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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
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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
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Microvascular Challenges: Low Velocities
-clutter removal issues- velocity resolution issues
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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
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• 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)
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Microvascular Challenges: Spatial Resolution
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Microvascular Assessment: Higher Frequencies
- Improves blood signals
- Improves velocity resolution
- Improves spatial resolution
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Microvascular Assessment: Higher Frequencies
Problem:
- Attenuation
- Clutter
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Microbubble Contrast Agents
• Encapsulated gas microbubbles
(e.g. lipids, albumin, polymers)
• ~ 2-8 m in diameter
• Injected intraveneously
into the bloodstream
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Scattering from Bubbles
Bubbles: highly compressible, low density relative to plasma
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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
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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
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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…
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Bubble Radius
Time
Three regimes can be considered
-Linear (lower pressure)-Non-linear (intermediate pressure)-Destruction (higher pressure)
Acoustically Driven Bubbles
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US: f=1 MHz, 70 kPaSoft-shelled agent4 micron bubble
Linear regime
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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
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US: f=1 MHz, 200 kPa
Nonlinear regime
Soft-shelled agent4 micron bubble
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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
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US: f=1.7MHz, 1.3 MPaHard-shelled agent
Bubble Destruction
hard-shelled agent3 micron bubble
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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’)