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In this paper, an extracorporeal shock wave source composed of small ellipsoidal sparker units is described. The sparker units were arranged in an array designed to produce a coherent shock wave of sufficient strength to fracture kidney stones. The objective of this paper was to measure the acoustical output of this array of 18 individual sparker units and compare this array to commercial lithotripters. Representative waveforms acquired with a fiber-optic probe hydrophone at the geometric focus of the sparker array indicated that the sparker array produces a shock wave (P+ ∼40–47 MPa, P− ∼2.5–5.0 MPa) similar to shock waves produced by a Dornier HM-3 or Dornier Compact S. The sparker array's pressure field map also appeared similar to the measurements from a HM-3 and Compact S. Compared to the HM-3, the electrohydraulic technology of the sparker array produced a more consistent SW pulse (shot-to-shot positive pressure value standard deviation of ±4.7 MPa vs ±3.3 MPa).

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...

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.]

Shock waves in liquids are known to cause spherical gas bubbles to rapidly collapse and form strong re-entrant jets in the direction of the propagating shock. The interaction of these jets with an adjacent viscous liquid is investigated using finite-volume simulation methods. This configuration serves as a model for tissue injury during shock-wave lithotripsy, a medical procedure to remove kidney stones. In this case, the viscous fluid provides a crude model for the tissue. It is found that for viscosities comparable to what might be expected in tissue, the jet that forms upon collapse of a small bubble fails to penetrate deeply into the viscous fluid “tissue.” A simple model reproduces the penetration distance versus viscosity observed in the simulations and leads to a phenomenological model for the spreading of injury with multiple shocks. For a reasonable selection of a single efficiency parameter, this model is able to reproduce in vivo observations of an apparent 1000-shock threshold before wide-spread tissue injury occurs in targeted kidneys and the approximate extent of this injury after a typical clinical dose of 2000 shock waves.

This laboratory is involved in studies to determine the mechanism(s) responsible for cellular injury to the kidney during shock wave lithotripsy for the treatment of upper urinary tract stones. The studies are performed using an electrohydraulic lithotripter (Dornier HM3) and injury to isolated, cultured renal tubular epithelial cells was assessed. In this demonstration our experiences with the practical aspects of performing in vitro SW exposures are shared. Issues to be discussed and/or demonstrated include the following: (a) choice of cultured cell models and the handling of isolated cells, (b) factors that influence in vitro cell injury, (c) selection and preparation of specimen vials, (d) lithotripter setup and operation, (e) positioning the specimen and control of exposure parameters, (f) electrode performance and variability, (g) characterization of waveforms and determination of SW pressures, (h) markers of cell injury and cell response to SW insult, and (i) safety in the lithotripsy suite. [Work ...

A pilot study was conducted to assess whether extracorporeal shock wave lithotripsy (SWL) treatment of the kidney influences the onset and severity of metabolic syndrome (MetS)—a cluster of conditions that includes central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension. Methods: Three-month-old juvenile female Ossabaw miniature pigs were treated with either SWL (2000 SWs, 24 kV, 120 SWs/min using the HM3 lithotripter; n = 2) or sham-SWL (no SWs; n = 2). SWs were targeted to the upper pole of the left kidney so as to model treatment that would also expose the pancreas—an organ involved in blood glucose homeostasis—to SWs. The pigs were then instrumented for direct measurement of arterial blood pressure via implanted radiotelemetry devices, and later fed a hypercaloric atherogenic diet for ~7 months to induce MetS. The development of MetS was assessed from intravenous glucose tolerance tests. Results: The progression and severity of MetS were similar in the sham-trea...

A consecutive case study was conducted to assess the clinical performance of the Lithogold, an electrohydraulic lithotripter having a relatively low P + and broad focal width (FW) (~20 MPa, ~20 mm), and the electromagnetic Storz-SLX having higher P + and narrower FW (~50 MPa, 3–4 mm). Treatment was at 60 SW/min with follow-up at ~2 weeks. Stone free rate (SFR) was defined as no residual fragments remaining after single session SWL. SFR was similar for the two lithotripters (Lithogold 29/76 = 38.2%; SLX 69/142 = 48.6% p = 0.15), with no difference in outcome for renal stones (Lithogold 20/45 = 44.4%; SLX 33/66 = 50%, p = 0.70) or stones in the ureter (Lithogold 9/31 = 29%; SLX 36/76 = 47.4%, p = 0.08). Stone size did not differ between the two lithotripters for patients who were not stone free (9.1±3.7 mm for Lithogold vs. 8.5±3.5 mm for SLX, P = 0.42), but the stone-free patients in the Lithogold group had larger stones on average than the stone-free patients treated with the SLX (7.6±2.5 mm vs. 6.2±3.2 mm, P = 0.005). The percentage of stones that did not break was similar (Lithogold 10/76 = 13.2%; SLX 23/142 = 16.2%). These data present a realistic picture of clinical outcomes using modern lithotripters, and although the acoustic characteristics of the Lithogold and SLX differ considerably, outcomes were similar. [NIH-DK43881.]

This study provides an independent assessment of a novel lithotripter (LG-380, Tissue Regeneration Technologies), marketed as having a long-life self-adjusting spark gap electrode and producing a low-pressure, broad-focal-zone acoustic field. For acoustic characterization we coupled the therapy head of the lithotripter to a water tank and mapped the field using a fiber-optic hydrophone (FOPH-500, RP Acoustics). At the target point of the lithotripter, the peak positive pressure (P +) remained relatively stable (~19±5 MPa at power level 9) during the 6000 shock waves (SWs) lifetime of the electrode. The position of maximum P + (~35 MPa at PL9) was 35mm distal to target point and shifted progressively toward the therapy head as the electrode aged, reaching the target point (while reducing to P + ~20 MPa) after ~5000 SWs. This was likely due to a slight movement in position of the self-adjusting spark gap—changing the focus of the shock wave and the dimensions of the focal volume of the lithotripter. Kidney ...

Ed Carstensen has made many contributions to biomedical ultrasound but among those that are becoming more and more relevant to current clinical practice are those that determine the conditions under which cavitation is induced in vivo. For many years, it was assumed that the medical ultrasound devices were unable to induce cavitation in living tissue because either the acoustic conditions were not sufficient or the nucleation sites that are required were too small. With the advent of lithotripters and high‐intensity focused ultrasound (HIFU) devices, cavitation generation in vivo is commonplace. Our current research at the University of Washington has focused on the role that cavitation plays in stone comminution and tissue damage during lithotripsy, as well as the enhancement or reduction of desirable coagulative necrosis during HIFU application. During HIFU application, we find enhanced heating that results from nonlinear acoustic wave propagation (a key Carstensen contribution) leads to vapor bubble formation. This presentation will review our recent studies in this area. [Work supported in part by the NIH under CA109557 and DK43881, and the NSBRI SMS00402 under NCC9‐58‐50.]

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 30,000 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 min at various intensities. The perfusion-fixed tissue was scored by three blinded independent experts. Above a threshold of 20,000 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. [Work supported by NIH DK43881, DK092197, and NSBRI through NASA NCC 9-58.]

A case is presented for the important role of cavitation in stone comminution and tissue injury in shock wave lithotripsy (SWL). Confocal hydrophones and a coincidence algorithm were used to detect cavitation in kidney parenchyma. Elevated hydrostatic pressure dissolved cavitation nuclei and suppressed cell injury and stone comminution in vitro. A low‐insertion‐loss, thin, mylar film nearly eliminated stone erosion and crack formation only when in direct contact with the stone. This result indicates not only that cavitation is important in both cracking and erosion but also that bubbles act at the surface. Time inversion of the shock wave by use of a pressure‐release reflector reduced the calculated pressure at bubble collapse and the measured depth of bubble‐induced pits in aluminum. Correspondingly tissue injury in vivo was nearly eliminated. Cavitation was localized and intensified by the use of synchronously triggered, facing lithotripters. This dual pulse lithotripter enhanced comminution at its focus and reduced lysis in surrounding blood samples. The enhancement of comminution was lost when stones were placed in glycerol, which retarded bubble implosion. Thus, cavitation is important in comminution and injury and can be controlled to optimize efficacy and safety. [Work supported by NIH DK43381, DK55674, and FIRCA.]

Recently, a system that uses focused ultrasound to expel renal stone fragments from the kidney by radiation force was developed by Shah etal. [Urol. Res. 38, 491–495 (2010)]. A worst-case treatment protocol using this system would require a total exposure time of 10 min, with a spatial peak pulse average intensity (I_SPPA) of 3600 W/cm2 in water (16 MPa peak positive pressure) and a 3% duty cycle. As the system operates above the FDA limits for diagnostic ultrasound, our goal is to verify the safety of the system by determining the threshold for renal injury. A 2-MHz annular array generating I_SPPA up to 29 000 W/cm2 in water was placed on the surface of in vivo porcine kidneys and focused in the proximal parenchyma. Exposures of 10 min duration with varying I_SPPAs and duty cycles were repeated at least 6 times. Mechanical tissue damage and cell viability were evaluated histologically using H&E, PAS, and NADH diaphorase stains. The proportion of samples showing injury was plotted versus duty cycle and I_SPPA. The results indicate that the system to expel renal stones operates below the threshold for kidney injury. [Work supported by NIH DK043881, DK086371, DK092197, and NSBRI through NASA NCC 9–58.]

Although lithotripters can differ substantially in acoustic output, renal response to SWs has been thoroughly characterized for only one type of lithotripter (moderate‐pressure ∼40 MPa, intermediate‐focal‐width 8–9 mm, Dornier‐HM3). Therefore, we assessed injury using a high‐pressure (∼85 MPa), narrow‐focal‐width (3–4 mm) device (Storz‐SLX). SWs were administered to the lower renal pole of pigs (15 kg) (PL‐9, 2000 or 4000 SWs at 120 SWs/min; or 2000SWs at 60 SW/min) followed by serial sectioning to quantify lesion. Tissue damage with the SLX showed an abrupt transition between injured and unaffected tissue. Core of lesion was typically devoid of recognizable structure, with renal tubules, glomeruli, vessels essentially eliminated. The lesion extended from cortex to medulla, and in some kidneys homogenized tissue could be tracked across full thickness of the kidney. In comparison, the lesion using HM3 was not as severe with only focal spots of hemorrhage and no areas of complete tissue destruction. Doubling the SW‐dose with SLX did not increase lesion volume as occurred with HM3. Also, slowing the SW‐rate of the SLX to 60 SW/min did not have a protective effect as observed with other lithotripters. These findings suggest that lithotripters having different acoustic characteristics are capable of producing different forms of tissue damage. [Work supported by NIH‐DK43881.]

Ultrasonically activated microbubbles are promising candidates for targeted therapeutic applications such as drug and gene delivery. Understanding vascular permeability is thus important. In this study, ultra high‐speed microphotography was used to directly visualize the dynamics of microbubbles in microvessels, under the excitation of ultrasound pulses with a duration time of about 2 μs, a center frequency of 1 MHz, and peak negative pressures (PNPs) between 0.8 and 7.2 MPa. Correlated vascular permeability was examined by imaging extravasation of bubbles from the vessels and by looking at the treated region histologically and under transmission electron microscopy. Local vessel distention and invagination caused by microbubble oscillations and liquid jet impinging on the vessel wall all appear to contribute to enhanced permeability for microvessels with diameters 4 MPa. Vascular permeation was also observed in larger vessels. However, in these cases vessel invagination was greater than distention in more than 80% of the cases and liquid jets always directed away from the vessel wall. We thus hypothesize that the dominant mechanisms for microbubble‐induced permeation of smaller microvessels are different from larger microvessels. [Work supported by NIH EB000350 and AR053652.]

Pretreating the kidney with low‐energy shock waves (SWs) before administering a clinical dose of high‐energy SWs has been found to greatly decrease the hemorrhagic lesion that normally results from high‐energy shock wave lithotripsy (SWL) treatment alone. We tested the hypothesis that this novel pretreatment SWL protocol results in a greater and/or earlier renal vasoconstriction than clinical SWL alone, which could potentially explain the reduced bleeding in the kidney. Anesthetized pigs were treated with a clinical dose of SWs (2000 SWs, 24 kV, 120 SWs/min) or the pretreatment protocol (500 SWs, 12 kV, 120 SWs/min + 3‐min pause + 2000 SWs, 24 kV, 120 SWs/min) using the HM3 lithotripter. Sonography (color and pulsed ultrasound) was used to locate a resistance artery within the SW‐treated pole of the kidney and to take resistance index (RI) measurements from the blood vessel to estimate the resistance/impedance to blood flow. The results demonstrated that RI increased (renal vasoconstriction) earlier and g...

Shock wave lithotripsy (SWL) is known to induce oxidative stress and a rapid inflammatory response in renal tissue. The purpose of this study was to determine the location and quantify markers for oxidative stress and inflammation in a porcine model of acute SWL‐induced renal injury. The lower pole calyx of left kidneys of female pigs received 2000 shock waves at 24 kV/2 Hz from a Dornier HM3 lithotripter and subsequently monitored for 4 h. Heme oxygenase‐1 protein (HO‐1) was measured in renal microsomes by Western blot. Renal medulla HO‐1/β‐actin ratios were 1.186 ± 0.48 for treated pole (F2), 0.293 ± 0.23 for treated kidney upper pole, and 0.122 ± 0.075 for contralateral kidney (n=6). Thus, we observed an eightfold induction of HO‐1 in renal medulla at F2 compared to the upper pole medulla of the treated kidney and the contralateral kidney medulla. In contrast, renal cortex at F2 did not show a similar HO‐1 induction. The highly localized HO‐1 induction in SWL‐treated renal medulla parallels our previou...

The renal papilla is particularly susceptible to injury by shock waves (SWs). Since the papilla is vital for urinary pH regulation, we hypothesized that shock wave lithotripsy (SWL)‐induced damage of papillae will alter the pH of the urine. Experiments were conducted in four female adult Gottingen minipigs. The HM3 lithotripter delivered a total of 8000 SWs (24 kV, 120 SWs/min) among all papillae of one kidney, while the untreated, opposite kidney was used as control. The pigs were allowed to recover and 5 weeks later they were anesthetized. Serial urine collections were obtained from the SW‐treated and untreated kidney. Urine was collected under mineral oil and immediately tested for its pH. Both kidneys were then perfusion fixed for histological analysis. Urinary pH was 0.17 units greater (P

Kidney injury in lithotripsy can lead to long‐term adverse effects, so minimizing injury is beneficial. We have found that injury is significantly reduced when shock wave (SW) administration is halted briefly‐ 3‐minutes‐early in treatment. Previous studies have shown that SWs stimulate renal blood vessels to constrict. Therefore, we tested the idea that vasoconstriction mediates SW‐induced protection of the kidney. Doppler ultrasound was used to measure resistive index (RI), a ratio of systolic and diastolic velocities, indicating vasoconstriction. RI was determined for single intralobar arteries in targeted porcine kidneys treated by standard versus protection protocols (2,000SW, uninterrupted vs 500SW‐3‐min pause‐2,000SW) using a Dornier‐HM3 lithotripter (2Hz, 24kV). Significant differences in RI from baseline within a group and between groups at various time points were determined using mixed‐effect models for repeated measures with Holm's step‐down method for multiple comparison adjustment. All animal...

A clinical dose of SWL consistently and specifically disrupts the cellular layers of renal veins and arteries, first in the medulla, but progressing into the cortex with an associated inflammatory response. The resulting hemorrhage within the focal zone produces regions of intraparenchymal and subcapsular hematomas of varying size. Renal blood flow and glomerular filtration rate fall acutely by 50% in the treated kidney and by 20% in the untreated kidney. The sites of acute injury form scars with a permanent loss of renal function and have been associated with apatite/brushite stone formation and hypertension. Our team has shown that the size of the SWL‐induced lesion can be dramatically reduced by lowering the kV level, applying fewer shock waves, slowing the shock wave rate, and by pretreating the kidney with 100–500 shock waves at 12 kV prior to standard SWL. The mechanism of tissue injury caused by SWL has not been defined; however, protocols that reduce cavitation activity also reduce the size of the...

Lithotripter SWs rupture blood vessels in the kidney. This acute trauma, accompanied by a fall in renal function, can lead to significant long‐term effects such as profound scarring of the kidney cortex and renal papillaea permanent loss of functional renal mass. SWL has been linked to new‐onset hypertension in some patients, and recent studies suggest that multiple lithotripsies can actually alter a patient’s stone disease leading to formation of stones (brushite) that are harder to break. Cavitation and shear appear to play a role in stone breakage and tissue damage. Progress in understanding these mechanisms, and the renal response to SWs, has led to practical strategies to improve treatment. Slowing the SW‐rate, or initiating treatment at low kV/power both improve stone breakage and reduce the number of potentially tissue‐damaging SWs needed to achieve comminution. The observation that SWs cause transient vasoconstriction in the kidney has led to studies in pigs showing that a pre‐conditioning dose of...

A system was built to detect cavitation in pig kidney during shock wave lithotripsy (SWL) with a Dornier HM3 lithotripter. Active detection, using echo on B‐mode ultrasound, and passive cavitation detection (PCD), using coincident signals on confocal, orthogonal receivers, were equally sensitive and were used to interrogate the renal collecting system (urine) and the kidney parenchyma (tissue). Cavitation was detected in urine immediately upon SW administration in urine or urine plus X‐ray contrast agent, but in tissue, cavitation required hundreds of SWs to initiate. Localization of cavitation was confirmed by fluoroscopy, sonography, and by thermally marking the kidney using the PCD receivers as high intensity focused ultrasound sources. Cavitation collapse times in tissue and native urine were about the same but less than in urine after injection of X‐ray contrast agent. Cavitation, especially in the urine space, was observed to evolve from a sparse field to a dense field with strong acoustic collapse ...

Artificial stones break significantly better when shock waves (SWs) are delivered at 0.5 Hz than at 2 Hz, and patients treated at slower rates have improved stone‐free rates. One possible explanation may be cavitation bubbles that might persist between SWs at high rate and distort subsequent SWs sufficiently to reduce their effectiveness at stone comminution. High‐speed photography gives evidence that bubble numbers are greater at higher rates. B‐mode ultrasound echo in the free field typically disappears between pulses administered at 0.5 Hz but persists at 2 Hz. Fiberoptic hydrophone measurements at 2 Hz showed, in the free field of an electrohydraulic lithotripter, that SW negative tail was truncated, and proximal to a stone, that SW waveform varied and was distorted such that often the positive pressure amplitude was reduced. Changes in waveform proximal to stone declined as the stone disintegrated and fell away. Thus, data support the persistence of cavitation bubbles at high SW rate, and consequent ...

We have characterized the acoustic output and in vitro stone breakage of the first dual‐pulse lithotripter approved for patient treatment. Direx Medical Systems provided their Duet lithotripter and two timing circuits—a standard circuit that fires both electrodes in synchrony and a modified circuit that allows pulse delay. We assessed the effect of synchronous and ∼10‐μs delayed dual pulses on breakage of model stones. When synchrony was very close the waveform had a single peak ∼70 MPa P+, followed by a negative trough ∼12 MPa The waveform from one head was about half this amplitude. Pulses close in timing but not synchronous (∼1–2‐μs apart) showed amplitude‐summed conjoined peaks. Dual pulses fired ∼10 μs apart appeared as independent SWs. Simultaneous pulses broke stones better than pulses delivered by only one head (p

The foundation for understanding SWL‐injury has been well‐controlled renal structural and functional studies in pigs, a model that closely mimics the human kidney. A clinical dose (2000 shocks at 24 kV) of SWL administered by the Dornier HM3 induces a predictable, unique vascular injury at F2 that is associated with transient renal vasoconstriction, seen as a reduction in renal plasma flow, in both treated and untreated kidneys. Unilateral renal denervation studies links the fall in blood flow in untreated kidneys to autonomic nerve activity in the treated kidney. SWL‐induced trauma is associated with an acute inflammatory process, termed Lithotripsy Nephritis and tubular damage at the site of damage that leads to a focal region of scar. Lesion size increases with shock number and kV level. In addition, risk factors like kidney size and pre‐existing renal disease (e.g., pyelonephritis), can exaggerate the predicted level of renal impairment. Our new protection data show that lesion size can be greatly reduced by a pretreatment session with low kV and shock number. The mechanisms of soft tissue injury probably involves shear stress followed by acoustic cavitation. Because of the perceived enhanced level of bioeffects from 3rd generation lithotripters, these observations are more relevant than ever.

Cavitation bubble cluster collapse at the surface of artificial kidney stones during shock wave lithotripsy was investigated in vitro by means of multiframe high‐speed photography, passive cavitation detection (PCD), and pressure waveform measurements using a fiber‐optic probe hydrophone (FOPH). It was observed that after the passage of the lithotripter shock pulse the stone was covered by numerous individual bubbles. During their growth phase the bubbles coalesced into bubble clusters, with the biggest cluster at the proximal face of the stone. High‐speed camera images suggested that cluster collapse started at the periphery and ended with a violent collapse in a small region in the center of the surface of the stone. Shadowgraphy resolved numerous secondary shock waves emitted during this focused collapse. Shock wave emission during cluster collapse was confirmed by PCD. Measurement with the FOPH showed that these shock waves were typically of short duration (0.2 μs). The majority of the shock waves ema...

Treating one kidney with high‐energy acoustic shock waves reduces blood flow 65% in that kidney and 33% in the contralateral unshocked kidney. We tested the hypothesis that renal nerves were involved in this response. Six‐week old pigs underwent unilateral renal denervation. Nerves along the renal artery of one kidney were cut and the artery was painted with 10% phenol. After 2 weeks, the pigs were anesthetized and bilateral renal function was determined using inulin and PAH (para‐aminohippurate) clearance. Glomerular filtration rate (GFR, inulin clearance) and renal blood flow (PAH clearance) were measured both before and after lithotripsy to the lower pole of the innervated kidney (2000 shocks, 24 kV, unmodified Dornier HM‐3) or sham lithotripsy. Both kidneys were then removed to measure norepinephrine content in the tissue. Norepinephrine levels were significantly reduced (more than 90%) in denervated kidneys indicating complete denervation. As expected, blood flow and GFR fell (approximately 50%) afte...

Shock‐wave lithotripsy (SWL) damages renal tissue and reduces renal perfusion. These studies asked whether SW‐induced injury or reduced perfusion might cause oxidative stress. Two groups of 3 anesthetized pigs received 2000 shock waves (SWs) at 24 kV (Dornier HM3, 2 Hz) to one renal pole. Renal hemodynamics were measured 1 h before and 1 and 4 h after SWL. Samples of renal tissue from upper and lower poles of each kidney were analyzed for malonaldehyde (lipid peroxidation) and 8‐OH‐deoxyguanosine (OH8dG, DNA damage). SWL reduced perfusion in both kidneys, but injured only the shocked kidneys. Malonaldehyde levels were elevated in both poles of the shocked kidneys, but were not elevated in the contralateral unshocked kidneys. In contrast, OH8dG levels were elevated in the treated pole of the shocked kidneys, and in both poles of the contralateral unshocked kidneys. In conclusion, (1) The elevated levels of malonaldehyde seen in the shocked kidneys but not in the unshocked kidneys are consistent with lipid ...

Natural kidney stones are heterogeneous in structure, composition, material properties and fragility, and as such are problematic for use in determining the mechanisms of SW‐action in SWL. A variety of model stones have been developed. We have adopted Ultracal‐30 gypsum [Dahake and Gracewski, J. Acoust. Soc. Am. 102, 2138 (1997)] for in‐vitro and in‐vivo studies. U‐30 stones (7.5×6.5 mm) cast in polystyrene molds were liberated with chloroform and stored in water. Drop‐impact testing of dry stones showed a linear relationship between increase in surface area of fragments and energy applied. Breakage of hydrated stones in a research‐electrohydraulic lithotripter, likewise showed a linear increase in fragment area with increased SW‐number and SW‐voltage. The density (1800 kg/m3) and transverse (1520 m/s) and longitudinal (3100 m/s) wave speeds of U‐30 stones place them in the range determined for natural stones. U‐30 stones implanted in pig kidneys exhibited cavitation erosion and spall fracture similar to stones in‐vitro, and U‐30 stones in‐vitro and in‐vivo showed equivalent response to SW‐rate (200% higher fragmentation at 0.5 Hz compared to 2 Hz). U‐30 stones softened with prolonged exposure to water and degraded during long‐term implantation in‐vivo. With these cavaets U‐30 stones provide a useful model for SWL research. [Work supported by NIH P01‐DK43881.]

High‐speed photography was used to investigate cavitation at the surface of artificial and natural kidney stones during exposure to lithotripter shock pulses in vitro. It was observed that numerous individual bubbles formed over virtually the entire surface of the stone, but these bubbles did not remain independent and combined with one another to form larger bubbles and bubble clusters. The movement of bubble boundaries across the surface left portions of the stone bubble free. The biggest cluster grew to envelop the proximal end of the stone (6.5 mm diameter artificial stone) then collapsed to a small spot that over multiple shots formed a crater in that face of the stone. The bubble clusters that developed at the sides of stones tended to align along fractures and to collapse into these cracks. High‐speed camera images demonstrated that cavitation‐mediated damage to stones was due not to the action of solitary, individual bubbles, but to the forceful collapse of dynamic clusters of bubbles. [Work supported by NIH DK43881.]

High‐energy shock waves (SWs) to one kidney (2000 SWs at 24 kV) reduces blood flow in both kidneys (65% in shocked kidneys, 33% in contralateral unshocked kidneys). We determined if unilateral renal denervation of the unshocked kidney alters renal blood vessel constriction after SWL. Six‐week‐old pigs underwent unilateral kidney denervation. Visible renal nerves along the renal artery of one kidney were isolated, cut, and painted with 10% phenol. Two weeks later, the pigs were anesthetized and kidney function was followed with inulin and PAH clearance. 2000 SWs (at 24 kV, Dornier HM3) were applied to the lower pole of the innervated kidney. Bilateral glomerular filtration rate (inulin clearance) and renal plasma flow (PAH clearance and extraction) were measured 1 h before and 1 h after SWL. Both kidneys were then removed to determine norepinephrine (NE) content in the tissue. Denervation reduced NE levels to 8.7% of innervated kidneys. While blood flow fell as expected in the innervated shocked kidney, th...

A step in determining cavitation’s deleterious role in shock wave lithotripsy (SWL) is spatially correlating cavitation and tissue damage: Can cavitation be detected in kidney tissue? A system for localized cavitation detection and tests is described. Our lithotripter source and two single‐element ring transducers (1.1 MHz, focal length 6.3 cm, radius 1.1–3.5 cm) were aligned confocal and orthogonal. An ultrasound scanhead fit in the central opening. B‐mode imaging and fluoroscopy showed the position of the focus within the kidney. Hyperechoic clouds in the image indicated pockets of bubbles during SWL. A coincidence‐detection algorithm and the confocal transducers made it possible to localize cavitation to within an 8‐mm3 region. Cavitation was detected in a pig kidney during SWL. Following SWL, the tissue region interrogated can be marked with a lesion produced by using the detection transducers as high‐intensity focused ultrasound (HIFU) sources. This technique allows one to determine if the site of cavitation detection was located within the kidney tissue. Lesions were produced in pig kidney. Ultimately a ring of lesion might be drawn around the interrogation region so that SWL damage to the region might be assessed and coorelated with cavitation. [Work supported by NIH DK43881 and DK55674.]

The trend toward ungated SWL means that SW’s are often delivered at a fast rate (≥2 Hz). This is a concern, since rapid SW delivery causes increased renal injury in experimental animals. Also, in vitro studies show that slowing the SW rate ( % (n=6), compared to the faster rate, 19.4±5.6 % (n=6) [p

A clinical dose of 2000 shockwaves applied at 12 kV induces renal vasoconstriction but causes no hemorrhagic lesion. Two thousand shockwaves applied at 24 kV causes the same vasoconstriction as 12 kV but lesion size is increased. These findings led us to ask whether lesion size would be smaller after 2000 shockwaves at 24 kV to one pole if a vasoconstrictive state was induced in that kidney by first applying 2000 shockwaves at 12 kV to the lower pole of that kidney. Anesthetized pigs received 2000 shockwaves to the lower pole followed by 2000 shockwaves to the upper pole of the same kidney. Structural and functional analyses were performed 4 hours post‐SWL. Results from these experiments show renal vasoconstriction induced from the first application of SWL at 12 kV to one pole appears to limit bleeding/hemorrhage caused by 24 kV to the other pole.

These studies characterized the effects of normal and high ‘‘doses’’ of shock waves on renal structure and function in healthy and compromised kidneys of young, anesthetized pigs. A ‘‘normal’’ dose of 2000 shock waves (24 kV, unmodified HM3 lithotripter) to one kidney produced lesions comprising about 8% of functional renal mass, transiently reduced renal blood flow and glomerular filtration rate (GFR) in both kidneys, and reduced regional perfusion in shocked kidneys. High doses of shock waves to one kidney (8000 shocks at 24 kV) produced larger lesions (about 14%), intensified the initial vasoconstriction in both kidneys, and sustained the reduction of GFR in the shocked kidneys for at least 24 h after treatment. The administration of 2000 shock waves (24 kV) to pyelonephritic (compromised) kidneys exaggerated the structural/functional impairment by inducing large lesions and intense vasoconstriction normally seen only after 8000 shock waves in healthy kidneys. We conclude that both shock wave number and preexisting renal disease increase the severity of tissue injury and functional impairment produced by shock wave lithotripsy. Since renal ischemia and inflammation occur in association with such injury, subsequent renal scarring and permanent loss of functional renal mass may also be related to shock wave dosage.

Fast shock wave (SW) rates in lithotripsy (SWL) generate enhanced cavitation that could promote stone fragmentation. We tested the idea that SWL at the high end of clinical SW rate (2 Hz) acts to improve stone comminution. Model stones (Ultracal‐30 cement) were exposed to SWs (20 kV, 400 SWs) at 0.2, 0.5, 1, and 2 Hz in a research electrohydraulic lithotripter. Fragmentation was assessed by measuring number, size, and projected surface area of the fragments. Stones treated at 0.2 Hz exhibited significantly greater fragmentation (p

These experiments examined the size of the renal lesions produced by SWL after 2000 shocks applied first to one pole and then immediately to the other pole of the same kidney. Anesthetized, 6‐week‐old pigs received 2000 shock waves at 24 kV (Dornier HM3) first to the lower pole and then to the upper pole of the same kidney (4000 shocks in all). Bilateral measurements of renal blood flow (RBF) were obtained 1 h before and 1 and 4 h after SWL. Lesion sizes in each pole were determined by serial sectioning and digital photography. SWL successively to lower and then upper poles in each of two pigs caused marked bilateral renal vasoconstriction (reduction of RBF). In one pig, the upper‐pole lesion was only about 5% the size of the initial lower‐pole lesion. In the second pig, the lesions in the upper and lower poles were of similar sizes. In both pigs, the combined lesion sizes after 4000 shocks (6.81% and 5.72%, respectively) were nearly the same as the size of lesions produced by a single application of 2000 shocks to only one pole (6.1±1.7). The data suggest that renal vasoconstriction limits the renal injury caused by SWL.

To better understand the role of cavitation in kidney stone comminution and renal injury pressurization (Delius UMB23:1997) to regulate cavitation bubble activity in vitro was used. A low acoustic impedance chamber (8×15 cm) that only minimally altered lithotripter shock‐wave pressure and waveform was constructed to house targets (aluminum foils or vials of kidney epithelial cells) under pressure (0–1400 psi). Cells exhibited lytic injury and foils sustained pitting at atmospheric pressure, but high pressure (1400 psi) prevented lysis and pitting. The pressure threshold for reduced damage was dramatically different for cells versus foils. Cell lysis was prevented at very low pressure (> 30 psi), while substantially greater pressure (∼600 psi) was needed to prevent pitting. Modest pressure (25–300 psi) actually enhanced pitting. SWL in vitro cell lysis and foil pitting are both likely due to cavitation. However, interactions between cavitation bubbles and these two targets appear to be quite different. Our observations are consistent with those of Delius and support his suggestion that it may be possible to reduce cavitation‐mediated cell damage by regulating ambient pressure. The finding that slight pressure increased the number of cavitation events on foils suggests that modest overpressure might enhance stone comminution. [Supported by NIH PO1‐DK43881.]

SWL to one kidney causes localized tissue damage and impairment of tubular function, but reduces renal plasma flow (RPF) in both kidneys. We examined the effect of SWL voltage (kV) and inversion of the waveform (IW) on these localized and bilateral effects of SWL. Five‐week‐old pigs were anesthetized for either sham‐SWL or SWL (2000 shocks, unmodified HM3) at 12, 18, or 24 kV or 2000 shocks, 24 kV, with a reflector that inverts the waveform. RPF and tubular extraction of PAH (EPAH) were measured 1 h before and 1 and 4 h after SWL. EPAH estimates tubular secretion function. SWL significantly reduced RPF to similar degrees at each kV. EPAH was not significantly reduced in the 12‐kV group, but was reduced to progressively greater degrees in the 18 and 24 kV groups. IW eliminated ultrasonic evidence of cavitation, produced minimal tissue damage, and eliminated the reduction of EPAH. It did not eliminate the reduction of RPF. The data suggest that shock‐wave voltage and cavitation may be related to the tissue ...

Acoustic cavitation is thought to play a major role in both stone comminution and tissue injury during shock wave lithotripsy (SWL). Although ultrasound machines cannot directly observe cavitation events, remnant gas bubbles appear as echogenic regions. We treated young pigs in an unmodified Dornier HM3 and used a standard clinical ultrasound machine (Bruel and Kjaer 3535) to image the kidney while SWL was being administered. We observed large regions of in vivo echogenicity within the renal pelvis (collecting system), which has not been reported before. When the ureter was blocked, up to 30% of the renal pelvis was covered with echogenicity. Clouds of echogenicity progressed through the collecting system with consecutive shots. The echogenic regions in the renal pelvis could be temporarily enhanced when nondegassed fluid was injected through a ureter catheter. Echogenicity was observed on the posterior and anterior surfaces of the kidney and appeared to occur at sites of subcapsular hematomas. The presence of echogenicity is consistent with the claim that cavitation plays an important role in both stone comminution and tissue damage. [Work supported by NIH and the Hunt Fellowship.]

Mechanisms of stone comminution and tissue damage in lithotripsy are sensitive to the acoustic field within the kidney, yet prediction of shock wavesin vivo is difficult. Measurements of lithotripsy shock waves have been made inside pigs with small hydrophones constructed of a 50‐μm PVdF membrane stretched over a 21‐mm‐diam ring. A thin layer of silicone rubber was used to electrically isolate the membrane from pig fluid. An incision was made in the pig flank and a hydrophone inserted either on the anterior (shock wave entrance) or posterior (shock wave exit) surface of the left kidney. The incision was flooded with saline during closure to minimize entrapped air. Four pigs were treated in a Dornier HM‐3 lithotripter. Fluoroscopic imaging was used to orient the hydrophone perpendicular to the shock wave. For each pig, various power settings and movement of the shock wave focus throughout the kidney were used. Waveforms measured within the pig had a shape very similar to those measured in water. However, pressure amplitude in the pig was about 60% of that measured in water. The shock rise times were on the order of 100 μs and were hydrophone limited. [Work supported by NIH and the ASA Hunt Fellowship.]

It has been suggested that kidney size is a risk factor for increased shock wave lithotripsy‐ (SWL) induced damage. This relationship was investigated in pigs of two different ages; ten weeks of age (group 1) and five weeks of age (group 2). Each pig received 2000 shocks, 24 kV to the right kidney. Glomerular filtration rate (GFR), PAH clearance and extraction were measured 1 h before and 1 and 4 h after SWL treatment. The kidneys were harvested at the end of the clearance study. Values for GFR, PAH clearance, and extraction were reduced in the shocked kidney of both groups 1 h post‐SWL. Calculated values for true renal plasma flow showed a greater reduction in the treated kidneys of group 2 versus group 1. The degree of subcapsular hemorrhage and intraparenchymal bleeding and tubular disruption was more extensive in group 2 versus group 1 treated kidneys. The data document the degree of structural and functional injury induced by SWL and support the hypothesis that the effect of SWL is greatest in kidney...