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In vitro comminution of model renal calculi using histotripsy.

ABSTRACT: Shock wave lithotripsy (SWL) suffers from the fact that it can produce residual stone fragments of significant size (>2 mm). Mechanistically, cavitation has been shown to play an important role in the reduction of such fragments to smaller debris. In this study, we assessed the feasibility of using cavitationally-based pulsed ultrasound therapy (histotripsy) to erode kidney stones. Previous work has shown that histotripsy is capable of mechanically fractionating soft tissue into fine, acellular debris. Here, we investigated the potential for translating this technology to renal calculi through the use of a commonly accepted stone model. Stone models were sonicated using a 1-MHz focused transducer, with 5-cycle pulses delivered at a rate of 1 kHz. Pulses having peak negative pressures ranging from 3 to 21 MPa were tested. Results indicate that histotripsy is capable of effectively eroding the stone model, achieving an average stone erosion rate of 26 mg/min at maximum treatment pressure; substantial stone erosion was only observed in the presence of a dense cavitational bubble cloud. Sequential sieving of residual stone fragments indicated that debris produced by histotripsy was smaller than 100 ?m in size, and treatment monitoring showed that both the cavitational bubble cloud and model stone appear as hyperechoic regions on B-mode imaging. These preliminary results indicate that histotripsy shows promise in its use for stone comminution, and an optimized erosion process may provide a potential adjunct to conventional SWL procedures.

SUBMITTER: Duryea AP

PROVIDER: S-EPMC3807937 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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In vitro comminution of model renal calculi using histotripsy.

Duryea Alexander P AP Maxwell Adam D AD Roberts William W WW Xu Zhen Z Hall Timothy L TL Cain Charles A CA

IEEE transactions on ultrasonics, ferroelectrics, and frequency control 20110501 5

Shock wave lithotripsy (SWL) suffers from the fact that it can produce residual stone fragments of significant size (>2 mm). Mechanistically, cavitation has been shown to play an important role in the reduction of such fragments to smaller debris. In this study, we assessed the feasibility of using cavitationally-based pulsed ultrasound therapy (histotripsy) to erode kidney stones. Previous work has shown that histotripsy is capable of mechanically fractionating soft tissue into fine, acellular ...[more]

PMID: 21622053

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Project description:Stone comminution in shock wave lithotripsy (SWL) has been documented to result from mechanical stresses conferred directly to the stone, as well as the activity of cavitational microbubbles. Studies have demonstrated that the presence of this cavitation activity is crucial for stone subdivision; however, its exact role in the comminution process remains somewhat weakly defined, in part because it is difficult to isolate the cavitational component from the shock waves themselves. In this study, we further explored the importance of cavitation in SWL stone comminution through the use of histotripsy ultrasound therapy. Histotripsy was used to target model stones designed to mimic the mid-range tensile fracture strength of naturally occurring cystine calculi with controlled cavitation at strategic time points in the SWL comminution process. All SWL was applied at a peak positive pressure (p+) of 34 MPa and a peak negative pressure (p-) of 8 MPa; a shock rate of 1 Hz was used. Histotripsy pulses had a p- of 33 MPa and were applied at a pulse repetition frequency (PRF) of 100 Hz. Ten model stones were sonicated in vitro with each of five different treatment schemes: A) 10 min of SWL (600 shocks) with 0.7 s of histotripsy interleaved between successive shocks (totaling to 42 000 pulses); B) 10 min of SWL (600 shocks) followed by 10 min of histotripsy applied in 0.7-s bursts (1 burst per second, totaling to 42 000 pulses); C) 10 min of histotripsy applied in 0.7-s bursts (42 000 pulses) followed by 10 min of SWL (600 shocks); D) 10 min of SWL only (600 shocks); E) 10 min of histotripsy only, applied in 0.7-s bursts (42 000 pulses). Following sonication, debris was collected and sieved through 8-, 6-, 4-, and 2-mm filters. It was found that scheme D, SWL only, generated a broad range of fragment sizes, with an average of 14.9 ± 24.1% of the original stone mass remaining > 8 mm. Scheme E, histotripsy only, eroded the surface of stones to tiny particulate debris that was small enough to pass through the finest filter used in this study (<2 mm), leaving behind a single primary stone piece (>8 mm) with mass 85.1 ± 1.6% of the original following truncated sonication. The combination of SWL and histotripsy (schemes A, B, and C) resulted in a shift in the size distribution toward smaller fragments and complete elimination of debris > 8 mm. When histotripsy-controlled cavitation was applied following SWL (B), the increase in exposed stone surface area afforded by shock wave stone subdivision led to enhanced cavitation erosion. When histotripsy-controlled cavitation was applied before SWL (C), it is likely that stone surface defects induced by cavitation erosion provided sites for crack nucleation and accelerated shock wave stone subdivision. Both of these effects are likely at play in the interleaved therapy (A), although shielding of shock waves by remnant histotripsy microbubble nuclei may have limited the efficacy of this scheme. Nevertheless, these results demonstrate the important role played by cavitation in the stone comminution process, and suggest that the application of controlled cavitation at strategic time points can provide an adjunct to traditional SWL therapy.

Project description:BackgroundMicro computed tomography (micro CT) has been shown to provide exceptionally high quality imaging of the fine structural detail within urinary calculi. We tested the idea that micro CT might also be used to identify the mineral composition of urinary stones non-destructively.MethodsMicro CT x-ray attenuation values were measured for mineral that was positively identified by infrared microspectroscopy (FT-IR). To do this, human urinary stones were sectioned with a diamond wire saw. The cut surface was explored by FT-IR and regions of pure mineral were evaluated by micro CT to correlate x-ray attenuation values with mineral content. Additionally, intact stones were imaged with micro CT to visualize internal morphology and map the distribution of specific mineral components in 3-D.ResultsMicro CT images taken just beneath the cut surface of urinary stones showed excellent resolution of structural detail that could be correlated with structure visible in the optical image mode of FT-IR. Regions of pure mineral were not difficult to find by FT-IR for most stones and such regions could be localized on micro CT images of the cut surface. This was not true, however, for two brushite stones tested; in these, brushite was closely intermixed with calcium oxalate. Micro CT x-ray attenuation values were collected for six minerals that could be found in regions that appeared to be pure, including uric acid (3515 - 4995 micro CT attenuation units, AU), struvite (7242 - 7969 AU), cystine (8619 - 9921 AU), calcium oxalate dihydrate (13815 - 15797 AU), calcium oxalate monohydrate (16297 - 18449 AU), and hydroxyapatite (21144 - 23121 AU). These AU values did not overlap. Analysis of intact stones showed excellent resolution of structural detail and could discriminate multiple mineral types within heterogeneous stones.ConclusionsMicro CT gives excellent structural detail of urinary stones, and these results demonstrate the feasibility of identifying and localizing most of the common mineral types found in urinary calculi using laboratory CT.

Dataset Information

In vitro comminution of model renal calculi using histotripsy.

Publications

In vitro comminution of model renal calculi using histotripsy.

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