Biomedical Engineering Reference
In-Depth Information
the exposure time is 1 second [26],
irreversible cell death will be
induced through coagulation necrosis. In fact, the temperature
at a focal volume may rise rapidly above 80°C during HIFU treat-
ments [27].
A steep temperature gradient is detected between the
focus and normal non-focal surrounding tissue, and therefore
sharp demarcation between the treated and untreated tissue is
demonstrated in histological examination.
The second mechanism is acoustic cavitation [28].
Acoustic
cavitation can be defined as the interaction of a sound field with
the microscopic gas bodies in a sonicated medium. The presence
of small gaseous nuclei existing in subcellular organelles and
fluid in tissue are the source of cavitation, which can expand and
contract under influence of the acoustic pressure. During the
collapse of bubbles, the acoustic pressure is more than several
thousand pascals, and the temperatures reach several thousand
degrees Celsius [29]. Therefore, it may cause tissue damage that
is less predictable than the effect to tissue shape and position
caused by heating [30].
However, recent experimental studies
have been investigating the idea of promoting cavitation for
enhancing the level of ablation and reducing required exposure
t i me is [31].
This is in contrast to previous approaches, where cavi-
tation was viewed as an unpredictable damage mechanism that
should be avoided [32].
In addition, acoustic cavitation, one of mechanical effects
induced by HIFU ablation, is the most important nonthermal
mechanism for tissue disruption in the ultrasound field [28]. The
presence of small gaseous nuclei existing in subcellular organ-
elles and fluid in tissue are the source of cavitation, which can
expand and contract under influence of the acoustic pressure.
During the collapse of bubbles, the acoustic pressure is more
than several thousand pascals, and the temperatures reach sev-
eral thousand degrees Celsius, resulting in the local destruction
of the tissue [29, 30].
15.3.2 thermal Effects on tumor Vasculature
Structural and functional changes are directly observed in
tumor vasculature after thermal ablation. These changes are
not as well described as thermal effects on the tissues, but they
rely on varying temperatures. At temperatures between 40°C
and 42°C, there is no significant change in tumor blood flow
after 30-60 min exposure [38]. Beyond 42°C to 44°C, there
is an irreversible decrease in tumor blood flow, with vascu-
lar stasis and thrombosis, resulting in heat trapping and pro-
gressive tissue damage [39]. When temperatures exceed 60°C,
immediate destruction of tumor microvasculature occurs [40].
It cuts the blood supply to the tumor directly through the
cauterization of the tumor feeder vessels, leading to depriva-
tion of nutrition and oxygen. Thus, tissue destruction can be
enhanced by the damage caused by thermal ablation to tumor
blood vessels.
15.3 Biological Effects of thermal
ablation on tumor
Thermal ablation can cause direct and indirect damage to a tar-
geted tumor. Direct and indirect heat injury occurs during the
period of heat deposition, and it is predominately determined by
the total energy delivered to the targeted tumor [33]. Secondary
injury usually occurs after thermal ablation, which produces a
progression in tissue damage. It may involve a balance of sev-
eral factors, including microvascular damage, cellular apoptosis,
Kupffer cell activation, altered cytokine release, and antitumor
immune response [34]. Direct injury is generally better defined
than the secondary indirect effects.
15.3.3 Secondary Effects on tumor
Indirect injury is a secondary damage to tissue, which progresses
after the cessation of thermal ablation stimulus [34]. It is based
on histological evaluation of tissue damage at various time points
after thermal ablation. The full extent of the secondary tissue
damage becomes evident one to seven days after thermal abla-
tion, depending on the model and energy source used [41, 42].
The exact mechanism of this process is still unknown. However,
it may represent a balance of several promoting and inhibiting
mechanisms, including induction of apoptosis, Kupffer cell acti-
vation, and cytokine release.
Cellular apoptosis may contribute to the progressive injury
of tissue after thermal ablation. It is well established that apop-
tosis increases in a temperature-dependent manner, and tem-
peratures between 40°C and 45°C cause inactivation of vital
enzymes, thus initiating apoptosis of tumor cells [43, 44]. Most
thermal ablation techniques create a temperature gradient
that progressively decreases away from the site of probe inser-
tion. The induction of apoptosis at a distance from the heat
source may potentially contribute to the progression of injury.
Increased rate of apoptosis is observed in the liver 24 hours
after microwave ablation. The stimulation of apoptosis may be
directly induced by temperature elevations, alterations in tissue
microenvironment, and the release of various cytokines after
thermal ablation.
15.3.1 Direct thermal and Nonthermal
Effects on tumor
The effects of thermal ablation on a targeted tumor are determined by
increased temperatures, thermal energy deposited, rate of removal
of heat, and the specific thermal sensitivity of the tissue. As the tissue
temperature rises, the time required to achieve irreversible cellular
damage decreases exponentially. At temperatures between 50°C
and 55°C, cellular death occurs instantaneously in cell culture [35].
Protein denaturation, membrane rupture, cell shrinkage, pyknosis,
and hyperchromasia occur
ex vivo
between 60°C and 100°C, lead-
ing to immediate coagulation necrosis [36]. Tissue vaporization and
boiling are superimposed on this process when the temperature is
greater than 105°C. Carbonization, charring, and smoke generation
occur while the temperature is over 300°C [37].
