o_1977r8vv9vk1ts2ms0kd8pksa.pdf

98 D. Maulik
fluid media develops shock waves with high-frequency
harmonics before entering soft-tissue media.
Tissue Characteristics for Thermal Effect
Ultrasound-induced tissue heating is determined by
the balance between heat generation and heat loss
(Fig. 8.1). The ultrasound-induced temperature increase
in biological tissue depends on the inherent
acoustic properties of the tissue that determine heat
generation. These include its acoustic impedance and
the attenuation and absorption of the sound in the
tissue which leads to conversion of sound energy to
thermal energy. The degree of ultrasound-induced
temperature is directly related to the absorption coefficient
of the tissue [16, 17]. The actual temperature
elevation is also dependent on the factors that control
dissipation of heat in the tissue and include tissue
perfusion and thermal conduction and diffusion. The
impact of tissue heating depends on the mechanisms
that control cellular response to heating, the specific
types of tissue, and the anatomic configuration, such
as proximity to bone. These are discussed below.
Cellular Response to Heating,
Acoustic Power, and Temporal Threshold
The cellular and tissue response to hyperthermia has
been extensively investigated in relation to cancer
therapy. Cells and tissues differ in their response to
heat. Nonlethal temperature elevation induces cells to
mobilize defensive mechanisms constituting what is
known as the heat-shock response. The response essentially
involves induction of genes that encode a
spectrum of protective proteins known as heat-shock
proteins (HSP) [18]. The dominant group in eukaryotic
cells is the HSP70 family although other HSP
families are also involved. Nonlethal temperature elevations
above the normal induce synthesis of the
HSPs which then act as molecular chaperones and
prevent protein denaturation or aggregation. These
protective mechanisms, however, become rapidly ineffective
if the tissue temperature exceeds 438C. Beyond
this threshold the duration and the magnitude
of temperature elevation determine the thermal injury,
with each degree of temperature elevation reducing
the temporal threshold for thermal effect by a
factor of 2 [19]. As discussed by Duck [20], these
considerations, especially the exponentially decreasing
temporal threshold for producing thermal injury
with the increasing acoustic power, assist in defining
the safe upper limits of power. For example, if insonation
with an acoustic power equivalent to a TI of
6.0 raises tissue temperature to 43 8C, and thermal injury
occurs after 30 min of such exposure, doubling
that acoustic power will markedly reduce the time
threshold to only 30 s. This theoretical scenario is
based on the available experimental evidence and
theoretical analyses. The practical implications are
further considered below. As many currently marketed
devices are capable of producing a TI of 6.0
[21], great caution should be exercised in using such
instruments.
Experimental Evidence of Thermal Effects
Because of the importance of thermal injury in any
consideration of ultrasound biosafety and the potential
of temperature elevation from the current generation
of ultrasound diagnostic devices especially with
spectral pulsed Doppler applications, thermal effects
have been extensively investigated. Animal studies
have demonstrated that embryonic and fetal tissues
are more prone to thermal injury during organogenesis
with rapidly replicating and differentiating cells
[22]. Furthermore, germ cells in the fetal gonads,
especially the testes, continue to be vulnerable to
temperature elevation; this may compromise future
fertility. Hyperthermia is a proven teratogen and thermal
teratogenesis is threshold dependent [23]. The
spectrum of thermal teratogenic effects include abortion,
neural tube defects, decreased brain growth, anophthalmia,
cataracts, cleft lip and cleft palate, and
heart, skeletal, spinal, vertebral, and dental defects
[17].
However, extrapolating experimental findings to
clinical situations remains challenging. It is difficult
to justify that experimental conditions such as wholebody
heating are applicable to the circumstances of
clinical diagnostic ultrasound. Nevertheless, these
data help to define boundary conditions of safe use.
For exposures lasting up to 50 h, no significant biological
effects have been observed when temperature
Fig. 8.1. Factors contributing to the
thermal effect of ultrasound in a tissue
medium