Biomedical Engineering Reference
In-Depth Information
fields, acoustic power and intensity are important quantities for
physiotherapy, hyperthermia, and HIFU applications.
thermal therapies, it is necessary to divide the discussion into
the three regimes described previously, as the overall nature and
desired outcome depends strongly on the treatment parameters.
Additional nonthermal effects resulting from interactions of
ultrasound with tissues are addressed in Section 5.4.2.
5.4.1.2 Heating regimes Using Ultrasound Sources
There are three main categories of thermal therapy that use ultra-
sound as their energy source. Broadly speaking, physiotherapy is
intended to induce a beneficial response in cells using tempera-
ture rises of less than 5°C. Hyperthermia raises the temperature
of tissues by a few degrees, reaching 42-46°C for many minutes,
with the aim of causing cell death, and often inducing a syner-
gistic effect with radio- or chemotherapy. Weakly focused trans-
ducers are used in hyperthermia to treat volumes of the order
of a cubic centimeter in a single exposure over many minutes.
In contrast, HIFU uses highly focused transducers to induce
rapid cell death in small regions of tissue, fractions of a cubic
centimeter in size, relying on mechanical or electronic move-
ment of the focal region to treat larger volumes. This effect, in
which tissues undergo protein denaturation (coagulative necro-
sis) once temperatures in excess of 56°C have been maintained
for 1-2 seconds (ter Haar 1986a), is known as thermal ablation.
Each of these regimes is described in more detail later in this
section. Some typical values of frequency, required power, and
treatment depths for each of these regimes are given in Table 5.1.
5.4.1.4 physiotherapy
When providing relief from muscle pain or promoting wound
healing, the desired effect of heating is not to damage tissues but
to induce a therapeutic response. Small temperature rises (∼1°C)
induced by plane wave transducers have been shown to produce
numerous physiological effects. Cellular reactions to tempera-
ture elevation may lead to vasodilation, promotion of blood flow,
muscle cell activation that may promote relaxation, and tissue
regeneration that may be aided by promoting DNA synthesis,
and thus cell proliferation, in vivo. Both pulsed and continuous
wave (CW) beams are used, depending on the desired level of
heating and mechanical effects. Studies have used a vast range of
endpoints, such as wound healing (Freitas 2010), muscle healing
(Chan 2010), bone healing (Malizos 2006, Guerino 2008), and
pain relief and increased mobility of joints (Ozgonenel 2009).
It is thought that acoustic streaming plays an important role
in these processes (Dyson and Pond 1973), and this mechani-
cal phenomenon is addressed in Section 5.4.2. Despite its com-
mon use in physiotherapy clinics, there is still some debate as
to whether the effects produced by ultrasound are above and
beyond that which can be achieved by physical manipulation
and exercise (Marks et al. 2000, Saunders 2003).
5.4.1.3 thermal Dose
The extent of damage to tissues caused by ultrasound depends
on a number of factors, again related to the acoustic field param-
eters and to the exposed tissue properties. For a given tissue
type, the overall effect is dependent on a combination of temper-
ature elevation and duration of heating. A single metric, referred
to as thermal dose, quantifies these effects using an integration
of temperature over time, and the quantity is expressed in terms
of cumulative equivalent minutes at 43°C (
CEM
43
). This is calcu-
lated from knowledge of temperature history using
5.4.1.5 Hyperthermia
Plane wave transducers are commonly used in hyperthermia
to provide bulk heating, but employ higher output powers than
those used in physiotherapy. These are designed to give higher
spatial and temporal average intensities (see Table 5.1). Many
studies of cells in culture and of different tissue types have been
performed, and have indicated a range of different effects (ter
Haar 1986b). These include microscopic effects such as increased
cell membrane permeability and a lowering of the pH level within
the cytoplasm, as well as bulk effects such as ischemia and lack of
perfusion. Although it is not clear which is the dominant effect
of the treatment on a cellular level, it has been shown that the
physical state of the cell membrane is critically important. For
example, changes in its structure leading to greater fluidity may
result from increased temperature. In turn, the permeability of
the membrane increases, causing chemical imbalance within
the cell. Membrane fluidity is affected by other factors such as
cholesterol and the presence of unsaturated fatty acids, however,
there is also clear evidence correlating it with temperature rise
and with cell death (Anghileri 1986). Also associated with an
increase in temperature to hyperthermic levels is the inhibition
of DNA synthesis and a loss of ability to repair damaged DNA.
This is thought to result from changes in ion concentration in
the cell due to membrane permeability alteration, which illus-
trates that although the cellular effects of heat are many and
complex, they may be heavily linked, with one process leading
t final
=
∫
43
−
T
CEM
=
R
∂
t
(5. 21)
43
t
=
0
where the constant
R
depends on properties of the tissue.
Commonly used values are 0.25 for
T
≤ 43°C and 0.5 for
T
>
43°C (Sapareto and Dewey 1984), and the commonly accepted
threshold for protein denaturation is 240
CEM
43
(Sapareto and
Dewey 1984, Damianou 1994), although there is some depen-
dence on tissue type.
In order to illustrate the effects of different temperature histo-
ries on tissue in such a way that is relevant to ultrasound-based
TABLE 5.1
Typical Ultrasound Parameters and Treatment Depths
Associated with Different Thermal Therapies
Frequency
(MHz)
Intensity
(W/cm
2
)
Treatment
Depth (cm)
Physiotherapy
0.75-5
<1 SATA
≤5
Hyperthermia
0.5-5
<10 SPTA
<12
HIFU
1-3
>1500 SPTA
<20
