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Effects of laser parameters on pulsed Er-YAG laser skin ablation

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a promising tool for the careful removal of superficial skin lesions. In order to provide optimized ... In contrast, no significant effects of the laser parameters on the.
Effects of Laser Parameters on Pulsed Er-YAG Laser Skin Ablation

RAIMUND HIBST a, ROLAND KAUFMANN b alnstitut fEtr Lasertechnologien in der Medizin an der Universit~t UIm, Helmholtzstrasse 12, D-7900 UIm, Germany ~Department of Dermatology, University of UIm, 7900-UIm, Germany

A b s t r a c t . Previous studies demonstrated that pulsed 2.94~m Er-YAG laser radiation allows a precise etching of organic tissue with only minimal thermal damage. This makes the Er-YAG laser a promising tool for the careful removal of superficial skin lesions. In order to provide optimized laser parameters for potential clinical use and to enhance our understanding of the mid-infrared ablation process, we measured the ablation rate, temperature profile and damage zones for various pulse numbers, radiant energies and pulse repetition rates. Ablation is very efficient (about 6 t~m j - 1 cm 2 for high radiant exposure) and the crater depth is exactly (1 Hz) or nearly (2 Hz) linearly related to the radiant exposure. In contrast, no significant effects of the laser parameters on the thermal damage of the epidermis and the crater bottom were observed. In conclusion, for a future clinical use high radiant energies should be applicable without the disadvantage of enhanced damage.

INTRODUCTION Current use of lasers in dermatological surgery for skin cutting or tissue removal is mainly based on the thermal effect of radiation emitted by continuous wave (cw) lasers. The choice of wavelength, irradiance and exposure time thereby determines the interplay between tissue coagulation and removal. Depending on the parameters used, conventional cw laser ablation of superficial skin lesions (Ar § NdYAG, CO2 laser) or skin incisions (CO2 laser) will result in varying amounts of adjacent thermal tissue injury. Apart from the benefit in controlling capillary bleeding, excessive thermal destruction of viable tissue is a major disadvantage when treating more delicate lesions or larger areas, followed by an impaired wound healing and the risk of hypertrophic scar formation (1). In order to minimize the adjoining heat damage, pulsed lasers were tested in the past using wavelengths that are highly absorbed by tissue (ultra-violet laser) or by tissue water (midinfrared laser, CO2-TEA laser). They have been shown to precisely etch a variety of organic tissues including skin, with only minimal thermal injury (2-7). Based on our own preliminary results (8) and first reports of others Paper received 27 September 1990

(9, 10), the Er-YAG laser seems to be very promising. In our present work we investigated the effects of different 2.94 t~m Er-YAG laser parameters (various radiant energies, pulse numbers and pulse repetition rates) on skin ablation. The study describes measurements of in vitro ablation rates and in vivo damage and temperature effects, in order to understand better the underlying mechanisms of mid-infrared skin ablation and to provide baseline data for optimized laser parameters in future clinical applications.

MATERIALS AND METHODS Laser system The experiments were performed with a flashlamp-pumped Er-YAG laser (Quantronix 294) operated in the normal spiking-mode. The laser pulse consists of micropulses (spikes) of l t~s duration (FWHM) each. N u m b e r and height of the micropulses increase with the flashlamp energy. For high energies the basic parts of the single spikes are no longer separated, but form a quasi continuous pulse basis. As measured with a fast pyroelectric detector (Molectron P5), experiments were done with a Lasers in Medical Science Vol 6:391 1991 9 Bailliere Tindall

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laser emission of about 250 t~s total duration, with a few dominant spikes at the beginning of the pulse. The spatial beam profile was adjusted approximately to a Gaussian shape. Both for in vivo and in vitro experiments the laser light was transmitted through a mirror system and focused perpendicularly onto the specimens. The focus diameter was once measured by the knife-edge method and then controlled using burn paper. The 1/e2-diameter was 690 t~m. The radiant energy per pulse was measured with an energy meter (Gentec ED200, ED-500) always at the sample site.

In vitro measurements The quantitative amount of tissue removal was determined using freshly excised pig skin. Skin specimens of 2 • 4cm 2 (epidermis and corium; thickness about 2 mm) were laid on a microscope slide in front of an energy meter and irradiated. Irradiation was stopped when radiant energy of the laser pulse was detected by the energy meter. The number of pulses needed to perforate the skin was counted. From this number and the thickness of the specimens the (average) crater depth per pulse was calculated. In order to keep both the spatial beam shape and the temporal pulse profile constant, radiant energy was varied by attenuating the laser beam by means of microscope slides. Experiments were done under the same conditions for pulse repetition rates of 1 Hz and 2 Hz. For each parameter set experiments were repeated at least 10 times.

In viva experiments For the in vivo studies anaesthetized (i.v. ketamin lOmg kg l h) domestic pigs were irradiated on the shaved lateral trunk. Radiant energy and repetition rate were varied in the range possible with the laser system. The irradiation parameters are summarized in the first parts

R. Hibst, R. K a u f m a n n

of Tables 1 and 2. The number of pulses was chosen in such a manner, that both the influence of the radiant energy (same crater depth) and the effect of the pulse number could be evaluated. Irradiations were reproduced for all parameter combinations at least three times. All lesions were excised and examined under the light microscope after standard histopathological preparation and staining (HE, Elastica). The temperature distribution on the skin surface was observed using a thermal imaging system (Hughes Aircraft Company, Probeeye Thermal Video System Series 3000). To determine the emissivity coefficient e, skin was heated and temperature was measured both with the thermal imaging system and a thermocouple. With e = 0.97 both measurements were consistent. Each second 20 thermal pictures were taken and stored on a video system. Temperatures were observed for radiant energies from 100mJ to 300mJ, repetition rates from 0.5 to 5 Hz, and pulse numbers up to 200.

RESULTS Ablation rate Er-YAG laser radiation results in conical craters. Their diameter at the skin surface was about 900~m and thus larger than the 1/e 2diameter of the beam profile (690 t~m). So the r a d i a n t exposure calculated from the total r a d i a n t energy and the 1/e2-diameter describes r a t h e r the energy density at the beam centre, which is also essential for the perforation, than the average energy density. For a pulse repetition rate of 1 Hz, the crater depth per pulse is linearly related to the energy and the radiant exposure (Fig. 1). The straight line intersects

500,

400:

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~ 300 o.

9 zoo•

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Fig. 1. Ablation rate for pig skin. The correlation coefficient for the straight line fitted to the data obtained for a repetition rate of 1 Hz is 0.9998.

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0

~,T

,

,

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20 40 80 80 Radiant expo=ure per pulse (,J cm-Z)

I00

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393

Pulsed Er-YAG Laser Skin Ablation

Fig. 2. Distance of isotherms from the crater centre. (a) Radiant energy 100 m J, repetition rate 1 Hz. (b) Radiant energy 300 m J, repetition rate 1 Hz. (c) Radiant energy 300 m J, repetition rate 4 Hz,

2.0

Ca) 1.5 40~

1.0

0.5

5

o

the x-axis at 9.4J cm -2. This point marks the radiant exposure which is at least necessary to perforate the specimens. Additional measurements indicate that this radiant exposure depends on the beam profile, including the focus diameter, and the thickness of the specimen, both affecting the shape of the crater. The radiant exposure needed for perforation is usually larger than the (ablation) threshold for producing shallow craters. The slope of the line is influenced much less by the focus diameter and the specimen thickness. When increasing the repetition rate to 2 Hz, ablation rate increases for low radiant exposures, but decreases for higher ones (Fig. 1). These data agree with measurements of Walsh and Deutsch (10) also obtained for a repetition rate of 2 Hz.

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50

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Temperature

The time resolution of the thermal imaging system is 50 ms. This is slow compared to the pulse duration of about 250t~s. Therefore instead of the maximum temperatures during the laser pulse, only average temperatures following the pulse are measured. The Er-YAG laser irradiation results in a temperature profile with concentric isotherms around the crater. In Fig. 2(a, b, c) the radii of three different isotherms are plotted for an irradiation with laser pulses of 1 0 0 m J and 300 mJ, respectively. While for the 300 mJ application isotherms of 40~ 50~ and 60~ can be observed, the temperature effect of 100 mJ pulses does not reach 50 ~ even when the repetition rate is increased to 5Hz. The radii increase with the number of pulses, but the slope of the curve decreases, resulting in a steady-state temperature profile. The higher the radiant energy and the repetition rate are, the more pulses are needed to reach the steady state, but maximum radii are significantly larger then. Lasers in Medical Science 1991 @ Bailliere Tindall

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=o 30 ,o

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The temperature measurements indicate, that for a smaller number of pulses or for low radiant e n e r g i e s - - a s used in the experiments to evaluate damage (see Table 1)--temperatures which are high enough to cause thermal damage are limited to the close vicinity of the crater.

Damage

Corresponding to the measured temperature profile, the clinical pictures of all Er-YAG laser induced lesions show sharp and clean margins with no apparent signs of thermal tissue injury. Accordingly, capillary bleeding occurred when craters reached the papillary dermis. The histology presents only little signs of coagulation at the crater walls and the bottom,

R. Hibst, R. Kaufmann

394

Fig. 3. Light photomicrograph of ablation crater edge. The crater was produced with 25 pulses of 200 mJ each, applied with a repetition rate of 1 Hz. Thermal damage zones are indicated by arrows (scale bar: lO0#m).

Table 2. Thermal damage zones for various repetition rates

,(Hz) 0.5

Table 1. Thermal damage zones for various radiant

energies E (mJ) 50 150 250 350 430

N

31 (tLm)

S~ (t~m)

$3 (tLm)

16, 32, 64 8, 16, 32 4, 8, 16 2, 4,6 1, 3,5

197+89 213 + 3 3 190+ 38 221+40 1 9 4 + 19

162+74 184+37 161+44 195+28 177+24

69+37 3 5 + 12 3 1 + 12 2 1 + 10 4 4 + 14

E: radiant energy per pulse; N: number of pulses; S: thermal damage zone (mean + SD) (N = 9); 1: epidermal, 2: subepidermal, 3: basal; repetition rate was 1 Hz, focus diameter (1/e 2) was 690 ~m.

S1 (t~m)

$2 (gm)

$3 (gm)

2 5

100 100 100 100

350 157 175 200

+ + + +

55 40 25 25

183 150 165 133

+ + + +

29 87 15 42

130 80 70 70

+ + + +

70 44 10 26

0.5 1 2 5

200 200 200 200

217 233 267 170

+ + + +

76 61 58 26

190 210 200 133

+ + + +

66 66 96 58

30 35 45 40

+ + + +

12 16 8 13

0.5 1 2 5

300 300 300 300

267 200 250 226

+ + + +

76 91 62 40

240 163 160 177

+ + + +

115 85 56 25

35 25 50 35

+ + + +

6 15 11 15

1

b u t a l a r g e r d a m a g e zone in the a d j a c e n t e p i d e r m i s a n d u p p e r d e r m i s (Fig. 3). D a m a g e w i d t h is u s u a l l y not c o n s t a n t a l o n g t h e c r a t e r surface, b u t i r r e g u l a r . For a s y s t e m i c study, t h e m a x i m u m c o a g u l a t i o n w i d t h found at the c r a t e r b o t t o m or t h e wall n e a r b y w a s measured. E p i d e r m a l a n d s u b e p i d e r m a l d a m a g e were d e t e r m i n e d from the zone of cell distortion. The results are s u m m a r i z e d in Tables 1 a n d 2. No statistical s i g n i f i c a n t influence of t h e pulse n u m b e r on the d a m a g e was found. As a consequence, Table 1 gives the m e a n v a l u e s for t h e complete set of pulse n u m b e r s . Cons i d e r i n g t h e u n c e r t a i n t y g i v e n by the s t a n d a r d d e v i a t i o n , t h e r e is no influence of t h e r a d i a n t

E (mJ)

v: pulse repetition rate; E: radiant energy per pulse; S: thermal damage zone (mean + SD) (N = 3); 1: epidermal, 2: subepidermal, 3: basal; pulse number was 10, focus diameter (1/e 2) was 690 #m. e n e r g y , except a little increase of the basal c o a g u l a t i o n zone for low energies. Likewise, T a b l e 2 shows no significant dependence of the d a m a g e on the repetition rate. E x c e p t - f o r low r a d i a n t exposures, the c o a g u l a t i o n zone at the c r a t e r b o t t o m is less t h a n 50t~m, in a g r e e m e n t with previous reports (8, 9).

DISCUSSION Ablation rate T h e w a v e l e n g t h of 2.94/xm of the E r - Y A G laser coincides w i t h a s t r o n g a b s o r p t i o n peak of water. A l t h o u g h published a b s o r p t i o n d a t a differ (11-13), an absortion coefficient of about 1 4 0 0 0 c m -1 can be a s s u m e d for pure water. Since w a t e r is the m a i n a b s o r b e r of the ErY A G laser r a d i a t i o n in skin, the w a t e r content of 70% should cause an a b s o r p t i o n coefficient in t h e order 1 0 0 0 0 c m -1. F r o m the m e a s u r e m e n t of the a b l a t i o n rate, it is obvious t h a t the c r a t e r d e p t h per pulse is m u c h b i g g e r t h a n the Lasers in Medical Science 1991 @ Bailliere Tindall

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Pulsed Er-YAG Laser Skin Ablation

penetration depth 1/a = ltLm. In agreement with previous work (9, 10), we suppose t h a t tissue removal takes place during the laser pulse, and not in a single explosion after the complete laser pulse is absorbed. For a rough quantitative modelling of the ablation process, let us consider a tissue surface layer with a thickness corresponding to the penetration depth 1/a. In a very short time interval (no ablation during this time) in this layer about 60% of the actual incoming light energy is absorbed and transferred to heat. When neglecting heat loss from this layer due to heat conduction during this short time, the temperature rise AT of the tissue is given by: AT

-

0.6aI pc

t

(1)

where p is the density, c the specific heat and I the (average) irradiance (Wcm-2). In order to estimate the time scale of tissue heating we rearrange Eq. (1) and choose the constants of w a t e r ( p = l g c m 3, c = 4 . 2 J g K -1) a n d a = 10 000 cm-1: t ~ 7-

Wcm 2 AT 10

-4

s.

-

-

I

For a radiant

exposure

of 25 J cm

(2)

s

2 and a pulse

duration 250 t~s, i.e. an average irradiance of 25J cm-2/250~s = 100kW cm -2, the time needed to heat the surface layer from 37 ~ to 100 ~ is about 0.5 tLs. Although until now the exact temperature which must be reached to cause an explosive tissue removal is unknown, Eq. (2) shows t h a t it will be fast compared to the pulse duration. If the laser pulse is not shielded by a plasma or by the ejected material, ablation will be continuous (perhaps modulated by the spikes) during the complete laser pulse. Both conditions should be true for the experimental situation: a plasma formation was not observed, and water vapour absorbs the 2.94~m radiation much less than the liquid water (14). A simple model described in (15) shows, t h a t in agreement with thermodynamicat calculations (16, 17), a continuous tissue removal causes a linear relationship between crater depth per pulse and radiant exposure. From the slope of the straight line measured for a repetition rate of 1Hz (Fig. 1), one can calculate the energy which must be absorbed per cm 3 skin to cause ablation to be 1.5 kJ cm 3. This is in the same range measured for other pulsed lasers (see Table I in (8)). The threshold energy density obtained for skin is 60% of the energy density Lasers in Medical Science 1991 @ Baifliere Tindall

to heat and vaporize water (2.6 kJ cm-3), which is not very different from the water content. From this result one might conclude t h a t the temperature needed for pulsed Er-YAG laser induced skin ablation is not much higher t h a n 100~ This temperature would fit to the absorption characteristic of water for the 2.94 t~m radiation. Once the water is vaporized, absorption decreases and further heating of the vapour is inhibited. I f H 2 0 is the only absorber, temperature will not exceed 100 ~ (like a water bath). Indeed, because carbonization was never observed, temperature should be lower t h a n about 150~ The measurements indicate, t h a t tissue is not completely vaporized, but will be ejected by a sudden vaporization of the water content. F u r t h e r mechanical mechanisms as observed in gelatine (17, 18) might also occur. The deviations from the straight line observed for the repetition rate of 2 Hz might be due to thermal and experimental side effects. The increase for low radiant exposures can result from a decrease of the ablation threshold caused by an enhanced tissue preheating by the previous pulse. When the r a d i a n t exposure becomes higher, for 2 Hz an increasing scattering of the visible aiming beam was observed. The scattering by the ejected material and the absorption by condensed water might attenuate the incoming Er-YAG laser to such a degree, t h a t the ablation rate becomes apparently lower t h a n for 1Hz. The lower the repetition rate, the more material is removed from the beam path.

Temperature and damage Thermal damage due to protein denaturation is a time and temperature dependent process. It can be described by a rate process equation derived from the Arrhenius equation d~ aexp[ B l dt - ~-

(3)

where t2 is the damage parameter (~ -> 0.53: irreversible damage begins to occur; ~ -> 1: complete epidermal necrosis), R the gas cons t a n t (R = 8.314J mole -1 K), T the absolute temperature and A, B are constants (for pig skin: A = 3.1 • 109Ss -1, B = 6 2 8 0 2 0 J mole -1) (19). According to this model there should be a direct relationship between temperature and damage. However, when comparing in vivo measurements of epidermal temperature and

396

damage revealed by histology, there seems to be a discrepancy: the observed temperature profile clearly depends on the radiant energy of the laser pulses and the repetition rate. The thermal epidermal damage zones should correspond to this profile, but no significant dependence on laser parameters was found. For application of 1 0 0 m J laser pulses (Fig. 2(a)), the observed m a x i m u m temperature does not reach 50 ~ According to Eq. (3) thermal damage should not occur within about 500 s (d~/dt = 9.4 x 10-4s-1). However, the histological evaluation reveals epidermal damage zones in the order of 200 ~m (Tables 1 and 2). This observation can be explained by the assumption that under the described experimental conditions, epidermis is damaged by a temperature rise too fast to be detected by the thermal imaging system. This short t e m p e r a t u r e rise can occur during the laser pulse in parts of the skin directly exposed to the light, i.e. in the non-ablative parts of the laser beam (sub-threshold for ablation) which are nearly the same for all radiant energies. This fast mechanism of thermal damage could explain the observed independence of the epidermal damage from radiant energy and repetition rate. Epidermal damage observed for higher radiant energies (e.g. 300mJ) could be explained by this process too, but the observed (average) temperatures (Fig. 2(b, c)) for small pulse numbers) are also high enough to cause thermal damage. For a temperature of 60~ thermal damage should occur after 0.5 s, and complete necrosis after 1 s. Since heat is added with each laser pulse, damage by an integral warming up of the tissue becomes more dominant for higher pulse numbers. Due to heat conduction temperature rise and epidermal damage then are not limited to the directly irradiated tissue area (Fig. 2(b, c) for big pulse numbers). Damage to the crater walls and bottom could be explained by the same subablative heating as discussed before. Additional heat sources could be hot ejected material (vapour or liquid) or the thin vaporizing layer during the laser pulse. The boundary between tissue and vapour moves during the laser pulse from the surface to the crater bottom. Therefore the velocity of the vaporizing layer is given by the quotient from crater depth per pulse and the pulse duration. For our experiments this is in the range from 0.1 to 1.6t~m tzs 1. Assuming a thickness of this layer in the order of the

R. Hibst, R. Kaufmann

penetration depth (1 t~m), the interaction time of this hot layer with the crater wall is in the range of 0.1 to 1.6 t~s. Since the temperature of this layer is at least 100 ~ this time is long enough to cause damage (gt = 0.53: r -< ns). As discussed for the subablative heating, only minimal effects of the repetition rate and pulse number should be expected. In order to analyse the mechanism of thermal damage more exactly, quantitative studies of heat and heat transfer would be necessary. For clinical applications it can be concluded, that the use of high radiant exposures increases the ablation rate without affecting the damage zone. Even a relative high repetition rate can be used, especially when the laser spot is moved. For the clinical practice, lasers with both high energy output per pulse and high repetition rate would be desirable.

ACKNOWLEDGEMENTS We t h a n k Dr R. Steiner for providing all necessary resources for the experiments, Dr Th. Meier for helpful discussions, D. SchrSder and Mines. A. BOhmler and K. H a u l for technical assistance.

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Pulsed Er-YAG Laser Skin Ablation

11 Zolotatrev VM, Mikhailov BA, Alperovich LI, Popov SI. Dispersion and absorption of liquid water in the infrared and radio regions of the spectrum. Opt Spectrosc 1969, 26:430-2 12 Esterowitz L, Hoffman C. Laser tissue/water interaction of the erbium 2.9t~m laser. Proc SPIE 1987, 712:196-7 13 Robertson CW, Williams D. Lambert absorption coefficients of water in the infrared. J Opt Soc Am 1971, 61:1316-20 14 Young JS. Evaluation of nonisothermal band model for H20. J Quant Spectrosc Radiat Transfer 1977, 18:2945 15 Hibst R, Keller U. Experimental studies of the application of the Er:YAG laser on dental hard substances: I.

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16

17

18

19

m e a s u r e m e n t of the ablation rate. Lasers Surg Med 1989, 9:338-44 Partovi F, Izatt JA, Cothren RM et al. A model for t h e r m a l ablation of biological tissue using laser radiation. Lasers Surg Med 1987, 7:141-54 Zweig AD, Weber HP. Mechanical and t h e r m a l parameters in pulsed laser cutting of tissue. IEEE J Quant Electron 1987, QE-23(10):1787-93 Zweig AD, Frenz M, Romano V, Weber HP. A comparative study of laser tissue interaction at 2.94 t~m and 10.6#m. Appl Phys B 1988, 47:259-65 Henriques FC, Moritz AR. Studies of t h e r m a l injury, I, II. Am J Path 1947, 23:531-49, 695-720

Key words: Ablation; Damage; Er-YAG laser; Efficiency