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.

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.

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.

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.

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.

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.

Focused ultrasound to expel calculi from the kidney.

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

Pretreatment with low-energy shock waves induces renal vasoconstriction during standard shock wave lithotripsy (SWL): a treatment protocol known to reduce SWL-induced renal injury.

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 (approximately 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.

Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation.

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 CO2 measurements. (

Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization.

BACKGROUND: In order to establish a consistent method for brachial artery reactivity assessment, we analyzed commonly used approaches to the test and their effects on the magnitude and time-course of flow mediated dilation (FMD), and on test variability and repeatability. As a popular and noninvasive assessment of endothelial function, several different approaches have been employed to measure brachial artery reactivity with B-mode ultrasound. Despite some efforts, there remains a lack of defined normal values and large variability in measurement technique. METHODS: Twenty-six healthy volunteers underwent repeated brachial artery diameter measurements by B-mode ultrasound. Following baseline diameter recordings we assessed endothelium-dependent flow mediated dilation by inflating a blood pressure cuff either on the upper arm (proximal) or on the forearm (distal). RESULTS: Thirty-seven measures were performed using proximal occlusion and 25 with distal occlusion. Following proximal occlusion relative to distal occlusion, FMD was larger (16.2 +/- 1.2% vs. 7.3 +/- 0.9%, p < 0.0001) and elongated (107.2 s vs. 67.8 s, p = 0.0001). Measurement of the test repeatability showed that differences between the repeated measures were greater on average when the measurements were done using the proximal method as compared to the distal method (2.4%; 95% CI 0.5-4.3; p = 0.013). CONCLUSION: These findings suggest that forearm compression holds statistical advantages over upper arm compression. Added to documented physiological and practical reasons, we propose that future studies should use forearm compression in the assessment of endothelial function.

Functional tissue pulsatility imaging of the brain during visual stimulation.

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.

Ultrasonic interrogation of tissue vibrations in arterial and organ injuries: preliminary in vivo results.

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.

Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study.

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.

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.

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.

In vivo feasibility of image-guided transvaginal focused ultrasound therapy for the treatment of intracavitary fibroids.

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.

Treatment of uterine fibroid tumors in an in situ rat model using high-intensity focused ultrasound.

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.

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.

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.