Biomedical Engineering Reference
In-Depth Information
HIFU exposure has been shown to result in nonuniform energy
deposition due to interactions of bubbles with the incoming
sound beam (Bailey et al. 2001). Without full knowledge of the
distribution of bubbles and their interaction with the acoustic
field, particular areas of tumors may be over- or undertreated
through cavitation-enhanced heating, or scattering of the field
out of the treatment area. Recent developments in cavitation
detection allow bubble populations in vivo to be spatially mapped
by listening to the acoustic emissions with an array made up of
many piezoelectric crystals. This technique is known as passive
cavitation mapping and has the potential for use as a monitor-
ing tool during HIFU treatments (Jensen et al. 2011). Through
knowledge of specific bubble locations, researchers may be able
to utilize the additional heating they provide in order to enhance
thermal ablation.
where
p
r
.3
is the peak rarefactional pressure derated by 0.3 dB
cm
−1
MHz
−1
(to account for the attenuation of the field by soft
tissue) and
f
c
is the center working frequency of the transducer.
The explanation for this relationship is that the higher the nega-
tive pressure, the more tension the dissolved gas will be under
in order to pull it out of solution, and the lower the frequency,
the longer the time period over which the medium will sit below
a certain negative pressure level, resulting in greater bubble
growth and/or a greater number being produced.
5.4.2.4 acoustic Dose
We have seen how defining a thermal dose (Section 5.4.1) can
relate temperature history to biological effect. A second defini-
tion relating to ultrasound exposure has been proposed more
recently, namely the acoustic dose, which aims to overcome the
limitations of thermal dose such as its lack of ability to relate to
different tissue or cell types, and the fact that it ignores addi-
tional mechanical effects and their contribution to biological
effects. Acoustic dose is defined as the energy deposited per unit
mass in a medium within which an ultrasonic wave propagates
(Duck 2009). Associated with this is the acoustic dose rate, or
acoustic dose per unit time.
One aspect of this that deserves particular discussion is that
relating to damage resulting from cavitation activity. For many
years there has been discussion of a so-called inertial cavitation
dose, pertaining to the amount of broadband noise generated by
these events. Chen et al. (2003) have defined a cavitation dose
as the cumulative root-mean-square of the detected broadband
noise, in the frequency domain, arising from inertial cavitation
during ultrasound exposure. Although this appears at first to
be a clear definition, the ability to detect this broadband noise
is dependent not only on the properties of the medium being
exposed but on the response of the detection device. As such, the
chosen broadband frequency range for measurement, and thus
the specific value quoted for inertial cavitation dose, depends
heavily on the experimental arrangement and any signal pro-
cessing performed. Taking into account the induced tempera-
ture rise, radiation force effects, and the presence of cavitation,
acoustic dose is a more thorough but complex idea than ther-
mal dose, and has not yet come into widespread use due to the
amount of knowledge required of acoustic field parameters and
tissue properties in spatially and temporally varying scenarios
(Duck 2011).
5.4.2.2 Streaming
Although ultrasound transducers produce an oscillatory pres-
sure field centered about the ambient pressure of the medium,
some momentum is transferred as a force, primarily along
the direction of propagation. In a generalized sense, the term
streaming
when related to ultrasonic fields refers to the motion
of fluid occurring due to this so-called radiation force. The
resulting effects on cells from streaming in tissues depend on
the magnitude of the force and the proximity of the cells to
streaming currents. Motion of fluid close to cell membranes
can cause breakages in protein bonds and can damage cells by
creating holes in surface membranes, either reversibly or irre-
versibly, through shear stress (Wu 2001, 2002; Collis et al. 2010).
However, as well as causing direct mechanical damage to the
closest cells, streaming has been identified as an important con-
tribution to the healing effect of acoustic fields of the levels used
in physiotherapy (Dyson and Pond 1973).
In the same way that incident ultrasound fields cause stream-
ing in tissues, the oscillation of cavitation bubbles causes extra-
cellular fluid in the vicinity to be pushed around, forming small,
localized currents. This is known as cavitation microstreaming.
Not only may this cause direct mechanical damage as described
earlier, but it has also been implicated as a mechanism for drug
delivery, whereby the cell wall permeability can be increased to
allow a targeted agent to enter, in a process termed
sonoporation
(Coussios and Roy 2008, Collis et al. 2010).
5.4.2.3 Mechanical Index
The concept of the mechanical index (MI) is similar in nature
to the thermal index described in Section 5.4.1, as it is a safety
index used to quantify the potential to cause damage. Similarly
to the TI, it is primarily relevant to diagnostic systems, where
these effects are to be avoided. In essence, the MI is a measure
of the likelihood of cavitation occurring due to the effects of a
particular acoustic field. Its form is:
5.5 Characterization and Calibration
5.5.1 Introduction
The delivery of a successful treatment relies upon some knowl-
edge of the energy deposited in a given region of tissue. It is there-
fore important to know in detail the distribution of the acoustic
field produced by a given transducer and how important param-
eters vary with the input power. Acoustic fields are commonly
described in terms of three main parameters: pressure, intensity,
p
.
=
r
MI
(5.23)
f
c
