Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study
Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the p...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Ultrasonics Sonochemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1350417723001475 |
| _version_ | 1797820753574363136 |
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| author | Jeongmin Heo Jun Hong Park Hyo Jun Kim Kisoo Pahk Ki Joo Pahk |
| author_facet | Jeongmin Heo Jun Hong Park Hyo Jun Kim Kisoo Pahk Ki Joo Pahk |
| author_sort | Jeongmin Heo |
| collection | DOAJ |
| description | Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively. |
| first_indexed | 2024-03-13T09:42:56Z |
| format | Article |
| id | doaj.art-d91e7932df2a47d18dcb5f91f235fd0d |
| institution | Directory Open Access Journal |
| issn | 1350-4177 |
| language | English |
| last_indexed | 2024-03-13T09:42:56Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ultrasonics Sonochemistry |
| spelling | doaj.art-d91e7932df2a47d18dcb5f91f235fd0d2023-05-25T04:24:10ZengElsevierUltrasonics Sonochemistry1350-41772023-06-0196106435Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept studyJeongmin Heo0Jun Hong Park1Hyo Jun Kim2Kisoo Pahk3Ki Joo Pahk4Bionics Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaDepartment of Radiology, Stanford University, Stanford, CA 94305, USALAAS-CNRS, University of Toulouse, CNRS, Toulouse, FranceDepartment of Nuclear Medicine, Korea University College of Medicine, Seoul 02841, Republic of KoreaDepartment of Biomedical Engineering, Kyung Hee University, Yongin 17104, Republic of Korea; Corresponding author.Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively.http://www.sciencedirect.com/science/article/pii/S1350417723001475High intensity focused ultrasoundBoiling histotripsyAcoustic cavitationSonothrombolysisAcoustic netAcoustic trapping |
| spellingShingle | Jeongmin Heo Jun Hong Park Hyo Jun Kim Kisoo Pahk Ki Joo Pahk Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study Ultrasonics Sonochemistry High intensity focused ultrasound Boiling histotripsy Acoustic cavitation Sonothrombolysis Acoustic net Acoustic trapping |
| title | Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study |
| title_full | Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study |
| title_fullStr | Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study |
| title_full_unstemmed | Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study |
| title_short | Sonothrombolysis with an acoustic net-assisted boiling histotripsy: A proof-of-concept study |
| title_sort | sonothrombolysis with an acoustic net assisted boiling histotripsy a proof of concept study |
| topic | High intensity focused ultrasound Boiling histotripsy Acoustic cavitation Sonothrombolysis Acoustic net Acoustic trapping |
| url | http://www.sciencedirect.com/science/article/pii/S1350417723001475 |
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