Browsing by Author "Thiel, Jeff"
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Item First In-Human Burst Wave Lithotripsy for Kidney Stone Comminution: Initial Two Case Studies(Mary Ann Liebert, Inc., 2021) Harper, Jonathan D.; Metzler, Ian; Hall, Michael Kennedy; Chen, Tony T.; Maxwell, Adam D.; Cunitz, Bryan W.; Dunmire, Barbrina; Thiel, Jeff; Williams, James C., Jr.; Bailey, Michael R.; Sorensen, Mathew D.; Anatomy, Cell Biology and Physiology, School of MedicinePurpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to <2 mm fragments. Participant B tolerated the procedure without pain from BWL, required no anesthesia, and passed the stone on day 15. Conclusions: The first-in-human tests of BWL pulses were successful in that a renal stone was comminuted in <10 minutes, and BWL was also tolerated by an awake subject for a distal ureteral stone.Item First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones(American Urological Association Education and Research, Inc., 2022) Hall, M. Kennedy; Thiel, Jeff; Dunmire, Barbrina; Samson, Patrick C.; Kessler, Ross; Sunaryo, Peter; Sweet, Robert M.; Metzler, Ian S.; Chang, Helena C.; Gunn, Martin; Dighe, Manjiri; Anderson, Layla; Popchoi, Christina; Managuli, Ravi; Cunitz, Bryan W.; Burke, Barbara H.; Ding, Lisa; Gutierrez, Brianna; Liu, Ziyue; Sorensen, Mathew D.; Wessells, Hunter; Bailey, Michael R.; Harper, Jonathan D.; Biostatistics and Health Data Science, School of MedicinePurpose: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. Materials and methods: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. Results: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. Conclusions: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.Item First-in-human clinical trial of ultrasonic propulsion of kidney stones(First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones, 2016-04) Harper, Jonathan D.; Cunitz, Bryan W.; Dunmire, Barbrina; Lee, Franklin C.; Sorensen, Mathew D.; Hsi, Ryan S.; Thiel, Jeff; Wessells, Hunter; Lingeman, James E.; Bailey, Michael R.; Urology, School of MedicinePURPOSE: 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.Item Fragmentation of Stones by Burst Wave Lithotripsy in the First 19 Humans(Wolters Kluwer, 2022) Harper, Jonathan D.; Lingeman, James E.; Sweet, Robert M.; Metzler, Ian S.; Sunaryo, Peter L.; Williams, James C., Jr.; Maxwell, Adam D.; Thiel, Jeff; Cunitz, Bryan W.; Dunmire, Barbrina; Bailey, Michael R.; Sorensen, Mathew D.; Urology, School of MedicinePurpose: We report stone comminution in the first 19 human subjects by burst wave lithotripsy (BWL), which is the transcutaneous application of focused, cyclic ultrasound pulses. Materials and methods: This was a prospective multi-institutional feasibility study recruiting subjects undergoing clinical ureteroscopy (URS) for at least 1 stone ≤12 mm as measured on computerized tomography. During the planned URS, either before or after ureteroscope insertion, BWL was administered with a handheld transducer, and any stone fragmentation and tissue injury were observed. Up to 3 stones per subject were targeted, each for a maximum of 10 minutes. The primary effectiveness outcome was the volume percent comminution of the stone into fragments ≤2 mm. The primary safety outcome was the independent, blinded visual scoring of tissue injury from the URS video. Results: Overall, median stone comminution was 90% (IQR 20, 100) of stone volume with 21 of 23 (91%) stones fragmented. Complete fragmentation (all fragments ≤2 mm) within 10 minutes of BWL occurred in 9 of 23 stones (39%). Of the 6 least comminuted stones, likely causative factors for decreased effectiveness included stones that were larger than the BWL beamwidth, smaller than the BWL wavelength or the introduction of air bubbles from the ureteroscope. Mild reddening of the papilla and hematuria emanating from the papilla were observed ureteroscopically. Conclusions: The first study of BWL in human subjects resulted in a median of 90% comminution of the total stone volume into fragments ≤2 mm within 10 minutes of BWL exposure with only mild tissue injury.Item Improving burst wave lithotripsy effectiveness for small stones and fragments by increasing frequency: theoretical modeling and ex vivo study(Liebert, 2022) Bailey, Michael R.; Maxwell, Adam D.; Cao, Shunxiang; Ramesh, Shivani; Liu, Ziyue; Williams, James Caldwell, Jr.; Thiel, Jeff; Dunmire, Barbrina; Colonius, Tim; Kuznetsova, Ekaterina; Kreider, Wayne; Sorensen, Mathew D.; Lingeman, James E.; Sapozhnikov, Oleg A.; Biostatistics, School of Public HealthIntroduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying BWL frequency may more effectively fragment stones to dust. Methods: A linear elastic model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone’s size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1-5 mm) were treated at 1) 390 kHz, 2) 830 kHz, and 3) 390 kHz followed by 830 kHz. The mass of fragments greater than 1 and 2 mm was measured over 10 minutes of exposure. Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at higher frequency, but not lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p=0.0003), whereas larger stones broke equally well to sub-millimeter dust at high, low, or mixed frequency. Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.Item In Vitro Evaluation of Urinary Stone Comminution with a Clinical Burst Wave Lithotripsy System(Mary Ann Liebert, Inc., 2020-11) Ramesh, Shivani; Chen, Tony T.; Maxwell, Adam D.; Cunitz, Bryan W.; Dunmire, Barbrina; Thiel, Jeff; Williams, James C., Jr.; Gardner, Anthony; Liu, Ziyue; Metzler, Ian; Harper, Jonathan D.; Sorensen, Mathew D.; Bailey, Michael R.; Anatomy, Cell Biology and Physiology, School of MedicineObjective: Our goals were to validate stone comminution with an investigational burst wave lithotripsy (BWL) system in patient-relevant conditions and to evaluate the use of ultrasonic propulsion to move a stone or fragments to aid in observing the treatment endpoint. Materials and Methods: The Propulse-1 system, used in clinical trials of ultrasonic propulsion and upgraded for BWL trials, was used to fragment 46 human stones (5-7 mm) in either a 15-mm or 4-mm diameter calix phantom in water at either 50% or 75% dissolved oxygen level. Stones were paired by size and composition, and exposed to 20-cycle, 390-kHz bursts at 6-MPa peak negative pressure (PNP) and 13-Hz pulse repetition frequency (PRF) or 7-MPa PNP and 6.5-Hz PRF. Stones were exposed in 5-minute increments and sieved, with fragments >2 mm weighed and returned for additional treatment. Effectiveness for pairs of conditions was compared statistically within a framework of survival data analysis for interval censored data. Three reviewers blinded to the experimental conditions scored ultrasound imaging videos for degree of fragmentation based on stone response to ultrasonic propulsion. Results: Overall, 89% (41/46) and 70% (32/46) of human stones were fully comminuted within 30 and 10 minutes, respectively. Fragments remained after 30 minutes in 4% (1/28) of calcium oxalate monohydrate stones and 40% (4/10) of brushite stones. There were no statistically significant differences in comminution time between the two output settings (p = 0.44), the two dissolved oxygen levels (p = 0.65), or the two calyx diameters (p = 0.58). Inter-rater correlation on endpoint detection was substantial (Fleiss' kappa = 0.638, p < 0.0001), with individual reviewer sensitivities of 95%, 86%, and 100%. Conclusions: Eighty-nine percent of human stones were comminuted with a clinical BWL system within 30 minutes under conditions intended to reflect conditions in vivo. The results demonstrate the advantage of using ultrasonic propulsion to disperse fragments when making a visual determination of breakage endpoint from the real-time ultrasound image.Item An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model(Acoustical Society of America, 2019-02-06) Wang, Yak-Nam; Kreider, Wayne; Hunter, Chris; Cunitz, Bryan W.; Thiel, Jeff; Starr, Frank; Dai, Jessica C.; Nazari, Yasser; Lee, Donghoon; Williams, James C.; Bailey, Micheal R.; Maxwell, Adam D.; Anatomy and Cell Biology, School of MedicineBurst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6–7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.Item Quantification of Renal Stone Contrast with Ultrasound in Human Subjects(Liebert, 2017) Cunitz, Bryan W.; Harper, Jonathan D.; Sorensen, Mathew D.; Haider, Yasser A.; Thiel, Jeff; May, Philip C.; Liu, Ziyue; Bailey, Michael R.; Dunmire, Barbrina; Bruce, Matthew; Department of Biostatistics, School of Public HealthPurpose: Greater visual contrast between calculi and tissue would improve ultrasound (US) imaging of urolithiasis and potentially expand clinical use. The color Doppler twinkling artifact has been suggested to provide enhanced contrast of stones compared with brightness mode (B-mode) imaging, but results are variable. This work provides the first quantitative measure of stone contrast in humans for B-mode and color Doppler mode, forming the basis to improve US for the detection of stones. Materials and Methods: Using a research ultrasound system, B-mode imaging was tuned for detecting stones by applying a single transmit angle and reduced signal compression. Stone twinkling with color Doppler was tuned by using low-frequency transmit pulses, longer pulse durations, and a high-pulse repetition frequency. Data were captured from 32 subjects, with 297 B-mode and Doppler images analyzed from 21 subjects exhibiting twinkling signals. The signal to clutter ratio (i.e., stone to background tissue) (SCR) was used to compare the contrast of a stone on B-mode with color Doppler, and the contrast between stone twinkling and blood-flow signals within the kidney. Results: The stone was the brightest object in only 54% of B-mode images and 100% of Doppler images containing stone twinkling. On average, stones were isoechoic with the tissue clutter on B-mode (SCR = 0 dB). Stone twinkling averaged 37 times greater contrast than B-mode (16 dB, p < 0.0001) and 3.5 times greater contrast than blood-flow signals (5.5 dB, p = 0.088). Conclusions: This study provides the first quantitative measure of US stone to tissue contrast in humans. Stone twinkling contrast is significantly greater than the contrast of a stone on B-mode. There was also a trend of stone twinkling signals having greater contrast than blood-flow signals in the kidney. Dedicated optimization of B-mode and color Doppler stone imaging could improve US detection of stones.