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Duryea AP et al, 2013. Controlled cavitation to augment SWL stone comminution: mechanistic insights in vitro

Duryea AP, Roberts WW, Cain CA, Hall TL
Biomedical Engineering Department, University of Michigan, Ann Arbor, USA


Abstract

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, totalling 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 (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.

IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Feb;60(2):301-9. doi: 10.1109/TUFFC.2013.2566
PMID:23357904 [PubMed - in process]

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Hans-Göran Tiselius on Monday, 08 April 2013 07:21

This article is a highly interesting report of an experimental set up aimed to study the role of cavitation in SWL stone disintegration. Briefly the authors used an electro-hydraulic shock wave source with an ellipsoidal reflector in combination with histotripsy (HT)-controlled cavitation. The latter technique was accomplished by eleven transducers that were mounted on the reflector and directed towards the same focal point as that for the electro-hydraulic shock wave.

Significant differences in stone comminution were recorded when SWL and HT were used alone or in various combinations. The approximate percentages of fragments less than 2 mm in the experiments are summarized below.

/images/blog/DuryeaAP2013klein.jpg

The HT that resulted in a P- of 33MPa was administered as a series of pulses at a frequency of 1 Hz either between shock waves (n=70) or in separate series (n=600) before or after a series of 600 shock waves.

The results are indeed very promising from a clinical point of view, inasmuch as the combination of SWL followed by a series of HT pulses was able to improve disintegration in a pronounced way. It is tempting to speculate that significantly improved disintegration might be possible when series of shock waves are intervened by repeated series of HT-pulses. In contrast HT-pulses interleaved between two successive shock waves (1Hz) did not result in the same efficient disintegration as that seen when SWL was followed by HT, although the size distribution apparently was better than with SWL alone. Pre-treatment with HT might result in a more favourable size distribution of fragments than that observed when HT series were interleaved between shock wave pulses.

It will be extremely interesting to follow the further experience with this technology in order to see how the combined application of shock waves and HT can influence the outcome of non-invasive stone removal in a clinical setting.

Hans-Göran Tiselius

This article is a highly interesting report of an experimental set up aimed to study the role of cavitation in SWL stone disintegration. Briefly the authors used an electro-hydraulic shock wave source with an ellipsoidal reflector in combination with histotripsy (HT)-controlled cavitation. The latter technique was accomplished by eleven transducers that were mounted on the reflector and directed towards the same focal point as that for the electro-hydraulic shock wave. Significant differences in stone comminution were recorded when SWL and HT were used alone or in various combinations. The approximate percentages of fragments less than 2 mm in the experiments are summarized below. [img]/images/blog/DuryeaAP2013klein.jpg[/img] The HT that resulted in a P- of 33MPa was administered as a series of pulses at a frequency of 1 Hz either between shock waves (n=70) or in separate series (n=600) before or after a series of 600 shock waves. The results are indeed very promising from a clinical point of view, inasmuch as the combination of SWL followed by a series of HT pulses was able to improve disintegration in a pronounced way. It is tempting to speculate that significantly improved disintegration might be possible when series of shock waves are intervened by repeated series of HT-pulses. In contrast HT-pulses interleaved between two successive shock waves (1Hz) did not result in the same efficient disintegration as that seen when SWL was followed by HT, although the size distribution apparently was better than with SWL alone. Pre-treatment with HT might result in a more favourable size distribution of fragments than that observed when HT series were interleaved between shock wave pulses. It will be extremely interesting to follow the further experience with this technology in order to see how the combined application of shock waves and HT can influence the outcome of non-invasive stone removal in a clinical setting. Hans-Göran Tiselius
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