment of pigmented lesions,” Dermatol. Clin. 15(3), 397–407 (1997). [CrossRef]
18. B. Brazzini, G. Hautmann, I. Ghersetich, J. Hercogova, and T. Lotti, Laser Tissue Interaction in Epidermal Pigmented Lesions (Blackwell Science Ltd Oxford, 2001), pp. 388–391.
19. M. Takeo, W. Lee, and M. Ito, “Wound healing and skin regeneration,” Cold Spring Harbor Perspect. Med. 5(1), a023267 (2015). [CrossRef]
20. D. M. Reilly and J. Lozano, “Skin collagen through the lifestages: Importance for skin health and beauty,” Plastic and Aesthetic Research 8, 2 (2021). [CrossRef]
21. M. H. Niemz, “Interaction mechanisms,” in Laser-Tissue Interactions (Springer, 2002), pp. 45–149.
