Renal Vasoconstriction Occurs Early During Shockwave Lithotripsy in Humans.

INTRODUCTION: In animal models, pretreatment with low-energy shock waves and a pause decreased renal injury from shockwave lithotripsy (SWL). This is associated with an increase in perioperative renal resistive index (RI). A perioperative rise is not seen without the protective protocol, which suggests that renal vasoconstriction during SWL plays a role in protecting the kidney from injury. The purpose of our study was to investigate whether there is an increase in renal RI during SWL in humans. MATERIALS AND METHODS: Subjects were prospectively recruited from two hospitals. All subjects received an initial 250 shocks at low setting, followed by a 2-minute pause. Treatment power was then increased. Measurements of the renal RI were taken before start of procedure, at 250, after 750, after 1500 shocks, and at the end of the procedure. A linear mixed-effects model was used to compare RIs at the different time points. RESULTS: Fifteen patients were enrolled. Average treatment time was 46 ± 8 minutes. Average RI at pretreatment, after 250, after 750, after 1500 shocks, and post-treatment was 0.67 ± 0.06, 0.69 ± 0.08, 0.71 ± 0.07, 0.73 ± 0.07, and 0.74 ± 0.06, respectively. In adjusted analyses, RI was significantly increased after 750 shocks compared with pretreatment (p = 0.05). CONCLUSION: Renal RI increases early during SWL in humans with the protective protocol. Monitoring for a rise in RI during SWL is feasible and may provide real-time feedback as to when the kidney is protected.

Tools to improve the accuracy of kidney stone sizing with ultrasound.

PURPOSE: Ultrasound (US) overestimates stone size when compared with CT. The purpose of this work was to evaluate the overestimation of stone size with US in an in vitro water bath model and investigate methods to reduce overestimation. MATERIALS AND METHODS: Ten human stones (3-12 mm) were measured using B-mode (brightness mode) US by a sonographer blinded to the true stone size. Images were captured and compared using both a commercial US machine and software-based research US device. Image gain was adjusted between moderate and high stone intensities, and the transducer-to-stone depth was varied from 6 to 10 cm. A computerized stone-sizing program was developed to outline the stone width based on a grayscale intensity threshold. RESULTS: Overestimation with the commercial device increased with both gain and depth. Average overestimation at moderate and high gain was 1.9±0.8 and 2.1±0.9 mm, respectively (p=0.6). Overestimation increased an average of 22% with an every 2-cm increase in depth (p=0.02). Overestimation using the research device was 1.5±0.9 mm and did not vary with depth (p=0.28). Overestimation could be reduced to 0.02±1.1 mm (p<0.001) with the computerized stone-sizing program. However, a standardized threshold consistent across depth, system, or system settings could not be resolved. CONCLUSION: Stone size is consistently overestimated with US. Overestimation increased with increasing depth and gain using the commercial machine. Overestimation was reduced and did not vary with depth, using the software-based US device. The computerized stone-sizing program shows the potential to reduce overestimation by implementing a grayscale intensity threshold for defining the stone size. More work is needed to standardize the approach, but if successful, such an approach could significantly improve stone-sizing accuracy and lead to automation of stone sizing.

Detection of mild traumatic brain injury in rodent models using shear wave elastography: preliminary studies.

OBJECTIVES: Traumatic brain injury (TBI) can cause adverse physiologic changes in fluid content within the brain, which may lead to changes in tissue elasticity (eg, stiffness). This study evaluated the ability of ultrasonic shear wave elastography to observe these changes in the brain after TBI in vivo. METHODS: Mice and rats received a mild TBI or sham surgery and were imaged acutely or 24 hours after injury using shear wave elastography, and the hemispheric stiffness values were compared. RESULTS: Stiffness values were consistent across brain hemispheres of sham TBI rodents. By 24 hours after TBI, relative brain tissue stiffness values for mice and rats each decreased ipsilaterally and increased contralaterally, both relative to each other and compared to sham TBI rodents (P < .05). The absolute tissue elasticity value increased for rats (P < .05) but not for mice. CONCLUSIONS: Differences between intrahemispheric stiffness values of rodent brains by 24 hours after mild TBI may reflect the observed edema and hemorrhage ipsilateral to TBI and the known reduction of cerebral blood flow in both brain hemispheres. If these hypotheses hold true, ultrasonic shear wave elastography may offer a method for detecting adverse changes in fluid content within the brain after mild TBI.

Preclinical safety and effectiveness studies of ultrasonic propulsion of kidney stones.

OBJECTIVE: To provide an update on a research device to ultrasonically reposition kidney stones transcutaneously. This article reports preclinical safety and effectiveness studies, survival data, modifications of the system, and testing in a stone-forming porcine model. These data formed the basis for regulatory approval to test the device in humans. MATERIALS AND METHODS: The ultrasound burst was shortened to 50 ms from previous investigations with 1-s bursts. Focused ultrasound was used to expel 2- to 5-mm calcium oxalate monohydrate stones placed ureteroscopically in 5 pigs. Additionally, de novo stones were imaged and repositioned in a stone-forming porcine model. Acute safety studies were performed targeting 2 kidneys (6 sites) and 3 pancreases (8 sites). Survival studies followed 10 animals for 1 week after simulated treatment. Serum and urine analyses were performed, and tissues were evaluated histologically. RESULTS: All ureteroscopically implanted stones (6/6) were repositioned out of the kidney in 14 ± 8 minutes with 13 ± 6 bursts. On average, 3 bursts moved a stone more than 4 mm and collectively accounted for the majority of relocation. Stones (3 mm) were detected and repositioned in the 200-kg stone-forming model. No injury was detected in the acute or survival studies. CONCLUSION: Ultrasonic propulsion is safe and effective in the porcine model. Stones were expelled from the kidney. De novo stones formed in a large porcine model were repositioned. No adverse effects were identified with the acute studies directly targeting kidney or pancreatic tissue or during the survival studies indicating no evidence of delayed tissue injury.

Focused ultrasound to displace renal calculi: threshold for tissue injury.

BACKGROUND: The global prevalence and incidence of renal calculi is reported to be increasing. Of the patients that undergo surgical intervention, nearly half experience symptomatic complications associated with stone fragments that are not passed and require follow-up surgical intervention. In a clinical simulation using a clinical prototype, ultrasonic propulsion was proven effective at repositioning kidney stones in pigs. The use of ultrasound to reposition smaller stones or stone fragments to a location that facilitates spontaneous clearance could therefore improve stone-free rates. The goal of this study was to determine an injury threshold under which stones could be safely repositioned. METHODS: Kidneys of 28 domestic swine were treated with exposures that ranged in duty cycle from 0%-100% and spatial peak pulse average intensities up to 30 kW/cm(2) for a total duration of 10 min. The kidneys were processed for morphological analysis and evaluated for injury by experts blinded to the exposure conditions. RESULTS: At a duty cycle of 3.3%, a spatial peak intensity threshold of 16,620 W/cm(2) was needed before a statistically significant portion of the samples showed injury. This is nearly seven times the 2,400-W/cm(2) maximum output of the clinical prototype used to move the stones effectively in pigs. CONCLUSIONS: The data obtained from this study show that exposure of kidneys to ultrasonic propulsion for displacing renal calculi is well below the threshold for tissue injury.

Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model.

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy.

PURPOSE: Focused ultrasonic propulsion is a new noninvasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, to our knowledge the extent of tissue injury associated with this technique is not known. We quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions and under conditions of higher power or continuous duty cycles. We compared those results to extracorporeal shock wave lithotripsy injury. MATERIALS AND METHODS: A human calcium oxalate monohydrate stone and/or nickel beads were implanted by ureteroscopy in 3 kidneys of live pigs weighing 45 to 55 kg and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to extracorporeal shock wave lithotripsy level pulse intensity or continuous ultrasound exposure 10 minutes in duration using an ultrasound probe transcutaneously or on the kidney. These kidneys were compared to 6 treated with an unmodified Dornier HM3 lithotripter (Dornier Medical Systems, Kennesaw, Georgia) using 2,400 shocks at 120 shock waves per minute and 24 kV. Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique according to the percent of functional renal volume. RESULTS: Extracorporeal shock wave lithotripsy produced a mean ± SEM lesion of 1.56% ± 0.45% of functional renal volume. Ultrasonic propulsion produced no detectable lesion with simulated clinical treatment. A lesion of 0.46% ± 0.37% or 1.15% ± 0.49% of functional renal volume was produced when excessive treatment parameters were used with the ultrasound probe placed on the kidney. CONCLUSIONS: Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters but produced injury comparable in size to that of extracorporeal shock wave lithotripsy when using excessive treatment parameters.

Improved Detection of Kidney Stones Using an Optimized Doppler Imaging Sequence.

Kidney stones have been shown to exhibit a "twinkling artifact" (TA) under Color-Doppler ultrasound. Although this technique has better specificity than conventional Bmode imaging, it has lower sensitivity. To improve the overall performance of using TA as a diagnostic tool, Doppler output parameters were optimized in-vitro. The collected data supports a previous hypothesis that TA is caused by random oscillations of micron sized bubbles trapped in the cracks and crevices of kidney stones. A set of optimized parameters were implemented such that that the MI & TI remained within the FDA approved limits. Several clinical kidney scans were performed with the optimized settings and were able to detect stones with improved SNR relative to the default settings.

Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study.

One in 11 Americans has experienced kidney stones, with a 50% average recurrence rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to expel small stones or residual fragments before they become a recurrent problem. Reported here are preliminary findings from the first investigational use of UP in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2 probe to generate real-time B-mode imaging and targeted "push" pulses on demand. There are three arms of the study: de novo stones, post-lithotripsy fragments, and the preoperative setting. A pain questionnaire is completed prior to and following the study. Movement is classified based on extent. Patients are followed for 90 days. Ten subjects have been treated to date: three de novo, five post-lithotripsy, and two preoperative. None of the subjects reported pain associated with the treatment or a treatment related adverse event, beyond the normal discomfort of passing a stone. At least one stone was moved in all subjects. Three of five post-lithotripsy subjects passed a single or multiple stones within 1-2 weeks following treatment; one subject passed two (1-2 mm) fragments before leaving clinic. In the pre-operative studies we successfully moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments where the clinical image and initial ultrasound examination indicated a single large stone.

Shockwave lithotripsy with renoprotective pause is associated with renovascular vasoconstriction in humans.

Animal studies have shown that shock wave lithotripsy (SWL) delivered with an initial course of low-energy shocks followed by a pause reduces renal injury. The pause correlates with increased arterial resistive index (RI) during SWL as measured by ultrasound. This suggests that renal vasoconstriction is associated with protecting the kidney from injury. This study explored whether a similar increase in RI is observed in humans. Patients were prospectively recruited from two hospitals. All received an initial dose of 250 lowest energy shocks followed by a two-minute pause. Shock power was then ramped up at the discretion of the physician; shock rate was maintained at 1 Hz. Spectral Doppler velocity measurements were taken from an interlobar artery at baseline after induction, during the pause at 250 shocks, after 750 shocks, after 1500 shocks, and at the end of the procedure. RI was calculated from the peak systolic and end diastolic velocities and a linear mixed-effects model was used to compare RIs. The statistical model accounted for age, gender, laterality, and body mass index (BMI). Measurements were taken from 15 patients. Average RI ± standard deviation pretreatment, after 250 shocks, after 750 shocks, after 1500 shocks, and post treatment was 0.68 ± 0.06, 0.71 ± 0.07, 0.73 ± 0.06, 0.75 ± 0.07 and 0.75 ± 0.06, respectively. RI was found to be significantly higher after 250 shocks compared to pretreatment (p = 0.04). RI did not correlate with age, gender, BMI, or treatment side. This is suggestive that allowing a pause for renal vascular vasoconstriction to develop may be beneficial, and can be monitored for during SWL, providing real-time feedback as to when the kidney is protected.

Focused ultrasonic propulsion of kidney stones: review and update of preclinical technology.

INTRODUCTION: A noninvasive tool to reposition kidney stones could have significant impact in the management of stone disease. Our research group has developed a noninvasive transcutaneous ultrasound device. A review and update of the current status of this technology is provided. DISCUSSION OF TECHNOLOGY: Stone propulsion is achieved through short bursts of focused, ultrasonic pulses. The initial system consisted of an eight-element annular array transducer, computer, and separate ultrasound imager. In the current generation, imaging and therapy are completed with one ultrasound system and a commercial probe. This generation allows real-time ultrasound imaging, targeting, and propulsion. Safety and effectiveness for the relocation of calyceal stones have been demonstrated in the porcine model. ROLE IN ENDOUROLOGY: This technology may have applications in repositioning stones as an adjunct to lithotripsy, facilitating clearance of residual fragments after lithotripsy, expelling de novo stones, and potentially repositioning obstructing stones. Human trials are in preparation.

Ultrasound-targeted microbubble destruction-mediated gene delivery into canine livers.

Ultrasound (US) was applied to a targeted canine liver lobe simultaneously with injection of plasmid DNA (pDNA)/microbubble (MB) complexes into a portal vein (PV) segmental branch and occlusion of the inferior vena cava (IVC) to facilitate DNA uptake. By using a 1.1 MHz, 13 mm diameter transducer, a fivefold increase in luciferase activity was obtained at 3.3 MPa peak negative pressure (PNP) in the treated lobe. For more effective treatment of large tissue volumes in canines, a planar unfocused transducer with a large effective beam diameter (52 mm) was specifically constructed. Its apodized dual element configuration greatly reduced the near-field transaxial pressure variations, resulting in a remarkably uniform field of US exposure for the treated tissues. Together with a 15 kW capacity US amplifier, a 692-fold increase of gene expression was achieved at 2.7 MPa. Transaminase and histology analysis indicated minimal tissue damage. These experiments represent an important developmental step toward US-mediated gene delivery in large animals and clinics.

Focused ultrasound to expel calculi from the kidney: safety and efficacy of a clinical prototype device.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evidence of changes in brain tissue stiffness after ischemic stroke derived from ultrasound-based elastography.

OBJECTIVES: Ischemia, edema, elevated intracranial pressure, and reduced blood flow can occur in the brain as a result of ischemic stroke, including contralateral to the stroke via a process known as diaschisis. In this study, ultrasound elastography, an imaging process sensitive to the stiffness of tissue, including its relative fluid content, was used to study changes in the stiffness of individual cerebral hemispheres after transient ischemic injury. METHODS: Elastographic images of mouse brains were collected 24 and 72 hours after middle cerebral artery occlusion. The shear moduli of both ipsilateral and contralateral brain hemispheres for these mice were measured and compared to corresponding values of control animals. RESULTS: At 24 hours (but not 72 hours) after induction of ischemic stroke, there was a significant decrease in the shear modulus in the ipsilateral hemisphere (P < .01) and a significant increase in the shear modulus in the contralateral hemisphere compared to that of control animals (P < .01). Significant differences were also evident between ipsilateral and contralateral shear modulus values at 24 and 72 hours after infarction (P < .01 for both). CONCLUSIONS: The differences between intrahemispheric averages of shear moduli of the brains of animals with stroke at 24 and 72 hours after stroke induction likely reflect the initial formation of edema and reduction of cerebral blood flow known to develop ipsilateral to ischemic infarction, the known transient increase in intracranial pressure, as well as the known initial reduction of blood flow and subsequent development of edema in the contralateral hemisphere (diaschisis). Thus, elastography offers a possible method to detect subtle changes in brain after ischemic stroke.

B-mode ultrasound versus color Doppler twinkling artifact in detecting kidney stones.

PURPOSE: To compare color Doppler twinkling artifact and B-mode ultrasonography in detecting kidney stones. PATIENTS AND METHODS: Nine patients with recent CT scans prospectively underwent B-mode and twinkling artifact color Doppler ultrasonography on a commercial ultrasound machine. Video segments of the upper pole, interpolar area, and lower pole were created, randomized, and independently reviewed by three radiologists. Receiver operator characteristics were determined. RESULTS: There were 32 stones in 18 kidneys with a mean stone size of 8.9±7.5 mm. B-mode ultrasonography had 71% sensitivity, 48% specificity, 52% positive predictive value, and 68% negative predictive value, while twinkling artifact Doppler ultrasonography had 56% sensitivity, 74% specificity, 62% positive predictive value, and 68% negative predictive value. CONCLUSIONS: When used alone, B-mode is more sensitive, but twinkling artifact is more specific in detecting kidney stones. This information may help users employ twinkling and B-mode to identify stones and developers to improve signal processing to harness the fundamental acoustic differences to ultimately improve stone detection.

Three-dimensional ultrasonography measurements after endovascular aneurysm repair.

BACKGROUND: Ultrasonographic (US) assessment of abdominal aortic aneurysms is typically performed by measuring maximal aneurysm diameter from two-dimensional images. These measurements are prone to inaccuracies owing to image planes and interobserver variability. The purpose of this study was to compare the variability in diameter, cross-sectional area (CSA), and volume measurements of abdominal aortic aneurysms obtained using a three-dimensional (3D) US imaging system with those obtained using computed tomographic (CT) angiography, and to determine the reliability of these measures. METHODS: Seven patients in whom endovascular aneurysm repairs were performed underwent CT angiography in addition to a 3D US scan. Measurements computed using 3D surface reconstructions of CT and 3D US scans included maximum diameter, CSA, and aneurysm volume. The seven matched CT and 3D US scans were compared at baseline and 6 to 8 weeks later. RESULTS: The average aneurysm measured 57.2 mm on CT and 56.2 mm on US (P = 0.14). Correlation coefficients for diameter, CSA, and volume were 0.88, 0.90, and 0.93, respectively (all P values < 0.001). A Bland-Altman analysis demonstrated a strong agreement between 92% of the diameter, 96.4% of the CSA, and 100% of the volume measurements. The interrater reliability was remarkably high comparing the modalities (CT vs. US), and ranged from 0.934 to 0.997 for single measurements and 0.965 to 0.998 for all measurements together; moreover, there was a strong reliability when the tests were reviewed 6 to 8 weeks later, with a reliability of 0.962 to 0.998 for single measurements and 0.992 to 0.999 for all tests (all P values < 0.001). CONCLUSIONS: The 3D US is an accurate and noninvasive method of determining aneurysm size and geometry that is reproducible. Volumetric measurements may represent a significant advancement in long-term follow-up after endovascular aneurysm repair.

Focused Ultrasonic Propulsion of Kidney Stones.

Introduction: Our research group is studying a noninvasive transcutaneous ultrasound device to expel small kidney stones or residual post-treatment stone fragments from the kidney.1-3 The purpose of this study was to evaluate the efficacy and safety of ultrasonic propulsion in a live porcine model. Materials and Methods: In domestic female swine (50-60 kg), human stones (calcium oxalate monohydrate) and metalized glass beads (2-8 mm) were ureteroscopically implanted.4 Target stones and beads were placed in the lower half of the kidney and a reference bead was placed in the upper pole. Ultrasonic propulsion was achieved through a single ultrasound system that allowed targeting, stone propulsion, and ultrasound imaging using a Philips HDI C5-2 commercial imaging transducer and a Verasonics diagnostic ultrasound platform. Stone propulsion was achieved through the delivery of 1-second bursts of focused, ultrasound pulses, which consist of 250 finely focused pulses 0.1 milliseconds in duration. Stone propulsion was then observed using fluoroscopy, ultrasound, and visually with the ureteroscope. The kidneys were then perfusion-fixed with glutaraldehyde, embedded in paraffin, sectioned, and stained. Samples were histologically scored for injury by a blinded independent expert. Using the same pulsing scheme, while varying acoustic intensities, an injury threshold and patterns of injury were determined in additional pigs.5,6 Results: Stones were successfully implanted in 14 kidneys. Overall, 17 of 26 (65)% stones/beads were moved the entire distance to the renal pelvis, ureteropelvic junction (UPJ), or proximal ureter. The average procedure time for successfully repositioned stones was 14.2±7.9 minutes with 23±16 push bursts. No gross or histologic damage was identified from the ultrasound propulsion procedure. Under this pulsing scheme, a maximum exposure of 2400 W/cm2 was delivered during each treatment. An intensity threshold of 16,620 W/cm2 was determined at which, above this level, tissue injury consistent with emulsification, necrosis, and hemorrhage appeared to be dose dependent. Conclusions: Ultrasonic propulsion is effective with most stones being relocated to the renal pelvis, UPJ, or proximal ureter in a timely fashion. The procedure appears safe with no evidence of injury. The acoustic intensities delivered at maximum treatment settings are well below the threshold at which injury is observed. The angle and alignment of directional force are the most critical factors determining the efficacy of stone propulsion. We are now pursuing FDA approval for a human feasibility study. No competing financial interests exist. Runtime of video: 5 mins 44 secs Acknowledgments: This work was supported by NIH DK43881, DK092197, NSBRI through NASA NCC 9-58, the Coulter Foundation, and the University of Washington. This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. We are very grateful for the help of a large team at the University of Washington and the Consortium for Shock Waves in Medicine, which we cannot list in detail.

3aBAb5. Ultrasound intensity to propel stones from the kidney is below the threshold for renal injury.

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.

1pPAb5. Acoustic radiation force to reposition kidney stones.

Our group has introduced transcutaneous ultrasound to move kidney stones in order to expel small stones or relocate an obstructing stone to a nonobstructing location. Human stones and metalized beads (2-8 mm) were implanted ureteroscopically in kidneys of eight domestic swine. Ultrasonic propulsion was performed using a diagnostic imaging transducer and a Verasonics ultrasound platform. Stone propulsion was visualized using fluoroscopy, ultrasound, and the ureteroscope. Successful stone movement was defined as relocating a stone to the renal pelvis, ureteropelvic junction (UPJ) or proximal ureter. Three blinded experts evaluated for histologic injury in control and treatment arms. All stones were moved. 65% (17/26) of stones/beads were moved the entire distance to the renal pelvis (3), UPJ (2), or ureter (12). Average successful procedure per stone required 14±8 min and 23±16 pushes. Each push averaged 0.9 s in duration. Mean interval between pushes was 41±13 sec. No gross or histologic kidney damage was identified in six kidneys from exposure to 20 1-s pushes spaced by 33 s. Ultrasonic propulsion is effective with most stones being relocated to the renal pelvis, UPJ, or ureter. The procedure appears safe without evidence of injury.

Quantitative assessment of shockwave lithotripsy accuracy and the effect of respiratory motion.

BACKGROUND AND PURPOSE: Effective stone comminution during shockwave lithotripsy (SWL) is dependent on precise three-dimensional targeting of the shockwave. Respiratory motion, imprecise targeting or shockwave alignment, and stone movement may compromise treatment efficacy. The purpose of this study was to evaluate the accuracy of shockwave targeting during SWL treatment and the effect of motion from respiration. PATIENTS AND METHODS: Ten patients underwent SWL for the treatment of 13 renal stones. Stones were targeted fluoroscopically using a Healthtronics Lithotron (five cases) or Dornier Compact Delta II (five cases) shockwave lithotripter. Shocks were delivered at a rate of 1 to 2 Hz with ramping shockwave energy settings of 14 to 26 kV or level 1 to 5. After the low energy pretreatment and protective pause, a commercial diagnostic ultrasound (US) imaging system was used to record images of the stone during active SWL treatment. Shockwave accuracy, defined as the proportion of shockwaves that resulted in stone motion with shockwave delivery, and respiratory stone motion were determined by two independent observers who reviewed the ultrasonographic videos. RESULTS: Mean age was 51 ± 15 years with 60% men, and mean stone size was 10.5 ± 3.7 mm (range 5-18 mm). A mean of 2675 ± 303 shocks was delivered. Shockwave-induced stone motion was observed with every stone. Accurate targeting of the stone occurred in 60% ± 15% of shockwaves. CONCLUSIONS: US imaging during SWL revealed that 40% of shockwaves miss the stone and contribute solely to tissue injury, primarily from movement with respiration. These data support the need for a device to deliver shockwaves only when the stone is in target. US imaging provides real-time assessment of stone targeting and accuracy of shockwave delivery.