.png){kind=icon}
Return
Microbubble dynamics in brain microvessels
.png){kind=icon}
OA
AI
DOI：10.1371/journal.pone.0310425.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
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 (R) 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.
Keywords:
ULTRASOUND CONTRAST AGENT
MEDIATED DRUG-DELIVERY
FOCUSED ULTRASOUND
BARRIER
DISRUPTION
DESTRUCTION
BEHAVIOR
TISSUE
Journal
IF:
2.6
Papers:
2.6W
Citations:
81.6W
Organization
Cited Papers
ShareSaveConsistent opening of the blood brain barrier using focused ultrasound with constant intravenous infusion of microbubble agent.png)
SCIENTIFIC REPORTS
OAAI
SCIENTIFIC REPORTSIF3.9
OAAIShareSaveBlood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility StudySCIENTIFIC REPORTSOAAI
SCIENTIFIC REPORTSIF3.9
OAAIShareSaveShareSaveThree Decades of Ultrasound Contrast Agents: A Review of the Past, Present and Future ImprovementsOAAI
OAAIShareSaveShareSaveShareSaveShareSave
View more