Browsing by Author "Kreider, Wayne"

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    Functional and Morphological Changes Associated with Burst Wave Lithotripsy-Treated Pig Kidneys
    (Mary Ann Liebert Inc., 2022-11-28) Connors, Bret A.; Gardner, Tony; Liu, Ziyue; Lingeman, James E.; Kreider, Wayne; Williams , James C.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Purpose: Burst wave lithotripsy (BWL) is a new technique for comminution of urinary stones. This technology is noninvasive, has a low positive pressure magnitude, and is thought to produce minor amounts of renal injury. However, little is known about the functional changes related to BWL treatment. In this study, we sought to determine if clinical BWL exposure produces a functional or morphological change in the kidney. Materials and Methods: Twelve female pigs were prepared for renal clearance assessment and served as either sham time controls (6) or were treated with BWL (6). In the treated group, 1 kidney in each pig was exposed to 18,000 pulses at 10 pulses/s with 20 cycles/pulse. Pressure levels related to each pulse were 12 and −7 MPa. Inulin (glomerular filtration rate, GFR) and para-aminohippuric acid (effective renal plasma flow, eRPF) clearance was measured before and 1 hour after treatment. Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment (% FRV). Results: No visible gross hematuria was observed in any of the collected urine samples of the treated kidneys. BWL exposure also did not lead to a change in GFR or eRPF after treatment, nor did it cause a measurable amount of hemorrhage in the tissue. Conclusion: Using the clinical treatment parameters employed in this study, BWL did not cause an acute change in renal function or a hemorrhagic lesion.
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    Impact of stone type on cavitation in burst wave lithotripsy
    (Acoustical Society of America, 2018-12-26) Hunter, Christopher; Maxwell, Adam D.; Cunitz, Bryan; Dunmire, Barbrina; Sorensen, Mathew D.; Williams, James C.; Randad, Akshay; Bailey, Michael; Kreider, Wayne; Anatomy and Cell Biology, School of Medicine
    Non-invasive kidney stone treatments such as shock wave lithotripsy (SWL) and burst wave lithotripsy (BWL) rely on the delivery of pressure waves through tissue to the stone. In both SWL and BWL, the potential to hinder comminution by exciting cavitation proximal to the stone has been reported. To elucidate how different stones alter prefocal cavitation in BWL, different natural and synthetic stones were treated in vitro using a therapy transducer operating at 350 kHz (peak negative pressure 7 MPa, pulse length 20 cycles, pulse repetition frequency 10 Hz). Stones were held in a confined volume of water designed to mimic the geometry of a kidney calyx, with the water filtered and degassed to maintain conditions for which the cavitation threshold (in the absence of a stone) matches that from in vivo observations. Stone targeting and cavitation monitoring were performed via ultrasound imaging using a diagnostic probe aligned coaxially with the therapy transducer. Quantitative differences in the extent and location of cavitation activity were observed for different stone types—e.g., “softer” stones (natural and synthetic) that disintegrate into “dusty” fragments produced larger prefocal cavitation clouds. Future work will focus on correlation of such cavitation metrics with stone fragmentation.
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    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 Health
    Introduction 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.
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    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 Medicine
    Burst 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.
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    The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact
    (IOP Publishing, 2018-01-09) Simon, Julianna C.; Sapozhnikov, Oleg A.; Kreider, Wayne; Breshock, Michael; Williams, James C.; Bailey, Michael R.; Anatomy and Cell Biology, IU School of Medicine
    The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging. On filming stones that twinkle, consecutive rarefaction pulses from a lithotripter caused some bubbles to reproducibly grow from specific locations on the stone surface, suggesting the presence of pre-existing crevice bubbles. Hyperbaric and hypobaric static pressures were found to modify the twinkling artifact; however, the simple expectation that hyperbaric exposures reduce and hypobaric pressures increase twinkling by shrinking and enlarging bubbles, respectively, largely held for rough-surfaced stones but was inadequate for smoother stones. Twinkling was found to increase or decrease in response to elevated static pressure on smooth stones, perhaps because of the compression of internal voids. These results support the crevice bubble hypothesis of twinkling and suggest the kidney stone crevices that give rise to the twinkling phenomenon may be internal as well as external.
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    Update on clinical trials of kidney stone repositioning and preclinical results of stone breaking with one system
    (Acoustical Society of America, 2018-12-21) Bailey, Michael R.; Wang, Yak-Nam; Kreider, Wayne; Dai, Jessica C.; Cunitz, Bryan W.; Harper, Jonathan D.; Chang, Helena; Sorensen, Mathew D.; Liu, Ziyue; Levy, Oren; Dunmire, Barbrina; Maxwell, Adam D.; Biostatistics, School of Public Health
    Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary collecting system to facilitate natural clearance. Repositioning of stones in humans (maximum 2.5 MPa, and 3-second bursts) and breaking of stones in a porcine model (maximum 50 cycles, 20 Hz repetition, 30 minutes, and 7 MPa peak negative pressure) have been demonstrated using the same 350-kHz probe. Repositioning in humans was conducted during surgery with a ureteroscope in the kidney to film stone movement. Independent video review confirmed stone movements (≥ 3 mm) in 15 of 16 kidneys (94%). No serious or unanticipated adverse events were reported. Experiments of burst wave lithotripsy (BWL) effectiveness on breaking human stones implanted in the porcine bladder and kidney demonstrated fragmentation of 8 of 8 stones on post mortem dissection. A 1-week survival study with the BWL exposures and 10 specific-pathogen-free pigs, showed all findings were within normal limits on clinical pathology, hematology, and urinalysis. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective.