Microbubble dynamics in brain microvessels.
Focused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential,...
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| Format: | Article |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0310425 |
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| author | James H Bezer Paul Prentice William Lim Kee Chang Sophie V Morse Kirsten Christensen-Jeffries Christopher J Rowlands Andriy S Kozlov James J Choi |
| author_facet | James H Bezer Paul Prentice William Lim Kee Chang Sophie V Morse Kirsten Christensen-Jeffries Christopher J Rowlands Andriy S Kozlov James J Choi |
| author_sort | James H Bezer |
| collection | DOAJ |
| description | Focused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in brain microvessels have never been previously recorded. The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue. Microbubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue® and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2-1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second. We observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index ≥ 0.6. These results present the first direct observations of ultrasound-driven microbubbles within brain tissue, and illustrate a range of microbubble behaviors that have the potential to lead to safe drug delivery or tissue damage. |
| format | Article |
| id | doaj-art-a1c3b9fa8a6b4f2d89ea206ce20ba395 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a1c3b9fa8a6b4f2d89ea206ce20ba3952025-02-10T05:30:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031042510.1371/journal.pone.0310425Microbubble dynamics in brain microvessels.James H BezerPaul PrenticeWilliam Lim Kee ChangSophie V MorseKirsten Christensen-JeffriesChristopher J RowlandsAndriy S KozlovJames J ChoiFocused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in brain microvessels have never been previously recorded. The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue. Microbubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue® and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2-1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second. We observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index ≥ 0.6. These results present the first direct observations of ultrasound-driven microbubbles within brain tissue, and illustrate a range of microbubble behaviors that have the potential to lead to safe drug delivery or tissue damage.https://doi.org/10.1371/journal.pone.0310425 |
| spellingShingle | James H Bezer Paul Prentice William Lim Kee Chang Sophie V Morse Kirsten Christensen-Jeffries Christopher J Rowlands Andriy S Kozlov James J Choi Microbubble dynamics in brain microvessels. PLoS ONE |
| title | Microbubble dynamics in brain microvessels. |
| title_full | Microbubble dynamics in brain microvessels. |
| title_fullStr | Microbubble dynamics in brain microvessels. |
| title_full_unstemmed | Microbubble dynamics in brain microvessels. |
| title_short | Microbubble dynamics in brain microvessels. |
| title_sort | microbubble dynamics in brain microvessels |
| url | https://doi.org/10.1371/journal.pone.0310425 |
| work_keys_str_mv | AT jameshbezer microbubbledynamicsinbrainmicrovessels AT paulprentice microbubbledynamicsinbrainmicrovessels AT williamlimkeechang microbubbledynamicsinbrainmicrovessels AT sophievmorse microbubbledynamicsinbrainmicrovessels AT kirstenchristensenjeffries microbubbledynamicsinbrainmicrovessels AT christopherjrowlands microbubbledynamicsinbrainmicrovessels AT andriyskozlov microbubbledynamicsinbrainmicrovessels AT jamesjchoi microbubbledynamicsinbrainmicrovessels |