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OBJECTIVES/GOALS: Develop strong network of science teachers interested in promoting scientific research to their students.Place students in an immersive summer research internship that, when possible, matches their career interests.Expose students to the numerous career paths within the STEM field.METHODS/STUDY POPULATION: The program recruits socio-economically disadvantaged students and provides them a stipend, and also accepts students who can participate unpaid.Local school teachers are engaged in a summer fellowship to learn biotechnologies and research. In Spring these teachers help recruit students and during the subsequent Fall help students with college and scholarship applications.Students are placed in a variety of laboratories within the Schools of Medicine, Science, Dentistry, Public Health, Informatics, Health and Human Sciences, Engineering and Technology, especially in biomedical engineering. Students are also placed in industry laboratories such as Eli Lilly and the Indiana Bioscience Research Institute.Long-term program follow-up is done through post-internship surveys to assess impact on graduate and professional school admission.RESULTS/ANTICIPATED RESULTS: Since the Indiana CTSI was established in 2008, 872 students have participated in the summer internship.71% of past interns are underrepresented minorities in science or classified as disadvantaged by NIH criteria.17% of students interned during grade 10, 72% during grade 11, and 11% during grade 12.21% of students engage in the program for more than one year.100% of past interns are currently enrolled in or have graduated college.Over 60% of those with a bachelors degree proceed to graduate and professional schools and over 80% stay in STEM related fields. These rates are equal for interns from underrepresented minorities or those classified as disadvantaged by NIH criteria.DISCUSSION/SIGNIFICANCE OF IMPACT: Students engaged in the Indiana CTSI STEM program are progressing through the translational science pipeline based on their graduating from college and remaining in the STEM field.

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.

OBJECTIVE To assess the renal injury response in a pig model treated with a clinical dose of shock waves (SWs) delivered at a slow rate (27 SW/min) using a novel wide focal zone (18 mm), low acoustic pressure ( 0.05) and renal plasma flow (P = 0.064) in the treated kidney, but that was not significantly different from the control group. Although most HM3-treated pigs showed no evidence of renal tissue injury, two had focal injury measuring 0.1% FRV, localized to the renal papillae. The width of the focal zone for the XX-ES was ≈ 18 mm and that of the HM3 ≈ 8 mm. Peak positive pressures at settings used to treat pigs and break model stones were considerably lower for the XX-ES (17 MPa at 9.3 kV) than for the HM3 (37 MPa at 18 kV). The XX-ES required fewer SWs to break stones to completion than did the HM3, with a mean (sd) of 634 (42) and 831 (43) SWs, respectively (P

Previous in vitro studies of acoustic coupling in shock wave lithotripsy (SWL) have shown that air pockets trapped at the surface of the treatment head significantly reduce transmission of shock wave (SW) energy to the focal zone of the lithotripter, reducing the effectiveness of stone breakage. Since there are no reliable means to monitor the quality of coupling during SWL, we looked for a practical protocol to improve how coupling is achieved. In vitro studies were performed using a Dornier DoLi-50 lithotripter. LithoClear gel was used to couple the treatment head to the acoustic window of a clear acrylic test tank. Numerous methods of applying gel were tested including common sense variations of routine protocols typically used with patients. For each method the coverage of air pockets (% defects) was determined using digital imaging. Different coupling regimes were tested for effect on the breakage of gypsum model stones. The quality of acoustic coupling was affected by how the gel was handled--how it was dispensed and applied, and whether the gel was applied only to the treatment head or to both the lithotripter water cushion and the test tank (surrogate patient). Dispensing gel from a squeeze bottle for application by hand created significantly more defects than when a large volume (approximately 250 ml) of gel from the stock jug was applied as a mound to just the treatment head (26.5+/-2.7 vs. 1.2+/-0.5% defects, P0.001). The efficiency of stone breakage was better when gel was applied from the stock jug compared to application by hand (P0.006). Poor coupling was substantially improved by using the inflation feature of the water cushion to collapse air pockets, but this strategy was not a substitute for establishing good coupling at the outset. The quality of coupling in shock wave lithotripsy can be improved by minimizing the handling of the coupling medium. Hand application of coupling gel is clearly not the best way to prepare for lithotripsy. Better results can be obtained by delivering lithotripsy gel as a bolus to the treatment head alone, and allowing it to spread upon contact between the treatment head and the skin. These in vitro tests also suggest that the inflation feature of the lithotripter may be useful in reducing defects in coupling.

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.

The classification of cystine stones into rough and smooth varieties has been suggested as an aid to choosing treatment for these difficult stones. Since the surface of stones is difficult to visualize preoperatively, we tested the hypothesis that the surface morphology of cystine stones correlates with their internal structure, as viewed by helical computerized tomography (CT).Cystine stones were examined visually and categorized into rough (15 stones) and smooth (16 stones) subpopulations of similar size. Each stone was scanned in a helical CT scanner (GE Quad Scanner) to assess radiological characteristics and to measure attenuation values. Scans were also performed using a microCT 20 high resolution laboratory scanner (Scanco Medical AG, Bassersdorf, Switzerland) at 34 microm voxel size and the percent of internal voids was determined.Mean helical CT attenuation values +/- SD for rough stones were lower than for smooth stones (702 +/- 206 vs 921 +/- 51 HU, p0.002) and the radiological appearance of rough stones suggested radiolucent voids. Internal voids in rough stones were confirmed using micro CT. Rough cystine stones contained a higher percent of internal voids (0.30% vs 0.06%, p0.0001).Rough cystine stones can be distinguished from smooth stones using helical CT in vitro, suggesting that it may be possible to distinguish these stones preoperatively. Since rough cystine stones have been reported to be susceptible to shock wave lithotripsy, the identification of this morphology of cystine stones in the patient using attenuation values and appearance on helical CT could be valuable for planning treatment.

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)

Ureteral stones can be difficult to treat with shock wave (SW) lithotripsy. A strategy for lithotripsy of proximal ureteral stones is to push them back into the renal pelvis prior to administering SWs. However, push-back is invasive and not always possible. Since there are few clues to suggest how best to treat ureteral stones with SWs in situ, we developed an animal model for research on lithotripsy for ureteral stones.Gypsum model stones were implanted bilaterally in the proximal ureter and renal calix of the pig via percutaneous access. Lithotripsy was performed using a HM3 lithotripter (Dornier Medical Systems, Marietta, Georgia) and stones at each location were treated with the same dose (400 SWs, 20 kV and 30 SWs per minute). Fragments were collected and the percent increase in projected surface area of the particles was determined.The breakage (mean percent area increase) of stones implanted in the proximal ureter was significantly less than that of stones located in the renal calix treated with the same dose of shock waves (134% vs 327%, p0.001). Also, stones that were fully confined by the ureter did not break as well as stones located at the ureteropelvic junction. This indicates that the physical environment surrounding a stone can have a significant effect on the efficiency of SW action.The observation that stones implanted in the ureter showed decreased breakage compared with stones in the kidney is consistent with clinical experience. This finding is a valuable and even essential prerequisite for any experimental animal model system intended for the study of SW action in the breakage of ureteral stones.

Objectives To assess the ability of helical computed tomography (CT) to differentiate regions of known mineral composition in typical, heterogeneous urinary stones. Interest is substantial in the urologic community in using radiologic imaging to determine accurately the composition of urinary calculi. Recent advances in CT make this a viable prospect, but the heterogeneity of most stones is a complicating factor. Methods The ability of micro-CT (a high-resolution laboratory instrument) to identify the mineral composition of stones was confirmed by calibrating micro-CT attenuation values to pure mineral regions of sliced stones using infrared microspectroscopy. Intact human urinary stones were then analyzed by micro-CT, and regions-of-interest of pure mineral were correlated with identical regions-of-interest from quad slice multi-detector row helical CT images. With helical CT, narrow slice widths were used to decrease volume-averaging errors, and bone windows were used so that internal stone structure was visible. Results When stones were imaged using helical CT at narrow slice widths, mineral-specific regions-of-interest yielded nonoverlapping attenuation values for uric acid (566 to 632 Hounsfield units [HU]), struvite (862 to 944 HU), calcium oxalate (1416 to 1938 HU), and hydroxyapatite (2150 to 2461 HU). Conclusions High resolution helical CT yields unique attenuation values for common types of stone mineral, but proper windowing is required to localize regions of homogeneity. The results of this in vitro study suggest that high-resolution helical CT may be able to identify stone composition at patient diagnosis.

Shockwave lithotripters have evolved considerably since the introduction of the Dornier HM3 machine 20 years ago. Although shockwave lithotripsy (SWL) remains the preferred treatment for the majority of symptomatic upper urinary-tract calculi, newer lithotripters are not as effective and may have a higher risk of side effects. Lack of progress in lithotripter evolution is attributable to inadequate understanding of how and why shockwaves produce effects on stone and tissue. Current knowledge suggests that stones fragment by the mechanisms of compression fracture, spallation, squeezing, and acoustic cavitation, while tissue damage from shockwaves is secondary to cavitation and non-cavitational forces such as sheer stress. It appears likely that most tissue damage from shockwaves is caused by cavitation. As the understanding of SWL matures, new lithotripter designs may emerge that truly represent an improvement on the original Dornier HM3 machine.

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.

Objectives To measure, in an in vitro study, the number of shock waves to complete comminution for 195 human stones, representing six major stone types. Not all renal calculi are easily broken with shock wave lithotripsy. Different types of stones are thought to have characteristic fragilities, and suggestions have been made in published reports of variation in the fragility within some types of stones, but few quantitative data are available. Methods Kidney stones classified by their dominant mineral content were broken in an unmodified Dornier HM3 lithotripter or in a research lithotripter modeled after the HM3, and the number of shock waves was counted for each stone until all fragments passed through a sieve (3-mm-round or 2-mm-square holes). Results The mean ± SD number of shock waves to complete comminution was 400 ± 333 per gram (n = 39) for uric acid; 965 ± 900 per gram (n = 75) for calcium oxalate monohydrate; 1134 ± 770 per gram (n = 21) for hydroxyapatite; 1138 ± 746 per gram (n = 13) for struvite; 1681 ± 1363 per gram (n = 23) for brushite; and 5937 ± 6190 per gram (n = 24) for cystine. The variation for these natural stones (83% ± 15% coefficient of variation) was greater than that for artificial (eg, gypsum-based) stones (17% ± 8%). Conclusions The variability in stone fragility to shock waves is large, even within groups defined by mineral composition. Thus, knowing the major composition of a stone may not allow adequate prediction of its fragility in lithotripsy treatment. The variation in stone structure could underlie the variation in stone fragility within type, but testing of this hypothesis remains to be done.

Purpose: The current trend toward ungated shock wave lithotripsy means that more patients are being treated with shock waves delivered at a rapid rate (120 shock waves per minute or greater). However, no benefit of an increased shock wave rate has been shown and in vitro studies indicate that slowing the shock wave rate actually improves stone fragmentation. We tested the effect of the shock wave rate on stone comminution in a new animal model.Materials and Methods: Gypsum model stones were inserted via upper pole percutaneous access into the lower pole calix of the kidneys of female pigs weighing approximately 100 pounds. Shock wave lithotripsy was performed (400 shock waves uninterrupted at 20 kV. and 30 or 120 shock waves per minute) 2 hours later using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia). After en bloc excision of the urinary tract stone fragments were collected and sieved through 2 mm. mesh. The particles were weighed and surface area was determined.Res...

Background: Homozygous adenine phosphoribosyltransferase (APRT) deficiency is associated with 2,8-dihydroxyadenine (DHA) nephrolithiasis. Using whole kidney RNA from Aprt knockout mice, we previously showed that the renal deposition of DHA leads to changes in the expression of genes involved in tissue injury. To determine the cellular basis for these changes, we investigated gene expression in cultured human kidney (NHK-C) and African green monkey (BSC-1) epithelial cells exposed to DHA or calcium oxalate monohydrate (COM) crystals. Methods: First-strand cDNAs, synthesized from mRNA isolated from treated and untreated cells, were hybridized to membrane-bound cDNA arrays containing 588 genes associated with various physiological and pathological processes. Changes in gene expression were confirmed by reverse transcription PCR. Results: Twenty-seven percent of the array cDNAs were expressed in untreated NHK-C cells at varying levels relative to a housekeeping gene. The expression of three adhesion molecules (α-catenin, integrin α3, and integrin β6) and platelet-derived growth factor B (PDGF-B) was elevated following exposure of NHK-C cells to DHA. Increased expression of the adhesion molecules was also observed in BSC-1 cells, but PDGF-B expression could not be detected. COM crystals also stimulated the expression of these four genes in NHK-C cells, but the expression profile was quantitatively different compared with DHA. Conclusions: These findings suggest that DHA crystals stimulate the expression of specific genes in kidney epithelial cells and that the pathways for DHA-induced cell injury may be similar to those for COM crystals. The induction of adhesion molecules and PDGF-B may affect cell-cell or cell-matrix interactions and/or alter the actin cytoskeleton. These alterations may ultimately contribute to crystal-induced renal injury.

Purpose: In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage. Materials and Methods: We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses. Results: Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector. Conclusions: These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

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.

Helical CT has become the preferred methodology for identifying urinary calculi. However, the ability to predict stone composition, which influences patient treatment, depends on the accurate measurement of the radiographic attenuation of stones. We studied the effects of stone composition, stone size, and scan collimation width on the measurement of attenuation in vitro.One hundred twenty-seven human urinary calculi of known composition and size were scanned at 120 kVp, 240 mA, and a 1:1 pitch at different collimations. A model, based on the physics of helical CT, was used to predict the effect of scan collimation width and stone size on measured attenuation.At a 1-mm collimation, stone groups could be differentiated by attenuation: the attenuation of uric acid was less than that of cystine or struvite, which overlapped; these were less than the attenuation of calcium oxalate monohydrate, which was in turn lower than that of brushite and hydroxyapatite, which overlapped and showed the highest values. At a wider collimation, attenuation was lower and the ability to differentiate stone composition was lost. Attenuation also decreased with smaller stones. At a 10-mm collimation, some uric acid stones (approximately 6 mm) and other stones (approximately 4 mm) had very low attenuation, so low that they could remain undetected on helical CT. The model predicted well the degree that attenuation was affected by stone size and collimation width.Stone composition and stone size, relative to CT collimation, independently influenced CT attenuation. The effect of stone size and collimation generally conformed to the model's predictions. We determined that small stones with low attenuation can be overlooked on helical CT.

Acoustic cavitation has been implicated as a cause of cell damage by lithotripter shock waves, particularly under in vitro conditions. When red blood cells were exposed to shock waves (from an electrohydraulic lithotripter) while under high hydrostatic pressure (> 80 atm), cell lysis was dramatically reduced over that seen at atmospheric pressure, which is consistent with damage due to acoustic cavitation. However, even at > 120 atm of pressure, lysis was still 97% above that of cells not exposed to shock waves, revealing significant damage that apparently was due to mechanisms other than cavitation. Hydrostatic pressure alone did not cause cell lysis, and shock-wave-dependent damage occurred when the cells were in fluid suspension, or when they were centrifuged to the end of the vial. Shock-wave damage at high pressure increased with increasing shock-wave number, and was seen at 24 and 20 kV, but not at 16 kV. This shock-wave damage at high pressure makes up a noteworthy portion of the total cell injury seen at atmospheric pressure (about 10% at 24 kV), suggesting significant noncavitational injury to cells in vitro. Because cavitation occurs far more readily in vitro than in vivo, the noncavitational damage seen in the present study could represent a substantial portion of cell injury seen in vivo with shock-wave lithotripsy.

In studies of cells or stones in vitro, the material to be exposed to shock waves (SWs) is commonly contained in plastic vials. It is difficult to remove all air bubbles from such vials. Because SWs reflect at an air-fluid interface, and because existing gas bubbles can serve as nuclei for cavitation events, we sought to determine in our system whether the inclusion of small, visible bubbles in the specimen vial has an effect on SW-induced cell lysis. We found that even small bubbles led to increased lysis of red blood cells (1- to 3-mm diameter bubbles, 9.8+/-0.5% lysis, n = 7; no bubbles, 4.4+/-0.8%, n = 4), and that the degree of lysis increased with bubble size. Damage could not be reduced by centrifuging the cells to the opposite end of the vial, away from the bubble. B-scan ultrasound imaging of blood in polypropylene pipette bulbs showed that, with each SW, bubbles were recruited from the air interface, mixing throughout the fluid volume, and these appeared to serve as nuclei for increased echogenicity during impact by subsequent SWs; thus, bubble effects in vials could involve the proliferation of cavitation nuclei from existing bubbles. Whereas injury to red blood cells was greatly increased by the presence of bubbles in vials, lytic injury to cultured epithelial cells (LLC-PK1, which have a more complex cytoarchitecture than red blood cells) was not increased by the presence of small air bubbles. This suggests different susceptibility to SW damage for different types of cells. Thus, the presence of even a small air bubble can increase SW-induced cell damage, perhaps by increasing the number of cavitation nuclei throughout the vial, but this effect is variable with cell type.

Increased ambient pressure (excess hydrostatic pressure) was used to regulate cavitation in the aqueous media surrounding isolated red blood cells and aluminum foils used as targets in studies of the mechanisms of shock wave (SW) damage in shock wave lithotripsy (SWL). Foils or cells were placed in a cylindrical chamber (bronze-aluminum alloy) connected to a regulator and nitrogen source. The ends of the cylinder were capped with planar, plastic plates 12.7 mm thick. Tests performed with a PVDF membrane hydrophone showed that SW's passed through the plastic without significant loss of amplitude or change in waveform. Pitting of foils, a form of damage that can only be due to cavitation, was eliminated by very high (∼70 atm) added pressure. It took substantially greater added pressure to reduce damage to foils than has been reported to reduce damage to cells, suggesting differences in how cavitation is regulated in bulk fluid versus a solid surface. This report describes the design of the pressure chamber used in these studies and explains how SW exposures of isolated cells and foil targets were performed.

Open surgery for removal of upper urinary tract stones has long been associated with a high morbidity and mortality. So when shock wave (SW) lithotripsy (SWL) was introduced in the early 1980s, the climate was right for acceptance of a noninvasive method for stone comminution. The growth in popularity of SWL was extremely rapid, based in part on the perception that it was entirely safe [1]. Now, after a decade of clinical SWL, experience tells us differently. SWL may be very effective at breaking kidney stones, but it can also cause severe renal trauma that can lead to irreversible long-term complications [2, 3].

In studies to understand the mechanisms responsible for shock wave lithotripsy (SWL) cell injury, we observed that shock waves (SWs) are influenced by the shape of the specimen vial. Lytic injury to kidney cells treated in a Dornier HM3 lithotripter was higher (p < 0.0001) when SWs entered the vial through the flat end (cap end) compared to the round end. Measurements of the acoustic field within polypropylene vials were carried out using both lithotripter SWs and pulsed ultrasound (US) in the megahertz frequency range. We compared pressure amplitudes inside the round and flat vials and found significant differences. When SWs entered through the round end, the average peak positive pressure was 40% of free-field pressure, due mostly to a dramatic reduction in pressure off axis. The average peak pressure inside the flat vial was twice that of the round vial. Experiments with US demonstrated that sound field focusing was induced by the curved interface of the round vial. Ray analysis for the round vial indicates the presence of "hot spots" on axis and "cold spots" off axis, in qualitative agreement with pressure profiles. We conclude that the shape of the specimen vial is an important factor that should be considered in model systems of SWL cell injury.

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.]

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.

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...