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Determine the influence of passage through the body wall on the properties of lithotripter shock waves (SWs) and the characteristics of the acoustic field of an electromagnetic lithotripter.Full-thickness ex vivo segments of pig abdominal wall were secured against the acoustic window of a test tank coupled to the lithotripter. A fiber-optic probe hydrophone was used to measure SW pressures, determine shock rise time, and map the acoustic field in the focal plane.Peak positive pressure on axis was attenuated roughly proportional to tissue thickness-approximately 6% per cm. Irregularities in the tissue path affected the symmetry of SW focusing, shifting the maximum peak positive pressure laterally by as much as ∼2 mm. Within the time resolution of the hydrophone (7-15 ns), shock rise time was unchanged, measuring ∼17-21 ns with and without tissue present. Mapping of the field showed no effect of the body wall on focal width, regardless of thickness of the body wall.Passage through the body wall has minimal effect on the characteristics of lithotripter SWs. Other than reducing pulse amplitude and having the potential to affect the symmetry of the focused wave, the body wall has little influence on the acoustic field. These findings help to validate laboratory assessment of lithotripter acoustic field and suggest that the properties of SWs in the body are much the same as have been measured in vitro.

Focused ultrasound has the potential to expel small stones or residual stone fragments from the kidney, or move obstructing stones to a nonobstructing location. We evaluated the efficacy and safety of ultrasonic propulsion in a live porcine model.Calcium oxalate monohydrate kidney stones and laboratory model stones (2 to 8 mm) were ureteroscopically implanted in the renal pelvicalyceal system of 12 kidneys in a total of 8 domestic swine. Transcutaneous ultrasonic propulsion was performed using an HDI C5-2 imaging transducer (ATL/Philips, Bothell, Washington) and the Verasonics® diagnostic ultrasound platform. Successful stone relocation was defined as stone movement from the calyx to the renal pelvis, ureteropelvic junction or proximal ureter. Efficacy and procedure time was determined. Three blinded experts evaluated histological injury to the kidney in the control, sham treatment and treatment arms.All 26 stones were observed to move during treatment and 17 (65%) were relocated successfully to the renal pelvis (3), ureteropelvic junction (2) or ureter (12). Average ± SD successful procedure time was 14 ± 8 minutes and a mean of 23 ± 16 ultrasound bursts, each about 1 second in duration, were required. There was no evidence of gross or histological injury to the renal parenchyma in kidneys exposed to 20 bursts (1 second in duration at 33-second intervals) at the same output (2,400 W/cm(2)) used to push stones.Noninvasive transcutaneous ultrasonic propulsion is a safe, effective and time efficient means to relocate calyceal stones to the renal pelvis, ureteropelvic junction or ureter. This technology holds promise as a useful adjunct to surgical management for renal calculi.

The presence of infectious microorganisms in urinary stones is commonly inferred from stone composition, especially by the presence of struvite in a stone. The presence of highly carbonated apatite has also been proposed as a marker of the presence of bacteria within a stone. We retrospectively studied 368 patients who had undergone percutaneous nephrolithotomy, and who also had culture results for both stone and urine. Urine culture showed no association with stone mineral content, but stone culture was more often positive in struvite containing stones (73% positive) and majority apatite stones (65%) than in other stone types (54%, lower than the others, P

Conduct a laboratory evaluation of a novel low-pressure, broad focal zone electrohydraulic lithotripter (TRT LG-380).Mapping of the acoustic field of the LG-380, along with a Dornier HM3, a Storz Modulith SLX, and a XiXin CS2012 (XX-ES) lithotripter was performed using a fiberoptic hydrophone. A pig model was used to assess renal response to 3000 shockwaves (SW) administered by a multistep power ramping protocol at 60 SW/min, and when animals were treated at the maximum power setting at 120 SW/min. Injury to the kidney was assessed by quantitation of lesion size and routine measures of renal function.SW amplitudes for the LG-380 ranged from (P(+)/P(-)) 7/-1.8 MPa at PL-1 to 21/-4 MPa at PL-11 while focal width measured ~20 mm, wider than the HM3 (8 mm), SLX (2.6 mm), or XX-ES (18 mm). For the LG-380, there was gradual narrowing of the focal width to ~10 mm after 5000 SWs, but this had negligible effect on breakage of model stones, because stones positioned at the periphery of the focal volume (10 mm off-axis) broke nearly as well as stones at the target point. Kidney injury measured less than 0.1% FRV (functional renal volume) for pigs treated using a gradual power ramping protocol at 60 SW/min and when SWs were delivered at maximum power at 120 SW/min.The LG-380 exhibits the acoustic characteristics of a low-pressure, wide focal zone lithotripter and has the broadest focal width of any lithotripter yet reported. Although there was a gradual narrowing of focal width as the electrode aged, the efficiency of stone breakage was not affected. Because injury to the kidney was minimal when treatment followed either the recommended slow SW-rate multistep ramping protocol or when all SWs were delivered at fast SW-rate using maximum power, this appears to be a relatively safe lithotripter.

Artificial stones are used in research on the mechanisms of stone breakage in shock wave lithotripsy (SWL) and in assessing lithotripter performance. We have adopted Ultracal-30 gypsum as a model, finding it suitable for SWL studies in vitro, acute animal experiments in which stones are implanted in the kidney, and as a target to compare the in vitro performance of intracorporeal lithotripters. Here we describe the preparation of U-30 stones, their material properties, shock wave (SW) breakage characteristics, and methods used for quantitation of stone fragmentation with this model. Ultracal-30 gypsum cement was mixed 1:1 with water, cast in plastic multi-well plates, then, the stones were liberated by dissolving the plastic with chloroform and stored under water. Stone breakage in SWL was assessed by several methods including measures of the increase in projected surface area of SW-treated stones. Breakage of hydrated stones showed a linear increase in fragment area with increased SW-number and SW-voltage. Stones stored in water for an extended time showed reduced fragility. Dried stones could be rehydrated so that breakage was not different from stones that had never been dry, but stones rehydrated for less than 96 h showed increased fragility to SWs. The physical properties of U-30 stones place them in the range reported for natural stones. U-30 stones in vitro and in vivo showed equivalent response to SW-rate, with approximately 200% greater fragmentation at 30 SW/min compared to 120 SW/min, suggesting that the mechanisms of SW action are similar under both conditions. U-30 stones provide a convenient, reproducible model for SWL research.

An electrohydraulic lithotripter has been designed that mimics the behavior of the Dornier HM3 extracorporeal shock wave lithotripter. The key mechanical and electrical properties of a clinical HM3 were measured and a design implemented to replicate these parameters. Three research lithotripters have been constructed on this design and are being used in a multi-institutional, multidisciplinary research program to determine the physical mechanisms of stone fragmentation and tissue damage in shock wave lithotripsy. The acoustic fields of the three research lithotripters and of two clinical Dornier HM3 lithotripters were measured with a PVDF membrane hydrophone. The peak positive pressure, peak negative pressure, pulse duration, and shock rise time of the focal waveforms were compared. Peak positive pressures varied from 25 MPa at a voltage setting of 12 kV to 40 MPa at 24 kV. The magnitude of the peak negative pressure varied from -7 to -12 MPa over the same voltage range. The spatial variations of the peak positive pressure and peak negative pressure were also compared. The focal region, as defined by the full width half maximum of the peak positive pressure, was 60 mm long in the axial direction and 10 mm wide in the lateral direction. The performance of the research lithotripters was found to be consistent at clinical firing rates (up to 3 Hz). The results indicated that pressure fields in the research lithotripters are equivalent to those generated by a clinical HM3 lithotripter. © 2000 American Institute of Physics.

A multi-frame high-speed photography was used to investigate the dynamics of cavitation bubbles induced by a passage of a lithotripter shock wave in a water tank. Solitary bubbles in the free field each radiated a shock wave upon collapse, and typically emitted a micro-jet on the rebound following initial collapse. For bubbles in clouds, emitted jets were directed toward neighboring bubbles and could break the spherical symmetry of the neighboring bubbles before they in turn collapsed. Bubbles at the periphery of a cluster underwent collapse before the bubbles at the center. Observations with high-speed imaging confirm previous predictions that bubbles in a cavitation cloud do not cycle independently of one another but instead interact as a dynamic bubble cluster. © 2006 American Institute of Physics.

OBJECTIVE To determine how the size and location of coupling defects caught between the therapy head of a lithotripter and the skin of a surrogate patient (acoustic window of a test chamber) affect the features of shock waves responsible for stone breakage. METHODS Model defects were placed in the coupling gel between the therapy head of a Dornier Compact-S electromagnetic lithotripter and the Mylar window of a water-filled coupling test system. A fiber-optic hydrophone was used to measure acoustic pressures and map the lateral dimensions of the focal zone of the lithotripter. The effect of coupling conditions on stone breakage was assessed using Gypsum model stones. RESULTS Stone breakage decreased in proportion to the area of the coupling defect; a centrally located defect blocking only 18% of the transmission area reduced stone breakage by an average of almost 30%. The effect on stone breakage was greater for defects located on-axis and decreased as the defect was moved laterally; an 18% defect located near the periphery of the coupling window (2.0 cm off-axis) reduced stone breakage by only ~15% compared to when coupling was completely unobstructed. Defects centered within the coupling window acted to narrow the focal width of the lithotripter; an 8.2% defect reduced the focal width ~30% compared to no obstruction (4.4 mm versus 6.5 mm). Coupling defects located slightly off center disrupted the symmetry of the acoustic field; an 18% defect positioned 1.0 cm off-axis shifted the focus of maximum positive pressure ~1.0 mm laterally. Defects on and off-axis imposed a significant reduction in the energy density of shock waves across the focal zone. CONCLUSIONS In addition to blocking the transmission of shock wave energy, coupling defects also disrupt the properties of shock waves that play a role in stone breakage, including the focal width of the lithotripter and the symmetry of the acoustic field; the effect is dependent on the size and location of defects, with defects near the center of the coupling window having the greatest effect. These data emphasize the importance of eliminating air pockets from the coupling interface, particularly defects located near the center of the coupling window. INTRODUCTION The quality of acoustic coupling in shock wave lithotripsy (SWL) is often overlooked and may be one of the most important factors affecting treatment outcomes (1,2). SWL can be very effective in breaking stones but only if the shock waves (SWs) can get to the target. In early lithotripters such as the Dornier HM3 the patient was immersed in a water bath, providing an ideal medium for SW propagation. Modern lithotripters on the other hand are dry-head devices in which the cushion of the treatment head must be coupled, usually with gel or oil, to the skin of the patient. Unfortunately, air can get trapped at the coupling interface and this interferes with SW transmission to the patient (3,4). Reports have suggested that newer lithotripters are not nearly as effective as the Dornier HM3 (1, 5–7). Clearly there are multiple factors that distinguish one lithotripter from the next so it is difficult to know what contributes to higher success rates with the HM3. The HM3 is not the most powerful lithotripter nor does the acoustic output or dimensions of the focal volume distinguish this lithotripter from most others. The HM3 is, however, the only lithotripter that employs a complete immersion water bath, the only lithotripter where the quality of coupling is not potentially problematic, and this could be the primary reason the HM3 has proven to be more effective than newer machines. In previous studies with dry-head lithotripters we have shown that air pockets caught at the coupling interface between the cushion of the treatment head and the acoustic window (surrogate skin) of the test tank interfere with the transmission of SW energy (8). As the area occupied by air pockets increased, acoustic pressure at the focal point of the lithotripter decreased, as did the efficiency in breakage of model stones. There was considerable variability in the system in that every coupling attempt yielded a different pattern of air pockets with defects of different shape, size and location depending on how the gel was handled and applied. This was found to be the case for tests using a Mylar membrane as surrogate skin, but also when a treatment cushion affixed to a viewing port was pushed against the skin of a volunteer. It was also observed that coupling attempts having a similar total area occupied by air pockets could yield stone breakage values differing by greater than 30%, suggesting that not only does the area of coupling defects matter, but perhaps that the location of the air pockets is also important (9). Air pockets caught at the coupling interface are acoustically opaque and block the SW transmission path, but they also have smooth or regular edges that could create diffraction with the potential to further disrupt the acoustic field at the target (10). Since the mechanisms of SW action in stone breakage and tissue damage are dependent on the acoustic output and dimensions of the focal zone of the lithotripter there is value in learning more about the potential mechanistic effects of defects at the coupling interface. Therefore, we undertook a study to assess the role that size, shape and location of coupling defects may play in lithotripter performance.

Struvite in kidney stones is an important marker for infection. In kidney stone samples, struvite is known to be prone to chemical breakdown, but no data exist on the stability of samples stored in dry form. The objective of this study was to examine stability of struvite under increasingly poor conditions of storage.Samples of struvite kidney stones were broken to obtain 38 pieces averaging 67 mg in weight, and these were randomized into four storage conditions: Airtight containers stored in the dark, open containers in the dark, open containers in ambient light, and open containers at elevated temperature (40°C). Pieces were left for 6 months, and then analyzed for changes using micro CT and Fourier transform infrared spectroscopy (FT-IR).Initial samples proved to be struvite, indicating no transformation in the large specimens that had been stored in airtight containers in the dark for more than 6 years before this study. Pieces of struvite taken from these large specimens appeared unchanged by micro CT and FT-IR after being stored in closed containers for 6 months, but 8 of 9 pieces in open containers showed the presence of newberyite in surface layers, as did 10 of 10 pieces in open containers out in ambient light. All pieces stored at 40°C showed transformation of struvite, with 60% of the pieces showing the presence of amorphous phosphates, indicating complete breakdown of struvite in the surface layers of the pieces.We conclude that struvite in dry kidney stone samples is stable when the specimens are stored in airtight containers at room temperature, even after several years.

OBJECTIVE To test the idea that a pause (~3-min) in the delivery of shock waves (SW) soon after the initiation of treatment is unnecessary for achieving a reduction in renal injury, if treatment is begun at a low power setting that generates low-amplitude SWs. MATERIALS AND METHODS Anesthetized female pigs were assigned to one of three SWL treatment protocols that did not involve a pause in SW delivery of more than 10 seconds (2000 SWs at 24 kV; 100 SWs at 12 kV + ~10-sec pause + 2000 SWs at 24 kV; 500 SWs at 12 kV + ~10-sec pause + 2000 SWs at 24 kV; all SWs delivered at 120 SWs/min using an unmodified Dornier HM3 lithotripter). Renal function was measured before and after SWL. The kidneys were then processed for quantification of the SWL-induced hemorrhagic lesion. Values for lesion size were compared to previous data collected from pigs in which treatment included a 3-min pause in SW delivery. RESULTS All SWL treatment protocols produced a similar degree of vasoconstriction (23–41% reduction in GFR and ERPF) in the SW-treated kidney. The mean renal lesion in pigs treated with 100 low-amplitude SWs delivered before the main dose of 2000 high-amplitude SWs (2.27% FRV) was statistically similar to that measured for pigs treated with 2000 SWs all at high-amplitude (3.29% FRV). However, pigs treated with 500 low-amplitude SWs before the main SW dose had a significantly smaller lesion (0.44% FRV) that was comparable to the lesion in pigs from a previous study in which there was a 3-min pause in treatment separating a smaller initial dose of 100 low-amplitude SWs from the main dose of 2000 high-amplitude SWs (0.46% FRV). Time between the initiation of the low- and high-amplitude SWs was ~4-min for these latter two groups compared to ~1-min when there was negligible pause after the initial 100 low-amplitude SWs in the protocol. CONCLUSIONS Pig kidneys treated by SWL using a 2-step low-to-high power ramping protocol were protected from injury with negligible pause between steps, provided the time between the initiation of low-amplitude SWs and switching to high-amplitude SWs was ~4-min. Comparison with results from previous studies shows that protection can be achieved using various step-wise treatment scenarios in which either the initial dose of SWs is delivered at low-amplitude for ~4-min, or there is a definitive pause before resuming SW treatment at higher amplitude. Thus, we conclude that renal protection can be achieved without instituting a pause in SWL treatment. It remains prudent to consider that renal protection depends on the acoustic and temporal properties of SWs administered at the beginning stages of a SWL ramping protocol, and that this may differ according to the lithotripter at hand. Keywords: kidney, lithotripsy, swine, tissue injury INTRODUCTION An undesirable side effect of SWL treatment is that SWs can injure renal and surrounding tissue [1]. The primary acute lesion is vascular trauma with breakage of blood vessels and pooling of blood within the parenchyma, which if extending to the kidney surface will result in subcapsular or perirenal hematomas [1]. Along with the vascular insult, there is damage to tubules and the production and release of proinflammatory cytokines and injurious agents (e.g. iron/reactive oxygen metabolites; vasoconstrictor peptides/ischemia; metabolic toxins) that can result in fibrosis and the loss of functional tissue [1,2]. Such SW-induced injury has been linked to adverse outcomes such as hypertension, diabetes and exacerbation of kidney stone disease [3–5]. This raises concern about the long-term safety of SWL, and developing SWL treatment strategies that reduce or prevent tissue injury would certainly help mitigate such concerns. One approach to reduce SWL-induced tissue injury has been to alter the manner in which SWs are delivered to the kidney [2,6], and in this regard we have reported that treatment of the pig kidney with low-amplitude SWs followed by a 3-min pause in treatment prior to applying high-amplitude SWs will reduce SWL-induced hemorrhagic lesion sizes by as much as 20-fold [7]. In fact, similar protocols in which low-amplitude SWs were substituted with a relatively small number of higher-amplitude SWs were also shown to reduce SW-induced tissue damage, implicating the 3-min pause in treatment to be a critical factor in the development of the renal protective response [8]. On the other hand, some clinical centers begin SWL treatment at a low power setting to condition the patient to treatment-related discomfort and then gradually ramp up to higher levels with continuous delivery of SWs. That is, there is typically no pause in treatment during the lithotripsy session [9–12]. It is unclear even with power ramping if continuous delivery of SWs can be used to protect the kidney from injury. Therefore, we sought to determine in our pig model, using a 2-step ramping protocol, whether a definitive pause in SW delivery is needed in order to protect the kidney from SWL-related tissue damage.

OBJECTIVE To assess renal injury in a pig model after treatment with a clinical dose of shock waves using a narrow focal zone (≈ 3 mm) lithotriptor (Modulith SLX, Karl Storz Lithotripsy). MATERIALS AND METHODS The left kidney of anaesthetized female pigs were treated with 2000 or 4000 shock waves (SWs) at 120 SWs/min, or 2000 SWs at 60 SWs/min using the Storz SLX. Measures of renal function (glomerular filtration rate and renal plasma flow) were collected before and 1 h after shock wave lithotripsy (SWL) and the kidneys were harvested for histological analysis and morphometric quantitation of haemorrhage in the renal parenchyma with lesion size expressed as a percentage of functional renal volume (FRV). A fibre-optic probe hydrophone was used to determine acoustic output and map the focal width of the lithotriptor. Data for the SLX were compared with data from a previously published study in which pigs of the same age (7–8 weeks) were treated (2000 SWs at 120 or 60 SWs/min) using an unmodified Dornier HM3 lithotriptor. RESULTS Treatment with the SLX produced a highly focused lesion running from cortex to medulla and often spanning the full thickness of the kidney. Unlike the diffuse interstitial haemorrhage observed with the HM3, the SLX lesion bore a blood-filled core of near-complete tissue disruption devoid of histologically recognizable kidney structure. Despite the intensity of tissue destruction at the core of the lesion, measures of lesion size based on macroscopic determination of haemorrhage in the parenchyma were not significantly different from kidneys treated using the HM3 (2000 SWs, 120 SWs/min: SLX, 1.86 ± 0.52% FRV; HM3, 3.93 ± 1.29% FRV). Doubling the SW dose of the SLX from 2000 to 4000 SWs did not significantly increase lesion size. In addition, slowing the firing rate of the SLX to 60 SWs/min did not reduce the size of the lesion (2.16 ± 0.96% FRV) compared with treatment at 120 SWs/min, as was the case with the HM3 (0.42 ± 0.23% FRV vs 3.93 ± 1.29% FRV). Renal function fell significantly below baseline in all treated groups but was similar for both lithotriptors. Focal width of the SLX (≈ 2.6 mm) was about one-third that of the HM3 (≈ 8 mm) while peak pressures were higher (SLX at power level 9: P+ ≈ 90 MPa, P− ≈ −12 MPa; HM3 at 24 kV: P+ ≈ 46 MPa, P−≈−8 MPa). CONCLUSIONS The lesion produced by the SLX (narrow focal width, high acoustic pressure) was a more focused, more intense form of tissue damage than occurs with the HM3. Slowing the SW rate to 60 SWs/min, a strategy shown to be effective in reducing injury with the HM3, was not protective with the SLX. These findings suggest that the focal width and acoustic output of a lithotriptor affect the renal response to SWL. Keywords: shock wave lithotripsy, renal injury, narrow focal zone INTRODUCTION Renal injury is an unfortunate but expected consequence of shock wave lithotripsy (SWL). All patients experience at least mild haematuria, some develop subcapsular or perinephric haematomas, and in rare cases excessive bleeding can develop, requiring intervention [1–6]. SWL injury has not been well studied in patients but there is a wealth of information describing the renal response to SWs in experimental animals. The most thorough characterization has been conducted in the pig model where the severity of tissue damage and size of the haemorrhagic lesion are dependent on many factors, including treatment settings for power and shock wave (SW) rate, the sequence of SW delivery, the number of SWs and the size of the kidney [7–10]. This work in assessing treatment variables has helped to estimate the potential for injury in the clinical setting and has revealed treatment strategies that significantly reduce tissue damage [8,9,11–13]. Thus, there is a growing understanding of how treatment settings contribute to injury in SWL. However, little has been done in a systematic way to compare the injuries produced by different lithotriptors. Lithotriptors are not all the same. The SWs of all lithotriptors have similar features, but the acoustic output and dimensions of the focal zone produced by different machines can be very different [14]. Focal width is a critical feature of a lithotriptor and in working terms describes how tightly SW energy is focused in the patient. Focal width is important because it affects the mechanisms at play in stone breakage. Shear stress contributing to stone breakage is enhanced when the focal width is wider than the stone [15,16]. Also, since respiratory motion moves the stone in and out of the focal zone, a lithotriptor with larger focal width has an improved chance of hitting the target [17]. Indeed, patient studies have suggested that focal width can affect outcomes with lower stone-free rates for narrow focal width lithotriptors [18–22]. Focal width has also been implicated in SWL injury, with the suggestion of an increased occurrence of adverse effects with narrow focal width machines [23,24]. The focal widths of current lithotriptors cover a broad range, from ≈ 2.1 mm (Wolf Piezolith P3000) to ≈ 20 mm (LithoGold LG-380). Most machines are reported have a focal width of about 6–10 mm and it is not uncommon to find considerable variance for the values reported for a given machine. For example, reported values of focal width for the unmodified Dornier HM3 lithotriptor (Dornier Medical Systems, Kennesaw, GA, USA) run from ≈ 8 to ≈ 12 mm, the difference being due to how the measurements were conducted [14,25]. Accurate measures require rigorous mapping of the pressure field with a fibre-optic probe hydrophone and this is not an assessment often performed beyond the characterization required for the licensing and approval of a new lithotriptor [26]. The Storz Modulith SLX (Karl Storz Lithotripsy, Atlanta, GA, USA) is an electromagnetic lithotriptor that has gained considerable popularity within the urology community. This machine emerged during the wave of technical development spurred by interest in making SWL an anaesthesia-free procedure. Since discomfort during SWL is due largely to cutaneous sensation, the strategy used by many manufacturers was to widen the aperture of the shock source to spread the area of contact between the acoustic pulse and the body. This reduced pain at the skin but also narrowed the focal zone [14]. The SLX has a focal width of only ≈ 3 mm and produces higher acoustic pressures (P+≈ 90 MPa) than broader focal width machines (i.e. LG-380: FW ≈ 20 mm, P+≈ 20 MPa; XiXin CS2012: FW ≈ 18 mm, P+ ≈ 17 MPa; HM3: FW ≈ 8 mm, P+≈ 40 MPa) [26,27]. As kidney injury has not been adequately assessed for a narrow focal zone lithotriptor, we used the pig model to characterize the renal response to SWs for the SLX. SWs were administered under conditions that simulated clinical SWL at settings for SW number, power level and SW rate that have been reported for treating patients using this lithotriptor [28]. Data for morphology, lesion size and renal function were compared with similar, previously published data for pigs treated using the Dornier HM3 [10]. The study included assessment of the renal response to slow SW rate, a treatment strategy shown to protect against renal trauma in the pig model [9,10].

Lithotripter shock waves (SWs) generated in non-degassed water at 0.5 and 2 Hz pulse repetition frequency (PRF) were characterized using a fiber-optic hydrophone. High-speed imaging captured the inertial growth-collapse-rebound cycle of cavitation bubbles, and continuous recording with a 60 fps camcorder was used to track bubble proliferation over successive SWs. Microbubbles that seeded the generation of bubble clouds formed by the breakup of cavitation jets and by bubble collapse following rebound. Microbubbles that persisted long enough served as cavitation nuclei for subsequent SWs, as such bubble clouds were enhanced at fast PRF. Visual tracking suggests that bubble clouds can originate from single bubbles.

Shock wave lithotripsy (SWL) is the only noninvasive method for stone removal. Once considered as a primary option for the treatment of virtually all stones, SWL is now recognized to have important limitations that restrict its use. In particular, the effectiveness of SWL is severely limited by stone burden, and treatment with shock waves carries the risk of acute injury with the potential for long-term adverse effects. Research aiming to characterize the renal response to shock waves and to determine the mechanisms of shock wave action in stone breakage and renal injury has begun to suggest new treatment strategies to improve success rates and safety. Urologists can achieve better outcomes by treating at slower shock wave rate using a step-wise protocol. The aim is to achieve stone comminution using as few shock waves and at as low a power level as possible. Important challenges remain, including the need to improve acoustic coupling, enhance stone targeting, better determine when stone breakage is complete, and minimize the occurrence of residual stone fragments. New technologies have begun to address many of these issues, and hold considerable promise for the future.

OBJECTIVE To determine the mechanism that underlies the effect of shock wave (SW) rate on the performance of clinical lithotripters. MATERIALS AND METHODS The effect of firing rate on the pressure characteristics of SWs was assessed using a fibre-optic probe hydrophone (FOPH 500, RP Acoustics, Leutenbach, Germany). Shock waves were fired at slow (5-27 SW/min) and fast (100-120 SW/min) rates using a conventional high-pressure lithotriptor (DoLi-50, Dornier MedTech America, Inc., Kennesaw, GA, USA), and a new low-pressure lithotriptor (XX-ES, Xi Xin Medical Instruments Co. Ltd, Suzhou, PRC). A digital camcorder (HDR-HC3, Sony, Japan) was used to record cavitation fields, and an ultrafast multiframe high-speed camera (Imacon 200, DRS Data & Imaging Systems, Inc., Oakland, NJ, USA) was used to follow the evolution of bubbles throughout the cavitation cycle. RESULTS Firing rate had little effect on the leading positive-pressure phase of the SWs with the DoLi lithotriptor. A slight reduction ( approximately 7%) of peak positive pressure (P+) was detected only in the very dense cavitation fields (approximately 1000 bubbles/cm(3)) generated at the fastest firing rate (120 SW/min) in nondegassed water. The negative pressure of the SWs, on the other hand, was dramatically affected by firing rate. At 120 SW/min the peak negative pressure was reduced by approximately 84%, the duration and area of the negative pressure component was reduced by approximately 80% and approximately 98%, respectively, and the energy density of negative pressure was reduced by >99%. Whereas cavitation bubbles proliferated at fast firing rates, HS-camera images showed the bubbles that persisted between SWs were very small (

Shock wave lithotripsy (SWL) has proven to be a highly effective treatment for the removal of kidney stones. Shock waves (SW’s) can be used to break most stone types, and because lithotripsy is the only non-invasive treatment for urinary stones SWL is particularly attractive. On the downside SWL can cause vascular trauma to the kidney and surrounding organs. This acute SW damage can be severe, can lead to scarring with a permanent loss of functional renal volume, and has been linked to potentially serious long-term adverse effects. A recent retrospective study linking lithotripsy to the development of diabetes mellitus has further focused attention on the possibility that SWL may lead to life-altering chronic effects 1. Thus, it appears that what was once considered to be an entirely safe means to eliminate renal stones can elicit potentially severe unintended consequences. The purpose of this review is to put these findings in perspective. The goal is to explain the factors that influence the severity of SWL injury, update current understanding of the long-term consequences of SW damage, describe the physical mechanisms thought to cause SWL injury, and introduce treatment protocols to improve stone breakage and reduce tissue damage.

Calcium oxalate monohydrate (COM) stones are often resistant to breakage using shock wave (SW) lithotripsy. It would be useful to identify by computed tomography (CT) those COM stones that are susceptible to SW's. For this study, 47 COM stones (4-10 mm in diameter) were scanned with micro CT to verify composition and also for assessment of heterogeneity (presence of pronounced lobulation, voids, or apatite inclusions) by blinded observers. Stones were then placed in water and scanned using 64-channel helical CT. As with micro CT, heterogeneity was assessed by blinded observers, using high-bone viewing windows. Then stones were broken in a lithotripter (Dornier Doli-50) over 2 mm mesh, and SW's counted. Results showed that classification of stones using micro CT was highly repeatable among observers (kappa = 0.81), and also predictive of stone fragility. Stones graded as homogeneous required 1,874 +/- 821 SW/g for comminution, while stones with visible structure required half as many SW/g, 912 +/- 678. Similarly, when stones were graded by appearance on helical CT, classification was repeatable (kappa = 0.40), and homogeneous stones required more SW's for comminution than did heterogeneous stones (1,702 +/- 993 SW/g, compared to 907 +/- 773). Stone fragility normalized to stone size did not correlate with Hounsfield units (P = 0.85). In conclusion, COM stones of homogeneous structure require almost twice as many SW's to comminute than stones of similar mineral composition that exhibit internal structural features that are visible by CT. This suggests that stone fragility in patients could be predicted using pre-treatment CT imaging. The findings also show that Hounsfield unit values of COM stones did not correlate with stone fragility. Thus, it is stone morphology, rather than X-ray attenuation, which correlates with fragility to SW's in this common stone type.

Measurements using a fiber-optic probe hydrophone, high-speed camera, and B-mode ultrasound showed attenuation of the trailing negative-pressure phase of a lithotripter shock pulse under conditions that favor generation of cavitation bubbles, such as in water with a high content of dissolved gas or at high pulse repetition rate where more cavitation nuclei persisted between pulses. This cavitation-mediated attenuation of the acoustic pulse was also observed to increase with increasing amplitude of source discharge potential, such that the negative-pressure phase of the pulse can remain fixed in amplitude even with increasing source discharge potential.

Objective—To test the hypothesis that feline calcium oxalate uroliths are intrinsically more resistant to comminution via shock wave lithotripsy (SWL) than canine calcium oxalate uroliths through comparison of the fragility of canine and feline uroliths in a quantitative in vitro test system. Sample Population—Calcium oxalate uroliths (previously obtained from dogs and cats) were matched by size and mineral composition to create 7 pairs of uroliths (1 canine and 1 feline urolith/pair). Procedure—Uroliths were treated in vitro with 100 shock waves (20 kV; 1 Hz) by use of an electrohydraulic lithotripter. Urolith fragmentation was quantitatively assessed via determination of the percentage increase in projected area (calculated from the digital image area of each urolith before and after SWL). Results—After SWL, canine uroliths (n = 7) fragmented to produce a mean ± SD increase in image area of 238 ± 104%, whereas feline uroliths (7) underwent significantly less fragmentation (mean image area increase of 78 ± 97%). The post-SWL increase in fragment image area in 4 of 7 feline uroliths was < 50%, whereas it was > 150% in 6 of 7 canine uroliths. Conclusions and Clinical Relevance—Results indicate that feline calcium oxalate uroliths are less susceptible to fragmentation via SWL than canine calcium oxalate uroliths. In some cats, SWL may not be efficacious for fragmentation of calcium oxalate nephroliths or ureteroliths because the high numbers of shock waves required to adequately fragment the uroliths may cause renal injury. (Am J Vet Res 2005;66:1651–1654)

Background and Purpose: There is strong evidence that cavitation bubble activity contributes to stone breakage and that shockwave-bubble interactions are involved in the tissue trauma associated with shockwave lithotripsy. Cavitation control may thus be a way to improve lithotripsy. Materials and Methods: High-speed photography was used to analyze cavitation bubble activity at the surface of artificial and natural kidney stones during exposure to lithotripter shockwaves in vitro. Results: Numerous individual bubbles formed on the surfaces of stones, but these bubbles did not remain independent but rather combined to form clusters. Bubble clusters formed at the proximal and distal ends and at the sides of stones. Each cluster collapsed to a narrow point of impact. Collapse of the proximal cluster eroded the leading face of the stone, and the collapse of clusters at the sides of stones appeared to contribute to the growth of cracks. Collapse of the distal cluster caused minimal damage. Conclusion: Cavitation-mediated damage to stones is attributable, not to the action of solitary bubbles, but to the growth and collapse of bubble clusters.

In the 1980s shockwave lithotripsy emerged as a revolutionary advancement for the treatment of kidney stones. Initial studies with patients showed SWL to be highly effective. The technology was elegant, outcomes exceptionally positive and early tests suggested treatment was safe. As experience with SWL grew, limitations surfaced. A key finding was that SWs have the potential to induce significant trauma to the kidney. Our group convinced the NIH it was time to conduct a rigorous assessment to characterize the adverse effects of SWL and determine the mechanisms of SW action in stone breakage and tissue injury. The NIH Program Project Grant mechanism mandated we establish a panel of external advisors to help guide our work. We needed expertise in physical acoustics, cavitation and animal models of ultrasound exposure. We wanted a leading expert. We were extremely fortunate to land Ed Carstensen. Ed worked with us for nearly 15 years, well into our third renewal cycle. He was a brilliant scientist, a man ded...

Edwin Carstensen, Ph.D., was an advisor of NIH NIDDK Program Project Grant DK043881, created to investigate shock wave lithotripsy (SWL). We now develop solutions to improve all aspects of the management of stone disease. Our goal in this paper is to report progress built on Dr. Cartsensen's advice and inspiration. The work ranges from numerical simulation to clinical trials and from device development to bioeffects and metrology. Much of our work involves bubbles and cavitation. This work has contributed to the body of knowledge defining limits for the safe use of ultrasound which Dr. Carstensen worked hard to establish. Specifically, an update will be given on the development of ultrasound to image, fragment, trap, and reposition stones. In particular, we demonstrated bubbles contribute to the twinkling artifact used by NASA and others to image stones, and we drew on Dr. Carstensen's paper [UMB, 19(2) 147-165 1993] to demonstrate that breathing the elevated carbon dioxide levels present in NASA vehicles...

We assessed patient outcomes using 2 widely different contemporary lithotripters.We performed a consecutive case series study of 355 patients in a large private practice group using a Modulith® SLX electromagnetic lithotripter in 200 patients and a LithoGold LG-380 electrohydraulic lithotripter (TRT, Woodstock, Georgia) in 155. Patients were followed at approximately 2 weeks. All preoperative and postoperative films were reviewed blindly by a dedicated genitourinary radiologist. The stone-free rate was defined as no residual fragments remaining after a single session of shock wave lithotripsy without an ancillary procedure.Patients with multiple stones were excluded from analysis, leaving 76 and 142 treated with electrohydraulic and electromagnetic lithotripsy, respectively. The stone-free rate was similar for the electrohydraulic and electromagnetic lithotripters (29 of 76 patients or 38.2% and 69 of 142 or 48.6%, p = 0.15) with no difference in the stone-free outcome for renal stones (20 of 45 or 44.4% and 33 of 66 or 50%, p = 0.70) or ureteral stones (9 of 31 or 29% and 36 of 76 or 47.4%, respectively, p = 0.08). The percent of stones that did not break was similar for the electrohydraulic and electromagnetic devices (10 of 76 patients or 13.2% and 23 of 142 or 16.2%) and ureteroscopy was the most common ancillary procedure (18 of 22 or 81.8% and 30 of 40 or 75%, respectively). The overall mean number of procedures performed in patients in the 2 groups was similar (1.7 and 1.5, respectively).We present lithotripsy outcomes in the setting of a suburban urology practice. Stone-free rates were modest using shock wave lithotripsy alone but access to ureteroscopy provided satisfactory outcomes overall. Although the acoustic characteristics of the electrohydraulic and electromagnetic lithotripters differ substantially, outcomes with these 2 machines were similar.

Rationale and Objectives Urinary calculi are now commonly detected with helical computed tomography (CT), and it has been proposed that stone composition can be determined from CT attenuation values. However, typical scans are made with a beam collimation of 5 mm or more, resulting in volume averaging and reduction in accuracy of attenuation measurement. The authors tested a model for correction of errors in attenuation values, even at section widths larger than the width of the object. Materials and Methods Human urinary stones were scanned with helical CT at different beam collimation widths. A computer model was used to predict the effect of beam width and stone size on accuracy of measured attenuation. Results At 3-mm collimation, the model corrected the attenuation readings with an underestimation of 12% ± 1 (compared with values at 1-mm collimation; 127 stones; diameters of 1.7–11.3 mm). With attenuation measured at 10-mm collimation, the model underestimated the true value by 34% ± 3 (103 stones), with a significant negative correlation with stone diameter on magnitude of error (diameters of 3.0–11.3 mm). Correlation of data from patient scans with subsequent in vitro scanning of the same stones confirmed the validity of the model, but corrected in vivo scans consistently yielded lower values for the stones than in vitro. Conclusion Volume averaging effects on attenuation in helical CT are predictable in vitro for urinary calculi—and presumably for other roughly spherical structures—as long as section width does not excessively exceed the diameter of the structure.

Cavitation generated by lithotripter shock waves (SWs) in non-degassed water was studied using a 60 frames-per-second camcorder—recording the migration of microbubbles over successive SWs. Lithotripter SWs were produced using a Dornier DoLi-50 electromagnetic lithotripter at 0.5 and 2 Hz pulse repetition frequency (PRF). Cavitation was affected by PRF and by the power level (PL) of the lithotripter. At slow PRF, such as shots fired many seconds apart, cavitation was relatively sparse and bubble clouds flowed in the direction of SW propagation. When PRF was increased, the bubble clouds generated by one SW were amplified by subsequent SWs. Cloud amplification was accompanied by an apparent change in the pattern of bubble migration. Whereas bubbles continued to enter the field of view from the prefocal side, the main bubble cloud remained near the focal point. This was due to a streaming of bubbles opposite to the direction of SW propagation. Increasing the PL grew the cavitation field and enhanced the flow of bubbles opposite to the direction of SW propagation. Stepping up the PL acted to push the broad cloud progressively pre-focally (toward the SW source), shifting the position of the plane at which the opposing directional bubble flows collided. [NIH DK43881.]

Polypropylene vials are commonly used in in vitro experiments to hold cell preparations that are exposed to ultrasound. The vial has an acoustic impedance very close to water, in which case there should be little transmission loss as sound propagates into the vial. Measurements of the acoustic field within polypropylene vials have been carried out using both pulsed medical ultrasound and lithotripter shock waves. It has been found that for certain orientations of the acoustic field and vial there is significant loss of pressure amplitude within the vial. In particular, sound that enters the vial through the round, hemispherical end is attenuated and distorted. Hot and cold spots within the vial are also measured. When the rounded end is replaced with a flat surface very little distortion and attenuation of the waveform occurs. The distortion induced by the round end is apparently due to refraction introduced by the vial—the speed of sound in polypropylene is about 1.7 times that of water. A simple ray ana...

Recent work in nephrolithiasis has benefited from 2 special kinds of imaging: endoscopic study of patient kidneys with high-quality instruments, and examina- tion of stones with microscopic computed tomogra- phy (micro CT). The combination of these has provided new evidence that there is more than 1 mechanism by which stones are retained in the kidney until they achieve sizes to be clinically relevant. This review de- scribes what is known about the formation of stones on Randall's plaque, the formation of stones on ductal plugs and the ways in which stones may grow in free solution within the calyceal or pelvic spaces. Stud- ies of urolithiasis need to recognize that any group of "stone formers" likely includes patients who differ fundamentally regarding which mechanism of stone formation is the primary route for their stones. Sepa- ration of patients on the basis of which mechanism (or combination of mechanisms) underlies their disease will be important for advancing research in the area of urolithiasis.

Therapeutic ultrasound has an increasing number of applications in urology, including shockwave lithotripsy, stone propulsion, tissue ablation, and hemostasis. However, the threshold of renal injury using ultrasound is unknown. The goal of this study was to determine kidney injury thresholds for a range of intensities between diagnostic and ablative therapeutic ultrasound. A 2 MHz annular array generating spatial peak pulse average intensities (ISPPA) up to 28,000 W/cm2 in water was placed on the surface of in vivo porcine kidneys and focused on the adjacent parenchyma. Treatments consisted of pulses of 100 μs duration triggered every 3 ms for 10 minutes at various intensities. The perfusion-fixed tissue was scored by 3 blinded independent experts. Above a threshold of 16,620 W/cm2, the majority of injury observed included emulsification, necrosis and hemorrhage. Below this threshold, almost all injury presented as focal cell and tubular swelling and/or degeneration. These findings provide evidence for a wide range of potentially therapeutic ultrasound intensities that has a low probability of causing injury. While this study did not examine all combinations of treatment parameters of therapeutic ultrasound, tissue injury appears dose-dependent.

Cultured inner medullary collecting duct (mIMCD-3) cells express Na+/H+ exchanger isoforms NHE-2 and NHE-1 (Soleimani et al. (1994) J. Biol. Chem. 269, 27973-27978). In the present studies we examined the effect of lethal acid stress on Na+/H+ exchanger activity and isoform expression in mIMCD-3 cells. mIMCD-3 cells were incubated for 10 min with 20 mM ammonium, and exposed to an ammonium-free acidic solution (pH 6.0) for 120 min. Thereafter, cells were recovered and grown in normal culture media. The surviving clones were isolated and subjected to two additional cycles of acid stress. A mutant clone was isolated and characterized for Na+/H+ exchange activity and isoform expression. The mutant mIMCD-3 clone demonstrated significant over-expression of Na+/H+ exchange activity as assessed by acid-stimulated 22Na influx (11.56 nmol/mg protein in mutant vs. 4.06 nmol/mg in parent cells, P < 0.001, n = 4) and sodium-dependent pHi recovery from an acid load (0.55 pH/min in mutant vs. 0.28 pH/min in parent cells, P < 0.01, n = 6). A dose-response inhibition of the exchanger showed that the mutant cells were very sensitive to dimethylamiloride (IC50 158 nM in mutant vs. 889 nM in parent mIMCD-3 cells, P < 0.001). To compare the Na+/H+ exchanger isoforms in mutant and parent mIMCD-3 cells, poly(A)+ RNA was isolated from each group and probed with radiolabeled NHE-1 or NHE-2 cDNA. The expression of NHE-1 mRNA was increased by approximately 100% in mutant cells. The NHE-2 mRNA, on the other hand, was found to be absent in mutant mIMCD-3 cells. Examination of the regulatory mechanisms of the Na+/H+ exchanger isoforms in parent mIMCD-3 cells, which express NHE-2 and NHE-1, and mutant mIMCD-3 cells, which only express NHE-1, would be helpful in elucidating the roles of NHE-2 and NHE-1 in inner medullary collecting duct cells.

Recent cloning experiments have identified the existance of four distinct Na+/H+ exchanger isoforms designated as NHE-1, NHE-2, NHE-3, and NHE-4. The cellular distribution, subcellular localization, and regulation of one of these isoforms, NHE-2, in the kidney remains unknown. Northern hybridization showed that NHE-2, along with NHE-1, is expressed in cultured renal medullary collecting duct (mIMCD-3) cells. Acid-stimulated, dimethyl amiloride-sensitive 22Na+ uptake and sodium-dependent pHi recovery occurred only from the basolateral surface of the cells, indicating localization of Na+/H+ exchanger to the basolateral membrane domain. Incubation of IMCD cells in high osmolality media (510 mosm/liter) for 72 h stimulated the Na+/H+ exchanger activity by 59% (p 0.05). Northern hybridization, however, indicated that NHE-1 mRNA increased, whereas NHE-2 mRNA decreased in acid media. In conclusion, mIMCD-3 cells express NHE-1 and NHE-2 mRNAs. The cell functional studies in mIMCD-3 cells strongly suggest that NHE-2, along with NHE-1, is expressed in the basolateral membrane domain. They further demonstrate differential regulation of NHE-1 and NHE-2 mRNAs in response to acidosis and high osmolality and suggest that NHE-2 may be involved in volume regulation of IMCD cells.

Na+/H+ exchanger isoform and the effect of high osmolality on its function was studied in cultured renal epithelial cells (LLC-PK1 and OK). Using NHE-3-specific antibody, immunoblots of luminal membranes from LLC-PK1 and OK cells specifically labeled proteins with molecular masses 90 and 95 kDa, indicating that NHE-3 is the isoform expressed on the luminal membranes of these epithelia. Proximal tubular suspensions from rabbit kidney cortex were incubated in control (310 mosm/liter) or high osmolality (510 mosm/liter) medium for 45 min and utilized for brush border membrane vesicle preparation. Influx of amiloride-sensitive 22Na+ at 10 s (pHo 7.5, pHi 6.0) into brush border membrane vesicles was 37% lower in the high osmolality group (p

Brushite stones were imaged in vitro and then broken with shock wave lithotripsy to assess whether stone fragility correlates with internal stone structure visible on helical computerized tomography.A total of 52 brushite calculi were scanned by micro computerized tomography, weighed, hydrated and placed in a radiological phantom. Stones were scanned using a Philips® Brilliance iCT 256 system and images were evaluated for the visibility of internal structural features. The calculi were then treated with shock wave lithotripsy in vitro. The number of shock waves needed to break each stone to completion was recorded.The number of shock waves needed to break each stone normalized to stone weight did not differ by HU value (p = 0.84) or by computerized tomography visible structures that could be identified consistently by all observers (p = 0.053). Stone fragility correlated highly with stone density and brushite content (each p0.001). Calculi of almost pure brushite required the most shock waves to break. When all observations of computerized tomography visible structures were used for analysis by logistic fit, computerized tomography visible structure predicted increased stone fragility with an overall area under the ROC curve of 0.64.The shock wave lithotripsy fragility of brushite stones did not correlate with internal structure discernible on helical computerized tomography. However, fragility did correlate with stone density and increasing brushite mineral content, consistent with clinical experience with patients with brushite calculi. Thus, current diagnostic computerized tomography technology does not provide a means to predict when brushite stones will break well using shock wave lithotripsy.

Context The introduction of new lithotripters has increased problems associated with shock wave application. Recent studies concerning mechanisms of stone disintegration, shock wave focusing, coupling, and application have appeared that may address some of these problems. Objective To present a consensus with respect to the physics and techniques used by urologists, physicists, and representatives of European lithotripter companies. Evidence acquisition We reviewed recent literature (PubMed, Embase, Medline) that focused on the physics of shock waves, theories of stone disintegration, and studies on optimising shock wave application. In addition, we used relevant information from a consensus meeting of the German Society of Shock Wave Lithotripsy. Evidence synthesis Besides established mechanisms describing initial fragmentation (tear and shear forces, spallation, cavitation, quasi-static squeezing), the model of dynamic squeezing offers new insight in stone comminution. Manufacturers have modified sources to either enlarge the focal zone or offer different focal sizes. The efficacy of extracorporeal shock wave lithotripsy (ESWL) can be increased by lowering the pulse rate to 60–80 shock waves/min and by ramping the shock wave energy. With the water cushion, the quality of coupling has become a critical factor that depends on the amount, viscosity, and temperature of the gel. Fluoroscopy time can be reduced by automated localisation or the use of optical and acoustic tracking systems. There is a trend towards larger focal zones and lower shock wave pressures. Conclusions New theories for stone disintegration favour the use of shock wave sources with larger focal zones. Use of slower pulse rates, ramping strategies, and adequate coupling of the shock wave head can significantly increase the efficacy and safety of ESWL.

Previous studies with our juvenile pig model have shown that a clinical dose of 2000 shock waves (SWs) (Dornier HM-3, 24 kV, 120 SWs/min) produces a lesion ~3–5% of the functional renal volume (FRV) of the SW-treated kidney. This injury was significantly reduced (to ~0.4% FRV) when a priming dose of 500 low-energy SWs immediately preceded this clinical dose, but not when using a priming dose of 100 SWs [BJU Int. 110, E1041 (2012)]. The present study examined whether using only 300 priming dose SWs would initiate protection against injury. METHODS: Juvenile pigs were treated with 300 SW’s (12 kV) delivered to a lower pole calyx using a HM-3 lithotripter. After a pause of 10 s, 2000 SWs (24 kV) were delivered to that same kidney. The kidneys were then perfusion-fixed and processed to quantitate the size of the parenchymal lesion. RESULTS: Pigs (n = 9) treated using a protocol with 300 low-energy priming dose SWs had a lesion measuring 0.84±0.43% FRV (mean ± SE). This lesion was smaller than that seen with a clinical dose of 2000 SWs at 24 kV. CONCLUSIONS: A treatment protocol including 300 low-energy priming dose SWs can provide protection from injury during shock wave lithotripsy. [Research supported by NIH grant P01 DK43881.]

Rigid intracorporeal lithotrites can be invaluable in the removal of large stone burdens during percutaneous nephrolithotomy. One such device, the Lithoclast Ultra Vario (LUV) has an outer ultrasound probe and inner pneumatic-ballistic probe. The ballistic probe can be advanced or retracted and run at 1–12 Hz. Since it can be difficult to predict optimal settings with any new device, we asked if in vitro testing could give insight into how best to operate this lithotrite. We tested the LUV under hands-free conditions that simulate treatment of fixed stones and freely movable stones. A fixed-stone test system measured the time to penetrate a gypsum model stone placed atop the probe and a movable-stone system determined time for comminution of a stone within a confined space. In addition, the time to evacuate 2-mm stone particles was measured. For hands-on testing, model stones were placed in a plastic dish submerged in water and the time to comminution was measured. Penetration time of fixed stones was faster with the ballistic probe extended 2.5 mm than when retracted (5.30 ± 0.85 vs. 8.75 ± 1.07 s, p < 0.0001). Comminution of free stones was faster with the ballistic probe retracted than when it was extended 1 mm or 2.5 mm (9.7 ± 0.9, 13.8 ± 1.3, 23.7 ± 3.2 s, p < 0.0001). In hands-on testing, extending the ballistic probe substantially reduced the efficiency of comminution (36.7 ± 6.4 vs. 131.3 ± 15.3 s, p < 0.0001). Clearance of fragments was considerably faster when the pneumatic-ballistic rate was 12 Hz compared to 1 Hz (12.3 ± 1.1 vs. 28.3 ± 2.2 s, p < 0.0001). These in vitro findings suggest ways to take advantage of the positive features while minimizing potential limitations of this lithotrite. Extending the ballistic probe is an advantage when the stone is immobile, as would be the case in treating a large stone that can be isolated against the wall of the pelvicalyceal system, but is a distinct disadvantage—due to retropulsion—when the stone is free to move. Operation of the LUV at fast ballistic rate significantly improved its ability to aspirate stone fragments.

We recently demonstrated that endothelial cells are more susceptible than renal tubular epithelial cells to oxidant injury and that renal tubular epithelial cells with proximal tubular characteristics including porcine proximal tubular epithelial cells, opossum kidney proximal tubular epithelial cells, and normal human kidney cortical epithelial cells are more susceptible to oxidant injury than the distal nephron-derived Madin Darby canine kidney cell line. To determine the basis of this differential response, we evaluated several antioxidant defenses in the five cell lines. Glutathione levels were not significantly different among the five cell lines, but catalase and glutathione reductase levels were significantly (p less than 0.01) lower in endothelial cells compared to all renal tubular epithelial cells. Among renal tubular epithelial cells, Madin Darby canine kidney cells had significantly (p less than 0.05) higher glutathione peroxidase activity. To further evaluate the role of antioxidant defenses in limiting oxidant injury, we determined two responses to oxidant injury (ATP depletion and 51Cr release) when glutathione was depleted with buthionine sulfoxamine and when catalase was inhibited with aminotriazole. Oxidant-induced ATP depletion was accentuated when catalase was inhibited as well as when glutathione was depleted with buthionine sulfoxamine. In contrast, inhibition of catalase had little or no effect on 51Cr release, whereas glutathione depletion resulted in accentuated 51Cr release. We conclude that the increased susceptibility of endothelial cells to oxidant injury as compared with epithelial cells is associated with lower antioxidant defenses. Disruption of the glutathione redox cycle results in accentuated ATP depletion and lytic injury, whereas inhibition of catalase results in accentuated ATP depletion with little effect on lytic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

NaCl transport by Madin Darby canine kidney (MDCK) cyst epithelial cells. The mechanism of NaCl transport across the epithelium of intact MDCK cysts grown in a collagen gel matrix was investigated. Double-barreled microelectrodes were used to measure basolateral membrane PD (V b1 ), transepithelial PD (V t ), and intracellular (Cl i ) and intralumenal (Cl cy ) Cl - activities in cysts under different conditions. In a control Ringer's solution (RS), Cl i (60 ± 1mM) and Cl cy (107 ± 2mM) exceeded the values corresponding to electrochemical equilibrium across the basolateral membrane and epithelium, respectively. Cl i was reduced by superfusing the cysts with a low Cl - RS (Cl i , 20 ± 3mM), a low Na + RS (Cl i , 40 ± 4mM), or by adding amiloride to the control RS (Cl i , 46 ± 1mM). Cl i was unaffected by removal of either K + or HCO 3 - from the RS or by adding furosemide or SITS to the control RS. V b1 in the control RS was -50 ± 2mV and was affected only by removal from the RS of K + (V b1 , -31 ± 3mV) or HCO 3 - (V b1 , -29 ± 4mV) or by the addition of SITS to the control RS (V b1 , -59 ± 5mV). V t in control RS was -2 ± 0.2mV (lumen negative), and was increased by reducing bath Na + (V t , -37 ± 2mV) but not by reducing bath Cl - . These data indicate that Cl - is secreted in a basolateral to apical direction by the cyst epithelium. Basolateral Cl - transport probably occurs mainly by an electroneutral Cl - /HCO 3 - exchanger. Transepithelial Na + transport seems to occur via a paracellular route which appears to be cation selective. These experiments also support the existence, in the basolateral membrane, of a Na + /K + ATPase, a Na + /H + exchanger, and possibly a Na + /HCO 3 - / CO 3 2- transporter.

Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for comparison. In ADPKD, immunoreactive renin was present in juxtaglomerular apparatus, associated arterioles, and in some cells within the connective tissue surrounding the cysts. Vascular immunoreactive renin was less prominent than in renal artery stenosis. Increased amounts of tubular immunoreactive renin were noted in polycystic kidneys, as compared to normal kidneys and kidneys with renal artery stenosis. Cyst fluids contained renin detected by Western analysis and enzymatic activity; concentrations were greater in gradient cysts than in nongradient cysts. Seventy-four percent of the renin in gradient cysts was active as compared to 23% in nongradient cysts and 15% in plasma. To determine whether cyst epithelial cells are capable of synthesizing renin, these cells were isolated in tissue culture. Enzymatic assay of extracts from these cells revealed the presence of renin-like enzymatic activity (1.3 ± 0.8ng AI/mg protein/hr). The synthesis of renin by tubulocystic epithelium was confirmed by [35S]-methionine radiolabeling of cyst-derived cells, followed by immunoprecipitation and SDS-PAGE and by detection of renin mRNA by the polymerase chain reaction. These results indicate that the tubulocystic epithelium has the potential to synthesize renin. Elevated levels of active renin in renal cysts may be linked to the pathogenesis of hypertension in ADPKD. The occurrence of renin in the lining epithelium of cyst walls raises the possibility that abnormal expression of the renin-angiotensin system may, by a paracrine or autocrine mechanism, regulate epithelial hyperplasia in growing renal cysts.

We determined the accuracy of stone composition analysis at commercial laboratories.A total of 25 human renal stones with infrared spectroscopy determined composition were fragmented into aliquots and studied with micro computerized tomography to ensure fragment similarity. Representative fragments of each stone were submitted to 5 commercial stone laboratories for blinded analysis.All laboratories agreed on the composition of 6 pure stones. Only 2 of 4 stones (50%) known to contain struvite were identified as struvite at all laboratories. Struvite was reported as a component by some laboratories for 4 stones previously determined not to contain struvite. Overall there was disagreement regarding struvite in 6 stones (24%). For 9 calcium oxalate stones all laboratories reported some mixture of calcium oxalate but the quantity of subtypes differed significantly among laboratories. In 6 apatite containing stones apatite was missed by the laboratories in 20% of samples. None of the laboratories identified atazanavir in a stone containing that antiviral drug. One laboratory reported protein in every sample while all others reported it in only 1. Nomenclature for apatite differed among laboratories with 1 reporting apatite as carbonate apatite and never hydroxyapatite, another never reporting carbonate apatite and always reporting hydroxyapatite, and a third reporting carbonate apatite as apatite with calcium carbonate.Commercial laboratories reliably recognize pure calculi. However, variability in the reporting of mixed calculi suggests a problem with the accuracy of stone analysis results. There is also a lack of standard nomenclature used by laboratories.

OBJECTIVE To determine if extracorporeal shock wave lithotripsy (ESWL) at 60 shock waves (SWs)/min reduces renal damage and haemodynamic impairment compared to treatment at 120 SWs/min. MATERIALS AND METHODS One kidney in each of 19 juvenile pigs (7–8 weeks old) was treated at 120 or at 60 SWs/min (2000 SWs, 24 kV) with an unmodified HM-3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA). Renal function was determined before and after ESWL treatment by inulin clearance, extraction and clearance of para-aminohippuric acid. Both kidneys were then removed to measure parenchymal lesion size by sectioning the entire kidney and quantifying the size of the haemorrhagic lesion in each slice. RESULTS ESWL at 60 SWs/min significantly reduced the size of the acute morphological lesion compared to 120 SWs/min (0.42% vs 3.93% of functional renal volume, P = 0.011) and blunted the decrease in glomerular filtration rate and renal plasma flow normally seen after treatment at 120 SWs/min. CONCLUSIONS Treatment at a firing rate of 60 SWs/min produces less morphological injury and causes less alteration in renal haemodynamics than treatment at 120 SWs/min in the pig model of ESWL-induced renal injury.

Growing concern over the acute and long-term adverse effects associated with shock wave lithotripsy calls for treatment strategies to reduce renal injury and improve the efficiency of stone breakage in shock wave lithotripsy.Experimental studies in the pig model show that lithotripter settings for power and shock wave rate and the sequence of shock wave delivery can be used to reduce trauma to the kidney. Step-wise power ramping as is often used to acclimate the patient to shock waves causes less tissue trauma when the initial dose is followed by a brief (3-4 min) pause in shock wave delivery. Slowing the firing rate of the lithotripter to 60 shock waves/min or slower is also effective in reducing renal injury and has the added benefit of improving stone breakage outcomes. Neither strategy to reduce renal injury -- not power ramping with 'pause-protection' nor delivering shock waves at reduced shock wave rate --- have been tested in clinical trials.Technique in lithotripsy is critically important, and it is encouraging that simple, practical steps can be taken to improve the safety and efficacy of shock wave lithotripsy.

Lithotriptors with 2 treatment heads deliver shock waves along separate paths. Firing 1 head and then the other in alternating mode has been suggested as a strategy to treat stones twice as rapidly as with conventional shock wave lithotripsy. Because the shock wave rate is known to have a role in shock wave lithotripsy induced injury, and given that treatment using 2 separate shock wave sources exposes more renal tissue to shock wave energy than treatment with a conventional lithotriptor, we assessed renal trauma in pigs following treatment at rapid rate (240 shock waves per minute and 120 shock waves per minute per head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel) fired in alternating mode.Eight adult female pigs (Hardin Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or 2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120 shock waves per minute per head and 240 shock waves per minute overall at a power level of 10) to the lower renal pole. Renal functional parameters, including glomerular filtration rate and effective renal plasma flow, were determined before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed in situ and the hemorrhagic lesion was quantified as a percent of functional renal volume.Shock wave treatment resulted in no significant change in renal function and the response was similar to the functional response seen in sham shock wave treated animals. In 6 pigs treated with alternating mode the renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal volume.Kidney tissue and function were minimally affected by a clinical dose of shock waves delivered in alternating mode (120 shock waves per minute per head and 240 shock waves per minute overall) with a Duet lithotriptor. These observations decrease concern that dual head lithotripsy at a rapid rate is inherently dangerous.

Objective: The focal zone width appears to be a critical factor in lithotripsy. Narrow focus machines have a higher occurrence of adverse effects, and arguably no greater comminution efficiency. Manufacturers have introduced new machines and upgrades to broaden the focus. Still, little data exists on how focal width plays a role in stone fracture. Thus, our aim was to determine if focal width interacts with established mechanisms known to contribute to stone fracture. Method: A series of experiments were undertaken with changes made to the stone in an effort to determine which is most important, the shock wave (SW) reflected from the back end of the stone (spallation), the SW ringing the stone (squeezing), the shear wave generated at surface of the stone and concentrated in the bulk of it (shear), or SWs generated from bubble collapse (cavitation). Shock waves were generated by a Dornier HM3-style lithotripter, and stones were made from U30 cement. Baffles were used to block specific waves that contribute to spallation, shear, or squeezing, and glycerol was used to suppress cavitation. Numerical simulation and high-speed imaging allowed for visualization of specific waves as they traveled within the stone. Results: For brevity, one result is explained. A reflective baffle was placed around the front edge of a cylindrical stone. The proximal baffle prevented squeezing by preventing the SW from traveling over the stone, but permitted the SW entering the stone through the proximal face and did not affect the other mechanisms. The distal baffle behaved the same as no baffle. The proximal baffle dramatically reduced the stress, and the stone did not break (stone broke after 45±10 SWs without the baffle and did not break after 400 SWs when the experiment stopped). The result implies that since removing squeezing halted comminution, squeezing is dominant. However, there is much more to the story. For example, if the cylindrical stone was pointed, it broke with the point on the distal end but not with the point on the proximal end. In both cases, squeezing was the same, so if squeezing were dominant, both stones should have broken. But the pointed front edge prevents the shear wave. The squeezing wave and its product - the shear wave - are both needed and work synergistically in a way explained by the model. Conclusions: A broad focus enhances the synergism of squeezing and shear waves without altering cavitation's effects, and thus accelerates stone fracture in SWL. © 2007 American Institute of Physics.

Great variability exists in the response of urinary stones to SWL, and this is true even for stones composed of the same mineral. Efforts have been made to predict stone fragility to shock waves using computed tomography (CT) patient images, but most work to date has focused on the use of stone CT number (i.e., Hounsfield units). This is an easy number to measure on a patient stone, but its value depends on a number of factors, including the relationship of the size of the stone to me resolution (i.e., the slicewidth) of the CT scan. Studies that have shown a relationship between stone CT number and failure in SWL are reviewed, and all are shown to suffer from error due to stone size, which was not accounted for in the use of Hounsfield unit values. Preliminary data are then presented for a study of calcium oxalate monohydrate (COM) stones, in which stone structure—rather than simple CT number values—is shown to correlate with fragility to shock waves. COM stones that were observed to have structure by micro CT (e.g., voids, apatite regions, unusual shapes) broke to completion in about half the number of shock waves required for COM stones that were observed to be homogeneous in structure by CT. This result suggests another direction for the use of CT in predicting success of SWL: the use of CT to view stone structure, rather than simply measuring stone CT number. Viewing stone structure by CT requires the use of different viewing windows than those typically used for examining patient scans, but much research to date indicates that stone structure can be observed in the clinical setting. Future clinical studies will need to be done to verify the relationship between stone structure observed by CT and stone fragility in SWL.Great variability exists in the response of urinary stones to SWL, and this is true even for stones composed of the same mineral. Efforts have been made to predict stone fragility to shock waves using computed tomography (CT) patient images, but most work to date has focused on the use of stone CT number (i.e., Hounsfield units). This is an easy number to measure on a patient stone, but its value depends on a number of factors, including the relationship of the size of the stone to me resolution (i.e., the slicewidth) of the CT scan. Studies that have shown a relationship between stone CT number and failure in SWL are reviewed, and all are shown to suffer from error due to stone size, which was not accounted for in the use of Hounsfield unit values. Preliminary data are then presented for a study of calcium oxalate monohydrate (COM) stones, in which stone structure—rather than simple CT number values—is shown to correlate with fragility to shock waves. COM stones that were observed to have structure by mi...

Current lithotriptors use a dry treatment head that must be coupled to the patient with gel or oil. We determined how the quality of coupling affects stone breakage under conditions that simulated patient treatment.Experiments were performed with a Dornier (DoLi-50 electromagnetic lithotriptor. The test tank had a clear Mylar membrane for coupling with the treatment head water cushion. Thus, air pockets trapped at the coupling interface could be photographed for quantitation. Coupling efficiency was assessed using a fiberoptic hydrophone and different coupling regimes were tested for the effect on gypsum stone breakage.The quality of coupling was variable with air pockets covering 1.5% to 19% of the coupling area, resulting in a mean decrease in shock wave amplitude of approximately 20%. Breaking and reestablishing contact, as when a patient is repositioned during treatment, decreased acoustic pressure almost 32%, representing a 57% decrease in acoustic energy transmission. Stone breakage was also decreased when air was trapped in coupling and only 2% coverage by air pockets decreased stone breakage by 20% to 40%.These in vitro results suggest that coupling in lithotripsy can pose a significant barrier to the transmission of shock wave energy to the patient. Stone breakage was sensitive to air pockets at the coupling interface. Recoupling was particularly disruptive, suggesting that repositioning the patient could substantially degrade coupling quality. It seems reasonable that variability in the quality of coupling could contribute to variability in clinical outcomes.

Stones break better when the rate of shockwave (SW) delivery is slowed. It has been hypothesized that the greater cavitation accompanying a fast rate shields pulse propagation, thus interfering with the delivery of SW energy to the stone. We tested this idea by correlating waveforms measured at the SW focus with cavitation viewed using high-speed imaging.A series of U30 gypsum stones held in a 2-mm mesh basket were exposed to 200 SWs at 30 or 120 SW/min from a research electrohydraulic lithotripter (HM3 clone). Waveforms were collected using a fiberoptic probe hydrophone. High-speed imaging was used to observe cavitation bubbles in the water and at the stone surface.Stone breakage was significantly better at 30 SW/min than at 120 SW/min. The rate had little effect on SW parameters in the water free field. In the presence of particulates released from stones, the positive pressure of the SW remained unaffected, but the trailing tensile phase of the pulse was significantly reduced at 120 SW/min.Cavitation bubbles do not persist between SWs. Thus, mature bubbles from one pulse do not interfere with the next pulse, even at 120 SW/min. However, cavitation nuclei carried by fine particles released from stones can persist between pulses. These nuclei have little effect on the compressive wave but seed cavitation under the influence of the tensile wave. Bubble growth draws energy from the negative-pressure phase of the SW, reducing its amplitude. This likely affects the dynamics of cavitation bubble clusters at the stone surface, reducing the effectiveness of bubble action in stone comminution.

Background and Purpose: Urinary stones are heterogeneous in their fragility to lithotripter shockwaves. As a first step in gaining a better understanding of the role of matrix in stone fragility, we measured extractible protein in calcium oxalate monohydrate (COM) stones that were extensively characterized by micro-computed tomography (micro CT). Materials and Methods: Stones were scanned using micro CT (Scanco mCT20, 34 μm). They were ground, and the protein extracted using four methods: 0.25M EDTA, 2% SDS reducing buffer, 9M urea buffer, and 10% acetic acid. Protein was measured using NanoOrange. The SDS extracts were also examined using polyacrylamide electrophoresis (PAGE). Results: Extracted protein was highest with the SDS or urea methods (0.28% ± 0.13% and 0.24% ± 0.11%, respectively) and lower using the EDTA method (0.17% ± 0.05%; P < 0.02). Acetic acid extracted little protein (0.006 ± 0.002%; P < 0.001). Individual stones were significantly different in extractability of protein by the different methods, and SDS-PAGE revealed different protein patterns for individual stones. Extracted protein did not correlate with X-ray-lucent void percentage, which ranged from 0.06% to 2.8% of stone volume, or with apatite content. Conclusions: Extractible stone-matrix protein differs for individual COM stones, and yield is dependent on the extraction method. The presence of X-ray-lucent voids or minor amounts of apatite in stones did not correlate with protein content. The amounts of protein recovered were much lower than reported by Boyce, showing that these methods extracted only a fraction of the protein bound up in the stones. The results suggest that none of the methods tested will be useful for helping to answer the question of whether matrix content differs among stones of differing fragility to lithotripter shockwaves.

Shock wave lithotripsy (SWL) for the non-invasive treatment of kidney stones was introduced in the United States in 1984. SWL virtually eliminated the need for open surgery to remove kidney stones, and it did not take long for physicians and patients to endorse this revolutionary technology. Early reports told of the efficient removal of even the most troublesome stones without apparent complications, and SWL quickly became the "treatment modality of choice." It was not long, however, before concerned physicians began to report the occurrence of adverse effects in SWL, particularly involving vascular trauma and including cases of severe hemorrhage in the kidney and acute renal failure — significant side effects of serious consequence. Researchers quickly recognized the challenge and opportunity to determine the mechanisms of shock wave action in lithotripsy, and in 1988, the Acoustical Society of America held the first in a series of popular sessions devoted to the topic of shock waves in medicine. The goal of the inaugural session was to improve the fundamental understanding of lithotripsy — to bring better devices and treatments to patients. The goal of this paper is to report on progress in this effort.