Signal Processing - March 2016 - 111

life sciences
Antonio Stanziola, Matthieu Toulemonde, Yesna O. Yildiz,
Robert J. Eckersley, and Meng-Xing Tang

Ultrasound Imaging with Microbubbles

edical ultrasound (US) imaging,
also known as echography, is one
of the most frequently used frontline clinical imaging modalities and is
characterized by its safety, affordability,
accessibility, and real-time image display. Sound pulses, typically in the
megahertz range, are sent into the body
and the backscattered echoes are used to
create a tomographic image. The contrast of an US image arises from local
variations in the physical properties of
the tissues, primarily density and elasticity, revealing tissue structures at depth.
The blood flow of a living organism
contains essential information related to
tissue function and pathology. However,
as blood is a fluid composed of plasma
and blood cells that are similar to each
other acoustically, the scattering of
sound from blood is very weak compared to surrounding tissue structures.
Consequently, it is difficult to detect vessels that are smaller in size than the
pulse length, as the echoes from blood
are completely masked by the neighboring tissue response. While for big vessels
it is still possible to obtain hemodynamic
information due to the weak scattering
of blood cells, in general, the signal-tonoise ratio (SNR) is poor and the information content is limited.
To overcome the limitations of conventional US, gas bubbles of micrometer radius can be introduced into a
patient's bloodstream as agents for
contrast enhanced US imaging
(CEUS). Microbubbles (MBs) act as
resonant oscillators and scatter US
Digital Object Identifier 10.1109/MSP.2015.2496914
Date of publication: 7 March 2016

signals efficiently
the gaseous core, the
The equilibrium radius
when excited at the
shell elastic properof an MB is a balancing
frequencies used in
ties, and the surface
act between the external
the clinical practice,
tension. When an US
pressure of the blood, the wave excites an MB,
typically in the range
internal pressure of the
of 1-15 MHz. They
since the bubble
are designed to have
diameter (a few nm )
gaseous core, the shell
a diameter (<7 μm)
elastic properties, and the is much smaller than
capable of passing
the clinical US wavesurface tension.
the pulmonary capillength (hundreds
laries (the smallest
of nm ), it causes a
vessels in the human body) and often
global change in the external pressure
include a lipid shell that encapsulates a
p 0 that results in an oscillation of the
low solubility gas, so as to increase
MB associated with the emission of
their longevity in the circulation.
sound waves [Figure 2(a) and (b)]. As
The use of MBs in US imaging genthe gas core is highly compressible,
erates new and exciting possibilities [1].
the bubble radius can oscillate signifiIt enables real-time imaging of blood
cantly around its equilibrium value r0
flow with unprecedented sensitivity and
if driven at or near its resonance freresolution in both large vessels and
quency, and this behavior is responsimicrovasculature and provides indicable for the strong scattering of the
tors of the perfusion of organs in, e.g.,
contrast agents.
liver [Figure 1(a) and (b)], kidney
MBs are inherently nonlinear oscil[Figure 1(c) and (d)], heart, limbs,
lation systems. Even with US amplibrain, breast, and lymphatic systems.
tudes of tens of kilopascal, well below
The safety of MBs in diagnostic US has
those typically used in clinical imagbeen well established. If the MB shell is
ing, the radius change for an MB is not
coated with specific molecules, complesymmetrical in the compression and
mentary to those expressed by the vasexpansion phases. This asymmetry is a
cular walls during specific pathological
key source of harmonic generation
processes such as the initiation of canfrom MBs.
cer or atherosclerosis, it is possible to
The MB oscillation and subsequent
bind MBs to these receptors (targeted
scattering is highly dependent on the
MBs) facilitating molecular imaging for
US parameters, including frequency
early detection and diagnosis [1].
and amplitude. A variety of analytical
models have been developed to
describe this process, most of them
MBs as nonlinear
assuming a time-invariant spherical
oscillation systems
bubble. The simplest is the Rayleigh-
The equilibrium radius of an MB is a
Plesset (RP) model, which considers a
balancing act between the external presshell-free bubble of polytropic gas in an
sure of the blood, the internal pressure of
IEEE Signal Processing Magazine

March 2016

111

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