Acoustic Bubble Removal to Enhance SWL Efficacy at High Shock Rate: An In Vitro Study

Rate-dependent efficacy has been extensively documented in shock wave lithotripsy (SWL) stone comminution, with shock waves (SWs) delivered at a low rate producing more efficient fragmentation in comparison to those delivered at high rates. Cavitation is postulated to be the primary source underlying this rate phenomenon. Residual bubble nuclei that persist along the axis of SW propagation can drastically attenuate the waveform's negative phase, decreasing the energy which is ultimately delivered to the stone and compromising comminution. The effect is more pronounced at high rates, as residual nuclei have less time to passively dissolve between successive shocks. In this study, we investigate a means of actively removing such nuclei from the field using a low-amplitude acoustic pulse designed to stimulate their aggregation and subsequent coalescence. To test the efficacy of this bubble removal scheme, model kidney stones were treated in vitro using a research electrohydraulic lithotripter. SWL was applied at rates of 120, 60, or 30?SW/min with or without the incorporation of bubble removal pulses. Optical images displaying the extent of cavitation in the vicinity of the stone were also collected for each treatment. Results show that bubble removal pulses drastically enhance the efficacy of stone comminution at the higher rates tested (120 and 60?SW/min), while optical images show a corresponding reduction in bubble excitation along the SW axis when bubble removal pulses are incorporated. At the lower rate of 30?SW/min, no difference in stone comminution or bubble excitation was detected with the addition of bubble removal pulses, suggesting that remnant nuclei had sufficient time for more complete dissolution. These results corroborate previous work regarding the role of cavitation in rate-dependent SWL efficacy, and suggest that the effect can be mitigated via appropriate control of the cavitation environment surrounding the stone.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140375/1/end.2013.0313.pd

Enhanced High-Rate Shockwave Lithotripsy Stone Comminution in an In Vivo Porcine Model Using Acoustic Bubble Coalescence

Cavitation plays a significant role in the efficacy of stone comminution during shockwave lithotripsy (SWL). Although cavitation on the surface of urinary stones helps to improve fragmentation, cavitation bubbles along the propagation path may shield or block subsequent shockwaves (SWs) and potentially induce collateral tissue damage. Previous in vitro work has shown that applying low-amplitude acoustic waves after each SW can force bubbles to consolidate and enhance SWL efficacy. In this study, the feasibility of applying acoustic bubble coalescence (ABC) in vivo was tested. Model stones were percutaneously implanted and treated with 2500 lithotripsy SWs at 120 SW/minute with or without ABC. Comparing the results of stone comminution, a significant improvement was observed in the stone fragmentation process when ABC was used. Without ABC, only 25% of the mass of the stone was fragmented to particles <2?mm in size. With ABC, 75% of the mass was fragmented to particles <2?mm in size. These results suggest that ABC can reduce the shielding effect of residual bubble nuclei, resulting in a more efficient SWL treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140087/1/end.2016.0407.pd

Histotripsy Homogenization of the Prostate: Thresholds for Cavitation Damage of Periprostatic Structures

Background and Purpose: Histotripsy is a noninvasive, pulsed ultrasound technology that produces mechanically homogenized tissue within targeted volumes. Previous work has demonstrated prostatic tissue debulking in a canine model. The aim was to establish safety thresholds by evaluating histologic changes of urinary sphincter, neurovascular bundle (NVB), and rectum after targeted histotripsy treatment of these critical structures. Materials and Methods: Rectum, urinary sphincter, and NVB in five anesthetized canines were targeted for histotripsy treatment (50 total points). Locations received 1k, 10k, or 100k acoustic pulses (4 microsecond, 1-MHz) at a repetition frequency of 500-Hz. Canine subjects were euthanized immediately (2), survived 3 days (1), or 2 weeks (3) after treatment. Prostates, periprostatic tissue, and rectum were harvested and processed for histology. Results: The sphincter was structurally intact with minimal muscle fiber disruption even after 100k pulses (n=10). Undamaged nerves, arteries, and veins of the NVB were seen despite mechanical homogenization of surrounding loose connective tissue (n=19). The rectum, however, exhibited dose-dependent damage (n=20). 1k pulses yielded mild submucosal hemorrhage. 10k pulses resulted in moderate collagen disruption and focal mucosal homogenization. 100k pulses produced damage to the mucosa and muscularis propria with extensive hemorrhage and collagen disruption. One canine treated with 100k pulses needed early euthanasia (day 3) because of complications from a urine leak. Conclusions: Histotripsy histologic tissue effect varied based on targeted structure with substantial structural preservation of NVB and sphincter. Rectal subclinical damage was apparent after 1k pulses and increased in extent and severity with escalating doses. Future work will include assessment of functional outcomes and refinement of these initial safety thresholds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90446/1/end-2E2010-2E0648.pd

Histotripsy Erosion of Model Urinary Calculi

Background and Purpose: Histotripsy is a pulsed focused ultrasound technology in which initiation and control of acoustic cavitation allow for precise mechanical fractionation of tissues. The present study examines the feasibility of using histotripsy for erosion of urinary calculi. Materials and Methods: Histotripsy treatment was delivered from a 750-kHz transducer in the form of 5-cycle acoustic pulses at a 1-kHz pulse repetition frequency. Model stones were sonicated for 5 minutes at peak negative pressures (p-) of 10, 15, 19, 22, and 24-MPa. Resulting fragment sizes and comminution rates were assessed and compared with those achieved with a piezoelectric lithotripter (Wolf Piezolith 3000) operated at 2-Hz pulse repetition frequency and power level 17 (p- = 14-MPa). Results: Histotripsy eroded the surface of stones producing fine (<100--m) particulate debris in contrast to the progressive and incomplete subdivision of stones achieved with piezoelectric lithotripsy. The histotripsy erosion rate increased with increasing peak negative pressure from 10 to 19-MPa and then saturated, yielding an average rate of 87.9+/-12.8 mg/min at maximum treatment intensity. Piezoelectric lithotripsy achieved an average treatment rate of 110.7+/-27.4 mg/min. Conclusions: Histotripsy comminution of urinary calculi is a surface erosion phenomenon that is mechanistically distinct from conventional shockwave lithotripsy (SWL), producing only fine debris as opposed to coarse fragments. These characteristics suggest that histotripsy offers a potential adjunct to traditional SWL procedures, and synergistic interplay of the two modalities may lead to possible increases in both rate and degree of stone fragmentation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90440/1/end-2E2010-2E0407.pd

Histotripsy of Rabbit Renal Tissue in Vivo: Temporal Histologic Trends

Background and Purpose: Histotripsy is defined as noninvasive, nonthermal, mechanical (cavitational) tissue ablation. We previously demonstrated the predictable acute tissue effects of histotripsy in rabbit kidney and other tissues. We sought to characterize the appearance and natural history of renal tissue after histotripsy. Materials and Methods: Following Institutional Animal Care Committee approval, the left kidneys of 29 rabbits were treated with 60,000 750-kHz, 15-cycle bursts of ultrasound energy from an 18-element phased-array transducer at a 1-kHz pulse-repetition frequency. The treated kidneys were harvested at 0, 1, 2, 7, 21, or 60 days; fixed in Formalin; then prepared for microscopic analysis with hematoxylin and eosin and trichrome stains. Results: For kidneys harvested acutely (day 0), a contiguous area of finely disrupted tissue was observed containing no recognizable cells or cellular components. Along the boundary of architectural disruption, a border several tubules wide contained cells that were not visibly disrupted but appeared damaged (pyknotic nuclei). At subsequent time intervals, an inflammatory response developed in association with a steadily decreasing area of cellular and architectural disruption. By day 60, only a small fibrous scar persisted adjacent to a wedge of tubular dilation and fibrosis underlying a surface-contour defect. Conclusions: Histotripsy produces mechanical fractionation of cellular and architectural structures. The resultant acellular material appears to be readily reabsorbed within 60 days in the rabbit. This may prove to be a significant advantage for imaging assessment of residual tumor after ablation of renal malignancy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63123/1/end.2007.9915.pd

Desorption by ultrasound: Phenol on activated carbon and polymeric resin

An experimental feasibility study of using ultrasound to accomplish the dificult desorption of phenol from activated carbon and polymeric resin adsorbents is discussed. The desorption rates of activated carbon were found to significantly increase by ultrasound at 40 kHz and 1.44 MHz. Attrition of the activated carbon due to cavitation could be prevented by operating at a higher frequency and with an intensity below the threshold of the pulverization of carbon. According to the structural stability study of Amberlite XAD-4 and Dowex Optipore L-493 resins to withstand the abrasive cavitational effects of ultrasound at 40 kHz, the Dowex Optipore resin was stable under experimental conditions and phenol desorption rates were enhanced significantly with sonication. The ultrasonic desorption rates were favored by decreased temperature, aerated liquid medium, and increased ultrasound intensity. The desorption rates obtained without ultrasound appeared to be limited by pore diffusion, whereas those obtained in the presence of ultrasound were limited by surface reaction. The rate enhancement was due to an increase in diffusive transport within the pores caused by acoustic vortex microstreaming. The activation energy for desorption decreased with an increase in ultrasonic power density, thus making the ultrasound weaken the adsorption bond.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34234/1/690440706_ftp.pd

Cavitation clouds created by shock scattering from bubbles during histotripsy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98656/1/JAS001888.pd

Revisiting the spectrum of bladder health: Relationships between lower urinary tract symptoms and multiple measures of well-being

Background: Little research to date has investigated the spectrum of bladder health in women, including both bladder function and well-being. Therefore, we expanded our previous baseline analysis of bladder health in the Boston Area Community Health (BACH) Survey to incorporate several additional measures of bladder-related well-being collected at the 5-year follow-up interview, including one developed specifically for women. Methods: At follow-up, participants reported their frequency of 15 lower urinary tract symptoms (LUTS), degree of life impact from and thought related to urinary symptoms or pelvic/bladder pain/discomfort, and perception of their bladder condition. Prevalence ratios were calculated by generalized linear models with robust variance estimation, adjusting for LUTS risk factors and individual LUTS. The BACH Survey was approved by the New England Research Institutes Institutional Review Board and all participants provided written informed consent. Results: Generally similar findings were observed in the 5-year cross-sectional analysis as at baseline, irrespective of how we categorized LUTS or measured bladder-related well-being. Approximately one in five women (16.2%-18.0% of 2527 eligible women) reported no LUTS and no diminished bladder-related well-being, the majority (55.8%-65.7%) reported some LUTS and/or diminished well-being, and a further one in five (16.9%-26.6%) reported the maximum frequency, number, or degree of LUTS and/or diminished well-being. Measures of storage function (urinating again after &lt;2 hours, perceived frequency, nocturia, incontinence, and urgency) and pain were independently associated with bladder-related well-being. Conclusions: Our similar distribution of bladder health and consistent associations between LUTS and bladder-related well-being across multiple measures of well-being, including a female-specific measure, lend confidence to the concept of a bladder health spectrum and reinforce the bothersome nature of storage dysfunction and pain

The spectrum of bladder health: The relationship between lower urinary tract symptoms and interference with activities

Background: Little research to date has focused on lower urinary tract symptom (LUTS) prevention and bladder health promotion in women. To address this gap, the Prevention of LUTS Research Consortium developed the following working bladder health definition: "A complete state of physical, mental, and social well-being related to bladder function [that] permits daily activities [and] allows optimal well-being." To begin to inform and quantify this definition, we used data from the Boston Area Community Health Survey, drawing upon its rare collection of information on LUTS and LUTS-specific interference with activities. Methods: At baseline, participants reported their frequency of 15 LUTS and interference with 7 activities. Prevalence ratios (PRs) were calculated by generalized linear models with robust variance estimation, adjusting for LUTS risk factors and individual LUTS. Results: Of the 3169 eligible participants, 17.5% reported no LUTS or interference, whereas the remaining 82.5% reported some frequency of LUTS/interference: 15.1% rarely; 21.7% a few times; 22.6% fairly often/usually; and 22.9% almost always. LUTS independently associated with interference were urgency incontinence, any incontinence, urgency, nocturia, perceived frequency, and urinating again after &lt;2 hours (PRs = 1.2-1.5, all p &lt; 0.05). Conclusions: Our findings suggest that bladder health exists on a continuum, with approximately one in five women considered to have optimal bladder health (no LUTS/interference), the majority to have intermediate health (LUTS/interference rarely to usually), and a further one in five to have worse or poor health (LUTS/interference almost always). These findings underscore the need for LUTS prevention and bladder health promotion