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Choi MJ. et al., 2022: First report on the persist time of the free radical produced by shock wave pulses employed in clinical ESWL.

Choi MJ, Lee JY, Park EJ.
Department of Medicine, College of Medicine, Jeju National University, Jeju, Korea; Interdisciplinary Postgraduate Program in Biomedical Engineering, Jeju National University, Jeju, Korea.
Department of Radiology, Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
Department of Radiology, Seoul National University Hospital, Seoul, Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

Abstract

The shock wave used in extracorporeal shock wave lithotripsy (ESWL) induces strong cavitation and generates a large amount of free radicals (FR). In order to evaluate the harmfulness of FR in the ESWL, information on the incidence and persist time of FR caused by shock waves is required. FR markers can estimate the amount of FR generated, but not how long the FRs will survive. The OH* FR generated by the ESWL shock wave reacts with luminol and emits blue light, which is called sonochemical luminescence (SCL) phenomenon. In this study, FR generation and persist time were measured by recording SCL phenomenon with a sensitive photomultiplier tube (PMT) that responds in nanoseconds. As a result of measurement with the PMT, when the electromagnetic shock wave used in clinical practice was irradiated to the luminol solution, the amount of light emitted per unit time reached its maximum value within a very short time (< ∼600us) and then exponentially decreased for a long time (∼several hundred ms). The measured FR persist time reaches a maximum of 1000 ms. As the output setting of the shock wave generator increases, the minimum or average FR persist time increases, but the maximum value does not show a high correlation with the output setting. The amount of generated FR shows a very high correlation with the shock wave setting, and when the setting is changed from low to high, it increases very sensitively, rapidly and non-linearly. In order to reduce the risk of FR in patient treatment using lithotripsy, the output setting of the shock wave should be minimized, and the interval between the shock wave pulses should be sufficiently larger than the FR persist time. Therefore, it is recommended to avoid increasing the output setting and setting the shock wave irradiation frequency below 1 Hz to shorten the treatment time in clinical practice. For the purpose of formulating these recommendations, additional studies on the generation and persist time of FR depending on the shock wave generation method and set conditions in living tissue or similar environment are required in the future.
Ultrason Sonochem. 2022 Feb;83:105927. doi: 10.1016/j.ultsonch.2022.105927. Epub 2022 Jan 20. PMID: 35081507. FREE ARTICLE

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Comments 2

Hans-Göran Tiselius on Friday, August 05 2022 08:30

The flavour of SWL is that the method is non-invasive and associated with few negative side effects. Accumulated experience has shown that a low frequency of shockwave generation apparently leads both to improved stone disintegration and reduced occurrence of tissue injuries. The latter factor is of particular interest when treating patients with stones in the kidney. There is, however, no global consensus in this regard and high frequency administration of shockwaves commonly is used to keep the treatment time short.

In this perspective it is of interest to learn from this experimental study how shockwaves affect formation of free radicals and for how long period free radicals remain after one or multiple shockwaves.

It is necessary to understand that free radicals are generated by collapse of cavitation bubbles.

In this experimental study the authors used a Korean lithotripter with properties like that of Storz Modulith. The occurrence and disappearance of free radicals was measured in vitro in a solution of luminol by a sonochemical luminescence reaction. The interested reader should carefully read this manuscript, but the essential information is as follows:

1. The peak shockwave pressure occurred 169 s after shockwave induction and was associated with formation of a large number of cavitation bubbles.
2. The shockwave power was varied between settings 1 and 9, where the highest power corresponded to 20 kV.
3. The collapse of generated cavitation bubbles resulted in formation of free radicals (OH* free radicals) measured with the method briefly described.
4. Although most cavitation bubbles collapsed early, others resulted in large bubbles remaining in the solution for up to 600 s.
5. It was noted that free radicals might persist in the solution for up to 1000 ms (1 sec). The recorded interval was 75-1000 ms.
It is of note that the formation and survival of free radicals may be different in biological tissues. That question needs to be further explored but based on the experimental data in this report it seems relevant to treat patients with stones in the kidney with shockwave frequencies not exceeding 60 per minute (1Hz).

Hans-Göran Tiselius

The flavour of SWL is that the method is non-invasive and associated with few negative side effects. Accumulated experience has shown that a low frequency of shockwave generation apparently leads both to improved stone disintegration and reduced occurrence of tissue injuries. The latter factor is of particular interest when treating patients with stones in the kidney. There is, however, no global consensus in this regard and high frequency administration of shockwaves commonly is used to keep the treatment time short. In this perspective it is of interest to learn from this experimental study how shockwaves affect formation of free radicals and for how long period free radicals remain after one or multiple shockwaves. It is necessary to understand that free radicals are generated by collapse of cavitation bubbles. In this experimental study the authors used a Korean lithotripter with properties like that of Storz Modulith. The occurrence and disappearance of free radicals was measured in vitro in a solution of luminol by a sonochemical luminescence reaction. The interested reader should carefully read this manuscript, but the essential information is as follows: 1. The peak shockwave pressure occurred 169 s after shockwave induction and was associated with formation of a large number of cavitation bubbles. 2. The shockwave power was varied between settings 1 and 9, where the highest power corresponded to 20 kV. 3. The collapse of generated cavitation bubbles resulted in formation of free radicals (OH* free radicals) measured with the method briefly described. 4. Although most cavitation bubbles collapsed early, others resulted in large bubbles remaining in the solution for up to 600 s. 5. It was noted that free radicals might persist in the solution for up to 1000 ms (1 sec). The recorded interval was 75-1000 ms. It is of note that the formation and survival of free radicals may be different in biological tissues. That question needs to be further explored but based on the experimental data in this report it seems relevant to treat patients with stones in the kidney with shockwave frequencies not exceeding 60 per minute (1Hz). Hans-Göran Tiselius
Othmar Wess on Friday, August 05 2022 09:30

It is an interesting idea to look at free radicals (FR) generated by shock wave pulses from lithotripters used medical routine. The mechanism of generating FR is supposed to be due to collapsing cavitation bubbles in the focal area of a shock wave lithotripter. The authors investigated the amount of FR in the treatment area (focus) of a Korean electro-magnetic (EM) type lithotripter with a maximum focal pressure of 95 megapascual (MPa). Lithotripter pressure fields generate cavitation bubbles which grow and collapse within ~ 600 microseconds. The violent collapse generates FR which are followed by several photo-chemical reactions under emission of photons. These photons can be detected by a very sensitive photomultiplier (PM) and can be taken as a measure for the numbers of FR generated by the shock wave.
Since FR are supposed to be harmful to biological tissue the question is, which amount of FR is generated during shock wave lithotripsy (SWL) and are there means, to reduce the harmful effect.
The answer of the authors is to reduce the power level of the lithotripter and decrease the shock wave pulse repetition to 1Hz or below. This is the appropriate consequence of their investigations and in accordance with common SWL-treatment strategies.
In view of these findings two questions are raised.
1. What is the amount of cavitation bubbles in biological tissue and is this significant in SWL?
2. What is role of cavitation in SWL in general; is it necessary for fragmentation or may we search for techniques to reduce or eliminate cavitation?

Answer to 1.:
The generation of cavitation bubbles in water depends on several factors such as purity, temperature and gas content. Other body liquids or body tissues have significantly different features such as viscosity and others. The conditions for cavitation in biological tissue are substantially different and supposedly of minor capability to generate cavitation bubbles.
Answer to 2.:
In spite of the harming effect of cavitation (generation of FR, puncture of small blood vessels) cavitation is claimed to be an essential part of the fragmentation process of kidney and other stone in the human body.
According Pei Zhong (1), the fragmentation process takes place in two phases first, to break stones into coarse fragments by mechanism of spallation (Hopkinson´s effect) and second, fragmentation to fine fragments (mm) by collapsing cavitation bubbles. Following this theory, Neisius et al.(2) developed a special acoustic lens to enhance cavitation in the focal spot of a lithotripter.
In so far, cavitation would be harmful but necessary for fine fragmentation and indispensible for the clinical success of lithotripsy procedures.
Our own investigations of stone fragmentation don´t support the importance of cavitation for fine fragmentation. According our experience (not yet published) cavitation plays a minor role in fine fragmentation and is not essential. The theory of momentum transfer (Wess, Mayer,3) can take the task to break coarse fragments produced by spallation, (Hopkinson), into fine fragments.
Eliminating the need of cavitation for successful stone fragmentation opens the way to search for techniques to reduce harming cavitation without impairing fragmentation efficiency.

1. Zhong P., Delale (Ed.): Bubble Dynamics & Shock Waves, SHOCKWAVES 8, pp. 291–338. DOI: 10.1007/978-3-642-34297-4 10 c Springer-Verlag Berlin Heidelberg 201
2. Neisius et al., Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter, March 2014, Proceedings of the National Academy of Sciences 111(13), DOI: 10.1073/pnas.1319203111
3. Wess O.J., Mayer J., Fragmentation of brittle material by shock wave lithotripsy. Momentum transfer and inertia: a novel view on fragmentation mechanisms. Urolithiasis 48, 137–149 (2020). https://doi.org/10.1007/s00240-018-1102-6

It is an interesting idea to look at free radicals (FR) generated by shock wave pulses from lithotripters used medical routine. The mechanism of generating FR is supposed to be due to collapsing cavitation bubbles in the focal area of a shock wave lithotripter. The authors investigated the amount of FR in the treatment area (focus) of a Korean electro-magnetic (EM) type lithotripter with a maximum focal pressure of 95 megapascual (MPa). Lithotripter pressure fields generate cavitation bubbles which grow and collapse within ~ 600 microseconds. The violent collapse generates FR which are followed by several photo-chemical reactions under emission of photons. These photons can be detected by a very sensitive photomultiplier (PM) and can be taken as a measure for the numbers of FR generated by the shock wave. Since FR are supposed to be harmful to biological tissue the question is, which amount of FR is generated during shock wave lithotripsy (SWL) and are there means, to reduce the harmful effect. The answer of the authors is to reduce the power level of the lithotripter and decrease the shock wave pulse repetition to 1Hz or below. This is the appropriate consequence of their investigations and in accordance with common SWL-treatment strategies. In view of these findings two questions are raised. 1. What is the amount of cavitation bubbles in biological tissue and is this significant in SWL? 2. What is role of cavitation in SWL in general; is it necessary for fragmentation or may we search for techniques to reduce or eliminate cavitation? Answer to 1.: The generation of cavitation bubbles in water depends on several factors such as purity, temperature and gas content. Other body liquids or body tissues have significantly different features such as viscosity and others. The conditions for cavitation in biological tissue are substantially different and supposedly of minor capability to generate cavitation bubbles. Answer to 2.: In spite of the harming effect of cavitation (generation of FR, puncture of small blood vessels) cavitation is claimed to be an essential part of the fragmentation process of kidney and other stone in the human body. According Pei Zhong (1), the fragmentation process takes place in two phases first, to break stones into coarse fragments by mechanism of spallation (Hopkinson´s effect) and second, fragmentation to fine fragments (mm) by collapsing cavitation bubbles. Following this theory, Neisius et al.(2) developed a special acoustic lens to enhance cavitation in the focal spot of a lithotripter. In so far, cavitation would be harmful but necessary for fine fragmentation and indispensible for the clinical success of lithotripsy procedures. Our own investigations of stone fragmentation don´t support the importance of cavitation for fine fragmentation. According our experience (not yet published) cavitation plays a minor role in fine fragmentation and is not essential. The theory of momentum transfer (Wess, Mayer,3) can take the task to break coarse fragments produced by spallation, (Hopkinson), into fine fragments. Eliminating the need of cavitation for successful stone fragmentation opens the way to search for techniques to reduce harming cavitation without impairing fragmentation efficiency. 1. Zhong P., Delale (Ed.): Bubble Dynamics & Shock Waves, SHOCKWAVES 8, pp. 291–338. DOI: 10.1007/978-3-642-34297-4 10 c Springer-Verlag Berlin Heidelberg 201 2. Neisius et al., Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter, March 2014, Proceedings of the National Academy of Sciences 111(13), DOI: 10.1073/pnas.1319203111 3. Wess O.J., Mayer J., Fragmentation of brittle material by shock wave lithotripsy. Momentum transfer and inertia: a novel view on fragmentation mechanisms. Urolithiasis 48, 137–149 (2020). https://doi.org/10.1007/s00240-018-1102-6
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