Barbrina Dunmire

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.

Focused Ultrasonic Propulsion of Kidney Stones: Review and Update of Preclinical Technology

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

In vivo ultrasonic measurement of tissue vibration at a stenosis: a case study

It is known that bruits often can be heard downstream from stenoses. They are thought to be produced by disturbed blood flow and vessel wall vibrations. Our understanding of bruits has been limited, though, to analysis of sounds heard at the level of the skin. For direct measurements from the stenosis site, we developed an ultrasonic pulse-echo multigate system using quadrature phase demodulation. The system simultaneously measures tissue displacements and blood velocities at multiple depths. This paper presents a case study of a severe stenosis in a human infrainguinal vein bypass graft. During systole, nearly sinusoidal vessel wall vibrations were detected. Solid tissue vibration amplitudes measured up to 2 microm, with temporal durations of 100 ms and frequencies of roughly 145 Hz and its harmonics. Cross-axial oscillations were also found in the lumen that correlate with the wall vibrations, suggesting coupling between wall vibration and blood velocity oscillation.

First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones

PURPOSE Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. MATERIALS AND METHODS Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. RESULTS Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. CONCLUSIONS Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure.

Use of the Acoustic Shadow Width to Determine Kidney Stone Size with Ultrasound

PURPOSE Ultrasound is known to overestimate kidney stone size. We explored measuring the acoustic shadow behind kidney stones combined with different ultrasound imaging modalities to improve stone sizing accuracy. MATERIALS AND METHODS A total of 45 calcium oxalate monohydrate stones were imaged in vitro at 3 different depths with the 3 different ultrasound imaging modalities of conventional ray line, spatial compound and harmonic imaging. The width of the stone and the width of the acoustic shadow were measured by 4 operators blinded to the true size of the stone. RESULTS Average error between the measured and true stone width was 1.4 ± 0.8 mm, 1.7 ± 0.9 mm, 0.9 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Average error between the shadow width and true stone width was 0.2 ± 0.7 mm, 0.4 ± 0.7 mm and 0.0 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Sizing error based on the stone width worsened with greater depth (p <0.001) while the sizing error based on the shadow width was independent of depth. CONCLUSIONS Shadow width was a more accurate measure of true stone size than a direct measurement of the stone in the ultrasound image (p <0.0001). The ultrasound imaging modality also impacted the measurement accuracy. All methods performed similarly for shadow size while harmonic imaging was the most accurate stone size modality. Overall 78% of the shadow sizes were accurate to within 1 mm, which is similar to the resolution obtained with clinical computerized tomography.

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.

Brief history of vector Doppler

Since the development of the directional Doppler by McLeod in 1967, methods of acquiring, analyzing, and displaying blood velocity information have been under constant exploration. These efforts are motivated by a variety of interest and objectives including, to: a) simplify clinical examination, examiner training, and study interpretation, b) provide more hemodynamic information, and c) reduce examination variability and improve accuracy. The vector Doppler technique has been proposed as one potential avenue to achieve these objects. Vector Doppler systems are those that determine the true 2D or 3D blood flow velocity by combining multiple independent velocity component measurements. Most instruments can be divided into two broad categories: 1) cross-beam and 2) time-domain. This paper provides a brief synopsis of the progression of vector Doppler techniques, from its onset in 1970 to present, as well as possible avenues for future work. This is not intended to be a comprehensive review of all vector Doppler systems.

Stone-mode ultrasound for determining renal stone size

PURPOSE The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo. MATERIALS AND METHODS Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S-mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency. Stone and shadow width were compared with a recent CT scan and, in 5 subjects with 18 stones, S-mode was compared with a clinical US system. RESULTS Overall, 84% of stones identified on CT were detected on S-mode and 66% of these shadowed. Seventy-three percent of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT. A posterior acoustic shadow was present in 89% of stones over 5 mm versus 53% of stones under 5 mm. S-mode visualized 78% of stones, versus 61% for the clinical system. S-mode stone and shadow measurements differed from CT by 1.6 ± 1.0 mm and 0.8 ± 0.6 mm, respectively, compared with 2.0 ± 1.5 mm and 1.6 ± 1.0 mm for the clinical system. CONCLUSIONS S-mode offers improved visualization and sizing of renal stones. With S-mode, sizing of the stone itself and the posterior acoustic shadow were similarly accurate. Stones that do not shadow are most likely <5 mm and small enough to pass spontaneously.

Characterizing an Agar/Gelatin Phantom for Image Guided Dosing and Feedback Control of High-Intensity Focused Ultrasound

The temperature dependence of an agar/gelatin phantom was evaluated. The purpose was to predict the material property response to high-intensity focused ultrasound (HIFU) for developing ultrasound guided dosing and targeting feedback. Changes in attenuation, sound speed, shear modulus and thermal properties with temperature were examined from 20°C to 70°C for 3 weeks post-manufacture. The attenuation decreased with temperature by a power factor of 0.15. Thermal conductivity, diffusivity and specific heat all increased linearly with temperature for a total change of approximately 16%, 10% and 6%, respectively. Sound speed had a parabolic dependence on temperature similar to that of water. Initially, the shear modulus irreversibly declined with even a slight increase in temperature. Over time, the gel maintained its room temperature shear modulus with moderate heating. A stable phantom was achieved within 2 weeks post-manufacture that possessed quasi-reversible material properties up to nearly 55°C.

Content and Face Validation of a Curriculum for Ultrasonic Propulsion of Calculi in a Human Renal Model

PURPOSE Ultrasonic propulsion to reposition urinary tract calculi requires knowledge about ultrasound image capture, device manipulation, and interpretation. The purpose of this study was to validate a cognitive and technical skills curriculum to teach urologists ultrasonic propulsion to reposition kidney stones in tissue phantoms. MATERIALS AND METHODS Ten board-certified urologists recruited from a single institution underwent a didactic session on renal ultrasound imaging. Subjects completed technical skills modules in tissue phantoms, including kidney imaging, pushing a stone through a translucent maze, and repositioning a lower pole calyceal stone. Objective cognitive and technical performance metrics were recorded. Subjects completed a questionnaire to ascertain face and content validity on a five-point Likert scale. RESULTS Eight urologists (80%) had never attended a previous ultrasound course, and nine (90%) performed renal ultrasounds less frequently than every 6 months. Mean cognitive skills scores improved from 55% to 91% (p<0.0001) on pre- and post-didactic tests. In the kidney phantom, 10 subjects (100%) repositioned the lower pole calyceal stone to at least the lower pole infundibulum, while 9 (90%) successfully repositioned the stone to the renal pelvis. A mean±SD (15.7±13.3) pushes were required to complete the task over an average of 4.6±2.2 minutes. Urologists rated the curriculums effectiveness and realism as a training tool at a mean score of 4.6/5.0 and 4.1/5.0, respectively. CONCLUSIONS The curriculum for ultrasonic propulsion is effective and useful for training urologists with limited ultrasound proficiency in stone repositioning technique. Further studies in animate and human models will be required to assess predictive validity.