Using optical scattering to measure properties of ultrasound contrast agent shells

A system for measuring properties of microbubble shells using scattered light, comprising:

• (a) a sampling volume configured to accommodate a microbubble having a shell comprising a physical membrane separating a volume of gas within the microbubble from an ambient fluid, the sampling volume including a region of interest;
• (b) an injection system configured to introduce the microbubble into the region of interest;
• (c) an acoustic driving section configured to deliver an acoustic pressure into the sampling volume, such that the acoustic pressure intersects with the region of interest;
• (d) a light providing section configured to illuminate the region of interest;
• (e) a light collecting section configured to capture light scattered by the microbubble in the region of interest;
• and
• (f) a processor coupled with the light collecting section, the processor being configured to determine at least one property of the physical membrane of the microbubble in the region of interest, based upon light scattered by the microbubble that is captured by the light collecting section, the processor being configured to implement the following steps:
• (i) controlling the acoustic driving section such that a pressure increase is induced in the region of interest, and such that scattered light is collected by the light collecting section from the microbubble during changing pressure conditions;
• (ii) correlating relative scattered light intensity changes collected during the changing pressure conditions with a radius of the microbubble;
• (iii) generating a radius and time relationship for tracking changes to the radius of the microbubble in the region of interest over time;
• (iv) fitting the radius and time relationship to a dynamic model for describing the motion of the microbubble, producing a fitted relationship, wherein the dynamic model includes at least one parameter corresponding to the physical membrane;
• and
• (v) determining one or more properties of the physical membrane of the microbubble using the fitted relationship.

A method for measuring properties of microbubble shells using scattered light, comprising the steps of:

• (a) collecting light scattered from a microbubble having a shell comprising a physical membrane separating a volume of gas within the microbubble from an ambient fluid during changing pressure conditions experienced by the microbubble;
• (b) correlating relative scattered light intensity changes collected during the changing pressure conditions with a radius of the microbubble;
• (c) generating a radius and time relationship for tracking changes to the radius of the microbubble in the region of interest over time;
• (d) fitting the radius and time relationship to a dynamic model for describing the motion of the microbubble, to produce a fitted relationship, wherein the dynamic model includes at least one parameter corresponding to the physical membrane;
• and
• (e) determining one or more properties of the physical membrane using the fitted relationship.

A method for differentiating a plurality of shelled microbubbles using scattered light, comprising the steps of:

• (a) collecting light scattered from the plurality of shelled microbubbles, each microbubble having a shell comprising a physical membrane separating a volume of gas within the microbubble from an ambient fluid during changing pressure conditions experienced by the microbubble;
• and
• (b) for each shelled microbubble:
• (i) correlating relative scattered light intensity changes collected during the changing pressure conditions with a radius of the shelled microbubble;
• (ii) generating a radius and time relationship for tracking changes to the radius of the shelled microbubble in the region of interest over time;
• and
• (iii) correlating the radius and time relationship to a compressibility of the shelled microbubble, such that the compressibility can be used to differentiate the plurality of shelled microbubbles.

A system for differentiating a plurality of shelled microbubbles using scattered light, comprising:

• (a) a sampling volume configured to accommodate one or more shelled microbubbles, wherein each such shelled microbubble includes a microbubble shell comprising a physical membrane separating a volume of gas within the microbubble from a surrounding fluid, the sampling volume including a region of interest;
• (b) an acoustic driving section configured to deliver an acoustic pressure into the sampling volume, such that the acoustic pressure intersects with the region of interest;
• (c) a light providing section configured to illuminate the region of interest;
• (d) a light collecting section configured to capture light scattered by one or more microbubbles in the region of interest;
• and
• (e) a processor coupled with the light collecting section, the processor being configured to differentiate the plurality of microbubbles based on optical scattering data, the processor being configured to implement the following function for each shelled microbubble:
• (i) correlating relative scattered light intensity changes collected during the changing pressure conditions with a radius of the shelled microbubble;
• (ii) generating a radius and time relationship for tracking changes to the radius of the shelled microbubble in the region of interest over time;
• and
• (iii) correlating the radius and time relationship to a compressibility of the shelled microbubble, such that the compressibility can be used to differentiate the plurality of shelled microbubbles.