Imaging Microbubbles
Antony Hsu
Shanti Bansal
Daniel Handwerker
Richard Lee
Cory Piette
Topics of Discussion
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Brownian Motion
What are these bubbles and why do we
use them?
Following the Great Perrin - Diffusion and
Gravitational Motion of Microbubbles
Optical Imaging of Microbubbles
What is ultrasound?
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Ultrasound uses high frequency sound
waves to image internal structures
The wave reflect off different density
liquids and tissues at different rates and
magnitudes
It is harmless, but not very accurate
Ultrasound and Microbubbles
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Air in microbubbles in the blood stream
have almost 0 density and have a
distinct reflection in ultrasound
The bubbles must be able to fit through
all capillaries and remain stable
We must examine the properties of
microbubbles before using this
technique
What is Brownian Motion?
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Small particles are effected by so many
different factors in a solution that they
move around at in a random walk
Even if a solution seems stagnate, the
microbubbles will still move
What is a Random Walk?
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After every  seconds, a particle moves
in a direction at a velocity v
There is an equal probability that the
particle will move in any direction no
matter what its past direction was
Each particle is independent of all other
particles
Characteristics of Random Walks
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Particles have a net
displacement of 0
(after  time)
Particles usually
remain in one region
and then wander to
other regions
We’re all about Microbubbles (1)
Shell
Air or High Molecular
Weight Gases
1-7mm
We’re all about Microbubbles (4)
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Used with ultrasound echocardiography and
magnetic resonance imaging (MRI)
Diagnostic imaging - Traces blood flow and
outlines images
Drug Delivery and Cancer Therapy
We’re all about Microbubbles (2)
Left Arrow: Lipid-Coated Microbubble
Right Arrow: Saline Microbubble
We’re all about Microbubbles (3)
We’re all about Microbubbles (5)
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Small (1-7 mm) bubbles of air (CO2,
Helium) or high molecular weight gases
(perfluorocarbon).
Enveloped by a shell (proteins, fatty acid
esters).
Exist - For a limited time only! 4 minutes-24
hours; gases diffuse into liquid medium
after use.
Size varies according to Ideal Gas Law
(PV=nRT) and thickness of shell.
How Bubbles Separate
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Given a volume filled with different sizes of
microbubbles, which bubbles move toward
which end due to gravity?
Following Perrin, we look at the characteristic
length (lambda) which will tell us about the
motion of the bubble.
FT=FD+FG
F G = -c(x,t) D
l
How Bubbles Separate(2)
How do we get lambda(l)?
K =Boltzman’s constant (1.38x10-23 J/K)
T = Temperature in Kelvin (300K)
g = gravity(9.81 m/s2)
meff = effective mass
kT
l=
meff g
meff = (4/3) p
r3 (r
p-
rw )
rp = density of particle
rw = density of water(1g/cm3)
r = radius of bubble(cm)
The size of of microbubbles is known(1-7mm). Therefore, the
only factor to be determined is the density of the microbubble.
With gas-filled bubbles, the thickness and density of the shell
gives the bubble its mass.
How Bubbles Separate(3)
 Why
is all this important?
Well, we want a bubble that will not “float” or “sink.”
By adjusting the shell thickness to the force of gravity,
we can achieve “neutral buoyancy.”
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Basically, by designing the bubble such that
the density as a whole has the density of
water, then the bubble will undergo only
diffusion flux.
Perrin’s light microscope
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Perrin did research on diffusion and brownian motion
He conducted experiments to examine diffusion
through emulsions
He built used a light microscope to visualize emulsions
at different depths
Perrin determined depth of pictures by the following
formula: H=CH’. C = relative refractive index of the
two media which the cover-glass separates. H’ =
height of microscope.
Perrin’s Light Microscope
Optical target tracking
on image sequences
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Computer equipment improvement has lead to higher resolution
optical imaging
Most computerized optical pattern recognition filters today have
been designed to process one image at a time. (isolated
images)
These filters would prove ineffective in recording microbubbles
moving through the blood stream (image sequencing).
Isolated images do not deal with changes in background,
sequential imaging does
this problem leads to the development of the “two image
system”--a model that takes into account two successive frames
this model is based on the maximum-likelihood (ML) estimation
The ML estimation takes into account the continuity between
two successive frames
Optical target tracking (cont.)
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One frame is taken at a known location, one at an “estimated”
location
This estimated location will depend on location and size of the
object
In this case, the size of microbubble will remain constant
(approximately the size of a red blood cell). However, the
location will vary.
Idle time between frames depends directly on probability factors.
The two frames are correlated, forming a clear and concise
picture of the object’s movement.
A Novel Technique to
Visualize Microbubbles
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An optical tracking system is placed on
Perrin’s light microscope
Allow easy visualization of microbubbles and
analysis
A Novel Method of Microbubble
Visualization
Future of Microbubbles
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Using microbubbles as a pressure
sensitive gauge (especially important for
heart)
Enhancing ultrasound/ MR images.
Novel gasses used for microbubbles.
Drug delivery