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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.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.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 (p0.001) with the computerized stone-sizing program. However, a standardized threshold consistent across depth, system, or system settings could not be resolved.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.

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.

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.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.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.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.

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.

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.

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.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.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 values0.001). 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 values0.001).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.

To compare color Doppler twinkling artifact and B-mode ultrasonography in detecting kidney stones.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.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.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.

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.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.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.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.

OBJECTIVE To test the hypothesis that the pretreatment of the kidney with low-energy shock waves (SWs) will induce renal vasoconstriction sooner than a standard clinical dose of high-energy SWs, thus providing a potential mechanism by which the pretreatment SW lithotripsy (SWL) protocol reduces tissue injury. MATERIALS AND METHODS Female farm pigs (6-weeks-old) were anaesthetized with isoflurane and the lower pole of the right kidney treated with SWs using a conventional electrohydraulic lithotripter (HM3, Dornier GmbH, Germany). Pulsed Doppler ultrasonography was used to measure renal resistive index (RI) in blood vessels as a measure of resistance/impedance to blood flow. RI was recorded from one intralobar artery located in the targeted pole of the kidney, and measurements taken from pigs given sham SW treatment (Group 1; no SWs, four pigs), a standard clinical dose of high-energy SWs (Group 2; 2000 SWs, 24 kV, 120 SWs/min, seven pigs), low-energy SW pretreatment followed by high-energy SWL (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, eight pigs) and low-energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, six pigs). RESULTS Baseline RI (≈0.61) was similar for all groups. Pigs receiving sham SW treatment (Group 1) had no significant change in RI. A standard clinical dose of high-energy SWs (Group 2) did not significantly alter RI during treatment, but did increase RI at 45 min after SWL. Low-energy SWs did not alter RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of high-energy SWs resulted in a significantly earlier (at 1000 SWs) and greater (two-fold) rise in RI than that in Group 2 pigs. This rise in RI during the low/high-energy SWL protocol was not due to a delayed vasoconstrictor response of pretreatment, as low-energy SW treatment alone (Group 4) did not increase RI until 65 min after SWL. CONCLUSIONS The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring after SWL. Thus, the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury.

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.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.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).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.

Soft tissues surrounding vascular injuries are known to vibrate at audible and palpable frequencies, producing bruits and thrills. We report the results of a feasibility study where Doppler ultrasound (US) was used to quantitatively estimate the tissue vibrations after induced trauma in an animal model. A software-programmable US system was used to acquire quadrature-demodulated ensembles of received US echoes bypassing clutter filtering and other conventional Doppler processing stages. The waveforms of tissue velocity surrounding the injury site were then estimated from the clutter data using autocorrelation and analyzed to determine vibration characteristics. Six New Zealand white rabbits and two juvenile pigs were used for the study. The femoral artery of the anesthetized animal was punctured with an 18-gauge needle to model a peripheral arterial trauma, and the liver was surgically exposed and incised to model organ trauma. Two types of oscillatory tissue motion were observed: "vibrations" with high frequency (50 Hz) and low peak-peak amplitude (1 microm) and "flutter" with low frequency (50 Hz) and high peak-peak amplitude (1 microm). Active bleeding in femoral artery punctures produced tissue vibrations at the frequency of 323 +/- 214 Hz (mean +/- standard deviation, pooled for both rabbits and pigs) and the amplitude of 0.24 +/- 0.15 microm. Active bleeding in liver incisions produced vibrations at the frequency of 120 +/- 47 Hz and the amplitude of 0.33 +/- 0.25 microm. Flutter was observed in punctured arteries at the frequency of 28 +/- 13 Hz the amplitude of 2.92 +/- 1.75 microm, and in incised livers at the frequency of 26 +/- 6 Hz and the amplitude of 1.53 +/- 0.76 microm. In a punctured artery, the vibration frequency and phase of tissue surrounding the artery were highly correlated between neighboring locations in tissue (correlation coefficient = 0.98), and with the flow oscillations in the lumen (correlation coefficient = 0.96). This preliminary study indicates that tissue vibrations could provide additional physiologic information for detecting, localizing and monitoring internal bleeding using US.

Objective To determine the feasibility of uterine tissue ablation in vivo using a transvaginal focused ultrasound applicator guided by ultrasound imaging. Design Randomized in vivo animal study. Setting Academic research environment. Animal(s) Healthy anesthetized sheep. Intervention(s) Uterine treatment location was determined using a computerized targeting system. Five sonications 10 seconds in duration and averaging 2,000 W/cm 2 of focal ultrasound intensity were applied in each animal's uterus. Animals were euthanized either immediately or 2, 7, or 30 days post-treatment. Main outcome measure(s) Gross and microscopic analysis of the dissected uterus was used to quantitatively and qualitatively determine the ablated region and treatment side effects. Result(s) Treatments resulted in coagulative necrosis. Histopathological analysis showed that over 7 days, inflammatory cells appeared and smooth muscle bundles regenerated. By day 30, treated tissues healed and scar tissue formed. None of the animals showed abnormal behavior or medical problems. Complications in three animals were damage to the vaginal wall and colon, possibly due to inadequate applicator cooling and an empty bladder during treatment. Conclusion(s) Transvaginal image-guided high-intensity focused ultrasound has potential for treating uterine fibroids. Further safety testing of this treatment will prepare it for human use.

OBJECTIVE Previous studies have shown that high-intensity focused ultrasound can effectively control bleeding from injuries of liver, spleen, and blood vessels. This study investigated long-term hemostasis and tissue repair after high-intensity focused ultrasound treatment in liver. METHODS A total of 21 rabbits were randomly assigned to 2 groups: high-intensity focused ultrasound treatment (n = 14) and sham treatment (n = 7). All animals had sterile laparotomy and liver exposure. The high-intensity focused ultrasound-treated animals received liver incisions, 20 to 25 mm long and 4 to 6 mm deep, followed immediately by high-intensity focused ultrasound application until complete hemostasis was achieved. After recovery, sonographic images, blood samples, and histologic samples were collected immediately and on days 1, 3, 7, 14, 28, and 60 after treatment. RESULTS All 14 liver injuries were hemostatic after an average +/- SD of 78 +/- 44 seconds of high-intensity focused ultrasound application, with no rebleeding at any time point after the treatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between the high-intensity focused ultrasound and sham groups. Alanine aminotransferase and aspartate aminotransferase levels increased immediately after surgery by as much as 285% up to day 3 and returned to normal values by day 7. Hematocrit and white blood cell counts showed no statistically significant difference from normal values at all time points. Histologic examination up to 60 days after treatment revealed scarring and liver tissue regeneration at the treatment site. CONCLUSIONS High-intensity focused ultrasound appears to provide long-lasting hemostasis of acute liver injury. Healing and repair mechanisms after high-intensity focused ultrasound application appear to be intact.

Background Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. Methods A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. Results All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. Conclusion HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.

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.

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.

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.

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.

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.

The failure of dialysis access is a frequent source of morbidity and hospitalization. Traditional methods of graft surveillance include: (1) clinical examination, (2) venous line pressure measurements during dialysis, (3) urea or tracer recirculation measurement, (4) continuous wave (CW) Doppler methods, (5) duplex ultrasonography, and (6) radiograph angiography. All these methods require special training and/or laboratory tests. The purpose of this study was to test a simple continuous-wave Doppler method that could be applied to measure the flow rate in dialysis access every time the patient undergoes dialysis. Twenty dialysis patients, 15 with polytetrafluoroethylene grafts and 5 with arteriovenous fistulae, were studied. Two hundred fifty-three examinations were performed over an 8-month period. Doppler waveforms of the access flow were obtained with the pump on, with the pump off, and with the pump on again. Systolic and diastolic Doppler frequency measurements were made, and the pump-on and pump-off measurements were compared. In an access functioning normally, the Doppler frequencies are higher with the pump off than with the pump on. In 22% of the cases, there were abnormal findings in which the Doppler frequencies were lower with the pump off than with the pump on. This occurs if the needles are incorrectly placed, suggesting that recirculation is occurring. Recirculation also occurs if there is stenosis of the access. Examining the hemodialysis access during each dialysis session with an inexpensive directional Doppler may identify a significant stenosis and improve the efficiency of dialysis by detecting those patients in whom the arterial and venous needles are reversed.

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 s. 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. [Work supported by NIH DK43881, DK092197, and NSBRI through NASA NCC 9-58.]

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.

A persistent stone burden after renal stone treatment may result in future patient morbidity and potentially lead to additional surgery. This problem is particularly common after treatment of lower pole stones. We describe a potential noninvasive therapeutic option using ultrasound waves to create a force sufficient to aid in stone fragment expulsion.Human stones were implanted by retrograde ureteroscopy or antegrade percutaneous access in a live porcine model. The calibrated probe of a system containing ultrasound imaging and focused ultrasound was used to target stones and attempt displacement. To assess for injury an additional 6 kidneys were exposed for 2 minutes each directly to the output used for stone movement. Another 6 kidneys were exposed to more than twice the maximum output used to move stones. Renal tissue was analyzed histologically with hematoxylin and eosin, and nicotinamide adenine dinucleotide staining.Stones were moved to the renal pelvis or ureteropelvic junction by less than 2 minutes of exposure. Stone velocity was approximately 1 cm per second. There was no tissue injury when tissue was exposed to the power level used to move stones. Localized thermal coagulation less than 1 cm long was observed in 6 of 7 renal units exposed to the level above that used for ultrasonic propulsion.Transcutaneous ultrasonic propulsion was used to expel calculi effectively and safely from the kidney using a live animal model. This study is the first step toward an office based system to clear residual fragments and toward use as a primary treatment modality in conjunction with medical expulsive therapy for small renal stones.

Duplex sonography was evaluated as a potential screening examination for arterial trauma in 89 patients with 93 injuries, mostly to the extremities (n = 74) or the cervicothoracic region (n = 17). Among 60 scans performed solely because of wound proximity to nearby vascular structures, 4 (6.7%) were positive. Thirteen of 19 (68%) scans performed for clinical indications were positive. Six of 12 (50%) postoperative studies were abnormal, and each of 4 arterial injuries followed serially remained stable. Four false-negative duplex scans (4.3%) were recorded; no major arterial injuries were missed, and no false-positive studies were noted. Duplex sonography is rapid, noninvasive, inexpensive, and portable. Since it also appears to be reliable in diagnosing and localizing sites of arterial disruption, duplex scanning may be of value in screening patients with trauma for the presence of occult vascular injuries.

This chapter is an April 2005 revision of a chapter written in April 1998. During that period, the basics of ultrasound examination have been surprisingly stable. Electronics have shrunk so that now full function ultrasound duplex scanners can fit in your pocket. The speed of personal computers has advanced so that the new scanners are just software residing in personal computers equipped with an ultrasound receiver on the front end and a printer or DICOM adaptor on the back end.

Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain as a result of blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older nonultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the “plethysmographic” signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject's end-tidal CO 2 measurements. (E-mail: kucewicz@u.washington.edu )

Functional tissue pulsatility imaging is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility as a result of changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, nonultrasound technology for measuring expansion of a whole limb or body part as a result of perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow, and it relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate analysis of variance was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 of 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex.

High-intensity focused ultrasound (HIFU) has been shown to provide an effective method for hemorrhage control of blood vessels in acute animal studies. The objective of the current study was to investigate the long-term effects of HIFU-induced hemostasis in punctured arteries. The femoral arteries ( approximately 2mm in diameter) of 25 adult anesthetized rabbits were surgically exposed, and either punctured and treated with HIFU (n=15), served as control (no puncture and no HIFU application: n=7), or were punctured and left untreated (n=3). Treated animals were allowed to recover, and examined and/or sacrificed on days 0, 1, 3, 7, 14, 28, and 60 after treatment to obtain ultrasound images and samples of blood and tissue. Hemostasis (arrest of bleeding) was achieved in all 15 of the HIFU-treated arteries. Eleven of the arteries were patent after HIFU treatment, and four arteries were occluded, as determined by Doppler ultrasound. The median HIFU application time to achieve hemostasis was 20s (range 7-55 s) for the patent arteries and 110 s (range 50-134 s) for the occluded arteries. In untreated animals, bleeding had not stopped after 120 s. One of the occluded arteries had reopened by day 14. No immediate or delayed re-bleeding was observed after HIFU treatment. Maximal blood flow velocities were similar in HIFU-treated patent vessels and control vessels. No significant difference in hematocrits was found between HIFU-treated and control groups at different time points after the procedure. Light microscopy observations of the HIFU-treated arteries showed disorganization of adventitia, and coagulation and thinning of the tunica media. The general organization of the adventitia and tunica media recovered to normal appearance within 28 days, with some thinning of the tunica media observed up to day 60. Neointimal hyperplasia was observed on days 14 and 28. The results show that HIFU can produce effective and long-term (up to 60 days) hemostasis of punctured femoral arteries while preserving normal blood flow and vessel wall structure in the majority of vessels.

The objective was to investigate the long‐term efficacy of hemostasis and healing of arteries after HIFU application. The femoral arteries of 22 adult rabbits were surgically exposed. Fifteen arteries were punctured with a needle and treated with HIFU, and 7 arteries were sham‐treated (no puncture or HIFU was applied). The tip of the HIFU applicator was positioned on the bleeding site, and HIFU energy was applied until hemostasis was achieved. The focal intensity was approximately 3,000 W/cm2, at the resonant frequency of 9.6 MHz. Serial ultrasound images, blood and tissue samples were collected immediately and on days 1, 3, 7, 14, 28, and 60 after the treatment. Eleven of the arteries were patent after the treatment, and four arteries were occluded, as confirmed using Doppler imaging. One of the occluded arteries reopened at day 14. HIFU exposure time to achieve hemostasis was 27 ±17 seconds for patent arteries and 101±38 seconds for the occluded arteries. The blood flow velocities were not statistically...

BACKGROUND High-intensity focused ultrasound (HIFU) is effective in producing hemostasis in injuries from organ lacerations and punctures in animals but has not been evaluated in impact injuries. METHOD High-energy blows were applied to 11 heparinized and anesthetized pigs, resulting in solid organ injury. HIFU was applied to injuries via laparotomy. The animals were closed, administered saline, observed under general anesthesia for 3.6 +/- 0.4 hours, reopened, and inspected, and abdominal free fluid was aspirated. RESULTS Organ hemostasis was achieved (mean +/- SD) with 15 +/- 6 minutes of HIFU treatment and 54 +/- 3 minutes of operating time, and 18.8 +/- 13.1 mL/kg of blood was recovered from the abdomen. One animal died from an untreated occult injury to a large vein. HIFU-treated sites were hemostatic at relaparotomy, with 8.6 +/- 6.2 mL/kg abdominal serosanguinous fluid recovered. CONCLUSION HIFU is effective in producing hemostasis by direct treatment of injured parenchyma in blunt trauma.

Objective To determine the efficacy and safety of high-intensity focused ultrasound (HIFU) for the treatment of uterine fibroid tumors in an in situ animal model. Design High-intensity focused ultrasound was applied intraoperatively to uterine fibroid tumors in rats. Setting Department of Bioengineering, and Applied Physics Laboratory, University of Washington, Seattle, Washington. Animal(s) Thirty-five tumors in 27 Eker rats that had spontaneous in situ uterine fibroids were randomly assigned into two groups receiving HIFU (n = 29) or sham (n = 6) treatments. Intervention(s) Animals were anesthetized, and tumors were exposed surgically. The HIFU was applied at 3.5 MHz in 10-second bursts to produce coagulative necrosis lesions (3 mm by 10 mm), spaced 5 mm apart. Sham treatments consisted of exposing the tumors, and handling them similarly to those in the HIFU treatment group, but HIFU was not applied. Main outcome measure(s) Tumor volume was measured every week transabdominally using B-mode ultrasound imaging. Gross examination and histological analysis were performed after euthanasia. Result(s) More than half of the tumors in the HIFU treatment group showed significant tumor volume reduction. The average tumor volume in the sham treatment group increased 40-fold. Gross and histological analysis showed coagulative necrosis of tumor cells in the HIFU treatment group. Conclusion(s) The HIFU may provide an effective and safe method of treating uterine fibroid tumors.

The ability to accurately track and monitor the progress of lesion formation during HIFU (High Intensity Focused Ultrasound) therapy is important for the success of HIFU-based treatment protocols. To aid in the development of algorithms for accurately targeting and monitoring formation of HIFU induced lesions, we have developed a software system to perform RF data acquisition during HIFU therapy using a commercially available clinical ultrasound scanner (ATL HDI 1000, Philips Medical Systems, Bothell, WA). The HDI 1000 scanner functions on a software dominant architecture, permitting straightforward external control of its operation and relatively easy access to quadrature demodulated RF data. A PC running a custom developed program sends control signals to the HIFU module via GPIB and to the HDI 1000 via Telnet, alternately interleaving HIFU exposures and RF frame acquisitions. The system was tested during experiments in which HIFU lesions were created in excised animal tissue. No crosstalk between the HIFU beam and the ultrasound imager was detected, thus demonstrating synchronization. Newly developed acquisition modes allow greater user control in setting the image geometry and scanline density, and enables high frame rate acquisition. This system facilitates rapid development of signal-processing based HIFU therapy monitoring algorithms and their implementation in image-guided thermal therapy systems. In addition, the HDI 1000 system can be easily customized for use with other emerging imaging modalities that require access to the RF data such as elastographic methods and new Doppler-based imaging and tissue characterization techniques.

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.

Previous studies have shown overestimation of kidney stone size in ultrasound images. We explored measuring the stone's acoustic shadow as a predictor of stone size. Forty-five calcium oxalate monohydrate (COM) kidney stones ranging from 1 to 10 mm were imaged in a water bath using a research-based ultrasound system and C5-2 transducer. Stones were imaged at depths of 6, 10, and 14 cm. The widths across the stone image and across acoustic shadow distal to the stone image were measured by the operator and through an automated algorithm. Measuring size across the stone image consistently overestimated: overestimation was 0.9±0.8 mm, 1.5±1.0 mm, 2.0±1.2 mm (manual) and 0.5±1.7 mm, 0.4±1.5 mm, 0.8±1.1 mm (automated) at 6, 10, and 14 cm depths. Measurement of the acoustic shadow width more accurately estimated stone size: 0.0±0.4 mm, 0.0±0.6 mm, and-0.2±0.8 mm (manual) and 0.2±0.5 mm, 0.1±0.8 mm, and 0.1±1.0 mm (automated) at 6, 10, and 14 cm depths. Measurement from the shadow reduced misclassification of passable stones 5 mm from 25% to 7%. The results have implications for directing treatment of asymptomatic stones based on ultrasound images. [Work supported by NIH DK043881, DK092197, and NSBRI through NASA NCC 9-58.]

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/cm2 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/cm2 was needed before a statistically significant portion of the samples showed injury. This is nearly seven times the 2,400-W/cm2 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.

The tortuous geometry of the human vasculature system, and pulsatile nature of blood flow, combine to generate a complex 3D blood flow pattern. Conventional Doppler ultrasound, however, provides velocity data only in one dimension - in the direction of the ultrasound beam. 3D velocity results are extrapolated form this one dimensional data by assuming the blood is parallel to the vessel axis. A two-dimensional vector Doppler system has been developed to improve hemodynamic visualization, and investigate the possible errors introduced by conventional Doppler methods. The results from a study of a normal human femoral bifurcation demonstrate that flow is not always para-axial. When flow is para-axial, conventional Doppler methods work as expected: the calculated velocity is independent of interrogation angle. When flow is non-axial, however, the velocity waveforms and measurements vary greatly with interrogation angle.

Objective: Accurate measurements of abdominal aortic aneurysms (AAAs) are required for surgical planning and monitoring over time. We have examined the feasibility of using a three-dimensional (3-D) ultrasound imaging system to derive quantitative measurements of interest from AAAs. Methods: A normal aorta, a small AAA, and an AAA repaired with an endovascular stent graft were scanned with a 3-D ultrasound imaging system. For each case, a 3-D surface reconstruction was generated from manual outlines of a sequence of two-dimensional ultrasound images, registered in 3-D space with a magnetic tracking system. The surfaces were resampled in planes perpendicular to the vessel center axis to calculate cross-sectional area and maximum diameter as a function of distance along the length of the aorta. Results: Cross-sectional area and maximum diameter were plotted along the length of the aneurysmal aortas from the renal arteries to the aortic bifurcation. The overall maximum diameter was found for both aneurysms. For the small AAA, the distances of the aneurysm from the renal arteries and the bifurcation were measured. For the repaired AAA, the location of the stent graft relative to the renal arteries was measured. Conclusions: 3-D surface reconstructions from ultrasound images show promise for quantitatively characterizing the geometry of AAAs both before surgery and after endovascular repair. (J Vasc Surg 2001;33:700-7.)

Since the invention of the stethoscope, the detection of vibrations and sounds from the body has been a touchstone of diagnosis. However, the method is limited to vibrations whose associated sounds transmit to the skin, with no means to determine the anatomic and physiological source of the vibrations save the cunning of the examiner. Using ultrasound quadrature phase demodulation methods similar to those of ultrasonic color flow imaging, we have developed a system to detect and measure tissue vibrations with amplitude excursions as small as 30 nanometers. The system uses wavelet analysis for sensitive and specific detection, as well as measurement, of short duration vibrations amidst clutter and time-varying, colored noise. Vibration detection rates in ROC curves from simulated data predict > 99.5% detections with = 0.5. Vibrations from in vivo arterial stenoses and punctures have been studied. The results show that vibration durations vary from 10 - 150 ms, frequencies from 100 - 1000 Hz, and amplitudes from 30 nanometers to several microns. By marking the location of vibration sources on ultrasound images, and using color to indicate amplitude, frequency or acoustic intensity, new diagnostic information is provided to aid disorder diagnosis and management.

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.]

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.]

Shock‐wave heating and millisecond boiling in high intensity focused ultrasound fields have been shown to result in mechanical emulsification of ex‐vivo tissue. In this work, the same in situ exposures were applied in vivo in pig liver and in mice bearing 5–7 mm subcutaneous tumors (B16 melanoma) on the hind limb. Lesions were produced using a 2‐MHz annular array in the case of pig liver (shock amplitudes up to 98 MPa) and a 3.4‐MHz single‐element transducer in the case of mouse tumors (shock amplitude of 67 MPa). The parameters of the pulsing protocol (1–500 ms pulse durations and 0.01–0.1 duty factor) were varied depending on the extent of desired thermal effect. All exposures were monitored using B‐mode ultrasound. Mechanical and thermal tissue damage in the lesions was evaluated histologically using H&E and NADH‐diphorase staining. The size and shape of emulsified lesions obtained in‐vivo agreed well with those obtained in ex‐vivo tissue samples using the same exposure parameters. The lesions were successfully produced both in bulk liver tissue at depths of 1–2 cm and in superficial tumors at depths less than 1 mm without damaging the skin. [Work supported by NIH (DK070618, EB007643, and DK007742) and NSBRI through NASA NCC 9‐58.]