Imaging Microbubbles

Antony Hsu

Shanti Bansal

Daniel Handwerker

Richard Lee

Cory Piette

Topics of Discussion

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?

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

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?

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?

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

Particles have a net displacement of 0 (after time)

Particles usually remain in one region and then wander to other regions

1-m

Shell

Air or High Molecular Weight Gases

We’re all about Microbubbles (1)

We’re all about Microbubbles (4)

Used with ultrasound echocardiography and magnetic resonance imaging (MRI)

Diagnostic imaging - Traces blood flow and outlines images

Drug Delivery and Cancer Therapy

Left Arrow: Lipid-Coated MicrobubbleRight Arrow: Saline Microbubble

We’re all about Microbubbles (2)

We’re all about Microbubbles (3)

We’re all about Microbubbles (5)

Small (1-7 m) 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

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.

G = -c(x,t) D

T = D + G

How Bubbles Separate(2)

How do we get lambda()?

= k Tmeff g

K =Boltzman’s constant (1.38x10-23 J/K)T = Temperature in Kelvin (300K)g = gravity(9.81 m/s2)meff = effective mass

meff = (4/3) r3 (p - w)p = density of particlew = 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.” 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

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 trackingon image sequences

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.)

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

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

Using microbubbles as a pressure sensitive gauge (especially important for heart)

Enhancing ultrasound/ MR images. Novel gasses used for microbubbles.

Drug delivery