Molecular Vascular Imaging and Therapy Lab.  Designing microbubbles to image and treat disease
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What are Microbubbles?

conventional microbubble
Targeted microbubble
  • Microbubbles are traditionally used as a contrast agent for ultrasound (US) imaging.
  • When they enter an US field they expand and contract, giving off a unique signal.
  • They consist of a shell (lipid, protein, polymer) and a core (usually a gas).
  • They are restricted to the vasculature because of their size.
  • They are quickly cleared from the vasculature after injection.
  • The addition of targeting agents to their shell allows them to bind to and accumulate on endothelial cells that express a targeted protein.

What can we do with them?

Imaging changes in blood flow

conventional MBs flowing through a blood vessel
  • Often in areas of disease there are changes in bloodflow.
  • By imaging how MBs move into and out of an US field of view, we can get measurements of: Perfusion, Blood Volume, Vascularity, etc.

Video: A bolus of microbubbles filling the vasculature of a mouse colon (cross-section). On the left is the B-mode US video, on the right is the contrast-enhanced US video (microbubbles).

What can we do with them?

Molecular Imaging: Visualizing Protein Expression

targeted microbubbles binding to a vessel
  • In regions of disease, vascular endothelial cells express proteins on their surface as a normal part of the body’s response (i.e. in areas of inflammation the vasculature expresses proteins that enable white blood cells to identify and move into the inflamed areas).
  • By adding targeting agents to the MB shell, we can image where these disease markers are present, and the extent of their expression.

Video: An inflamed mouse colon 4 minutes after injection of targeted MBs. Using the destruction-replenishment technique, we can determine how many bubbles were bound to the vasculature prior to destruction. This gives us the location and extent of inflammation in the colon.

What can we do with them?

Site-Specific Drug Delivery

modle of microbubble-mediated drug delivery
  • Ultrasound and MBs can interact in really interesting ways that can affect the biology of the vascular endothelial cells.
  • Though the mechanism is unknown, this interaction can lead to a temporary increase in the “leakiness” of the cell:cell junctions.
  • This allows us to target regions of the body where we want a therapeutic to be delivered.

Video: MBs and a green nanoparticle were injected into a mouse in order to visualize what happens inside a tumour when we apply a focused US pulse. We can see the nanoparticle flowing through the tumour vasculature. When we apply US, the MBs expand allowing the nanoparticles to move out of the vasculature and into the tumour.