VesselDiameter

(mm)Number

vpeak

(cm/s)

Doppler shift

(Hz)

Aorta 10 1 100 5,620

Large Arteries 3 40 18 1,010

Main branches 1 600 4.5 250

Terminal branches

0.6 1,800 1.5 84

Arterioles 0.02 40,000,000 0.18 12

Capillaries 0.008 1,200,000,000 0.08 4.5

Small Vessel Detection

Low Velocities (velocity resolution and ‘clutter’ issues)

Low Volume (small signals)

Low Flow rate

Small sizes (spatial resolution)

Microvascular Assessment: Challenges

Intravital microscopy ofrat cremaster muscleC Ellis U of Western Ontario

50 microns

Microvascular Challenges: Low Velocities

-clutter removal issues- velocity resolution issues

Figure 1.12: Simple illustration of the second factor limiting the ability of conventional frequency Doppler to examine the microcirculation - small Doppler shifts. One of the three reasons for this limitation is clutter which results from both phase noise within the master oscillator and relative motion between the tissue and transducer. The latter occurs because tissue can have velocities that are comparable to the blood velocities of the microcirculation and produces 2-10 MHz echo intensities thousands of times higher than blood. The net result is a high-amplitude, low-frequency clutter spectrum that can completely overwhelm the microcirculation spectrum, making it undetectable.

• Kidney tissue velocity: ~ 3 cm/s (30 x capillary velocity)

• Myocardium velocity: ~ 15 cm/s (150 x capillary velocity)

Low Velocities: Clutter removal

• hematocrit decreases with vessel size,

results in decreased signal strength

Microvascular Challenges: Small signals

Hem

atoc

rit

0 R

RB

C V

eloc

ity

0 R

Shea

r R

ate

0 R

R

R

0(a)

(b) (d)(c)

Microvascular Challenges: Spatial Resolution

Microvascular Assessment: Higher Frequencies

- Improves blood signals

- Improves velocity resolution

- Improves spatial resolution

Microvascular Assessment: Higher Frequencies

Problem:

- Attenuation

- Clutter

Microbubble Contrast Agents

• Encapsulated gas microbubbles

(e.g. lipids, albumin, polymers)

• ~ 2-8 m in diameter

• Injected intraveneously

into the bloodstream

Scattering from Bubbles

Bubbles: highly compressible, low density relative to plasma

Bubble Radius

Time

Pressure

• Wavelength of 3 MHz = 0.5 mm ( = v/f, v= 1500 m/s )

• Bubble size is 0.003 mm

Microbubble Contrast Agents

A mass on a spring has a resonant frequency determined by its

spring constant k and the mass m.

The resonant oscillating frequency (natural) is:

mk

o 2

Mass - Spring System

o

o

P

Rf

3

2

1 (the ‘Minnaert’ frequency)

- Assuming adiabatic condition- Surface tension neglected

mMHzrfr 3.3

For an air bubble in water

Free oscillating bubble: Analogy

With a bubble, the effective mass is provided by the surrounding liquid, and

the spring is due to the gas compressibility. For a ‘free’ bubble the resonant

frequency is…

Bubble Radius

Time

Three regimes can be considered

-Linear (lower pressure)-Non-linear (intermediate pressure)-Destruction (higher pressure)

Acoustically Driven Bubbles

US: f=1 MHz, 70 kPaSoft-shelled agent4 micron bubble

Linear regime

0 2 4 6 8 10 12

6.7

6.8

6.9

7

7.1

7.2

7.3

7.4

7.5

7.6

7.7

Dia

met

er [m

]

Time

dB

Frequency [MHz]0 1 2 3 4

-50

-40

-30

-20

-10

0

Diameter vs Time Frequency content

US: f=1 MHz, MI=0.05

Linear regime

US: f=1 MHz, 200 kPa

Nonlinear regime

Soft-shelled agent4 micron bubble

0 10 20 30 40 50 60 70 802.5

3

3.5

4

4.5

5

Dia

met

er [m

]

Time

0 1 2 3-50

-40

-30

-20

-10

0

dB

Frequency [MHz]

Nonlinear regime

US: f=1 MHz, 200 kPa

Diameter vs Time Frequency content

US: f=1.7MHz, 1.3 MPaHard-shelled agent

Bubble Destruction

hard-shelled agent3 micron bubble

Microbubble Imaging Methods

• Examine the kinetics of Bscan enhancement (earliest approach)

• Detect ‘nonlinear’ signals (bubble specific)

- energy: harmonic, subharmonic, differences in transmit band)

- methods: e.g.filtering; phase and/or amplitude modulation

• Employ ‘destruction-reperfusion’ approaches

(destroy agent in beam and images kinetics of inflow- ‘negative bolus’)