Chemical Decomposition of Urinary Stones during Holmium Laser Lithotripsy – Part I: Lack of a Photomechanical Effect Kin Foong Chana, George J Vassarb, T. Joshua Pfefera, Joel M. H. Teichmanb, Randolph D. Glickmanb, Susan E. Weintraubb, Ashley J. Welcha a
b
University of Texas at Austin, Austin, TX 78712 University of Texas Health Science Center, San Antonio, TX 78284 ABSTRACT
The Ho:YAG laser commonly used for clinical lithotripsy of urinary stones typically emits 250-µs pulses at a wavelength of 2.12 m and repetition rates of up to 10 Hz. This pulse duration is longer than the time required for a pressure wave to propagate beyond the optical penetration depth of this wavelength in water. Fast-flash photography was used to study the dynamics of urinary stone fragmentation by the Ho:YAG laser. Stone ablation began approximately 50 µs after the onset of the laser pulse, long before the collapse of the cavitation bubble at about 350 µs. Pressure measurements, made with a PVDF needle-hydrophone and correlated with the fast-flash images, indicated that the peak acoustical transient was less than 2 bars. Regardless of fiber orientation to the stone, no shockwaves were recorded at the beginning of the bubble, and the maximum pressure waves recorded at bubble collapse were approximately 20 bars. However, no fragmentation occurred during or subsequent to the bubble collapse. These measurements indicated that stone ablation was not due to a photomechanical effect. Keywords: holmium laser, laser lithotripsy, urinary calculi, photothermal, photomechanical, photoacoustic, bubble, cavitation, stress wave, chemical decomposition
1. INTRODUCTION For the past ten years, the most popular lithotriptors were the flashlamp-pumped pulsed-dye ( = 509, 590, 596, 640, 720 nm, etc.) and Q-switched Nd:YAG ( = 1.064 m) lasers. The mechanism of action for stone fragmentation was studied extensively by Watson 1, Dretler 2 and Nishioka et al.3 in the 1980s. However, it was not until Rink et al.4-5 that the conclusive fragmentation mechanism was identified and fully understood. For Q-switched Nd:YAG lasers, the 500-ns laser pulse produces large shockwaves as a result of plasma expansion and cavitation collapse. As for pulsed-dye lasers, the 3-s laser pulse creates a small stress wave during the first few microsecond because of a delay in plasma formation, and a large shockwave upon cavitation collapse. These large shockwaves are in excess of 100 bars, and are the cause of stone fragmentation. This fragmentation process has been coined laser-induced shockwave lithotripsy (LISL). The long pulse Ho:YAG laser ( = 2.12 m; p = 250 to 350 s) has been used extensively for lithotripsy since 1994. The holmium laser has several advantages over pulsed-dye and Q-switched Nd:YAG lasers. It was reported that the Q-switched Nd:YAG laser was not efficient in fragmenting calcium oxalate monohydrate (COM) stones 6 and that the pulsed-dye laser was not able to fragment cystine stones 7-8. On the other hand, the holmium laser worked well for all stone types. The holmium laser produced finer or smaller fragments compared to pulsed-dye and Q-switched lasers, allowing easier passage 9.
a
Author contact information: Kin Foong Chan,
[email protected], Tel: (512)471-9497, Fax: (512)475-8854 Department of Electrical and Computer Engineering, University of Texas at Austin, ENS 610; Austin, TX 78712, U.S.A.
Schafer et al.10 attempted to define the fragmentation mechanism of biliary stone by the long pulse Ho:YAG laser with some success. Observations made by Teichman 11,12,13,14, Dushinski 15, and Zhong 16 et al. point to a photothermal mechanism. From the fundamental point of view, the long-pulse holmium laser irradiation in water/urine is not stressed confined. This means that acoustic waves propagate beyond the penetration depth of the laser during the pulse duration; hence there is no accumulation of mechanical energy within the optical zone during the early stage of bubble formation, and consequently no shockwave is generated. Later, since laser energy continues to be deposited at the distal end of the vapor bubble, the resulting bubble is not symmetrical. This process produces asynchronous bubble collapse at multiple locations. When the acoustic energy from these multiple collapse is superimposed in the time domain, only a weak pressure wave is generated. The intensity of this pressure wave is further diminished in the case of clinical lithotripsy, where the delivery fiber for the holmium laser is in the proximity of or in contact with the urinary stone. The urinary stone surface impeded vapor bubble expansion and deteriorated the strength or role of the photomechanical effects in holmium laser lithotripsy. In this study, we intend to quantify the photomechanical and photothermal effects during holmium laser lithotripsy, and identify the dominant fragmentation mechanism. We shall only present in this paper our study on the photomechanical aspect, and leave the photothermal aspect to a separate article (cf. Part II, Paper # 3601A-43).
2. METHODS 2.1 Urinary Stones Urinary stones were used in this photomechanical study. The stones, obtained from a stone analysis laboratory (Louis C. Herring Co., Orlando, FL), consisted of > 98% calcium oxalate monohydrate (COM), and > 98% cystine. COM and cystine were natural urinary stones, chosen to represent an inorganic and an organic stone, respectively. 2.2 Laser Source and Delivery The experiments were performed with a Laser 1-2-3 from Schwartz Electro-Optics ( = 2.12 m, 250 to 350 s) and a VersaPulse Select clinical Ho:YAG laser ( = 2.12 m, 250 s). Low OH- fibers (Coherent Medical Group) of 365-, 550-, and 1000-m diameters were used to deliver energy from the holmium laser to a water bath in which the urinary stone was submerged. Before each experiment, the optical fiber tips were cleaved and polished as necessary. The laser energy was measured at the output of the delivery fiber prior to, in between, and after the experiments to ensure there was no major energy fluctuation. This was accomplished by using a Molectron EPM2000 powermeter with a J25-Series pyroelectric detector. 2.3 Fast-flash Photography Time-resolved flash photography was used to document the lithotripsy process for different delivery fiber orientations. Figure 1 shows the experimental setup for studying the photomechanical effects of holmium laser lithotripsy. In the experiment, the urinary stones were cut with a dental diamond band saw to provide a flat target surface. A stone was then placed in a water-filled glass cuvette at room temperature (~ 23 C). During lithotripsy, the delivery fiber was placed at three orientations; either perpendicular, at a 45 angle, or parallel to the stone surface. A personal computer with a LabVIEW controlled data acquisition software package was used to trigger a pulse generator (DG535, Stanford Research Systems, Sunnyvale, CA), which in turn controlled the delay time, (2-1), between the onset of the Ho:YAG laser pulse and the flashlamp for time-resolved photography. A nitrogen-dye laser (LN-1000 nitrogen gas laser and LN-102 dye module, Laser Photonics, Orlando, FL; p = 500 ps; = 540 nm) was initially used as the flashlamp because of its short pulse duration capable of detecting acoustic shockwaves. When no shockwaves were detected, the nitrogen-dye laser was replaced by a Xenon-arc flashlamp because of ease of use.
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Figure 1. Experimental setup for fast-flash photography and acoustic pressure measurement. A nitrogen-dye laser ( = 540 nm) was used as a flashlamp initially for obtaining high quality (500-ps exposure time) time-resolved images. When no shockwaves were observed, a broadband Xenon-arc flashlamp (5-s exposure time) was used in place of the nitrogen-dye laser, and a PVDF-needle-hydrophone was added during the pressure measurement experiment along with concurrent acquisition of fast-flash images.
The holmium laser flash-pump consistently produced a bright ‘glow’ at the interaction site in the water bath as a result of scattering. In order to prevent contamination of our images, a long pass filter (03-FCG-113, Melles Griot, Irvine, CA) was placed at the output coupler of the Fabry-Perot cavity to block the visible and near infrared wavelengths (< 1000 nm) emitted from the flash-pump. The holmium laser beam was then coupled into a low OH optical fiber to be delivered to the stone surface in the water bath. Two beam splitters were placed at the outputs of the long-pulse Ho:YAG laser and the flashlamp to couple a small fraction (~ 4%) of the light to two photodiodes. Signals from the photodiodes, representing the temporal beam profiles of the holmium laser and the flashlamp, were monitored on a digital oscilloscope (TDS-640A 500 MHz-200 GS/s, Tektronix, Beaverton, OR). Knowing the exact relative temporal displacement between the two signals allowed us to determine the delay time of our fast-flash images from the onset of the Ho:YAG laser pulse. The flashlamp used in photography was split into two beams for simultaneous reflectance and transmission imaging. Lithotripsy events were recorded with increment delay-times of 25 or 50 s. In the case of the nitrogen-dye laser, a line filter (03-FIV-113, Melles Griot) at (540 10) nm was placed in front of the CCD camera (GP-MF 602, Panasonic, Japan), allowing only the nitrogen-dye wavelength to be transmitted into the CCD array. This technique further enhanced our imaging capability by avoiding contamination from the Ho:YAG laser flashlamp. The images captured by the CCD camera were recorded on a VCR (HR-S5200U, JVC, Japan) and displayed on a video-monitor. A time counter (TG-50, Horita, Mission Viejo, CA) was used to label the images as they were recorded. From the videocassette, individual frames of images were analyzed in freeze-frame style on a video-monitor and captured with a frame-grabber (Snappy, Play Incorporated, Rancho Cordova, CA) on a computer monitor. The holmium laser energy employed in this experiment was maintained at 375 5 mJ/pulse for a pulse duration of 250 s. During the experiment, nine warm-up Ho:YAG laser pulses (1.5-2.0 Hz) were delivered to a beam dump with a mirror shutter to allow the laser to achieve a stable energy level. The tenth and final pulse was delivered to the target calculus in the water bath by removing the shutter from the beam path. The flashlamp was then triggered
at a pre-set delay time from the onset of the final Ho:YAG laser pulse. A sequence of laser pulses and delay times provided images of the complete dynamic lithotripsy event, extending to hundreds of microseconds after the end of the Ho:YAG laser pulse. At least five images were captured for each delay time for the COM calculus and the cystine calculus at each different fiber orientation; either perpendicular, at a 45 angle, or parallel to the stone surface. 2.4 Pressure/Acoustic Measurements An IMOTEC needle-hydrophone (40-ns rise time, 1.502 mV/bar, where 1 bar 105 Pa 1 atm) consisting of a piezoelectric polyvinylidenefluoride foil was used to measure the laser-induced pressure transients. Acoustic signals were recorded with three different configurations: (1) ablation in clear water, (2) ablation with delivery fiber perpendicular to the stone surface in contact mode, and (3) ablation with delivery fiber parallel to the stone surface in contact mode. The hydrophone was placed a few millimeters away from the stone surface to avoid possible damage due to ejected fragments. The holmium laser energy was delivered via a low OH - optical fiber with a 550-m core diameter. Pulse energies between 300 mJ and 1 J were used. The signal from the hydrophone was displayed and recorded on a digital oscilloscope (Tektronix TDS 640A). During analysis, all signals were back-calculated to a pressure transient 1-mm away from the origin of bubble collapse. Fast-flash images that were captured simultaneously were used to correlate the acoustic transients to the dynamics of cavitation bubbles or lithotripsy. The setup for this experiment was the same as the fast-flash photography experiment (Figure 1), but with a needle-hydrophone in the water bath. At least five pressure measurements were recorded for each configuration mentioned above.
3. RESULTS 3.1 The Dynamics of Lithotripsy by Fast-Flash Photography With laser energy maintained at 375 5 mJ/pulse (p = 250 s), a pear-shape vapor bubble was produced when the delivery fiber (fiber diameter = 550 m) was suspended in water, with the urinary stone (COM or cystine) located about 5 mm away from the fiber tip. At maximum expansion, the vapor bubble did not reach the stone surface. No fragmentation was visible at any time. When the delivery fiber was advanced to within approximately 1 mm of the stone surface, lithotripsy occurred if and only if the expanding bubble reached the surface of the stone. Because of the long pulse-duration, laser energy channeled through the vapor bubble (the ‘Moses effect’), and was directly absorbed by the stone surface. This off-contact lithotripsy produced few fragments with a large ‘hemispherical’ bubble that expanded to its maximum size around 250 s and collapsed around 450 s after the onset of the holmium laser pulse (Figure 2a-d). No fragmentation was observed after the bubble collapsed. With the delivery fiber placed in contact and perpendicular to the stone surface, fast-flash images showed lithotripsy began after about 50 s for both COM and cystine stones when a plume formation consisting of dust or fragments and bubbles appeared (Figure 3). The plume continued to enlarge, and reached its maximum expansion at approximately 200 s and 400 s for the COM and cystine stones, respectively, as shown in Figure 4a and 4b. No lithotripsy attributable to plasma expansion in the early stage of bubble formation or bubble collapse in the later stage was observed (Figure 4c). When the fiber was placed at a 45-degree angle in contact mode, the holmium laser produced a distorted bubble and a smaller plume. Again, no fragmentation was seen at either the onset of the holmium laser or after bubble collapse. When the delivery fiber was placed in contact but parallel to the calculus surface, no fragmentation was observed during bubble expansion or collapse. Figure 5 illustrates that an elongated half-bubble was formed along the surface of a COM calculus. It reached maximum expansion at 350 s (Figure 5a) and collapsed between 450 to 550 s (Figure 5b) after the initiation of the Ho:YAG laser pulse. Beyond 600 s (Figure 5c), no plume or fragmentation ejecting from the calculus surface was apparent.
3.2 The Role of Acoustic Force in Holmium Lithotripsy Figure 6 and Figure 7 were recorded with the Laser 1-2-3 from Schwartz Electro-Optics. The laser energy was set at 400 mJ/pulse and the corresponding pulse duration was approximately 350 s. Figure 6 shows an acoustic signature recorded in clear water. The small pressure bump at the laser onset is characteristic of long pulse midinfrared lasers17. The vapor bubble collapsed at about 450 s. Figure 7 shows the acoustic transients recorded for COM and cystine stones when the delivery fiber was placed perpendicular and parallel to the urinary stone surface, both in contact mode. Figure 7a and 7b illustrate the acoustic transients for a perpendicularly oriented fiber in contact with COM and cystine stones, respectively. It can be seen that the vapor bubble collapsed at 300 s (also see Figure 4c) on the COM stone, generating a pressure peak of about 2 bars. For the cystine stone, however, only a small pressure fluctuation on the order of 1 bar was recorded. Figure 7c and 7d show the acoustic transient for parallel-oriented delivery fiber in contact with the surface of a COM and a cystine stone, respectively. It can be seen that pressure peaks between 15 and 20 bars were generated for both stones. In general, the pressure peaks were smaller, and indicated a longer time to bubble collapse compared to that generated in clear water (Figure 6). This was because the solid boundary of the stone surface prevented the radial expansion of the vapor bubble, forcing it to expand axially. The result was a more elongated half bubble (Figure 5a), delaying the time to collapse.
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Figure 7. Acoustic signals (lower signals; in unit bars) generated by a holmium laser with (a-b) perpendicularly oriented and (cd) parallel-oriented fiber tips on urinary stones in contact mode. (a) and (c) are the signals for the COM stone, while (b) and (d) are those for the cystine stone. The upper signal shows the temporal profile of the holmium laser, in arbitrary unit. The laser was set at 400 mJ/pulse at a pulse-duration (FWHM) of about 350 s.
Figure 8 shows the lack of correlation between the photomechanical mechanism (acoustic waves) and the efficiency of stone fragmentation. Figure 8a shows that mass loss for various stone-types increases as a function of laser energy/pulse (also see Part II). However, acoustic measurements at an increasing energy/pulse did not seem to result in statistically larger pressure peaks (which would have indicated larger vapor bubbles). The acoustic pressure peaks remained relatively unchanged from about 300 mJ/pulse to 1 J/pulse. This indicated that mechanism(s) other that photomechanical or photoacoustical was dominant in stone fragmentation. 14 Acoustic Pressure Peak (bars)
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Figure 8. These figures show the lack of correlation between acoustic energy or photomechanical effects and the efficiency of stone fragmentation. (a) shows that the stone mass-loss increases as per-pulse-energy increases. On the other hand, (b) shows no apparent increases of acoustic pressure as a function of laser energy/pulse when the delivery fiber was in contact mode perpendicularly with the urinary stone. This is because in contact mode, the layer of water between the urinary stone and the fiber tip remained relatively small and constant, preventing substantially larger vapor bubbles (therefore larger acoustic signals) from forming for higher per-pulse-energy.
4. DISCUSSION The combination of time-resolved flash photography and acoustic measurements have revealed that unlike LISL, photomechanical effects (i.e. shockwaves, vapor bubble) were not the dominant cause of stone fragmentation in holmium laser lithotripsy. Evidence suggested that these photomechanical effects, however, only facilitates the lithotripsy process by allowing direct deposition of laser energy on the target (i.e. vapor channel), and dispersing fragmented material (i.e. turbulence in water due to bubble dynamics). The long pulse Ho:YAG laser did not initiate plasma expansion that would have produced shockwave generation. Previous studies have also shown that pulsed Ho:YAG laser-induced bubble collapse does not necessarily result in shockwave generation 16,17,18,19. This is because the long-pulse holmium laser produce pear-shape or elongated vapor bubbles that collapse asynchronously at multiple locations, thereby temporally and spatially distributing the mechanical energy and producing weak acoustic waves. At bubble collapse, pressure waves generated in clear water were generally not sufficient (< 100 bars, Figure 6) to cause fragmentation of nearby urinary stones. In non-contact lithotripsy (Figure 2), no fragmentation was observed until the vapor bubble exposed the stone surface to direct deposition of laser energy. In contact lithotripsy (Figure 3 and 4), fragmentation began 50 s after the onset of the holmium laser and ended before the bubble collapsed. Moreover, when the delivery fiber was perpendicularly oriented to the stone surface, contact mode lithotripsy only generated small pressure transient too weak to cause fragmentation (Figure 7a and 7b). These observations contradict LISL, where fragmentation occurs at laser onset and bubble collapse 4,5. With the parallel-oriented fiber (Figure 5), an elongated half-bubble produced acoustic pressure peaks that were slightly smaller than those in clear water (Figure 7c and 7d). No apparent fragmentation was observed at any time. If LISL were the dominant mechanism, the parallel fiber orientation would
have resulted in fragmentation because shockwaves are known to propagate spherically in all directions. This reaffirmed that holmium laser lithotripsy was not shockwave-induced. The lack of photomechanical effects was further proven by analyzing the acoustic signature in holmium lithotripsy as a function of laser energy-per-pulse. As shown in Figure 8, the mass loss of urinary stones increases as a function of laser energy-per-pulse. However, the experiments indicate that the magnitude of acoustic transients remain relatively unchanged as the per-pulse-energy is increased. This suggests that for contact lithotripsy, the layer of water between the urinary stone and the fiber tip is relatively small, preventing substantially larger vapor bubbles (therefore larger acoustic signals) from forming for higher pulse energies. Since our data indicated that the mechanism of action was not predominantly photomechanical, we have also investigated the photothermal mechanism. In part II of this study, experiments were performed to explore the role of photothermal interaction in holmium laser lithotripsy. Evidence suggested that direct deposition of laser energy on the urinary stone increased the temperature of the irradiated volume. When the temperature rose above the threshold breakdown temperature of individual stone composition, oxidation and reduction (chemical reaction) occurred that weakened the structural integrity of the urinary stone, causing fragmentation.
5. CONCLUSION It is shown in this study that photoacoustical or photomechanical effects play a minor role in holmium laser fragmentation of urinary stones. Our experimental results indicate that acoustic transients generated during holmium laser lithotripsy are too weak to cause significant damage or fragmentation to the urinary stones. With the evidence introduced in Part II of this research effort (Paper # 3601A-43), we conclude that long-pulse Ho:YAG laser lithotripsy is primarily a photothermal mechanism. We propose a fragmentation model as follows: In contact or non-contact (very close to stone surface) lithotripsy, laser irradiation rapidly vaporizes a layer of water within its optical penetration depth. Vaporization of water generates a rapidly expanding vapor bubble as laser energy continues to be deposited at the distal end of the bubble. This results in an elongated bubble that assumes very low absorption coefficients (the ‘Moses effect’), allowing direct irradiation of the urinary stone by the holmium laser. Laser energy deposition increases the temperature of the irradiated stone volume above a critical threshold temperature, causing chemical breakdown within the optical zone. The chemical breakdown weakens the mechanical integrity of the irradiated volume, allowing the vapor bubble and interstitial water or vapor expansion to facilitate the ejection of fragmented breakdown products.
6. ACKNOWLEDGEMENTS Funding for this research was provided in part by grants from the Air Force Office of Scientific Research through MURI from DDR&E (F49620-98-1-0480), the Texas Higher Education Coordinating Board (BER-ATP253), the Office of Naval Research Free Electron Laser Biomedical Science Program (N00014-91-J-1564), and the Albert W. and Clemmie A. Caster Foundation. Paper # 3601A-44
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