Microbubbles are used in medical diagnostics as a contrast agent for ultrasound imaging and as drug delivery vehicles. The size range of microbubbles is typically in the 1-5 µm range, preferably with a narrow size distribution. In order to enhance the stability of microbubbles they are typically encapsulated in a shell composed of lipid or a protein.
Figures 1 and 2 below1 show how microbubbles are used to enhance ultrasonic imaging. These are 7 MHz CPS images (MI=0.09) acquired before and after imaging and destruction of targeted bubbles in a Met-1 tumor in vivo. Figure 1 shows 10 seconds after injection of a targeted agent. Figure 2 shows 24 hours after destruction of adherent agents and 10 seconds after re-injection flow is extremely slow within tumor. The “black hole” indicates poorly perfused regions.
Figure 1: 10 seconds after injection Figure 2: 24 hours after destruction of adherent agents
Microbubbles for standard clinical imaging
Microbubbles for standard clinical imaging can be purchased, such as Definity2 and Optison3 . Other researchers prefer to create their own – typically for animal studies. Various publications detail methods for creating microbubbles 4,5. The PSS AccuSizer has proven to be the preferred method for quantifying the size and concentration of microbubbles. Figures 3 and 4 show AccuSizer results for non-targeted and CRPPR targeted microbubbles, respectively.
Figure 3: Non-targeted microbubbles Figure 4: Targeted microbubbles
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1. Images courtesy of the Dr. Katherine Ferrara Lab in the UC Davis Biomedical Engineering Department, http://ferraralab.bme.ucdavis.edu/
4. Zhang., H. et.al., Ultrasound molecular imaging of tumor angiogenesis with a neuropilin-1-targeted microbubble, Biomaterials 56 (2015) 104-113.
5. Feshitan JA, Chen CC, Kwan JJ, Borden MA. Microbubble size isolation by differential centrifugation. J Colloid Interface Sci 2009; 329:316-24.