Page 84 - Biomedical Engineering and Design Handbook Volume 1, Fundamentals

HEAT TRANSFER APPLICATIONS IN BIOLOGICAL SYSTEMS 61

1986; Song, 1991). Decreased tumor perfusion may induce changes in the tumor microenvironment,
such as reduced pH value and energy supply, thus enhance the thermal cytotoxicity (Gerweck, 1977;
Overgaard, 1976; Song et al., 1994). An injection of hydralazine to dogs was reported to decrease
the blood flow by 50 percent in the tumor and increase the blood flow in the underlying muscle by
a factor of three (Song, 1984). It was demonstrated that the use of vasoactive drugs led to intracel-
lular acidification of the tumor environment (Song et al., 1994). It has been shown that 1 hour after
an intravenous or intraperitoneal injection of KB-R8498, the blood flow in the SCK mammary car-
cinoma tumors of mice was reduced 30 to 60 percent (Griffin et al., 1998; Ohashi et al., 1998). The
effect has also been made to induce a blood flow increase in the normal tissue. It was reported that
preferentially dilating vessels in normal tissues using vasodilator such as sodium nitroprusside led to
shunting of blood away from the tumor, and thus reducing the cooling effect of the blood flow in a
tumor during local hyperthermia (Jirtle, 1988; Prescott et al., 1992). Not surprisingly, radiation
also altered the response of vasculatures to heat. It was reported that irradiation with 2000 R given
1 hour before heating at 42°C for 30 minutes, enhanced the heat-induced vascular damage in the
cervical carcinoma of hamsters. Another research showed that hyperthermia of 42°C for 1 hour,
given several weeks after irradiation, enhanced the capacity of blood flow increase in skin and
muscle (Song, 1984).
It has been increasingly evident that the response of vascular beds to heat in tumors differs con-
siderably from that in normal tissues. The effective clinical use of hyperthermia depends on a
careful application of these biological principles emerging from experimental work. More experi-
mental measurements of temperature response are needed for different tumor types at different ages.
It is also important to evaluate the applicability of the dynamic response measured in animal to
human subjects. Another issue to be addressed is the hyperthermia-induced blood flow change in
drug delivery, since the reduced tumor blood flow may decrease the drug delivered to the tumors.

2.5.5 Theoretical Modeling
In treatment planning, quantitative three-dimensional thermal modeling aids in the identification of
power delivery for optimum treatment. Thermal modeling provides the clinician with powerful tools
that improve the ability to deliver safe and effective therapy, and permits the identification of criti-
cal monitoring sites to assess tumor heating as well as to ensure patient safety. Thermal modeling
maximizes the information content of (necessarily sparse) invasive thermometry. The empirical tem-
perature expression (if it is possible) can be used to develop an online reference for monitoring tissue
temperatures and building a feedback control of the applied power to avoid overheatings in critical
tissue areas during the hyperthermia therapy.
Tissue temperature distributions during hyperthermia treatments can be theoretically determined
by solving the bioheat transfer equation (continuum model or vascular model), which considers the
contributions of heat conduction, blood perfusion, and external heating. In addition to geometrical
parameters and thermal properties, the following knowledge must be determined before the simu-
lation. The SAR distribution induced by the external heating device should be determined first. The
regional blood perfusion in the tissue and tumor and their dynamic responses to heating are also
required. All this information, with appropriate boundary and initial conditions, allows one to calcu-
late the temperature distribution of the tissue.
Analytical solution for the temperature field during the hyperthermia treatment is available for
certain tissue geometries (Liu et al., 2000; Zhu and Xu, 1999). In most of the situations, temperature
field is solved by numerical methods because of the irregular tissue geometry and complicated
dynamic response of blood flow to heating (Chatterjee and Adams, 1994; Charny et al., 1987; Clegg
and Roamer, 1993; Zhu et al., 2008a, 2008b).
Parametric studies can be performed to evaluate the influence of different parameters, such as
heating level, tissue perfusion, and cooling fluid, on the temperature elevation. Extensive parametric
studies can be performed quickly and inexpensively so that sensitive (and insensitive) parameters can
be identified, systems can be evaluated, and critical experiments can be identified. This is especially
important when the parameter is unknown. It is also possible to extract the ideal SAR distribution