0022-5347/03/1706-2190/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 170, 2190 –2194, December 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000094188.69698.f8
EVALUATION OF SYNCHRONOUS TWIN PULSE TECHNIQUE FOR SHOCK WAVE LITHOTRIPSY: DETERMINATION OF OPTIMAL PARAMETERS FOR IN VITRO STONE FRAGMENTATION KHALED Z. SHEIR,* NASIM ZABIHI, DAVID LEE, JOEL M. TEICHMAN, JAMIL REHMAN, CHANDRU P. SUNDARAM,† DIRK HEIMBACH, ALBRECHT HESSE, FERNADO DELVECCHIO, PEI ZHONG, GLENN M. PREMINGER AND RALPH V. CLAYMAN‡ From the Urology and Nephrology Center, Mansoura University (KZS), Mansoura, Egypt, Division of Urology, University of Texas Health Science Center (NZ, JMT), San Antonio, Texas, Department of Urology, College of Medicine, University of California-Irvine Medical Center (DL, RVC), Irvine, California, Divisions of Urology, Washington University School of Medicine (JR, CPS), St. Louis, Missouri, Department of Urology, Section of Experimental Urology, University of Bonn (DH, AH), Bonn, Germany, and Department of Mechanical Engineering and Materials Science, Duke Comprehensive Kidney Stone Center and Division of Urology/Department of Surgery, Duke University Medical Center (FD, PZ, GMP), Durham, North Carolina
ABSTRACT
Purpose: The Twinheads extracorporeal shock wave lithotriptor (THSWL) is composed of 2 identical shock wave generators and reflectors. One reflector is under the table and the other is over the table with a variable angle between the axes of the 2 reflectors. The 2 reflectors share a common second focal point, making it possible to deliver an almost synchronous twin pulse to the targeted stone. We studied the optimal parameters for in vitro stone fragmentation. Materials and Methods: Two types of 1 cm artificial stones were used, namely Bon(n)-stones of 3 compositions (75% calcium oxalate monohydrate [COM] plus 25% uric acid, struvite and cystine) and plaster of Paris. The parameters tested were shock wave number (100, 500 and 1,000), shock wave power (8, 11 and 14 kV) and angle between the reflector axes (67, 90 and 105 degrees). After the optimal parameters were determined we studied the disintegrative efficacy of THSWL for 3 types of human urinary calculi, including COM, calcium hydrogen phosphate (brushite) and cystine. Each stone received 1,000 twin shock waves at 14 kV with an angle of 90 degrees between the reflectors. All experiments were done using a rate of 60 twin shock waves per minute. Following lithotripsy stone fragments were processed and sized. The ratio of the weight of fragments greater than 2 mm-to-total weight of all fragments was calculated. Results: Optimal stone fragmentation results for THSWL were obtained with the maximum number of shock waves (1,000) and full power (14 kV). There was no significant statistical difference in fragment size or the ratio of fragments greater than 2 mm with the use of different angles except for cystine and plaster of Paris calculi, for which the right angle was most effective. At application of the optimal parameters to human stones THSWL produced small fragment size for COM and cystine stones, while brushite stones were not fragmented to the same extent. Conclusions: The efficacy of synchronous twin pulse technology improves as the number of shock waves and power increase. A 90-degree angle between the shock wave reflectors is advantageous for certain stones (that is cystine and plaster of Paris) but it is not a factor for other stone compositions. THSWL has satisfactory disintegrative efficacy for human stones, especially COM and cysteine calculi. KEY WORDS: kidney; kidney calculi; lithotripsy; high-energy shock waves; technology assessment, biomedical
Extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Inc., Marietta, Georgia) has become the treatment of choice for the majority of urinary stones. The original HM3 (Dornier Medical Systems, Inc.) delivered an effective clearance rate for renal and ureteral stones, although with some minor limitations and complications.1 A number of second and third generations devices have been
developed using different energy sources, focusing devices and coupling media.2 These devices overcome some of the limitations and lessen the complications of the HM3 but usually at the expense of a higher re-treatment rate and a lower overall success rate.2, 3 Despite technical alterations the basic principles and applications of shock wave lithotripsy have remained largely unchanged in the last decade. The physics of effective shock waves are applied in the same way in all currently available lithotriptors. Repeated shock waves focused on the stone eventually reduce it to small fragments that may be passed spontaneously.3 The feasibility of applying synchronous twin pulses using the Twinheads lithotriptor (THSWL) to increase the disintegrative power of the shock wave and its possible value for decreasing the number of applied shocks were investigated in an earlier study.4 We studied in vitro stone fragmentation in several stone models to define the optimal
Accepted for publication July 3, 2003. Supported by a Midwest Stone Institute research endowment to the Division of Urology, Washington University, St. Louis, Missouri. * Corresponding author: Department of Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt (telephone: ⫹2050– 2262222; FAX: ⫹2050–2263717; e-mail:
[email protected]). † Financial interest and/or other relationship with Computer Motion, Inc. ‡ Financial interest and/or other relationship with Applied Urology, Galil, Greenwald, Cook Urological, Orthopedic Systems, Inc., Microvasive, Urologix and Yamanouchi. 2190
SYNCHRONOUS TWIN PULSE TECHNIQUE FOR SHOCK WAVE LITHOTRIPSY
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parameters for this new ESWL technology. These parameters were then applied in vitro to human urinary calculi. MATERIALS AND METHODS
The Twinheads lithotriptor is composed of 2 identical shock wave generators and 2 identical shock wave reflectors. The generators are 60 nF with power settings from 7 kV (400 bar at focal point 2 [F2]) to 14 kV (1,100 bar at F2). The power of the 2 generators was adjusted independently, while shock wave emission was synchronous. The twin synchronous shock waves are counted as 1 shock wave and peak pressure at F2 was not significantly different from that of single shock wave when measured by a needle hydrophone with an angle between the reflectors of 90 or greater. This finding requires further evaluation. Each reflector has a focal depth of 12.7 cm (distance between the reflector rim and F2) and a cigarshaped focal zone of 16 ⫻ 30 mm, as defined using standard plaster of Paris blocks. One reflector is fixed under the table with an angle of 40 degrees over the horizontal plane. The second reflector is mobile and travels over the table. The 2 reflectors share the same F2, while the angle between the axes is variable as a function of changing the position of the reflector over the table. The minimum angle that can be achieved is 67 degrees and the maximum angle is 105 degrees. At angles greater than 105 degrees the reflectors interfere with the x-ray field, largely precluding clinical application (fig. 1). To determine optimal parameters for in vitro stone fragmentation using THSWL 2 types of stones 1 cm in diameter
FIG. 2. Coupling device
FIG. 1. Twinheads lithotriptor
were used, namely plaster of Paris, and Bon(n)-stones5, 6 of 3 compositions, that is mixed 75% calcium oxalate (COM) plus 25% uric acid, struvite and cystine. Five stones of each composition were used in each of the 9 study arms. THSWL variables were shock wave number (100, 500 and 1,000), shock wave power (8, 11 and 14 kV) and firing angle of the 2 shock heads (67, 90 and 105 degrees). In each study arm the middle value of the other parameters was the one held constant. For example, when testing different power settings, the firing angle was constant at 90 degrees and the number of shock waves was constant at 500, whereas when varying the shock wave number, shock wave power was constant at 11 kV and the firing angle was maintained at 90 degrees. All experiments were done using a rate of 60 twin shock waves per minute. To determine THSWL effectiveness for in vitro fragmenting human stones the optimal parameters for THSWL were used to treat 3 types of human urinary calculi, of which each was 97% or greater pure, including COM, calcium hydrogen phosphate (brushite) and cystine. Six stones per type were used. Each stone received 1,000 twin shock waves at 14 kV with a 90-degree angle between the reflectors. The THSWL test bath consisted of a lucent, lightweight acrylic water tank. One side was sealed by a 1 mm silicone rubber membrane with acoustic impedance close to that of water. The tank was placed on the THSWL table in the position usually occupied by the patient lumbar region during treatment for kidney stones, such that the membrane could be closely applied to the water cushions of the 2 reflectors with ultrasound jelly serving as an interface (fig. 2). The tank was filled with degassed water. The stones were dried at 60C for 4 hours and weighed prior to THSWL. Each calculus was placed in a finger cot containing sterile degassed water for 48 hours prior to treatment. The same brand talc-free,
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SYNCHRONOUS TWIN PULSE TECHNIQUE FOR SHOCK WAVE LITHOTRIPSY TABLE 1. Pre-lithotripsy stone mass
No. shocks: 100 500 1,000 p Value Power (kV): 8 11 14 p Value Reflector angle (degrees): 67 90 105 p Value
Mean Struvite ⫾ SD (mg)
Mean COM ⫹ Uric Acid ⫾ SD (mg)
Mean Plaster of Paris ⫾ SD (mg)
Mean Cystine ⫾ SD (mg)
525 ⫾ 47.62 505.6 ⫾ 37.53 532 ⫾ 14.54 0.5
954.6 ⫾ 38.27 967.6 ⫾ 35.17 965.4 ⫾ 39.11 0.8
726.2 ⫾ 20.52 704.4 ⫾ 20.22 712.6 ⫾ 19.27 0.3
514.8 ⫾ 50.88 465.8 ⫾ 45.23 477.6 ⫾ 76.36 0.4
503.20 ⫾ 47.04 529.60 ⫾ 48.39 535.20 ⫾ 38.99 0.7
955.20 ⫾ 29.59 962.80 ⫾ 36.55 944.80 ⫾ 34.35 0.7
694 ⫾ 18.71 714.20 ⫾ 19.92 704.60 ⫾ 27.66 0.4
478.6 ⫾ 31.26 509.80 ⫾ 26.63 488.00 ⫾ 27.86 0.3
495.00 ⫾ 19.75 493.80 ⫾ 20.14 514.60 ⫾ 34.81 0.4
917.20 ⫾ 31.99 933.40 ⫾ 34.51 951.40 ⫾ 18.64 0.2
705.80 ⫾ 14.96 693.80 ⫾ 13.85 708.20 ⫾ 20.22 0.4
467.80 ⫾ 53.00 467.60 ⫾ 26.20 494.00 ⫾ 73.73 0.7
nonlubricated finger cot was used throughout the study. The targeted material was fixed in a holder, immersed to the tank and moved into the focal zone under fluoroscopic guidance. Imaging was repeated after every 100 shock wave discharges. Following lithotripsy the finger cot was opened over a funnel, and fragments and fluid were collected. Gentle water irrigation and scraping with a spatula were used to ensure that all visible fragments were collected in a test tube. The test tube was centrifuged at 2,500 rpm for 15 minutes. The supernatant was discarded. Fragments were placed overnight at ⫺80C in the freezer and desiccated by vacuum lyophilization to sublimate water from the calculi. Fragments were passed through sequential geological brass sieves with 4, 2, 1.4, 1, 0.71, 0.425, 0.25, 0.125 and 0.063 mm sieve openings, respectively. The mass of fragments per size was measured. Fragment size was compared by 2 analyses. 1) Calculation was done of the mean percent mass of stone per category, namely greater than 4, 2 to 4, 1.5 to 1.9, 1 to 1.4, 0.7 to 0.9, 0.425 to 0.70, 0.25 to 0.424, 0.125 to 0.24, 0.063 to 0.124 and greater than 0.063 mm. A worksheet was made assuming 100 fragments per stone in proportion to the percent mass of stones per variable, assigning the described values for each stone. For example, if 37% of the mass of fragments of a stone were between 2 and 4 mm, 37 of 100 fragments were considered to be 3 mm. 2) The mass of fragments greater than 2 mm was converted to a percent mass of the total recovered mass. The percent of fragments greater than 2 mm was compared across the various trials.7 Statistical comparisons were performed for initial stone mass, mean fragment size and the percent of the mass of fragments greater than 2 mm for each of the various parameters tested according to stone composition. Group comparisons were done by ANOVA. When ANOVA was statistically significant, pairwise comparisons were made with Fisher’s protected least significant difference. Investigators blinded to cohort identity performed all post-lithotripsy procedures, including stone processing, lyophilization, sorting and statistical analysis. The rank order of parameters tested was done before the investigators were unblinded.7
higher power mean fragment size became finer with a decrease in the ratio of fragments greater than 2 mm. However, there was no significant difference between 11 and 14 kV (fig. 4). No differences in mean fragments size or the ratio of fragments greater than 2 mm were observed with variation in the angle between the reflectors except for plaster of Paris and cystine stones, in which a 90-degree angle was advantageous in producing smaller fragments and a lesser mass of fragments greater than 2 mm (fig. 5). Overall of the artificial calculi struvite and plaster of Paris stones were fragmented
RESULTS
FIG. 3. Number of shock waves. A, pairwise differences for mean fragment size comparisons were statistically significant differences (p ⬍0.05) for COM⫹UA between 100 vs 500, and 100 vs 1,000; no statistical differences for cystine between various shock counts; statistically significant differences (p ⬎0.05) for struvite between 100 vs 1,000, 500 vs 1,000; and statistically significant differences (p ⬍0.05) for plaster of paris between 100 vs 500 vs 1,000. B, pairwise differences for percent fragments greater than 2 mm were statistically significant differences (p ⬍0.05) for COM⫹UA between 100 vs 1,000 only; no statistically significant differences for cystine and struvite between various shock counts; and statistically significant differences (p ⬍0.05) for plaster of paris for each of 100 vs 500 vs 1,000. In each case power was held constant at 11 kV and angle between shock tubes was held constant at 90 degrees.
For the artificial stones experiment the pre-lithotripsy stone mass of each type was not statistically different in each study arm (table 1). By maintaining power at 11 kV with an angle of 90 degrees between the reflectors stone fragmentation was significantly improved with increased shock counts for all types of stones. Mean fragment size became finer with a decrease in the ratio of fragments greater than 2 mm (fig. 3). With application of 500 twin shock waves with an angle of 90 degrees between the reflectors a low power of 8 kV did not fragment stones as well as higher power at 11 and 14 kV. At
SYNCHRONOUS TWIN PULSE TECHNIQUE FOR SHOCK WAVE LITHOTRIPSY
FIG. 4. Generator power. A, pairwise differences for mean fragment size comparisons were statistically significant differences (p ⬍0.05) for COM⫹UA stones, between 8 vs 14 kV only; statistically significant differences (p ⬍0.05) for cystine, between 8 vs 11 kV and 8 vs 14 kV; statistically significant differences (p ⬍0.05) for struvite, between 8 vs 14 kV (p ⬍0.05) and near significance (p ⫽ 0.09) between 11 and 14 kV; and statistically significant differences (p ⬍0.05) for plaster of paris between 8 vs 11 kV and 8 vs 14 kV. For all types there was no statistical differences between 11 and 14 kV. B, pairwise differences for percent fragments greater than 2 mm were statistically significant differences (p ⬍0.05) for COM⫹UA, between 8 vs 14 and 11 vs 14 kV; no statistically significant differences between different power settings for cystine and struvite, and statistically significant differences for plaster of paris between 8 vs 11 kV and 8 vs 14 kV. In each case number of shock waves delivered was 500 and angle between shock tubes was held constant at 90 degrees.
into smaller fragments than cystine and COM plus uric acid stones, and with fewer fragments greater than 2 mm. Table 2 lists mean fragment size ⫾ SD and the percent of fragments larger than 2 mm for treated human stones. It was found that THSWL produced small fragment size with few fragments larger than 2 mm, especially for COM and cystine stones. Brushite stones were not fragmented to the same extent. DISCUSSION
The use of natural calculi in research presents several difficulties. Not enough stones are available for experimental work. In addition, the varying chemical compositions and physical properties of natural stones make their use in experiments problematic. Accordingly artificial stone models involving plaster, chalk and different ceramic materials have been used.8 –10 However, most artificial stones, such as those cited, are different from natural urinary stones in composition and physical properties. Recently a new group of artificially produced urinary calculi, namely Bon(n)-stones, have become available. These calculi are composed of the same materials as human urinary calculi and, thus, they have a density and crushing characteristics comparable to those of naturally occurring human urinary stones.5, 6 The objective of shock wave lithotripsy is to produce small, passable fragments to minimize the risk of post-ESWL complications. We have previously found that delivery of syn-
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FIG. 5. Angle between reflectors. A, pairwise differences for mean fragment size comparisons were no significant differences for COM⫹UA and struvite between different angles; statistically significant differences (p ⬍0.05) for cystine between 90 vs 105 degrees only, and statistically significant differences (p ⬍0.05) for plaster of paris between 90 vs 67 degrees and 90 vs 105 degrees. B, pairwise differences for percent fragments greater than 2 mm were no statistically significant differences for COM⫹UA, cystine and struvite, between different angles, and statistically significant differences for plaster of paris between 90 vs 67 degrees and 90 vs 105 degrees. In each case power was held constant at 11 kV and number of shock waves delivered was 500.
chronous twin pulse shock waves improved the quality and rate of stone disintegration during ESWL.4 Optimal results were achieved when the angle between the reflectors was 90 degrees. It was hypothesized that shock wave delivery in this manner could lessen the damage to the kidney and surrounding organs as a result of tighter localization of the shock wave effects specifically within the F2 zone and limitation of cavitation effects. Recently we completed a study of the acute tissue effects of THSWL on porcine kidneys and surrounding organs. There were no gross lesions of the surrounding organs, subcapsular hemorrhage or parenchymal damage at the outer surfaces of the kidneys treated with THSWL even after 3,000 twin shocks. The coronal section revealed minimal gross lesions in 4 of 28 kidneys. Microscopically parenchymal changes were minimal. On the other hand, in vivo study of the single under table head revealed that 5 of 6 kidneys had large subcapsular hematomas at the anterior and posterior surfaces, and on coronal section extending into the parenchyma.11,12 Microscopically the changes were significant. Thus, we concluded that synchronous, 90-degree, twin pulse induced tissue damage acutely appeared to be minimal, especially compared with that of a single head. It was the case not only for the same count and rate of generated shock waves, but also when a higher count or rate of twin shock waves was applied. In the current study Bon(n)-stones and plaster of Paris stones were subjected to THSWL to determine the optimal parameters for stone fragmentation. Subsequently natural human stones were used to test the disintegrative efficacy of THSWL using these optimal parameters. The study showed
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SYNCHRONOUS TWIN PULSE TECHNIQUE FOR SHOCK WAVE LITHOTRIPSY TABLE 2. Human stones
Stone mass (mg) Fragment size (mm) % Fragments greater than 2 mm
Mean Brushite ⫾ SD
Mean Cystine ⫾ SD
Mean COM ⫾ SD
291 ⫾ 112 1.7 ⫾ 1 38 ⫾ 19
478 ⫾ 254 0.9 ⫾ 0.8 7⫾5
375 ⫾ 255 1.1 ⫾ 0.7 5⫾7
that progressively smaller fragments and fewer fragments larger than 2 mm were produced as the shock count increased. The same findings were reported in the literature using standard ESWL in vitro with different types of artificial stones and different modes of shock wave generation.10, 13, 14 Also, the same result was observed for in vitro human stone disintegration.7 The lower 8 kV power did not fragment stones as well as higher power (11 and 14 kV). This finding is similar to that reported in the literature with the application of standard ESWL.5, 10, 15 Investigators found that fragmentation efficacy for natural and artificial stones improved as generator voltage increased. However, for THSWL there was no significant difference between 11 and 14 kV. This observation means that we can use a lower power setting and achieve the same results for clinical application. Different stone compositions respond unequally to THSWL. Artificial stones of cystine were the most resistant to fragmentation, as observed in literature for standard ESWL.16 In an in vitro comparison of different standard shock wave machines using human stones Teichman et al found that cystine and brushite stones were resistant to shock waves.7 Using THSWL human cystine stones were easily fragmented but human brushite calculi were resistant. CONCLUSIONS
The efficacy of synchronous twin pulse technology improves as the number of shock waves and power increase but with nonsignificant difference between medium and high power. This result means that we can use medium power and achieve the same results as high power. A 90-degree angle between the shock waves reflectors is advantageous for certain stones, that is cystine and plaster of Paris. THSWL appears to be highly effective for in vitro fragmentation of most human stones. REFERENCES
1. Fetner, C. D., Preminger, G. M., Seger, J. and Lea, T. A.: Treatment of ureteral calculi by extracorporeal shock wave lithotripsy at a multi-use center. J Urol, 139: 1192, 1988 2. Wilson, W. T. and Preminger, G. M.: Extracorporeal shock wave lithotripsy. An update. Urol Clin North Am, 17: 231, 1990
3. Rassweiler, J. and Alken, P.: ESWL ’90 —state of the art. Limitations and future trends of shock-wave lithotripsy. Urol Res, suppl., 18: s13, 1990 4. Sheir, K. Z., El-Sheikh, A. M. and Ghoneim, M. A.: Synchronous twin-pulse technique to improve efficacy of SWL: preliminary results of an experimental study. J Endourol, 15: 965, 2001 5. Heimbach, D., Jacobs, D., Winter, P., Suverkrup, R. and Hesse, A.: Production of artificial urinary stones from natural materials and their physical properties. First results. Scand J Urol Nephrol, 31: 9, 1997 6. Bachmann, R., Heimbach, D., Kersjes, W., Jacobs, D., Schild, H. and Hesse, A.: A new type of artificial urinary calculi: in vitro study by spiral CT. Invest Urol, 35: 672, 2000 7. Teichman, J. M. H., Portis, A. J., Cecconi, P. P., Bub, W. L., Endicott, R. C., Denes, B. et al: In vitro comparison of shock wave lithotripsy machines. J Urol, 164: 1259, 2000 8. Ziolkowski, F. and Perrin, D. D.: Dissolution of urinary stones by calcium-chelating agents: a study using a model system. Invest Urol, 15: 208, 1977 9. Vakil, N., Gracewski, S. M. and Everbach, E. C.: Relationship of model stone properties to fragmentation mechanisms during lithotripsy. J Lithotripsy Stone Dis, 3: 304, 1991 10. Whelan, J. P. and Finlayson, B.: An experimental model for the systematic investigation of stone fracture by extracorporeal shock wave lithotripsy. J Urol, 140: 395, 1988 11. Sheir, K. Z., Zabini, N., Lee, D., Teichman, J. M., Rehman, J., Landman, J. et al: Evaluation of synchronous twin pulse for shock wave lithotripsy: in vitro evaluation of optimal parameters. Presented at annual meeting of Research on Calculus Kinetics Society, San Antonio, Texas, February 8 –10, 2002 12. Sheir, K. Z., Lee, D., Humphrey, P. A., Morrissey, K., Sundaram, C. P. and Clayman, R. V.: Evaluation of synchronous twin pulse technique for shock wave lithotripsy: in vivo tissue effects. Unpublished data 13. Choung, C. J. C., Zhong, P. and Preminger, G. M.: A comparison of stone damage caused by different modes of shock wave generation. J Urol, 148: 200, 1992 14. Zhu, S., Cocks, F. H., Preminger, G. M. and Zhong, P.: The role of stress waves and cavitation in stone comminution in shock wave lithotripsy. Ultrasound Med Biol, 28: 661, 2002 15. Eisenmenger, W.: The mechanisms of stone fragmentation in ESWL. Ultrasound Med Biol, 27: 683, 2001 16. Heimbach, D., Munver, R., Zhong, P., Jacobs, J., Hesse, A., Mu¨ ller, S. C. et al: Acoustic and mechanical properties of artificial stones in comparison to natural kidney stones. J Urol, 164: 537, 2000
