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Phlebology OnlineFirst, published on May 30, 2014 as doi:10.1177/0268355514538248
Original Article
Histological difference between pulsed wave laser and continuous wave laser in endovenous laser ablation
Phlebology 0(0) 1–6 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514538248 phl.sagepub.com
Rei Kansaku1,2, Naoki Sakakibara1,2, Atsushi Amano2, Hisako Endo3, Takashi Shimabukuro1 and Michiaki Sueishi4
Abstract Background: Endovenous laser ablation to saphenous veins has been popular as a minimally invasive treatment for chronic venous insufficiency. However, adverse effects after endovenous laser ablation using continuous wave laser still remain. Pulsed wave with enough short pulse duration and sufficiently long thermal relaxation time may avoid the excess energy delivery, which leads to the perforation of the vein wall. Method: (1) Free radiation: Laser is radiated in blood for 10 s. (2) Endovenous laser ablation: Veins were filled with blood and placed in saline. Endovenous laser ablations were performed. Results: (1) There were clots on the fiber tips with continuous wave laser while no clots with pulsed wave laser. (2) In 980-nm continuous wave, four of 15 specimens had ulcers and 11 of 15 had perforation. In 1470-nm continuous wave with 120 J/cm of linear endovenous energy density, two of three presented ulcers and one of three showed perforation. In 1470-nm continuous wave with 60 J/cm of linear endovenous energy density, two of four had ulcers and two of four had perforation. In 1320-nm pulsed wave, there were neither ulcers nor perforation in the specimens. Conclusions: While endovenous laser ablation using continuous wave results in perforation in many cases, pulsed wave does not lead to perforation.
Keywords Chronic venous disease, chronic venous insufficiency, endovenous laser treatment, endovenous thermal ablation, pathology/histology
Introduction The importance of thermal relaxation time has been pointed out in laser dermatology.1 However, pulse duration and thermal relaxation time have rarely been noted in the field of endovenous laser ablation (EVLA). The efficacy of EVLA is said to be affected by the linear endovenous energy density (LEED) or the endovenous fluence equivalent (EFE).2 In addition to the amount of energy, the duration time of energy delivery would play a key role. EVLA using pulsed wave (PW) laser is said to lead to fewer side effects than using a continuous wave (CW) laser.3 The enough short pulse duration and sufficiently long thermal relaxation time would avoid the excess temperature elevation, which leads to the perforation of the vein wall. The purpose of the present study is to evidence the difference of the mechanism of EVLA using PW and CW at various energy settings.
Methods Free radiation in blood Laser is radiated in heparinized whole blood (Figure 1) for 10 s. The settings were 10 W of 980-nm CW diode laser (980 CW, Biolitec AG, Vienna), 8 W of 1470-nm CW diode laser (1470 CW, Diotech, Busan), and 6 W 40 Hz of 1320-nm Nd:YAG PW laser (1320 PW, 1 The Department of Cardiovascular Surgery, Edogawa Hospital, Tokyo, Japan 2 The Department of Cardiovascular Surgery, Juntendo University, Tokyo, Japan 3 The Department of Pathology, Edogawa Hospital, Tokyo, Japan 4 Shinagawa Heart Medical Clinic, Tokyo, Japan
Corresponding author: Rei Kansaku, The Department of Cardiovascular Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
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Figure 2. EVLA (in vitro). Great saphenous veins were filled with whole blood and heparin, and placed in saline. EVLAs were performed.
Figure 1. Laser radiation in whole blood. Laser is radiated in heparinized whole blood.
Table 1. Setting for the free radiation of laser in blood. Device
Fiber
Setting
980 nm CW 1470 nm CW 1320 nm PW
Bare Bare Covered
10 W 8W 6 W 40 Hz
980-nm continuous wave (980 CW) laser, 1470-nm continuous wave laser (1470 CW), and 1320-nm pulsed wave (1320 PW) laser are radiated in heparinized whole blood for 10 s.
Cooltouch, Roseville, CA) (Table 1). Bare fibers were used for 980 CW and 1470 CW, while fibers covered by Teflon buffer materials (SaphFire, Cooltouch, Roseville, CA) were used for 1320 PW. The visual changes are recorded with a digital video camera.
EVLA (in vitro) Great saphenous veins were obtained from patients who had undergone stripping surgeries for chronic venous insufficiency. Written informed consents were obtained from all patients. The veins were filled with whole blood and heparin, and placed in saline (Figure 2). EVLAs were performed using 980-nm CW diode laser (980 CW), 1470-nm CW diode laser (1470 CW), or 1320-nm Nd:YAG PW laser (1320 PW). In the group using 980 CW, the power and the velocity were (1) 10 W 1.4 mm/s (70 J/cm). In the group using 1470 CW, the power and the velocity were (2) 6 W 0.5 mm/s (120 J/cm) and (3) 6 W 1.0 mm/s (60 J/cm), respectively. In the group using 1320 PW, the power, the frequency of pulses, the pulling velocity, and the pulse duration times were (4) 6 W 40 Hz 1.0 mm/s 350 ms (60 J/cm), (5) 6 W 50 Hz 1.0 mm/s 350 ms (60 J/cm), (6) 12 W 40 Hz 2.0 mm/s 300 ms (60 J/cm), (7) 15 W 40 Hz
2.0 mm/s 300 ms (75 J/cm), and (8) 18 W 40 Hz 2.0 mm/s 300 ms (90 J/cm), respectively (Table 2). The veins were fixed in formalin and histologically investigated with a light microscopy.
Results Free radiation in blood We found a small bubble on the fiber tip during laser radiation in blood using both PW and CW. There were clots on the fiber tips after 10 s radiation using CW laser (Figure 3). However, there were no clots after radiation using PW laser (Figure 4).
EVLA (in vitro) In the group using 980 CW, four of 15 specimens (27%) had developed ulcers and 11 of 15 specimens (73%) had suffered perforation. In the group of 1470 CW with 120 J/cm of LEED, two of three specimens (67%) presented ulcers and one of three specimens (33%) showed perforation. In the group of 1470 CW with 60 J/cm of LEED, two of four specimens (50%) had developed ulcers and two of four specimens (50%) had perforation. In the group of 1320 PW, there were neither ulcers nor perforation in the specimens (Table 3). Figure 5 shows the typical changes of vein walls after EVLAs.
Discussion Although EVLA to saphenous veins is popular as a minimally invasive treatment for chronic venous insufficiency, the mechanism of EVLA is still significantly unknown. Several potential mechanisms of EVLA have been proposed: first, the optical-thermal response of the vein wall to scattered laser light4; second, the thermal response of the vein wall to condensing steam bubble4,5; third, the direct contact between the hot fiber tip and the wall5,6; and fourth, the thermal response of the vein wall to heat diffusion from the hot fiber tip.7,8
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Table 2. Setting for EVLA (in vitro). S.No.
Device
Energy (W)
Frequency (Hz)
Velocity (mm/s)
LEED (J/cm)
Pulse duration (ms)
Peak power (W)
1 2 3 4 5 6 7 8
980 CW 1470 CW 1470 CW 1320 PW 1320 PW 1320 PW 1320 PW 1320 PW
10.0 6.0 6.0 6.0 6.0 12.0 15.0 18.0
– – – 40 50 40 40 40
1.4 0.5 1.0 1.0 1.0 2.0 2.0 2.0
70 120 60 60 60 60 75 90
– – – 350 350 300 300 300
– – – 429 343 1000 1250 1500
Energy, frequency, velocity, and pulse duration are settings for experiments. Linear endovenous energy density (LEED) and peak power were calculated by settings.
Figure 3. Fiber tip after laser radiation using continuous wave laser.
Figure 4. Fiber tip after laser radiation using pulsed wave laser.
Also, the important role of blood in EVLA has been noted.8,9 During EVLA, thermal changes would be introduced in the vein walls through carbonized blood deposited on fibers.7 There are two concepts of how to make the thermal change to the vein walls beyond clots;
adding higher energy accepting the presence of clots or avoiding clot formation. Many efforts to avoid clots from forming have failed in the past. Wave length, targeting water, or hemoglobin would influence clot formation. However, free radiation experiments in the present study showed clots on the fibers after radiation by laser in blood even using 1470 nm of wave length, which is absorbed by water more than 980 nm. According to the absorption spectrum of hemoglobin and water,10 the wave length of 1320 nm and 1470 nm has been believed appropriate to change the vein wall, while wave length of 980 nm influences the hemoglobin more than the water. But because the wave length study was not conclusively resolved, various fibers have been developed, including covered or jacket fibers, radial fibers,11 and tulip catheters.12 We have treated saphenous veins with chronic venous insufficiency with EVLA using 1320 PW laser since 2007. PW laser has some advantages over CW laser. Anderson and Parrish13 proposed the theory of selective photothermolysis as an advantage of PW laser in 1983. Suitably brief pulses of selectively absorbed optical radiation can cause selective damage. When we develop EVLA, not only the energy setting, velocity, or wave length but also pulse duration time, or thermal relaxation time, and more details should be considered. In discussions about the appropriate energy of EVLA, at least three points should be distinguished accurately: (1) the energy setting of the devices, (2) the actual energy delivered at the top of the fiber, and (3) the distribution of energy from the top of the fiber and the vein wall. Clot formation suggests that excess energy is consumed at the top of fiber. We need to consider two things when we find carbonized clots on the fiber: (1) some of the energy was wasted, and (2) it shields energy from the top of the fiber and the vein wall. Thinking of the negative effect of clots, avoiding clot formation
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Table 3. Changes of venous walls after EVLA. Numbers S.No.
Device
Power (W)
Frequency (Hz)
LEED (J/cm)
Ulcer
Perforation
Specimens
1 2 3 4 5 6 7 8
980 CW 1470 CW 1470 CW 1320 PW 1320 PW 1320 PW 1320 PW 1320 PW
10.0 6.0 6.0 6.0 6.0 12.0 15.0 18.0
– – – 40 50 40 40 40
70 120 60 60 60 60 75 90
4 (27%) 2 (67%) 2 (50%) 0 0 0 0 0
11 (73%) 1 (33%) 2 (50%) 0 0 0 0 0
15 3 4 2 4 10 3 2
The numbers of specimen which had ulcer or perforation at the various power, frequency, and linear endovenous energy density (LEED). Laser devices included 980-nm continuous wave (980 CW) laser, 1470-nm continuous wave (1470 CW) laser, and 1320-nm pulsed wave (1320 PW) laser.
Figure 5. Typical changes of venous walls after EVLA. Histological differences of vein wall before EVLA (Pre), after EVLA using 980nm continuous wave (980 CW) laser, and 1320-nm pulsed wave (1320 PW) laser. Hematoxylin-eosin (HE) stain, Azan stain and Elastica van Gieson stain were used. Polarization emphasizes the change of the wall with Elastica van Gieson stain.
should be the basic and most important concept for developing EVLA. From this point of view, we propose using PW for EVLA. Some reasons could be supposed that why there were no clots on the fiber after free radiation examination using PW in this study. One reason may depend on the difference of amplitude of the energy settings. The settings of this study are decided from these clinical uses. Probably because clots are easily formed on the fiber tip during EVLA using CW, stronger energy would be required compared with PW. The second reason is the shock wave made by PW laser. PW leads to a shock wave with rapid localized heating,13 which also makes popping sounds during EVLA.
Because of the clear fiber tip, the energy through fibers would be delivered with minimal reduction during EVLA using PW. EVLA using PW achieved high occlusion rate even with lower energy setting comparing with CW.14,15 So we hypothesized that the mechanism of EVLA using PW is different from its using CW. To reveal more, the histological examination was performed in the present study. There are studies about EVLA histology using CW laser.4,12,16–20 The change in the vein wall after EVLA with CW includes (1) carbonization, (2) homogeneous basophilic discoloration, (3) coagulation necrosis, and (4) loss of distinction between collagen and muscular
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bundles.20 Fan and Rox-Anderson5 said that proper EVLA histology using CW laser was collagen denaturing, but too much energy leads to bilateral charring, ablation, or perforation. The histological changes were different in EVLA using PW and CW in the present study. EVLA using PW has more setting parameters compared with EVLA using CW. Not only energy setting and drawing velocity but also frequency and pulse duration time could be controlled. In our preliminary in vitro examination, the histological changes were varied depending on the frequency or pulse duration time. Increasing the pulse duration time induces clot formation even using PW. The threshold length of pulse duration seems to be influenced by the energy setting. From the limited number of experiments in the present study, a final answer does not become apparent, but we can see some suggestions about the difference between EVLA using PW laser and CW laser. One suggestion is that using PW laser may avoid elevating the temperature more than necessary. Many enzymes are heat-labile. Above 60 C to 70 C, structural proteins including collagens are also denatured. Above 70 C to 80 C, nucleic acids are denatured and membranes become permeable. Thus, essentially any mammalian tissue heated to 70 C to 100 C may suffer protein denaturation, leading to coagulation necrosis. Above 100 C, vaporization of tissue water occurs with rapid volume expansion.13 We think that the amount of energy that destroys the veins functionality is in fact not so different from the energy required to warm the blood in the veins from 60 C to 100 C. Chronic animal studies, including histological examinations, may be required to prove our hypothesis. The histological changes after EVLA using PW laser are found mainly as a change of the media of venous walls, when the changes after EVLA using CW are found as destruction of constructions. Although changes in color are thought to be denaturing of collagen fibers and/or elastic fibers, further studies are required to show which kind of denaturing happens. These changes of EVLA using PW include basophilic change, i.e. purple, in hematoxylin-eosin (HE) stain, redness in Azan stain, and yellowing in Elastica Van Gieson stain. Interestingly, polarization helped us to find the changes in the specimens with Elastica Van Gieson stain (Figure 5). Geometrical disarray may lead to difficulty of polarization in the heated vein wall.
Conclusion While EVLA using a CW laser results in perforation in most cases, EVLA using a PW laser does not lead to perforation even at a high energy setting.
Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Ross EV, McKinlay JR and Anderson RR. Why does carbon dioxide resurfacing work? A review. Arch Dermatol 1999; 135: 444–454. 2. Proebstle TM, Moehler T and Herdemann S. Reduced recanalization rates of the great saphenous vein after endovenous laser treatment with increased energy dosing: definition of a threshold for the endovenous fluence equivalent. J Vasc Surg 2006; 44: 834–839. 3. Proebstle TM, Moehler T, Gul D, et al. Endovenous treatment of the great saphenous vein using a 1,320 nm Nd:YAG laser causes fewer side effects than using a 940 nm diode laser. Dermatol Surg 2005; 31: 1678–1683. 4. Proebstle TM, Lehr HA, Kargl A, et al. Endovenous treatment of the greater saphenous vein with a 940-nm diode laser: thrombotic occlusion after endoluminal thermal damage by laser-generated steam bubbles. J Vasc Surg 2002; 35: 729–736. 5. Fan CM and Rox-Anderson R. Endovenous laser ablation: mechanism of action. Phlebology 2008; 23: 206–213. 6. Disselhoff BC, Rem AI, Verdaasdonk RM, et al. Endovenous laser ablation: an experimental study on the mechanism of action. Phlebology 2008; 23: 69–76. 7. Amzayyb M, Van den Bos RR, Kodach VM, et al. Carbonized blood deposited on fibres during 810, 940 and 1,470 nm endovenous laser ablation: thickness and absorption by optical coherence tomography. Lasers Med Sci 2010; 25: 439–447. 8. Mordon S, Wassmer B, Servell P, et al. Is a vein filled with blood a good model for studying endovenous laser ablation? Lasers Surg Med 2009; 41: 543–544. 9. Proebstle TM, Sandhofer M, Kargl A, et al. Thermal damage of the inner vein wall during endovenous laser treatment: key role of energy absorption by intravascular blood. Dermatol Surg 2002; 28: 596–600. 10. Roggan A, Friebel M, Do Rschel K, et al. Optical properties of circulating human blood in the wavelength range 400–2500 nm. J Biomed Opt 1999; 4: 36–46. 11. Pannier F, Rabe E, Rits J, et al. Endovenous laser ablation of great saphenous veins using a 1470 nm diode laser and the radial fibre–follow-up after six months. Phlebology 2011; 26: 35–39. 12. Vuylsteke M, Van Dorpe J, Roelens J, et al. Intraluminal fibre-tip centring can improve endovenous laser ablation: a histological study. Eur J Vasc Endovasc Surg 2010; 40: 110–116. 13. Anderson RR and Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 1983; 220: 524–527.
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14. Goldman MP, Mauricio M and Rao J. Intravascular 1320-nm laser closure of the great saphenous vein: a 6to 12-month follow-up study. Dermatol Surg 2004; 30: 1380–1385. 15. Yang CH, Chou HS and Lo YF. Incompetent great saphenous veins treated with endovenous 1,320-nm laser: results for 71 legs and morphologic evolvement study. Dermatol Surg 2006; 32: 1453–1457. 16. Goldman MP. Endovenous 1064-nm Nd:YAG laser treatment of the porcine greater saphenous vein. Cosmet Dermatol 2003; 16: 25–28. 17. Corcos L, Dini S, De Anna D, et al. The immediate effects of endovenous diode 808-nm laser in the greater saphenous vein: morphologic study and clinical implications. J Vasc Surg 2005; 41: 1018–1024.
18. Schmedt CG, Sroka R, Steckmeier S, et al. Investigation on radiofrequency and laser (980 nm) effects after endoluminal treatment of saphenous vein insufficiency in an ex-vivo model. Eur J Vasc Endovasc Surg 2006; 32: 318–325. 19. Bush RG, Shamma HN and Hammond K. Histological changes occurring after endoluminal ablation with two diode lasers (940 and 1319 nm) from acute changes to 4 months. Lasers Surg Med 2008; 40: 676–679. 20. Der Kinderen DJ, Disselhoff BC, Koten JW, et al. Histopathologic studies of the below-the-knee great saphenous vein after endovenous laser ablation. Dermatol Surg 2009; 35: 1985–1988.
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Phlebology OnlineFirst, published on May 30, 2014 as doi:10.1177/0268355514538248
Original Article
Histological difference between pulsed wave laser and continuous wave laser in endovenous laser ablation
Phlebology 0(0) 1–6 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514538248 phl.sagepub.com
Rei Kansaku1,2, Naoki Sakakibara1,2, Atsushi Amano2, Hisako Endo3, Takashi Shimabukuro1 and Michiaki Sueishi4
Abstract Background: Endovenous laser ablation to saphenous veins has been popular as a minimally invasive treatment for chronic venous insufficiency. However, adverse effects after endovenous laser ablation using continuous wave laser still remain. Pulsed wave with enough short pulse duration and sufficiently long thermal relaxation time may avoid the excess energy delivery, which leads to the perforation of the vein wall. Method: (1) Free radiation: Laser is radiated in blood for 10 s. (2) Endovenous laser ablation: Veins were filled with blood and placed in saline. Endovenous laser ablations were performed. Results: (1) There were clots on the fiber tips with continuous wave laser while no clots with pulsed wave laser. (2) In 980-nm continuous wave, four of 15 specimens had ulcers and 11 of 15 had perforation. In 1470-nm continuous wave with 120 J/cm of linear endovenous energy density, two of three presented ulcers and one of three showed perforation. In 1470-nm continuous wave with 60 J/cm of linear endovenous energy density, two of four had ulcers and two of four had perforation. In 1320-nm pulsed wave, there were neither ulcers nor perforation in the specimens. Conclusions: While endovenous laser ablation using continuous wave results in perforation in many cases, pulsed wave does not lead to perforation.
Keywords Chronic venous disease, chronic venous insufficiency, endovenous laser treatment, endovenous thermal ablation, pathology/histology
Introduction The importance of thermal relaxation time has been pointed out in laser dermatology.1 However, pulse duration and thermal relaxation time have rarely been noted in the field of endovenous laser ablation (EVLA). The efficacy of EVLA is said to be affected by the linear endovenous energy density (LEED) or the endovenous fluence equivalent (EFE).2 In addition to the amount of energy, the duration time of energy delivery would play a key role. EVLA using pulsed wave (PW) laser is said to lead to fewer side effects than using a continuous wave (CW) laser.3 The enough short pulse duration and sufficiently long thermal relaxation time would avoid the excess temperature elevation, which leads to the perforation of the vein wall. The purpose of the present study is to evidence the difference of the mechanism of EVLA using PW and CW at various energy settings.
Methods Free radiation in blood Laser is radiated in heparinized whole blood (Figure 1) for 10 s. The settings were 10 W of 980-nm CW diode laser (980 CW, Biolitec AG, Vienna), 8 W of 1470-nm CW diode laser (1470 CW, Diotech, Busan), and 6 W 40 Hz of 1320-nm Nd:YAG PW laser (1320 PW, 1 The Department of Cardiovascular Surgery, Edogawa Hospital, Tokyo, Japan 2 The Department of Cardiovascular Surgery, Juntendo University, Tokyo, Japan 3 The Department of Pathology, Edogawa Hospital, Tokyo, Japan 4 Shinagawa Heart Medical Clinic, Tokyo, Japan
Corresponding author: Rei Kansaku, The Department of Cardiovascular Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
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Figure 2. EVLA (in vitro). Great saphenous veins were filled with whole blood and heparin, and placed in saline. EVLAs were performed.
Figure 1. Laser radiation in whole blood. Laser is radiated in heparinized whole blood.
Table 1. Setting for the free radiation of laser in blood. Device
Fiber
Setting
980 nm CW 1470 nm CW 1320 nm PW
Bare Bare Covered
10 W 8W 6 W 40 Hz
980-nm continuous wave (980 CW) laser, 1470-nm continuous wave laser (1470 CW), and 1320-nm pulsed wave (1320 PW) laser are radiated in heparinized whole blood for 10 s.
Cooltouch, Roseville, CA) (Table 1). Bare fibers were used for 980 CW and 1470 CW, while fibers covered by Teflon buffer materials (SaphFire, Cooltouch, Roseville, CA) were used for 1320 PW. The visual changes are recorded with a digital video camera.
EVLA (in vitro) Great saphenous veins were obtained from patients who had undergone stripping surgeries for chronic venous insufficiency. Written informed consents were obtained from all patients. The veins were filled with whole blood and heparin, and placed in saline (Figure 2). EVLAs were performed using 980-nm CW diode laser (980 CW), 1470-nm CW diode laser (1470 CW), or 1320-nm Nd:YAG PW laser (1320 PW). In the group using 980 CW, the power and the velocity were (1) 10 W 1.4 mm/s (70 J/cm). In the group using 1470 CW, the power and the velocity were (2) 6 W 0.5 mm/s (120 J/cm) and (3) 6 W 1.0 mm/s (60 J/cm), respectively. In the group using 1320 PW, the power, the frequency of pulses, the pulling velocity, and the pulse duration times were (4) 6 W 40 Hz 1.0 mm/s 350 ms (60 J/cm), (5) 6 W 50 Hz 1.0 mm/s 350 ms (60 J/cm), (6) 12 W 40 Hz 2.0 mm/s 300 ms (60 J/cm), (7) 15 W 40 Hz
2.0 mm/s 300 ms (75 J/cm), and (8) 18 W 40 Hz 2.0 mm/s 300 ms (90 J/cm), respectively (Table 2). The veins were fixed in formalin and histologically investigated with a light microscopy.
Results Free radiation in blood We found a small bubble on the fiber tip during laser radiation in blood using both PW and CW. There were clots on the fiber tips after 10 s radiation using CW laser (Figure 3). However, there were no clots after radiation using PW laser (Figure 4).
EVLA (in vitro) In the group using 980 CW, four of 15 specimens (27%) had developed ulcers and 11 of 15 specimens (73%) had suffered perforation. In the group of 1470 CW with 120 J/cm of LEED, two of three specimens (67%) presented ulcers and one of three specimens (33%) showed perforation. In the group of 1470 CW with 60 J/cm of LEED, two of four specimens (50%) had developed ulcers and two of four specimens (50%) had perforation. In the group of 1320 PW, there were neither ulcers nor perforation in the specimens (Table 3). Figure 5 shows the typical changes of vein walls after EVLAs.
Discussion Although EVLA to saphenous veins is popular as a minimally invasive treatment for chronic venous insufficiency, the mechanism of EVLA is still significantly unknown. Several potential mechanisms of EVLA have been proposed: first, the optical-thermal response of the vein wall to scattered laser light4; second, the thermal response of the vein wall to condensing steam bubble4,5; third, the direct contact between the hot fiber tip and the wall5,6; and fourth, the thermal response of the vein wall to heat diffusion from the hot fiber tip.7,8
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Table 2. Setting for EVLA (in vitro). S.No.
Device
Energy (W)
Frequency (Hz)
Velocity (mm/s)
LEED (J/cm)
Pulse duration (ms)
Peak power (W)
1 2 3 4 5 6 7 8
980 CW 1470 CW 1470 CW 1320 PW 1320 PW 1320 PW 1320 PW 1320 PW
10.0 6.0 6.0 6.0 6.0 12.0 15.0 18.0
– – – 40 50 40 40 40
1.4 0.5 1.0 1.0 1.0 2.0 2.0 2.0
70 120 60 60 60 60 75 90
– – – 350 350 300 300 300
– – – 429 343 1000 1250 1500
Energy, frequency, velocity, and pulse duration are settings for experiments. Linear endovenous energy density (LEED) and peak power were calculated by settings.
Figure 3. Fiber tip after laser radiation using continuous wave laser.
Figure 4. Fiber tip after laser radiation using pulsed wave laser.
Also, the important role of blood in EVLA has been noted.8,9 During EVLA, thermal changes would be introduced in the vein walls through carbonized blood deposited on fibers.7 There are two concepts of how to make the thermal change to the vein walls beyond clots;
adding higher energy accepting the presence of clots or avoiding clot formation. Many efforts to avoid clots from forming have failed in the past. Wave length, targeting water, or hemoglobin would influence clot formation. However, free radiation experiments in the present study showed clots on the fibers after radiation by laser in blood even using 1470 nm of wave length, which is absorbed by water more than 980 nm. According to the absorption spectrum of hemoglobin and water,10 the wave length of 1320 nm and 1470 nm has been believed appropriate to change the vein wall, while wave length of 980 nm influences the hemoglobin more than the water. But because the wave length study was not conclusively resolved, various fibers have been developed, including covered or jacket fibers, radial fibers,11 and tulip catheters.12 We have treated saphenous veins with chronic venous insufficiency with EVLA using 1320 PW laser since 2007. PW laser has some advantages over CW laser. Anderson and Parrish13 proposed the theory of selective photothermolysis as an advantage of PW laser in 1983. Suitably brief pulses of selectively absorbed optical radiation can cause selective damage. When we develop EVLA, not only the energy setting, velocity, or wave length but also pulse duration time, or thermal relaxation time, and more details should be considered. In discussions about the appropriate energy of EVLA, at least three points should be distinguished accurately: (1) the energy setting of the devices, (2) the actual energy delivered at the top of the fiber, and (3) the distribution of energy from the top of the fiber and the vein wall. Clot formation suggests that excess energy is consumed at the top of fiber. We need to consider two things when we find carbonized clots on the fiber: (1) some of the energy was wasted, and (2) it shields energy from the top of the fiber and the vein wall. Thinking of the negative effect of clots, avoiding clot formation
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Table 3. Changes of venous walls after EVLA. Numbers S.No.
Device
Power (W)
Frequency (Hz)
LEED (J/cm)
Ulcer
Perforation
Specimens
1 2 3 4 5 6 7 8
980 CW 1470 CW 1470 CW 1320 PW 1320 PW 1320 PW 1320 PW 1320 PW
10.0 6.0 6.0 6.0 6.0 12.0 15.0 18.0
– – – 40 50 40 40 40
70 120 60 60 60 60 75 90
4 (27%) 2 (67%) 2 (50%) 0 0 0 0 0
11 (73%) 1 (33%) 2 (50%) 0 0 0 0 0
15 3 4 2 4 10 3 2
The numbers of specimen which had ulcer or perforation at the various power, frequency, and linear endovenous energy density (LEED). Laser devices included 980-nm continuous wave (980 CW) laser, 1470-nm continuous wave (1470 CW) laser, and 1320-nm pulsed wave (1320 PW) laser.
Figure 5. Typical changes of venous walls after EVLA. Histological differences of vein wall before EVLA (Pre), after EVLA using 980nm continuous wave (980 CW) laser, and 1320-nm pulsed wave (1320 PW) laser. Hematoxylin-eosin (HE) stain, Azan stain and Elastica van Gieson stain were used. Polarization emphasizes the change of the wall with Elastica van Gieson stain.
should be the basic and most important concept for developing EVLA. From this point of view, we propose using PW for EVLA. Some reasons could be supposed that why there were no clots on the fiber after free radiation examination using PW in this study. One reason may depend on the difference of amplitude of the energy settings. The settings of this study are decided from these clinical uses. Probably because clots are easily formed on the fiber tip during EVLA using CW, stronger energy would be required compared with PW. The second reason is the shock wave made by PW laser. PW leads to a shock wave with rapid localized heating,13 which also makes popping sounds during EVLA.
Because of the clear fiber tip, the energy through fibers would be delivered with minimal reduction during EVLA using PW. EVLA using PW achieved high occlusion rate even with lower energy setting comparing with CW.14,15 So we hypothesized that the mechanism of EVLA using PW is different from its using CW. To reveal more, the histological examination was performed in the present study. There are studies about EVLA histology using CW laser.4,12,16–20 The change in the vein wall after EVLA with CW includes (1) carbonization, (2) homogeneous basophilic discoloration, (3) coagulation necrosis, and (4) loss of distinction between collagen and muscular
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bundles.20 Fan and Rox-Anderson5 said that proper EVLA histology using CW laser was collagen denaturing, but too much energy leads to bilateral charring, ablation, or perforation. The histological changes were different in EVLA using PW and CW in the present study. EVLA using PW has more setting parameters compared with EVLA using CW. Not only energy setting and drawing velocity but also frequency and pulse duration time could be controlled. In our preliminary in vitro examination, the histological changes were varied depending on the frequency or pulse duration time. Increasing the pulse duration time induces clot formation even using PW. The threshold length of pulse duration seems to be influenced by the energy setting. From the limited number of experiments in the present study, a final answer does not become apparent, but we can see some suggestions about the difference between EVLA using PW laser and CW laser. One suggestion is that using PW laser may avoid elevating the temperature more than necessary. Many enzymes are heat-labile. Above 60 C to 70 C, structural proteins including collagens are also denatured. Above 70 C to 80 C, nucleic acids are denatured and membranes become permeable. Thus, essentially any mammalian tissue heated to 70 C to 100 C may suffer protein denaturation, leading to coagulation necrosis. Above 100 C, vaporization of tissue water occurs with rapid volume expansion.13 We think that the amount of energy that destroys the veins functionality is in fact not so different from the energy required to warm the blood in the veins from 60 C to 100 C. Chronic animal studies, including histological examinations, may be required to prove our hypothesis. The histological changes after EVLA using PW laser are found mainly as a change of the media of venous walls, when the changes after EVLA using CW are found as destruction of constructions. Although changes in color are thought to be denaturing of collagen fibers and/or elastic fibers, further studies are required to show which kind of denaturing happens. These changes of EVLA using PW include basophilic change, i.e. purple, in hematoxylin-eosin (HE) stain, redness in Azan stain, and yellowing in Elastica Van Gieson stain. Interestingly, polarization helped us to find the changes in the specimens with Elastica Van Gieson stain (Figure 5). Geometrical disarray may lead to difficulty of polarization in the heated vein wall.
Conclusion While EVLA using a CW laser results in perforation in most cases, EVLA using a PW laser does not lead to perforation even at a high energy setting.
Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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