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Handbook of Thermal Science and Engineering (B-Ok - CC) - 2278-2304

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Part VII
Heat Transfer in Biology and Biological
Systems
Thermal Properties of Porcine and Human
Biological Systems 54
Shaunak Phatak, Harishankar Natesan, Jeunghwan Choi,
Robert Sweet, and John Bischof

Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2280
2 Thermal Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2282
2.1 Thermal Conductivity Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2282
2.2 Specific Heat Capacity Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2284
3 Factors That Affect Thermal Property Values . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2285
3.1 High-Temperature Effects (37  C –100  C): Protein Phase Change
and Water Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2286
3.2 Low-Temperature Effects (37  C to 196  C): Water Phase Change
and Cryoprotectant Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2287
4 Modeling Case Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2290
5 Thermal Properties Dataset Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2293
6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2300
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2301

Abstract
For applications of bioheat transfer such as thermal therapies and cryopreserva-
tion, the temperature excursions experienced by a biomaterial can be directly
correlated to the injuries that may occur in the system. Thermal modeling is an
important tool in order to predict this temperature history as it is not always
possible to experimentally measure the temperature and cooling/heating rates

S. Phatak (*) · H. Natesan · J. Bischof


Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA
e-mail: [email protected]; [email protected]; [email protected]
J. Choi
Department of Engineering, East Carolina University, Greenville, NC, USA
e-mail: [email protected]
R. Sweet
Department of Urology, University of Washington, Seattle, WA, USA
e-mail: [email protected]

# Springer International Publishing AG, part of Springer Nature 2018 2279


F. A. Kulacki (ed.), Handbook of Thermal Science and Engineering,
https://doi.org/10.1007/978-3-319-26695-4_76
2280 S. Phatak et al.

experienced by the biomaterials. These models make use of temperature-


dependent thermal properties in order to accurately predict the thermal histories
experienced by the systems. This review chapter focuses on listing literature data
of human and porcine systems for thermal conductivity and specific heat capacity
in the cryogenic, subzero, and suprazero temperature ranges. At subzero and
cryogenic temperatures, thermal properties are affected by phase change (water to
ice) and vitrification or glass formation in the presence of cryoprotectants,
whereas water loss and protein denaturation are important factors at suprazero
temperatures. Finally, a modeling case study is provided demonstrating the use
and necessity of temperature-dependent properties in order to make accurate
predictions for thermal history.

1 Introduction

Bioheat transfer, a key component in the field of thermal medicine, has tradition-
ally been important to understand for the purpose of two main areas: thermal
therapies and bio- or cryopreservation. Thermal therapy is the application of hot or
cold temperatures to destroy undesirable tissues, such as tumors within the body
(Sapareto and Dewey 1984; Chu and Dupuy 2014). Cryopreservation is the
preservation of biomaterials for a number of applications, such as organ transplan-
tation, in vitro fertilization, and food preservation, through cooling systems to
very low temperatures (<80  C) to arrest biological activity (Karlsson and
Toner 1996). Cryopreservation can be achieved by slow freezing where addition
of cryoprotectants such as glycerol and dimethyl sulfoxide (DMSO) avoids
intracellular ice formation or by fast cooling techniques that result in vitrification
or glass formation due to the presence of cryoprotectants. Successful organ
banking through cryopreservation would increase the number of possible trans-
plantations; currently one in five patients dies due to a lack of an availability of
viable organs (Lewis et al. 2016). More information regarding these applications
can be found in the references provided in Table 1. More recently, interest in the
thermal properties of human tissues has increased for the purpose of developing
predictive models for training and assessment of skills related to thermal interven-
tions and conditions.
For all applications of bioheat transfer, the temperature excursions of the bio-
materials can be correlated to the injury that may occur in the system (He and
Bischof 2003). Thus, thermal modeling is necessary to predict the thermal history
and hence the injury, since it may not be always possible to measure temperature
experimentally. Hence, analytical or numerical models become valuable in order to
study the process. In cryopreservation, knowledge about thermal history and cooling
rates will help in understanding the phases through which a particular system passes,
i.e., liquid, crystal, and glassy/vitreous states. The cooling and heating rates encoun-
tered in these systems can help define whether a system will pass through these
various phases. Temperature gradients experienced due to fast cooling required
54 Thermal Properties of Porcine and Human Biological Systems 2281

Table 1 Overview of common bioheat transfer applications


Application Temperature Definition Rep. ref.a
Biopreservation Vitrification <140  C Preservation by Fahy et al. (1984)
attaining a glassy and Song et al.
state (2000)
Freezing <20  C Preservation by Mazur (1984) and
freezing in presence Karlsson and Toner
of cryoprotectants (1996)
Lyophilization/ <20  C Preservation by Crowe et al. (1992)
freeze-drying drying after freezing and Carpenter et al.
(1997)
Hypothermic 0–37  C Preservation at Belzer and
preservation temperatures between Southard (1988)
0 C and 37 C and Steponkus
(1996)
Biodestruction Cryotherapy/ <20  C Destruction of tissue Gage and Baust
cryoablation by freezing (1998) and
Hoffmann and
Bischof (2002)
Mild 37–45  C As an adjuvant to Sapareto and
hyperthermia sensitize tumors to Dewey (1984)
radiation and
chemotherapy
Thermal >50  C Destruction of tissue O’Neal et al.
ablation by heating (2004)
a
Representative reference (Reproduced from Natesan and Bischof (2016) with permission from
ACS Publications)

for vitrification also affect stress development in the sample and can cause cracking.
For more information on these topics, see Fahy et al. (1984), Rabin et al. (1998), and
Choi and Bischof (2010). In the case of cryosurgery, thermal history again would be
an indicator of destruction of the tissue or tumor in the biological system. Mecha-
nisms believed to cause damage include direct cell injury, vascular injury, and
immunological injury. These injuries depend upon the cooling and thawing rates,
the minimum end temperatures, and the hold times at these temperatures. As an
example, tumor destruction is associated with a minimum lethal temperature. A heat
transfer model can help understand these temperature distributions and cooling and
heating rates, so as to correlate with actual experimental results (Rabin and Shitzer
1998; Etheridge et al. 2013). The interested reader is directed to Rubinsky (2000),
Hoffmann and Bischof (2002), Baust and Gage (2005), and Sabel (2009) for more
details regarding the injury mechanisms associated with cryosurgery. During thermal
therapy, heating results in water loss and protein denaturation. These events lead to
reduction in the thermal conductivity and specific heat capacity of the system of
interest. Thus, temperature-dependent thermal properties are needed when used in a
model, as these directly will affect the thermal histories. For more information
regarding the effects of higher temperatures on thermal properties, please refer to
Rossmann and Haemmerich (2014).
2282 S. Phatak et al.

Heat transfer in biological systems is a complex process influenced by a variety of


mechanisms: for example, conduction within tissues, convection as well as perfusion
due to blood circulation, metabolic heat generation, heat exchange between different
blood vessels and also thermoregulation effects including shivering, and vasodila-
tion. An example is the classic Pennes bioheat equation (Pennes 1948),
 
@T @ @T
ρCp ¼ k þ q_ m þ q_ p
@t @x @x

where ρ, Cp , T, k and q_ m are the tissue density, specific heat capacity, temperature,
thermal conductivity, and metabolic heat generation per unit volume. Energy
exchange between blood and tissue is denoted by the perfusion term q_ p given as,

q_ p ¼ ωρb Cpb ðT a  T Þ

where ρb and Cpb are the blood density and specific heat capacity, respectively, ω is
the perfusion rate, and Ta is the arterial blood temperature. As seen in the Pennes
equation, the tissue thermal properties (i.e., density, specific heat capacity, and
thermal conductivity) need to be determined in order to obtain the thermal history
of the system for the abovementioned applications. In addition to the Pennes
equation, many other models have been formulated to study these processes. In
order to formulate these heat transfer models, readers may refer to Charny (1992),
Diller (1992), Arkin et al. (1994), and Baish (2000).

2 Thermal Properties

Thermal properties focused in this chapter include thermal conductivity and


specific heat capacity. The following are brief discussions on their measurement
techniques.

2.1 Thermal Conductivity Measurement

Thermal conductivity (k, W/mK) is a material property, a measurement of its ability


to conduct heat. It is influenced by composition (i.e., water, lipid, proteins, and
added cryoprotectants), phase (i.e., liquid, crystalline, and amorphous phases), and
temperature. Some methods used to measure thermal conductivity of biomaterials
have been given in Table 2. These measurements use either a known heat flux or a
known temperature gradient as depicted in the Fig. 1. Thermal conductivity mea-
surement techniques can be divided into two types: steady-state and transient
methods.
54 Thermal Properties of Porcine and Human Biological Systems 2283

Table 2 Overview of k measurement techniques


Heat
Heat Temperature transfer
Technique source measurement model Directionality References
Guarded hot Thermal Thermocouple Steady Cross-plane Hill et al. (1967)
plate method (TC) state, 1-D, and Poppendiek
longitudinal et al. (1967)
Thermal Thermal Probe Transient, Not sensitive Vendrik and Vos
comparator (effective TC) 1-D, (1957), Morley
cylindrical (1966) and
Vachon et al.
(1967)
Radial heat Thermal Thermocouple Steady In-plane Glassbrenner and
flow method (TC) state, 1-D, Slack (1964)
cylindrical
Heated Electrical Thermocouple Transient, Not sensitive Grayson (1952)
thermocouple (TC) 1-D,
method spherical
Transient hot Electrical Thermocouple Transient, Not sensitive Bhattacharya and
wire method (TC) 1-D, Mahajan (2003)
cylindrical and Ehrlich et al.
(2015)
Chato’s probe Electrical Thermocouple Transient, Not sensitive Chato (1968) and
(TC) 1-D, Balasubramaniam
spherical and Bowman
(1977)
Pulse decay Electrical Thermocouple Transient, Not sensitive Chen et al. (1981),
(single (TC) 1-D, Valvano et al.
pulse) spherical 1985), and Patel
et al. (1987)
3ω Electrical Third Quasi- Radial (bulk Cahill and Pohl
harmonic steady state, samples), (1987) and Lubner
voltage 1-D, cross-plane et al. (2015)
response cylindrical (thin films)
Reproduced from Natesan et al. (2016a) with permission from World Scientific

In the case of steady-state methods, information about heat flux and temperature
response from the sample is used in a heat transfer model in order to calculate
thermal conductivity. Some drawbacks of these methods include long times
( several hours depending on sample size) and are needed to reach steady state,
and a proper “guarding” is needed to prevent heat losses, thus leading to a need for a
1-D heat transfer model. Another problem with these methods is that of contact
resistance between the sample and energy source.
As compared to steady-state techniques, transient methods can be performed
quickly (<1 min). For these methods, a cylindrical or spherical probe can be inserted
into the sample to supply heat as well as measure temperature simultaneously.
Although faster than steady-state methods, these techniques also suffer from the
problem of contact resistance between the sample and probe. The heat flow thus
2284 S. Phatak et al.

Fig. 1 Schematic of most thermal conductivity measurement techniques (Reproduced from


Natesan et al. (2016a) and permission has been requested)

needs to penetrate deeper into the sample leading to negligible contact resistance at
long time scales of heating. This necessitates a size requirement of >10 mm thus
restricting these techniques for use in thick samples. Also being invasive, they may
cause tissue damage.
Lastly, a recent method used for thermal conductivity is the 3ω method which
belongs to a third category called as a “quasi-steady” technique. In this case, a thin
gold heater line is micro-fabricated on to a glass substrate. The measurement times
for this method are in the range of tens of minutes and can handle sample sizes in the
range 0.1–2 mm. These methods have been reviewed previously in the following
references: Diller et al. 2000, Choi and Bischof 2010, and Natesan et al. 2016a.

2.2 Specific Heat Capacity Measurement

Specific heat capacity (Cp, J/g- C) is a material property that denotes the amount of
heat that should be transferred to a material to raise its temperature by unit temper-
ature (e.g., degree Celsius). In the case of biomaterials, it is important to measure
their Cp as a function of temperature. For example, in a wide temperature range (say
150  C to 20  C), cryoprotectants pass through different states, such as liquid, ice,
and vitrified (amorphous or glassy states), with each of these phases having a
different Cp, thus necessitating temperature-dependent properties. The most com-
mon technique used to measure Cp is differential scanning calorimetry (DSC). DSC
is capable of measuring Cp as well as latent heat of relatively small sample sizes
(3–100 mg) over a wide temperature range of 180  C to 750  C (Natesan and
Bischof 2016). The technique measures the difference in the heat flow rate to the
sample and reference pans while maintaining the same temperature program (Höhne
et al. 1996). The reference sample has known thermal properties. This difference in
heat flow can then be plotted as function of temperature or time. Using this measured
differential heat flow (ϕsample), the Cp can then be calculated,
54 Thermal Properties of Porcine and Human Biological Systems 2285

1 dϕsample dt
Cp ¼ :
m dt dT
In terms of the heating technique used, there are two types of conventional DSC,
viz., standard DSC with linear heating and modulated DSC (M-DSC) with modu-
lated heating. In the case of standard DSC, the sample and reference are heated
through a linear temperature program. There are two types of standard DSC, viz., the
heat flux (HF) DSC and the power compensated (PC) DSC. The HF DSC consists of
a single furnace area in which the sample and reference pans are loaded and
temperatures measured with thermocouples. The temperature difference between
the sample and reference pans is then used to calculate the differential heat flow. For
a PC DSC, there are two separate furnaces wherein the sample and reference pans are
loaded separately. The principle of this DSC, as well as its differentiator from the HF
DSC, is that the temperature difference between sample and reference pans is kept
zero by increasing or decreasing the heat flow to the sample in the event of a
transition (e.g., phase change from water to ice) in the sample. For reliable mea-
surements, it is necessary to calibrate the DSC, which usually consists of three steps:
baseline calibration (accounts for instrument discrepancies), temperature calibration
(considers differences between measured and actual values of transition tempera-
tures), and heat flow calibration (calculates a factor to correct differences between
measured and actual heat flow rates). In the case of M-DSC, two simultaneous
heating rates are used, i.e., a sinusoidal heating rate along with a linear heating rate.
This DSC is capable of simultaneously measuring both the Cp of the sample as well
as kinetic processes such as phase change (Reading et al. 1993, 1994; Marcus and
Reading 1994; Natesan and Bischof 2016). The linear rate provides information
similar to the standard DSC (irreversible heat flow events such as crystallization),
whereas the sinusoidal rate is capable of making reversible heat flow measurements
such as Cp of the sample. A limitation of the conventional DSC is the comparatively
low scanning rates (<750  C/min) associated with it. For example, while studying
vitrification (glass formation) of dilute cryoprotectants, a very high cooling rate is
needed to vitrify the system without causing crystallization, and this cannot be
attained in a conventional DSC. This limitation can be addressed by the development
of nanocalorimetry (Yi et al. 2014) on a silicon-based membrane that can work with
a very small sample weight (10 ng), which leads to the possibility of very high
heating or cooling rates albeit with considerable sample preparation challenges
(107  C/min).

3 Factors That Affect Thermal Property Values

The focus of this chapter is on organizing literature data for thermal conductivity and
specific heat capacity of human and porcine systems in the cryogenic, subzero, and
suprazero temperature ranges. All the data provided here has resulted from actual
measurements presented in primary research papers. Apart from primary papers,
there are some databases available such as the one by IT’IS Foundation associated
2286 S. Phatak et al.

0.7
Porcine Liver 1
Human Liver 1
Porcine Liver 2
0.6
Porcine_Myocardium 2
Thermal Conductivity [W/m-K]

Porcine Pancreas 2
Porcine Renal Cortex 2
0.5 Human Liver 2
Human Renal Pelvis 2
Human Renal Medulla 2
0.4 Human Pancreas 2
Porcine Myocardium 3
Human Kidney 3
0.3 Human mesentary 3
Human Omentum 3
Human Gerota's Fascia 3

0.2 Human Fat of Spleen 2


0 20 40 60 80 100
Water
Temperature [oC]

Fig. 2 Thermal conductivity datasets in the suprazero range where “1” refers to Choi et al. (2013),
“2” refers to Valvano et al. (1985), and “3” refers to Choi et al. unpublished listed in Tables 6, 7, and 8

with ETH Zurich (Hasgall et al. 2015). In addition there are reviews on this topic
such as Bowman et al. (1975), Diller et al. (2000), and Duck (2013). Blood perfusion
results have not been taken into account in the data presented in this chapter. The
interested reader may refer to Valvano (1995), Yuan et al. (1998, Diller et al. (2000),
Liu et al. (2000), and Bhattacharya and Mahajan (2003) for details regarding
perfusion associated measurements.
Some factors that influence the thermal properties of biomaterials are discussed
below.

3.1 High-Temperature Effects (37  C –100  C): Protein Phase


Change and Water Loss

In the case of high temperatures, the values of thermal properties generally rise from
0  C up to roughly 45  C where protein denaturation and water loss can play a role.
After 45  C, there is much less data, although it would appear that water loss plays a
more prominent role as compared to protein denaturation resulting in lower values of
k and Cp. This drop in thermal conductivity can be seen in Fig. 2 for the human
kidney, mesentery, omentum, and Gerota’s fascia. The lower k values for mesentery,
Gerota’s fascia, and omentum are due to a higher fat content in these systems.
Similarly, human fat of spleen also exhibits lower k values due to the presence of
fat in the system. Protein denaturation occurs as a heat absorption event over a finite
54 Thermal Properties of Porcine and Human Biological Systems 2287

Porcine Liver
3
Porcine Pulmonary Vein

2.5 Porcine Esophagus


Thermal Conductivity [W/m-K]

Porcine Phrenic Nerve


2
Porcine Myocardium

Porcine Fat
1.5
Porcine Perpendicular to
Fiber
1 Porcine Parallel to Fiber

Porcine Leg
0.5 Porcine Neck

Porcine Exterior
0
-150 -100 -50 0 50 Water
Temperature [0C]

Fig. 3 Thermal conductivity datasets in the subzero and cryogenic range (datasets have been listed
in Tables 4 and 5)

temperature range. The interested reader can refer to Bhattacharya and Mahajan
(2003), Guntur et al. (2013), and Choi et al. (2013) for more details regarding these
high-temperature effects.

3.2 Low-Temperature Effects (37  C to 196  C): Water Phase


Change and Cryoprotectant Effects

Thermal properties of biomaterials at low temperatures are affected by two factors:


phase change (water to ice) and the presence of cryoprotectants. Freezing or crys-
tallization of water to ice results in an increase in thermal conductivity values at
subzero temperatures as ice has a higher thermal conductivity compared to water.
This general trend of increasing values of thermal conductivity can be observed in
Fig. 3 or various biomaterials. In contrast, specific heat capacity values show lower
values at subzero temperatures as ice has a lower specific heat capacity when
compared to water. This general trend of decreasing values of specific heat capacity
for various biomaterials can be observed in Fig. 4. The values of both thermal
conductivity and specific heat capacity of most biomaterials are lower than those
of water. The amount by which these values differ with respect to water depends
upon the water content in these systems although it is clearly accentuated at supra-
zero temperatures and when cryoprotectants are added.
2288 S. Phatak et al.

4.5
Human Liver
4
Specific Heat Capacity [J/g-K]

Porcine Lung
3.5

3 Porcine Myocardium

2.5
Phrenic Nerve
2
Porcine Esophagus
1.5

1 Pulmonary Vein

0.5
Water
0
-100 -50 0 50
Temperature [oC]

Fig. 4 Specific heat capacity for biomaterials without cryoprotectants (datasets have been listed in
Tables 4, 5, and 6)

3
Porcine Liver+ 2M Glycerol
2.5
Thermal Conductivity [W/m-K]

Porcine Liver+ 6M Glycerol


2

1.5 Porcine Liver+ 8M Glycerol

1 Porcine Liver

0.5
Water

0
-150 -100 -50 0 50
Temperature [0C]

Fig. 5 Thermal conductivity datasets for porcine liver with and without cryoprotectants (datasets
have been listed in Tables 5 and 10) (Reproduced from Choi and Bischof (2008) and permission has
been requested)

In addition to freezing effects, thermal properties of biomaterials are also affected


by the presence of cryoprotectants. At lower temperatures (<100  C), the systems
experience glass transition, i.e., formation of a glassy or vitreous state due to
cryoprotectants. Both thermal conductivity and specific heat capacity values are
54 Thermal Properties of Porcine and Human Biological Systems 2289

4.5
Porcine Liver
4
Specific Heat Capacity [J/g-K]

3.5
Glass Transition Porcine Liver+ 2M
3 Glycerol

2.5
Porcine Liver+6M Glycerol
2

1.5
Porcine Liver+ 8M
Glycerol
1

0.5 Water

0
-150 -100 -50 0 50
Temperature [oC]

Fig. 6 Specific heat capacity for porcine liver with and without cryoprotectants (datasets have been
listed in Tables 5 and 10) (Reproduced from Choi and Bischof (2008) with permission from
Elsevier)

lowered due to this glass formation in the system. As seen in Fig. 5, thermal
conductivity values for porcine liver treated with various concentrations of glycerol
are lower as compared to porcine liver without any glycerol and continue to drop
with higher concentrations of glycerol. The freezing or crystallization effects which
tend to increase thermal conductivity are suppressed at lower temperatures in the
presence of cryoprotectants which results in these lower thermal conductivity values.
In the case of specific heat capacity, as mentioned above, the values drop in the
presence of cryoprotectants (150  C to 100  C) due to the formation of the glassy
or vitreous phase. Further, glass transition effects can be seen as a slight jump in the
specific heat capacity values around 100  C in Fig. 6. This jump results from the
conversion of the glassy phase to a liquid phase. Beyond glass transition, the rise in
values at higher temperatures is initially due to conversion of the glassy phase to a
liquid phase as mentioned above and later due to melting of the ice present in the
system to water knowing that the specific heat capacity of water is greater than ice as
well as the glassy phase. Figure 7 consists of thermal conductivity datasets for a
number of cryoprotectants that can be useful when performing heat transfer simula-
tions for cryopreservation. In addition, data has also been provided for ultrasound gel
(US Gel) which can be used as tissue phantom in the absence of property data for the
required biomaterial.
The general trends seen in Fig. 7 are same as those observed in the case of porcine
liver treated with glycerol in Fig. 5. The thermal conductivity values increase at
lower temperatures due to ice formation, whereas the presence of the glassy phase
due to cryoprotectants at temperatures <100  C results in lower or constant
2290 S. Phatak et al.

3
2M Glycerol

2.5 6M Glycerol
Thermal Conductivity [W/m-K]

2M DMSO
2

6M DMSO

1.5
10M DMSO

1 DP6 Euro Collins Solution

US Gel
0.5
Water

0
-150 -100 -50 0 50
0
Temperature [ C]

Fig. 7 Thermal conductivity datasets for cryoprotectants (datasets have been listed in Table 9)

thermal conductivity values. Also, as the concentration of cryoprotectants increases,


the thermal conductivity values are lowered as the ice formation is suppressed by the
glassy phase. These trends can be seen in Fig. 7 for DMSO and glycerol. The
interested reader is directed to Zhang et al. (2002), Choi and Bischof (2008), and
Ehrlich et al. (2016) for more discussion regarding low temperature and cryopro-
tectants related to k and Cp measurements.

4 Modeling Case Study

This section provides an example from Bischof and Han (2002) showing the
importance of temperature-dependent properties for numerical predictions of heat
transfer applied for cryopreservation and cryosurgery. A numerical technique known
as the enthalpy method has been used to solve the heat transfer with phase change
problem for cryopreservation and cryosurgery. The governing equation for this
method (Ozisik 1994) is,

@H ðT Þ
ρ ¼ ∇  ðk∇T Þ þ gðT Þ
@t
where ρ , H , T , t , k , and g(T) are density, enthalpy, temperature, time, thermal
conductivity, and heat generation per unit volume.
The above equation is a modified version of the transient heat equation where
enthalpy and temperature are dependent variables. In other techniques used for
54 Thermal Properties of Porcine and Human Biological Systems 2291

Fig. 8 Thermal properties of 6


water used for modeling case Cp Water
study (Reproduced from k Water
5
Bischof and Han (2002) with

k [W/(m-K] or Cp [J/g-K]
permission from Elsevier)
4

0
65 115 165 215 265 315 365
Temperature [K]

solving phase change, such as source tracking method, two equations are needed to
solve for the frozen and unfrozen region. In addition, an energy balance equation is
included to track the interface between these two regions. The advantage of the
enthalpy method over such methods is that a single equation in terms of enthalpy is
used to solve for both regions and thus no tracking equation is needed. In the case of
pure materials like water, phase change happens at a single temperature, whereas for
biomaterials, phase change occurs over a temperature range called a mushy zone.
The enthalpy method can be used to solve for both these materials. For information
regarding this method and its applicability to cryosurgery and cryopreservation,
readers may refer to Zhang et al. (2005), Choi and Bischof (2010, and Etheridge
et al. (2013).
Constant as well as temperature-dependent thermal properties of water have been
used in these analyses. The thermal properties of water used in this analysis are
provided in Fig. 8 (Bald and Fraser 1982). As shown in Fig. 9, an important
distinction between cryopreservation and cryosurgery is that they have opposite
boundary conditions, i.e., cryopreservation involves cooling from outside to the
center of the system where a symmetric boundary condition can be applied, whereas
cryosurgery involves freezing from the center with a probe to the surface where a
temperature boundary condition (human body temperature) is applied.
Cryopreservation involves cooling the system to temperatures <80  C,
whereas cryosurgery freezes the system to a particular size so that unwanted tissue
is killed. Following are the figures showing temperature history and phase front
propagation for both applications. Each application considers a planar, cylindrical,
and spherical system for a thickness or diameter of 8 cm. For cryopreservation, an
initial condition of body temperature (37  C) is considered over the solution domain.
A temperature boundary condition of 160  C is applied at the surface with a
symmetric boundary condition at the center. As seen in Fig. 10, the phase front
propagation is the fastest for the sphere and lowest for the Cartesian system. Further,
2292 S. Phatak et al.

Fig. 9 Geometry in cylindrical coordinates (Reproduced from Bischof and Han (2002) with
permission from Elsevier)

a 0.08
b 50
Cartesian
Cylindrical
Spherical
Cartesian (T) 0
Temperature [°C]

0.06
Cylindrical (T)
Distance [m]

Spherical (T)

0.04 -50

0.02 -100
r=0 cm
r=2 cm
r=4 cm
r=6 cm
0 -150
0 600 1200 1800 2400 0 500 1000 1500 2000
Time [s] Time [s]

Fig. 10 Numerical simulation for cryopreservation: (a) Phase front propagation (lines with
symbols denote temperature-dependent properties and lines without symbols denote constant
temperature properties), (b) thermal history for a cylinder (lines with symbols denote
temperature-dependent properties and lines without symbols denote constant temperature proper-
ties) (Reproduced from Bischof and Han (2002) with permission from Elsevier)

the temperature-dependent boundary conditions speed up the ice-zone propagation,


which in turn affects the temperature history as shown below.
In the case of cryosurgery, a temperature boundary condition of 160  C (applied
by a cryoprobe) is considered at a radius of 1.5 mm for the radial systems or at one of
54 Thermal Properties of Porcine and Human Biological Systems 2293

a 0.05 b 40
Cartesian
Cartesian (T)
Cylindrical 20
0.04 Cylindrical (T)

Temperature [°C]
Spherical
0
Distance [m]

Spherical (T)
0.03
-20
0.02
-40

0.01
-60 r=4 cm
r=2 cm
r=1 cm
0 -80
0 300 600 900 1200 0 300 600 900 1200
Time [s] Time [s]

Fig. 11 Numerical simulation for cryosurgery: (a) phase front propagation (lines with symbols
denote temperature-dependent properties), (b) thermal history for a cylinder (lines with symbols
denote temperature-dependent properties) (Reproduced from Bischof and Han (2002) with permis-
sion from Elsevier)

Table 3 Organization of thermal property datasets


Table number Description
4 and 5 Porcine systems at subzero temperatures I and II
6 Porcine systems at suprazero temperatures
7 and 8 Human systems at suprazero temperatures I and II
9 Cryoprotectants
10 Porcine liver treated with cryoprotectants

the surfaces (0 mm) for the Cartesian system. The second boundary condition
considers a domain large enough to assume semi-infinite conditions (assuming the
system is at body temperature). The same thermal properties as cryopreservation are
used in this analysis. As seen from the results in Fig. 11, the phase front propagates
fastest for the Cartesian system and slowest for the sphere. As seen before, this
propagation is faster when temperature-dependent properties are used. The inter-
ested reader may refer to Bischof and Han (2002) for more information regarding
this analysis.

5 Thermal Properties Dataset Tables

Table 3 gives a summary of the organization of datasets for porcine and human
systems. These dataset Tables 4, 5, 6, 7, 8, 9, and 10 have been classified
based on the type of system, i.e., porcine or human; the temperature range
2294 S. Phatak et al.

Table 4 Thermal properties of porcine systems at subzero temperature I


Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Pulmonary 0.57(35.9  C) 3.34(39  C) k – (Natesan et al. 2016b)
vein 0.47(14.42  C) 3.27(5  C) Cp – (Unpublished,
1.14(13.77  C) 2.82(1  C) BHMT, UMN)
1.44(30.9  C) 1.87(34  C)
– 1.74(46  C)
– 1.49(72  C)
– 1.38(84  C)
Esophagus 0.55(35.58  C) 3.49(39  C)
0.48(13.99  C) 3.39(9  C)
1.61(17.43  C) 1.92(30  C)
1.84(36.95  C) 1.63(52  C)
– 1.43(74  C)
– 1.29(86  C)
Phrenic 0.45(35.53  C) 3.57(33  C)
nerve 0.5(14.01  C) 3.47(13  C)
1.29(14.01  C) 2.44(18  C)
1.84(34.18  C) 1.83(30  C)
– 1.7(44  C)
– 1.5(66  C)
– 1.35(90  C)
BHMT, UMN Bioheat and Mass Transfer Lab, University of Minnesota
n number of repetitions

Table 5 Thermal properties of porcine systems at subzero temperature II


Thermal
conductivity Specific heat
System type [W/mK] capacity [J/gK] References
Liver 1.6(11  C) 1.92(33.3  C) Choi and Bischof
1.75(64  C) 1.6(65.6  C) (2008)
1.9(112  C) 1.171(113.3  C)
2.01(147  C) 0.95(144  C)
Lung – 3.68(35  C) Unpublished,
– 3.62(13  C) BHMT, UMN
– 2.04(26  C)
– 1.62(58  C)
– 1.44(80  C)
Myocardium (n = 3 for “k,” 0.5352(37  C) 3.62(50  C) Unpublished,
n = 8 for “Cp”) 0.436(0.1  C) 3.59(30  C) BHMT, UMN
1.743(26.25  C) 1.75(34  C)
2.046(94.45  C) 1.508(62  C)
2.312(147.9  C) 1.241(98  C)
(continued)
54 Thermal Properties of Porcine and Human Biological Systems 2295

Table 5 (continued)
Thermal
conductivity Specific heat
System type [W/mK] capacity [J/gK] References
Lean, parallel to fiber 1.43(10  C) – Lentz (1961)
1.61(25  C) –
1.23(10  C) –
1.38(25  C) –
Lean, perpendicular to fiber 0.478(0  C) – Cherneeva (1956)
0.767(5  C) –
0.99(10  C) –
1.29(20  C) –
Lean, neck 0.783(8  C) – Chato (1968)
0.835(8.4  C) –
0.408(9  C) –
Leg 0.49(6  C) – Hill et al. (1967)
1.28(8  C) –
1.3(14  C) –
Fat 0.186(0  C) – Cherneeva (1956)
0.227(5  C) –
0.254(10  C) –
0.291(20  C) –
Fat 0.36(9.1  C) – Chato (1968)
0.366(10  C) – Moline et al.
(1961)
Exterior (93% fat) 0.21(+3 to 24  C) – Lentz (1961)
BHMT, UMN Bioheat and Mass Transfer Lab, University of Minnesota
n number of repetitions

Table 6 Thermal properties of porcine systems at suprazero temperatures


Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Liver 0.5061(10  C) – Valvano et al. (1985)
0.5165(23  C) –
0.5277(37  C) –
0.5341(45  C) –
Lung 0.2561(10  C) –
0.2849(23  C) –
0.3159(37  C) –
0.3336(45  C) –
Myocardium 0.4974(10  C) –
0.5148(23  C) –
0.5334(37  C) –
0.5441(45  C) –
(continued)
2296 S. Phatak et al.

Table 6 (continued)
Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Pancreas 0.4719(10  C) –
0.4745(23  C) –
0.4772(37  C) –
0.4787(45  C) –
Renal cortex 0.5085(10  C) –
0.5237(23  C) –
0.5402(37  C) –
0.5496(45  C) –
Spleen 0.499(10  C)
0.5154(23  C)
0.5332(37  C)
0.5433(45  C)
Liver 0.4889(25  C) 3.4802(23  C) Choi et al. (2013)
0.5021(37  C) 3.4992(31  C)
0.5239(50  C) 3.5864(85  C)
0.5479(80  C) –
Subcutaneous 0.15–0.17 (30–48  C) – Henriques and Moritz
fat (1947)
Skeletal 0.43–0.51 (30–48  C) –
muscle

Table 7 Thermal properties of human systems at suprazero temperature I


Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Renal pelvis 0.4987(10  C) – Valvano et al.
0.5237(23  C) – (1985)
0.5507(37  C) –
0.566(45  C) –
Renal 0.5104(10  C) –
medulla 0.5247(23  C) –
0.5402(37  C) –
0.549(45  C) –
Renal cortex 0.5118(10  C) –
0.5285(23  C) –
0.5466(37  C) –
0.5569(45  C) –
Myocardium 0.5045(10  C) –
0.52(23  C) –
0.5367(37  C) –
0.5463(45  C) –
(continued)
54 Thermal Properties of Porcine and Human Biological Systems 2297

Table 7 (continued)
Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Pancreas 0.4649(10  C) –
0.5019(23  C) –
0.5417(37  C) –
0.5645(45  C) –
Lung 0.4189(10  C) –
0.4341(23  C) –
0.4506(37  C) –
0.46(45  C) –
Liver 0.4808(10  C) –
0.4959(23  C) –
0.5122(37  C) –
0.5214(45  C) –
Spleen 0.5043(10  C) –
0.5212(23  C) –
0.5394(37  C) –
0.5498(45  C) –
Cerebral 0.5083(10  C) –
cortex 0.5121(23  C) –
0.5163(37  C) –
0.5186(45  C) –
Fat of spleen 0.3406(10  C) –
0.3373(23  C) –
0.3337(37  C) –
0.3317(45  C) –
Liver 0.497(25.6  C) 3.4535(29  C) Choi et al. (2013)
0.51(36.9  C) 3.452(35  C)
0.509(49.8  C) 3.4368(39  C)
0.519(78.3  C) –
BHMT, UMN Bioheat and Mass Transfer Lab, University of Minnesota
n Number of repetitions

considered, i.e., subzero or suprazero; thermal properties of cryoprotectants; and the


effect of cryoprotectants on porcine liver.
For porcine liver in Table 6 from Choi et al. (2013), specific heat data between
31  C and 85  C is not directly added as there is an endothermic heat
release associated with protein denaturation in that range. The specific heat capacity
available in that range is apparent specific heat and not sensible specific heat
capacity. The interested reader may refer to Choi et al. (2013) for more details.
The thermal conductivity measurements for porcine and human systems from
2298 S. Phatak et al.

Table 8 Thermal properties of human systems at suprazero temperature II


Thermal conductivity Specific heat capacity
System type [W/mK] [J/gK] References
Kidney (n  5) 0.591(25  C) – Unpublished,
0.585(37  C) – BHMT, UMN
0.56(50  C) –
0.555(80  C)
Liver 0.467–0.527(37  C) – Bowman (1981)
Lung 0.302–0.55(37  C) –
Pancreas 0.294–0.588(37  C) –
Kidney 0.513–0.564(37  C) –
Heart 0.492–0.562(37  C) –
Spleen 0.448–0.544(37  C) –
Stomach 0.489–0.565(37  C) –
Skeletal muscle 0.449–0.546(37  C) –
Adrenal gland 0.363–0.458(37  C) –
Colon 0.556(37  C) –
Brain (white- 0.503–0.576(37  C) –
gray)
Thyroid 0.526–0.533(37  C) –
Breast 0.499(37  C) –
Bone (rib) 0.373–0.496(37  C) –
Skin (without SF) 0.258–0.272(37  C) –
Fat 0.2–0.246(37  C) –
Skin 1.6 mm 0.498(37  C) –
Fat 4.8 mm 0.268(37  C) (surface –
of fat)
Fat 6.4 mm 0.248(37  C) –
(intermediate fat)
Fat 9.8 mm 0.219(37  C) (deeper –
fat)
Mesentery 0.303(25  C) – Unpublished,
(n  13) 0.279(37  C) – BHMT, UMN
0.242(50  C) –
0.243(80  C) –
Omentum (n  8) 0.26(25  C) –
0.299(37  C) –
0.251(50  C) –
0.237(80  C) –
Gerota’s fascia 0.324(25  C) –
(n  2) 0.279(37  C) –
0.255(50  C) –
0.178(80  C) –
BHMT, UMN Bioheat and Mass Transfer Lab, University of Minnesota
SF subcutaneous fat
n number of repetitions
54 Thermal Properties of Porcine and Human Biological Systems 2299

Table 9 Thermal properties of cryoprotectants


Thermal conductivity Specific heat
System type [W/mK] capacity [J/gK] References
US gel (tissue phantom) 0.52(38  C) 3.7(39  C) Etheridge et al.
0.47(2  C) 3.84(10  C) (2013)
1.71(45  C) 2.06(50  C)
2.3(85  C) 1.45(100  C)
2.28(125  C) 0.94(149  C)
2M glycerol solution 1.61(27  C) 3.781(5  C) Choi and Bischof
1.96(64  C) 1.712(73  C) (2010)
2.15(108  C) 1.206(110  C)
2.25(147  C) 0.903(148  C)
6M glycerol solution 0.82(28  C) 2.984(20  C)
1.27(65  C) 1.996(73  C)
1.05(108  C) 1.114(110  C)
0.97(147  C) 0.834(148  C)
2 M DMSO solution 1.443(20  C) – Ehrlich et al.
1.69(60  C) – (2015)
1.933(100  C) –
2.203(140  C) –
6M DMSO solution 0.378(20  C) –
0.592(60  C) –
0.721(100  C) –
0.773(140  C) –
10M DMSO solution 0.28(20  C) –
0.27(60  C) –
0.264(100  C) –
0.253(140  C) –
DP6 in EC solution 0.317(20  C) – Ehrlich et al.
(cryoprotectant) 0.53(40  C) – (2016)
0.356(70  C) –
0.35(140  C) –

Valvano et al. (1985) were carried out at temperatures 3  C, 10  C, 17  C, 23  C,


37  C, and 45  C. Linear regression fit constants were provided to be used in the
following formula to calculate thermal conductivity,

k ¼ k0 þ k1 T

W h i
where k0 mK and k1 W
mK 2
are regression fit constants and T is the temperature in  C.
Thermal conductivity values have been calculated using the above formula for
temperatures 10  C, 23  C, 37  C, and 45  C.
2300 S. Phatak et al.

Table 10 Thermal properties of porcine liver treated with cryoprotectants


Thermal conductivity Specific heat
System type [W/mK] capacity [J/gK] References
Porcine liver, treated with 1.56(10  C) 3.39(20  C) Choi and Bischof
1X PBS + 2M glycerol 1.68(64  C) 3.36(3.7  C) (2008)
1.78(108  C) 3.09(7.3  C)
1.73(146  C) 2.55(13  C)
– 2.1(36  C)
– 1.85(57.2  C)
– 1.58(72.8  C)
– 1.45(89  C)
– 1.17(104.9  C)
– 0.8638(143.8  C)
Porcine liver, treated with 1.0(13  C) 3.03(23.5  C)
1X PBS + 6M glycerol 1.55(64  C) 2.91(8.5  C)
1.42(110  C) 2.81(24.3  C)
1.24(148  C) 2.51(43.6  C)
– 2.28(57.4  C)
– 1.94(82.2  C)
– 1.76(98.3  C)
– 1.33(106  C)
– 1.05(114.4  C)
– 0.83(145.8  C)
Porcine liver, treated with 0.65(10  C) 2.91(20.3  C)
1X PBS + 8M glycerol 1.27(64  C) 2.69(23.2  C)
1.07(109  C) 2.42(36.2  C)
0.86(149  C) 2.15(56.2  C)
– 1.9(83.4  C)
– 1.62(103  C)
– 2.51(43.6  C)
– 1.19(111.2  C)
– 0.96(118.7  C)
– 0.81(142.8  C)

6 Conclusion

The goal of this review was to compile thermal conductivity and specific heat
capacity values of human and porcine systems in the subzero and suprazero tem-
perature ranges for the purposes of aiding the development of accurate models of
conditions and pathologic treatments involving bioheat transfer mechanisms. As
seen in Tables 4, 5, 6, 7, 8, 9, and 10 listed above, extensive datasets were available
for thermal conductivity in both temperature ranges for porcine systems. However,
limited data is available for both thermal conductivity and specific heat capacity for
54 Thermal Properties of Porcine and Human Biological Systems 2301

human systems in the subzero temperature range. Another area where there is limited
data available is the effect of cryoprotectants on biomaterials. As was seen in Figs. 5
and 6 for porcine liver, thermal properties of biomaterials are affected by the
presence of cryoprotectants due to the presence of a vitreous or amorphous phase
in addition to crystallization. Future thermal property measurements can be
conducted by incorporating these changes to get a more accurate behavior to be
applied in a model. As seen in the modeling case studies section, the importance of
temperature-dependent properties versus constant properties is reflected from the
significant differences in the thermal histories for planar, cylindrical, and spherical
systems using water properties. Similar analyses can be performed by considering
thermal properties of other biomaterials presented in this chapter.

Acknowledgments Funding for this work was provided by the Center for Research in Education
and Simulation Technologies at the University of Minnesota and the National Science Foundation
(Award Number CBET 1236760).

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