Medical Lasers; Engineering, Basic Research, and Clinical Application 2021; 10(2): 82-89  https://doi.org/10.25289/ML.2021.10.2.82
Development of Minimally Invasive Mid-infrared Lipolysis Laser System for Effective Fat Reduction
Ji-Young Lee, Han Young Ryu, Young-Seok Seo
R&D Center, Wontech Co., Ltd., Daejeon, Korea
Correspondence to: Ji-Young Lee
R&D Center Wontech Co., Ltd., 64 techno 8-ro, Yuseong-gu, Daejeon 34028, Korea
Tel.: +82-70-7841-6526
Fax: +82-70-7863-3350
E-mail: yw106707@wtlaser.com
Received: March 8, 2021; Accepted: March 31, 2021; Published online: June 30, 2021.
© Korean Society for Laser Medicine and Surgery. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background and Objectives
Due to changes in diet and lifestyle, the number of obese people worldwide is steadily increasing. Obesity has an adverse effect on a healthy life, so it needs treatment and improvement. Research related to this is continuously being conducted.
Materials and Methods
The laser system to compact designed using 808 nm laser diode and Neodymium Yttrium orthovanadate generates a 1064 nm wavelength, the periodically polarized nonlinear crystal pumping laser beam. The pulsed 1064 nm wavelength beam passing through the AO Q-switch is used as the pumping light of the nonlinear optical crystal and is irradiated to the periodic polarized nonlinear optical crystal with a quasi-phase matching period. Nonlinear optical crystals use an oven to control the temperature to generate the desired 1980 nm and 2300 nm wavelengths.
Results
The 1980 nm and 2300 nm wavelengths generated by temperature control of nonlinear optical crystals are effective for lipolysis. A fiber catheter was used so that the laser could be directly irradiated to the fat cells. In particular, the new wavelength (1980 nm, 2300 nm) can increase the fat reduction effect with low energy (1.3 W). When a laser with a combination wavelength of 1980 nm and 2300 nm was used, an average lipolysis effect of 20% was obtained.
Conclusion
A mid-infrared lipolysis laser system with excellent absorption of fat and water has been developed. We conducted a princlinical study to confirm the efficacy and safety of the lipolysis laser system, and obtained good results for lipolysis with low energy.
Keywords: Mid-infrared; Lipolysis laser; Nonlinear crystal; Preclinical
INTRODUCTION

Due to the development of medicine and science, the aging population is increasing as human life span. Due to aging, a lot of time and economic investment led to a healthy life without disease. One of the health-threatening causes is obesity. Obesity is the simple weight of the past means that much of the current obesity is a lot of body fat accumulated in the body, which means a state piled up. Due to changes in eating habits and lifestyles, the number of obese people worldwide is steadily increasing.1 Obesity affects health and self-esteem in social activities and medical techniques and devices developed. Laser lipolysis reduces fat and shortens recovery time and works to prevent bleeding by coagulating blood vessels and effective skin tightening by inducing collagen production.2-5 This study has developed the world’s first minimally invasive lipolysis laser system with 1,980-nm and 2,300-nm wavelengths. The fat reduction by the laser depends on the wavelength and energy of the laser.6 Each wavelength used by lipolysis laser has its own characteristics. It has a high hemostatic function, which is a unique role of the 1,064-nm wavelength, and has a high absorption rate of water, so that it also acts as a tightening function. The 1,320-nm wavelength has higher water absorption than 1,064 nm, and has a fat-dissolving effect. The 1,444-nm wavelength is currently the highest fat solubility wavelength used in laser-assisted liposuction (LAL) equipment, which is 40 times higher than 1,064 nm.7 As shown in Fig. 1, as the wavelength increases, the absorption of fat and water increase. In general, the subcutaneous fat layer does not contain only fat, but water and fat are mixed together. When the absorption rate for water and fat increases, the solubility of fat is high, increasing the therapeutic effect. The reason why the 2,000-nm band, which has a higher fat absorption rate at present, is not used because it is technically difficult to generate the desired wavelength and the high absorption of water poses a risk of burns. In this study, 1,980-nm and 2,300-nm laser were developed that are effective for lipolysis. In addition, since it used a lower power (1.3 W) than other wavelength lasers (1,444 nm/12 W), the risk of burns is reduced.

Figure 1. Comparison of laser absorption rate for fat and water.
MATERIALS AND METHODS

Laser system development

Generally, neodymium (Nd):yttrium aluminium garnet crystal (YAG) and Nd:Yttrium othovanadate crystal (YVO4) are used to generate a laser with a wavelength of 1,064-nm. Nd:YAG diode pumped solid state (DPSS) laser,8 the use of a side-pumping DPSS laser and a Faraday Rotator for polarization control through a polarization element limits the laser head size reduction. To overcome the limitation of size, we designed a modified laser head with a structure using Nd:YVO4 and 808-nm laser diode (LD).9-11 A high power fiber-coupled diode laser pumped the Nd:YVO4 crystal at 808 nm with a maximum power of 100 W. Nd:YVO4 has an absorption rate of 808 nm that is 5 times better than that of Nd:YAG and has the same power at a low output than Nd:YAG diode output, thus doubling the lifetime of the diode. It also has the advantage of generating a linear polarized beam of 1,064-nm wavelength. The lens was designed using CodeV to focus the beam diverging from the 808-nm LD onto Nd:YVO4. Since Nd:YVO4 has the characteristic of birefringence, only the beam having the polarization in the direction corresponding to the axial direction can pass. These characteristics affect the output power. As well know, we used a-cut Nd:YVO4 (4 × 4 × 20 mm, 0.2 % doping) because it has a maximum output power 7 times higher than c-cut.12 To keep the Nd:YVO4 temperature constant, an amount including a cooling system was designed. An acousto optical (AO) Q-switch was used to make a pulse beam. AO Q-switch was intended to have a pulse repetition rate of several kHz using crystal quartz.13 A pulsed 1,064-nm wavelength beam is used as a pumping beam for the opticla parametric oscillators (OPO) cavity. The OPO cavity consists of a periodically polarized nonlinear optical crystal with a quasi phasematching (QPM) period and a back mirror, and an out mirror. To obtain a wavelength of 2 μm suitable for lipolysis, periodically poled stoichiometric lithium tantalate (PPSLT) crystal (3 × 3 × 20 mm, 32.19 μm grating period) was selected as shown in Fig. 2. by calculating the wavelength change with the temperature of the nonlinear optical crystal.14-17

Figure 2. Wavelengths variation of nonlinear optical crystal with temperature. PPSLT, periodically poled stoichiometric lithium tantalate.

We used the depend on temperature Sellmeier equation for the extraordinary refractive index of stoichiometric lithium tantalate crystal (SLT) proposed by Bruner.18,19 All of the OPO cavity mirrors were flat mirrors. The back mirror is highly transmitting (T>95%) for the pump beam and highly reflective (R>97%) for the 2 μm wavelengths. Out mirror is highly reflective (R >99%) for the pump beam and partial transmitting (T >50%) for the 2 μm wavelengths. To control nonlinear optical crystal temperature to obtain a stable wavelength with heater oven using real-time temperature sensor was made. When the pumping beam of 1,064 nm is incident on the nonlinear optical crystal, the second harmonic of 532 nm wavelength is generated.20 It generated the crystal temperature changes, mid-infrared of 1,980-nm and 2,300-nm wavelengths. The result of the wavelength change calculation according to the nonlinear optical crystal temperature was 110°C. We designed and fabricated an oven to control nonlinear optical crystal temperature, as shown in Fig. 3.

Figure 3. Oven for temperature control of nonlinear optical crystal, (A) design, (B) production and application.

A beam of 1,064 nm is pumped into the nonlinear optical crystal, and the second harmonic of 532-nm wavelength is generated. The wavelengths generation from increasing the temperature of the oven were measured. As a result, we have achieved wavelengths of 1,980 nm and 2,300 nm at 175°C. We have a set of nonlinear optical crystal temperatures of about 175°C according to the experimental results.

As shown in Fig. 4, 532-nm second harmonic generation beam is reflected by the folding mirror, 1,980 nm and 2,300 nm are passed through the selection filter. We designed a coupling lens to focus at 1,980-nm and 2,300-nm wavelengths on the fiber. We developed a lipolysis laser system with 1,980-nm and 2,300-nm wavelengths included with laser head, temperature controller, power supply, and cooling system.

Figure 4. Output wavelength and power measurement results of the lipolysis laser system.
RESULTS

Lipolysis preclinical experiment results and discussion

We conducted preclinical ex-vivo and in-vivo to confirm the minimally invasive mid-infrared lipolysis laser safety and efficacy.

Ex-vivo experiment

First, ex-vivo experiments were performed to determine the power of wavelengths of 1,980 nm and 2,300 nm.21 It was designed and experimented as shown in Fig. 5. using pig bulk tissue. A cannula is used to deliver the laser irradiated from the fiber tip to the adipose tissue. To confirm reducing the fat cells by laser without damage by the cannula and tissue changes in the red line area were observed. Laser irradiation condition, as shown in Table 1.

Table 1 . Conditions of mid-infrared lipolysis laser irradiation in the ex-vivo experiment

WavelengthPowerTime
1,980 nm0.8 W1 min, 2 min, 4 min
2,300 nm0.4 W1 min, 2 min, 4 min
1,980 nm + 2,300 nm1.2 W1 min, 2 min, 4 min

Figure 5. Design of mid-infrared lipolysis laser in the ex-vivo experiment.

The guide beam was used to visually check where the laser was irradiated. After laser irradiation, a tissue sample was extracted and histological analysis was performed.

After laser irradiation, hematoxylin & eosin (H&E) staining was used to analyze changes in adipose tissue. As shown in Fig. 6, in the case of irradiation for 4 minutes with a combination of 1,980 nm and 2,300 nm, fat cells decomposed.

Figure 6. Hematoxylin & eosin (H&E) staining results after the ex-vivo experiment (original magnification, ×100).

In-vivo experiment

Based on the results of the ex-vivo experiment, in vivo animal experiment was performed. IRB approval was obtained for this experiment. In the experiment design, the abdomen of a 12 months old male mini-pig was divided into six parts and irradiated with a laser. Skin color, hair follicles, sweat glands, and subcutaneous fat were experimented with using mini pigs similar to humans.22,23 Pig skin, similar to humans, has relatively few coats, and the subcutaneous tissue is firmly connected. The overall shape of epidermal thickness, cellular composition, and cutaneous blood supply is similar to that of humans, expect that there is no apocrine sweat gland. The laser irradiation conditions are as shown in Table 2.

Table 2 . Conditions of mid-infrared lipolysis laser irradiation in the in-vivo experiment

Part #WavelengthPowerTime
1 ~ 5 (Experimental Group)1,980 nm + 2,300 nm1.2 W5 min
6 (Control)1,470 nm1.2 W5 min

After laser irradiation, safety was confirmed through blood tests and visual observation of skin and biopsy. To check the efficacy and the change in the thickness of the fat layer was measured using ultrasound. Visual observation of skin was performed before and at 0, 1, 7, 15, 30, 60, 90 days after laser irradiation. As shown in Fig. 7, the abnormal change due to the laser irradiation confirmed could not be.

Figure 7. Visual observation for 90 days before and after laser irradiation.

To confirm physiology safety, H&E staining of the tissue was performed 15, 30, 60, and 90 days after laser irradiation. As a result, it was observed that other cytoplasm, muscle cells and intracytoplasmic fibrous tissue were formed in the deformed part of the adipose tissue. As a result of observation, as shown in Fig. 8, after 30 days, other cytoplasm, muscle cells and intracytoplasmic fibrous tissue were generated in all areas, but #6 (control) was relatively lower than that of other elements (experimental group).

Figure 8. H&E staining results after laser irradiation (original magnification, ×100).

During 3 days after laser irradiation, a total of 8 blood tests (0, 2, 4, 8, 12, 18, 24, 48, 72 hours) were performed to confirm changes in liver function, kidney function, and lipid levels. As shown in Table 3, the aspartate transaminase (AST) level showed a tendency to increase between 4 and 24 hours of laser irradiation but returned to normal after 48 hours.

Table 3 . Blood test results after laser irradiation

ItemTPALBGLBA/GASTALTBUNT-BILT-CHOALPCaPTGCREAHDL-CLDL-CNEFA
Unitg/dLg/dLg/dLRatioIU/LIU/Lmg/dLmg/dLmg/dLIU/Lmg/dLmg/dLmg/dLmg/dLmg/dLmg/dLmEq/L
D9-15 0H7.14.13.01.4474210.40.00887311.16.9232.2740.938.9147
D9-15 2H6.73.92.81.4513910.60.02837510.66.4172.2737.938.3113
D9-15 4H8.14.63.51.31024614.30.05968411.87.4202.5444.343.4191
D9-15 8H7.94.63.31.41604817.80.06908511.47.9192.5341.742.1198
D9-15 12H7.54.43.11.42694822.20.09848610.88.2172.5337.140.9198
D9-15 24H7.34.23.11.4904319.80.02797610.25.4172.2238.035.980
D9-15 48H8.34.73.61.3575212.40.031018110.96.3212.2148.743.7141
D9-15 72H7.84.53.31.4425213.10.021158611.75.9402.2251.150.336
Mean7.64.43.21.41024615.10.04928111.16.8222.3542.541.7138
SD0.50.30.30.07854.40.031250.61.080.155.24.459
N8.08.08.08.0888.08.00888.08.088.008.08.08

D, day; H, hour; SD, standard deviation; TP, total protein; ALB, albumin; GLB, globulin; A/G, albumin/globulin ratio; AST, aspartate transaminase; ALT, alanine aminotransferase; BUN, blood urea nitrogen; T-BIL, total bilirubin; T-CHO, total cholesterol; ALP, alkaline phosphatase; TG, trigly­ceride; CREA, creatinine; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; NEFA, non-esterified fatty acid.


To confirm the efficacy and changes in the fat layer's thickness were measured by abdominal ultrasound before and immediately, 1, 7, 15, 30, 60, 90 days after laser irradiation. Fig. 9 showns the ultrasound measured before and 90 days after laser irradiation in #1. The thickness of the fat layer decreased by 33 % from 7.22 mm before laser irradiation to 4.86 mm after 90 days of laser irradiation. As shown in Fig. 10 of measurement results, found that the thickness of the fat layer increased in all areas after 1 day of irradiation. It can see that it increases by more than 40% in #1 and decreases rapidly after 7 days.

Figure 9. Ultrasound results measured before and 90 days after laser irradiation in #1.
Figure 10. Fat layer thickness change graph after laser irradiation.

The fat thickness of all parts decreased by 30 days and increased by 5% at #4, #5, #6 at 60 days. For 90 days after laser irradiation was the thickness, the difference depending on location decreased 5–35% of all parts. When the combination wavelength of 1,980 nm and 2,300 nm was irradiated (#1–#5), there was a tendency to decrease continuously after 60 days. However, when irradiated with a wavelength of 1,470 nm (#6), there is no tendency to fall.

DISCUSSION

We developed a minimally invasive lipolysis laser system that uses the nonlinear optical crystal to produce wavelengths of 1,980 nm and 2,300 nm with good absorption of water and fat. A preclinical study was conducted in mini pig to confirm the minimally invasive lipolysis laser safety and efficacy. When irradiated with a combination of 1,980-nm and 2,300-nm wavelengths has obtained an average of 20 % fat reduction. Blood tests and biopsies have confirmed the minimally invasive mid-infrared lipolysis laser system to be safe.

Based on the results of animal experiments, the minimally invasive mid-infrared lipolysis laser system was the first clinical trial with the approval of the clinical protocol of The Ministry of Food and Drug Safety (MFDS). Currently, the clinical trial is finished, and statistical processing is in progress.

FUNDING

It was carried out with support from Establishment of joint research corporation and operation support industry of Korea Innovation Foundation.

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