Biomedical Engineering Reference
In-Depth Information
on to the next, eventually resulting in programmed cell death
(Wong and Dewey 1986). Clinically, hyperthermic treatments
have been shown to be effective both alone and in combination
with chemo- and radiotherapy, particularly for hypoxic tumors
that may have a significant resistance to radiation therapy (Scott
1986). Additionally, the effect of reducing the ability to repair
subcellular damage, as described before, suggests that there is a
synergistic advantage in using hyperthermia alongside radiation
therapy. Finally, hyperthermia has been shown to provide bet-
ter tumor selectivity than alternative treatment types (Marchal
1992). Its success has improved significantly in recent years due
to developments in temperature imaging for treatment guidance
through real time feedback.
over many cycles, exerting shear stresses on the surrounding
cells. However, in the presence of higher peak negative pressures
and more rapid changes, oscillating bubbles no longer undergo
rectified diffusion. This leads to inertial, or collapse cavitation.
At the peak of rarefaction, a bubble will have its greatest surface
area, and more gas may enter the bubble than can be transferred
back to the medium during the following rapid compression.
Subsequent collapse of the bubble to a fraction of its original size
can cause both direct and indirect tissue damage, due to a num-
ber of effects. Shear forces, much greater than those associated
with stable cavitation, may firstly cause direct mechanical dam-
age, resulting in cell rupture. The large concentration of energy at
the center of the collapsing bubble also results in extremely high
temperatures, thereby denaturing cells and causing harmful free
radicals to be produced. A process known as sonoluminescence
may then occur, whereby photons are emitted due to recombina-
tion of these free radicals with surrounding atoms, which may
lead to additional subcellular damage (Duck 2008). Theoretically,
the dissipated power (
W
) emitted by a bubble of equilibrium
radius
R
0
,
which is then converted to heat, is given by
5.4.1.6 Focused Ultrasound therapy
In contrast to hyperthermia, the aim of HIFU is to heat cells rap-
idly to temperatures capable of causing coagulative necrosis in
a short time. Necrosis describes premature cell death, whereby
the tissue is damaged sufficiently rapidly that the dead tissue
remains in situ. This is in contrast to programmed cell suicide, or
apoptosis, where signals to neighboring cells allow macrophages
to absorb and recycle the waste from dead cells. Coagulative
necrosis caused by heating is also referred to as thermal ablation,
which, when performed using focused ultrasound beams, leads
to a small (typically of the order of a centimeter in length and a
millimeter in width at 1 MHz) ellipsoidal volume of dead tissue
in the focal region of the acoustic field. The need to ablate whole
tumors with this technique can result in lengthy treatment
times, as the focal region is moved so as to cover the complete
target volume. Similarly to hyperthermia, cell death is thought
to arise from the denaturation of cell proteins, causing loss of
communication with their environment. However, cell rupture
and structural damage can occur due to mechanical effects such
as cavitation, as described in the following discussion.
=
4
3
3
π α
WR
2
I
(5.22)
0
where
I
is the acoustic intensity incident on the bubble, and α
is the attenuation of the surrounding medium (Coussios 2007).
Following collapse, a single bubble can disintegrate into many
smaller bubbles, which may dissolve back into solution or act to
nucleate further cavitation activity.
A considerable amount of research in HIFU and hyper-
thermia relates to cavitation, and in particular its potential to
increase the amount of energy deposited as heat, and therefore
increase the volume of coagulative necrosis achieved in a given
time. Stable cavitation bubbles undergoing nonlinear oscilla-
tions act as emitters of ultrasound energy at the fundamental
frequency of the incident ultrasound beam, as well as harmonic,
subharmonic (particularly the half harmonic), and ultrahar-
monic (multiples of the half harmonic) frequencies. Inertial or
collapse cavitation events result in the emission of a broadband
noise. These emissions can be detected by listening with a piezo-
electric device situated outside the exposed material, a technique
known as passive cavitation detection. The energy carried by the
acoustic emissions can be deposited locally, with preferential
absorption of harmonics at higher frequencies as described in
Section 5.4.1, leading to further heating. This additional heat
transfer has been found, in some cases, to increase the volume
ablated by a single burst of HIFU, or increase the depth of treat-
ment, thus giving the potential to reduce the total treatment
time for a given target volume or allow for a greater variety of
treatment sites (Holt and Roy 2001, Melodelima et al. 2004, Liu
et al. 2006). Alternatively it may allow a lower output power to be
used to achieve the desired temperatures within the body, thus
reducing the possibility of side effects.
Due to the unpredictable nature of bubble activity in inho-
mogeneous media, the presence of cavitation in tissues during
5.4.2 Mechanical Effects
The effects described in this section are not directly related to the
thermal mechanisms of the interactions described previously, but
occur as a by-product of ultrasound interactions in tissues, which
may be undesirable in some circumstances and beneficial in others.
5.4.2.1 acoustic Cavitation
As described, sound propagates as a longitudinal pressure wave,
creating areas of compression (positive pressure) and rarefaction
(negative pressure) in the medium it traverses. Negative pressures
can cause gas or liquid vapor to be drawn out of solution, creating
bubbles, or cavities, in a process known as acoustic cavitation.
The resultant effect depends on properties of the field, and on the
peak negative pressures achieved at that point in the medium.
Cavitation bubbles will be driven to oscillate by a propagating
acoustic field. Stable cavitation describes the activities of bubbles
oscillating slowly enough that gas can diffuse across the mem-
brane during compression and rarefaction, in a process referred
to as rectified diffusion. Such stable oscillations can continue
