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Final Year Honours Project for the degree of

B.Eng. in Mechanical Engineering

Journal Paper

Nasim Mammadov

DEVELOPMENT OF AN EX-VIVO
TESTING PLATFORM FOR ANGIOPLASTY
May 2015

Project Supervisor: Dr Yuhang Chen

School of Engineering and Physical Sciences


Mechanical Engineering
1. Introduction
Coronary heart disease is the most common cause of death in the United Kingdom as more than
94,000 people die from this disease each year [1]. The fatty streaks accumulate in artery walls and
form plaque as a result the flow of blood to the heart becomes restricted. The described process also
known as atherosclerosis which eventually leads to the heart attack. A number of techniques have
been developed and successfully applied for the treatment of atherosclerosis. US radiologist Charles
Dotter first introduced catheter delivered stent treatment of atherosclerotic obstruction in 1964 [2].
His invention allowed for the treatment of arterial diseases without the amputations and was
nominated for a Nobel Prize. Zubkov et al [3] first introduced the balloon catheter technique for
dilatation of constricted cerebral arteries which is commonly known as balloon angioplasty.

Balloon angioplasty, also known as percutaneous coronary intervention (PCI) is a non-surgical


procedure that is used to treat arterial atherosclerosis. In Fig. 1 angioplasty procedure is shown
schematically. First a thin wire (called a catheter) goes into the narrowed artery and the balloon is
inflated to squash the plaque against the wall of the artery. Then, the balloon, which carries a steel
mesh known as stent expands during the inflation of balloon and keeps the artery open for
maintaining the normal blood flow within the coronal artery. Then, the balloon is deflated, the thin
wire is removed and the stent is left in place [4]. The angioplasty procedure is considered successful
by achieving the large deformation of the artery while causing the minimum mechanical damage to
the arterial wall [5].

Recent figures show that the number of angioplasty procedures doubled over the last 10 years in
United Kingdom. The number of procedures rose from 44,910 in 2002 to 92,445 in 2012. In about
95% of angioplasty procedures are completed successfully [1]. Angioplasty costs the NHS almost
£70 million a year [6] and this number increases every year. The development of current techniques
might lead to a decrease in the cost of angioplasty and an increase in the success rates.

Figure 1. Implementation of angioplasty procedure [21]


(a) a catheter is inserted into the narrowed artery (b) the baloon is inflated (c) the stent is expanded

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1.1. Objectives
The main objective is to find bio mimicking materials which mimics the real healthy and diseased
coronary arteries. To obtain the materials with close properties to the healthy and diseased tissues it
is needed to prepare and test the different concentrations. Then, by carrying out material
characterization techniques such as; the stress relaxation, material homogeneity and fatigue
experiments to obtain mechanical properties of both materials. The final objective is to develop a
technique that uses mechanical palpation to localize tumour in soft tissues including depth and size
characterization.

1.2. Background
Different factors, such as the pathological or physiological conditions [7] have been proved to cause
changes in the mechanical properties of soft tissue [8]. Hence, by testing the mechanical properties of
soft tissue it is possible to determine the abnormalities. Recently, a number of researches were
conducted to determine the location, depth and dimensions of the tumour in soft tissues. Indentation
[9] [10] [11] is a broadly used testing technique to detect the mechanical properties of soft tissue. Liu
et al [10] studied the mechanical behaviour of soft tissues under large deformations. The contact
property between indenter and the material surface was modelled as frictionless contact. This work
allows to determine the unique material properties of soft tissue from indentation experiments. Zheng
[11] carried out the manual indentation experiment to obtain elastic properties of lower limb soft
tissues. The determined Young’s modules were in a similar ranges as reported in the literature.
Kalanovic et al [12] found important discrepancies during the in-vivo and in vitro testing of soft tissue
viscoelasticity using indentation and rotary shear deformations. Clayton et al [13] reviewed
indentation versus tensile measurements of Young's Modulus for soft biological tissues. It was found
that soft tissues do not have a single Young’s Modulus value independent of experimental method,
and that modulus values for a single tissue can span several orders of magnitude.

Sangpradit et al [9] used an inverse finite element analysis of rolling indentation. In their experiment
the location of tumour was known; a rolling wheel indented into the silicone phantom and the
mechanical properties of tumour were identified. Also, inverse analysis method was used to
determine the depth of the tumour by initial guesses.

2
2. Methodology
The Mach-1 Micromechanical System (Biomomentum Inc.) was used to acquire the experimental data
(Fig. 2). Mach-1 is designed to determine the different mechanical properties of specimen; such as
viscoelasticity, stiffness, strength and stress relaxation by using displacement-controlled motion. The
load cells (±150 g to ±10 kg), motion controller and Mach-1 Motion software (Biomomentum Inc.)
were used to measure the force, displacement and time. The flat compression disc (Fig. 3 (c)) was
installed to carry out stress relaxation and fatigue tests. The spherical (Fig. 3 (b)) indenters with
different diameters were used to conduct sweeping indentation test. The load cell was calibrated
before each test session (Fig. 3(a)).

In this paper the stress and strain relationship was mostly used to represent the experimental data.
The reaction forces were the object of comparison when the spherical indenters were used for the
experiments. However, the flat surface of compression disc allows to calculate the stress applied to
the material. The stress was calculated by dividing applied force by the cross-sectional area of the
material and the strain was found by dividing material’s length by the change in length. For extracting
and processing the experimental data the different codes were used and developed in MATLAB (The
MathWorks, 2014b) software.

a c

Figure 2. Mach-1 testing machine Figure 3. (a) Calibration weight (b) spherical indenters with
different diameters (c) compression disc

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2.1. The workspace plate design
For the sweeping indentation test a 250 mm travel long linear track (Edmund Optics) was installed to
the base of Mach-1 (Biomomentum Inc.) testing machine. From the manufacturer the workspace of
the linear track (62×60 mm) was smaller than the standard size of testing material (100×60 mm).
Therefore, a new workspace plate was required to attach on top of the linear track. The mass of
workspace plate had to be light, because of the vertical load to the linear track was restricted with
2 kg weight. Additionally, the machine manual informs that it has 100 nanometres displacement
sensitivity during the testing, thus for the new designed plate the displacement sensitivity had to be
less than this value when the maximum force is applied. Aluminium was chosen as a material, since
its weight has a density one third that of steel, 2700 kg/m3. The Finite element analysis using ABAQUS
(Dassault Systemes, Vlizy-Villacoublay, France) was used to determine the optimal thickness with a
deformation small enough not to influence the results (Fig 4). The 7×10-6 m deformation was obtained
when the machine applied maximum load (10 kg) to the edge of workspace plate, which was enough
to satisfy the design criteria. The manufactured plate weights 453 g and is 8 mm thick. (Fig 5).

Figure 4. Simulation of plate with FEA Figure 5. Manufactured plate was installed to the machine

2.2. Sample Preparation


Gelatine powder (Dr. Oetker Ltd., UK) and water were used to prepare the bio-mimicking material.
Different gelatine-water concentrations were tested to obtain the materials which ideally had similar
mechanical properties to healthy and diseased tissues (See Section 2.3.).

For making the tissue with healthy properties, 300 ml of boiled water was measured into the
container, then 36 g of gelatine powder was added. The tissue with cancerous properties was
prepared by adding 36 g of gelatine powder and putting 250 ml of boiled water. The gelatine powder
was added slowly to prevent it from forming into lumps. Again, to avoid the formation of small bubbles
the mixture was stirred slowly.

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The concentration was mixed until all the gelatine powder was absorbed by the water and became
transparent. The container with the mixture was placed into another large container full of boiled
water. It helps gelatine to dissolve in water completely. When the mixture cools at room temperature
it becomes the semi-solid solution. In this state the solution was placed into the refrigerator and kept
for 18-20 hours. The cooling time of the sample is important, since the water evaporation of the
material continues in the refrigerator and leads to the change of mechanical properties. Therefore, all
samples were kept in the refrigerator the same period of time prior the experiment to reduce the
sources of uncertainty.

After withdrawing the sample from the refrigerator the material was removed from the container.
The samples needed to be cut it in a parallelepiped shape, since the experimental results will be used
for FE simulation. Other complex geometries might be hard to model the material for the simulation.
Different tools were used to try and cut the gelatine sample. The fishing line appeared to be a very
effective tool, since it is exceptionally thin and sharp. All samples prior to experiment were cut to
100×60 mm size and left for 90 minutes until they reach an ambient room temperature (Fig 6).

The different water-gelatine concentrations were prepared and their mechanical properties were
tested by conducting the stress relaxation test. First, the 4 containers were filled with 200, 250, 300
and 350 ml of water along with 24 g of gelatine powder in each container. Then, another 4 containers
were filled with equal volume of water as with the previous set of containers, but the amount of added
gelatine increased from 24 to 36 g. In total, 8 different concentrations were prepared and their
mechanical properties were checked and compared to determine the optimal material which ideally
could mimic heathy and diseased coronal arteries.

Figure 6. Preparation of the material

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2.3. Testing different water-gelatine concentrations
To obtain the materials with close properties to the healthy and diseased tissues the different
water-gelatine concentrations were prepared and tested. The flat compression disc was used to carry
out the stress relaxation test. After conducting the stress relaxation test, the strain-stress curves were
plotted to compare the elasticity modulus of the concentrations. The results for the concentrations
with equal volume of water and different amount of gelatine were plotted on the same graph to
observe the effect of the gelatine powder. Then, to determine the effect of the water ratio the
strain-stress curves of concentrations with the same amount of gelatine with differing volumes of
water were plotted at the same graph.

The strain rates had different values due to the varying thickness of the samples. From the Fig. 7 it can
be seen that by decreasing the water concentration the material becomes stiffer. At the small strain
rates the difference between the different concentrations were not very noticeable. However, by
increasing strain the alteration between the mechanical properties of the materials becomes clear.

200 ml 200 ml
a 24 g gelatine 250 ml
300 ml
b 36 g gelatine 250 ml
10 300 ml
8 350 ml 350 ml
7 8
Stress (kPa)

6
Stress (kPa)

5 6

4
4
3
2 2
1
0
0
0 5 10 15 20 25
0 5 10 15 20 25
Strain (%) Strain (%)

Figure 7. Comparison of the compression behaviour of different samples with varies concentrations (a) 24 g and (b) 36 g

Fig. 8 shows the strain-curves for different uniaxial compression tests for different concentration of
water and gelatine. From here it is observed that the stiffness of material is growing by increasing the
amount of the gelatine powder. The elasticity modulus of sample with different concentrations were
compared at different stress rates and the results can be seen in Table 1. From the Table it can be
seen at 20% strain rate the elasticity modulus of samples with 36 g of gelatine are 33-37 % higher than
the concentrations with 24 g of gelatine for all 200, 250, 300 and 350 ml water samples.

During the experiment it was observed that the samples containing 24 g gelatine powder are very
brittle and tend to break. The material is needed to be stiff enough to conduct the sweeping
indentation and stress relaxation test, since during these tests it was exposed to the large strains up
to 30 %. Among these only the sample containing 200 ml of water was stiffer, but its thickness was
small and potentially could break under the large strains. Therefore, the samples containing 36 g
gelatine powder were preferred. Here, again the sample containing 200 ml water was rejected due to
its small thickness. Among the remaining materials the samples containing 300 ml water, 36 g gelatine
and 250 ml water, 36 g gelatine were chosen to mimic the healthy and diseased tissue respectively.

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The reason for that was that they had close thicknesses and the difference between elasticity moduli
were large enough to simulate healthy artery containing the tumour.

25
200 ml water a 14 250 ml water b
12
20 10

Stress (kPa)
Stress (kPa)

15 8

10 6
24 g 4 24 g
5
36 g 2 36 g
0 0
0 10 20 30 40 0 10 20 30
Strain (%) Strain (%)

8
300 ml water c 8 350 ml water d

6 6
Stress (kPa)
Stress (kPa)

4 4

2 24 g 2 24 g
36 g 36 g
0 0
0 10 20 30 0 5 10 15 20 25
Strain (%) Strain (%)

Figure 8. Comparison of the compression behaviour of different samples with varies concentrations (a) 200 ml (b) 250 ml
(c) 300 ml and (d) 350 ml

Sample Concentration Elasticity modulus (kPa)


Water, Gelatine, 5% 10% 15% 20%
ml g strain strain strain strain
1 200 24 23.2 28.3 32.3 36.02
2 200 36 31.4 37.7 44 50.3
3 250 24 22 24.9 27 29
4 250 36 25.4 30.6 35.8 41
5 300 24 16.8 18.2 19.4 20.3
6 300 36 24.3 26.9 29.2 31.5
7 350 24 13.7 15.6 18.9 28.2
8 350 36 22 25.2 28.2 31.1

Table 1. The comparison of the elasticity modulus of different concentrations

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3. Results and discussion

3.1. The effect of water loss

Ashley et al [14] examined the human aorta to understand the effect of evaporative water loss in
ex-vivo soft tissues. It was found that a significant amount of water loss leads to a thickness reduction
of aorta about 20%. Therefore, the amount of the weight loss for both healthy and diseased samples
were investigated to see how it affects the mechanical properties of materials.

After removing the prepared tissue sample from the refrigerator, it was left to reach the ambient room
temperature for testing. By considering that the prepared normal and cancerous tissue phantoms
contain respectively 90.25% and 91.75% water, it was important to inspect the effect of water loss.

Two samples were prepared with the same dimensions to investigate the effect of water loss. The
tests were performed within 4 hours and both samples were measured every 20 minutes. The sample
with normal tissue properties has lost 5.3 g or 3% of its weight as can be seen in Fig. 9. The 5.75 g or
3.6% weight loss were detected for the sample with cancerous tissue properties. The evaporation
process is highly temperature dependant, consequently all material tests were performed under the
same temperature conditions for more accurate results. Hence, it can be concluded that during the
experiment period the water loss does not surpass 3-3.6%, which can be considered as negligible.

180

y = -0.022x + 177.87
170 R² = 0.9944
Weight (g)

Cancer

Normal

160 y = -0.0234x + 159.22


R² = 0.9863

150
0 50 100 150 200 250 300

Time (min)

Figure 9. The water loss rate in normal and cancer phantoms

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3.2. Material homogeneity test
When the properties of the material are the same in 𝑥, 𝑦 and 𝑧 direction it is characterized as isotropic
material. Also, a material is called homogeneous when it is made of the same material throughout
[15]. The uniaxial compression test (Fig. 14) was carried out to compare the mechanical properties of
the sample in three coordinate axes’ - 𝑥, 𝑦 and 𝑧 directions. In this test the sample with normal tissue
properties was cut into 3 parts with the same dimensions and the stress relaxation test was carried
out. The time interval between each test were identical to reduce the uncertainties. The flat disc
compressed the material in 7 amplitudes with 1 mm magnitude, and a 150 s relaxation time between
amplitudes. The samples were compressed in all 3 directions and the recorded reaction forces were
compared.

Figure 10. Strain–stress curves for x, y and z directions


From Fig. 10 it can be seen that the stiffness of material all three direction are similar with 3-5%
differences. Therefore, the sample can be considered as an isotropic material. It is assumed that after
removing the sample from the refrigerator the evaporation process might cause the changes in
mechanical properties of samples. Therefore, further tests were performed to examine the
mechanical behaviour of the top and bottom surfaces of sample. The centre of the sample with normal
tissue properties was removed and cut into 2 parts for stress relaxation test as shown in Fig. 13.

Figure 11. Strain-stress curve for healthy tissue Figure 12. Strain-stress curve for cancer tissue

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As can be seen in Fig. 11 the strain-stress curve of the sample with normal tissue properties has similar
elasticity modulus with maximum 3% error at the 20% strain point. The material with cancerous tissue
properties has slightly higher differences in their mechanical properties, however it does not exceed
7% error (Fig. 12). The performed test confirms that there are no substantial differences between the
mechanical properties of the top and bottom surfaces of the samples with normal and cancerous
tissue properties.

Figure 13. The samples for homogeneity test Figure 14. Uniaxial compression test

3.3. Stress relaxation test


Soft tissues including human artery have hysteresis, stress relaxation and creep properties and
nonlinear stress-strain relationships [16]. The aim of the stress relaxation test was to determine and
compare the viscoelastic behaviour of the phantoms with healthy and cancerous tissue properties. In
total 7 ramp forces were applied with 0.5 mm/s ramp velocity and 1 mm ramp amplitude to observe
the strain-dependent relaxation behaviour. In the test of stress relaxation the material was loaded to
overall 23.2% strain and the stress decreased with 150 s stress relaxation time. The ramp velocities
were identical for both healthy and cancerous tissue phantoms testing. Table 2 shows the
displacement of flat indenter and the strain applied to the material was shown.

Displacement 1 mm 2 mm 3 mm 4 mm 5 mm 6 mm 7 mm

Strain 3.3 % 6.6 % 10 % 13.3 % 16.6 % 20 % 23.3 %

Table 2. The variation of displacement and strain rate

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Figure 15. Stress relaxation test Figure 16. Comparison of Strain-stress curves for healthy
and diseased tissues

The surface area of the sample which contacts with compression disc was measured for the stress
calculation. As it can be seen from Fig. 15 that at small strain rates the reaction forces of the both
healthy and cancerous materials do not have big differences. However, under the large strain rate it
is observed that that the reaction force of material with cancerous properties increases faster than
healthy one at each applied strain phase.

At the end of each fixed relaxation time the data of reaction force was recorded. From the recorded
force data the stress was calculated at each strain range to plot the strain-stress curves showed in Fig.
16. The strain-stress curves are non-linear which represents one of the main characteristics of the soft
tissues. The secant and tangent modulus were compared to analyse the strain-stress curves of the
both materials. The secant modulus was obtained by fitting the linear line to the strain-stress curves
(Fig.16). The linear coefficients of the slops were respectively 28.5 and 44.1 (kPa) for normal healthy
and cancerous samples.

The gradient of a tangent line was fitted between 5-20% stress ranges to find the tangent modulus in
the stress-strain diagram. In both cases the curve fitting toolbox in MATLAB was used to find the
elasticity modulus.

Tangent Modulus (kPa)


Strain 5% 10% 15% 20%

Healthy 20.1 25.1 26.9 28.7

Cancer 26.2 33.4 39.3 45.1

Table 3. Value of Tangent Modulus

From the Table 3 it can be seen that the tangent modulus of material with cancerous tissue properties
has 45.1 kPa elasticity modulus which is 36% more than normal tissue sample when 20% strain applied.

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3.4. Effect of Time constant
The stress relaxation curves were plotted in the same graph to investigate the differences between
the material properties of normal and healthy tissue. The black curve in Fig. 18 is significantly greater
than the black curve in Fig. 17 which can be explained as material with cancerous properties is much
stiffer than the material with healthy tissue properties. It is observed that the lost in stiffness of
material reduces when the applied strain rate increases.

Figure 17.Comparison of stress relaxation curves at Figure 18. Comparison of stress relaxation curves at
different strain rates (Normal) different strain rates (Cancer)

The function of 𝑦 = 𝑎𝑒 −𝑡/𝑏 + 𝑐 is used to find the time constant of both material at different strain.
The stress relaxation curves fitted to the function in MATLAB software stating that 𝑦 is the reaction
force and 𝑏 is the time constant. The acquired 𝑏-time constants were recorded and another diagram
was plotted to see how it varies as the applied strain is becoming larger. Time constant also called as
stress memory time constant, since each applied stress level has relation with the initial stress phase
[17].

Figure 19. Comparison of time constants for healthy and diseased tissues

The shape of curves both healthy and cancerous samples shows that material has non-linear
viscoelasticity behaviour. From the Fig. 19 it can be seen that as the strain increases the time constant
becomes smaller for both material.

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During the compression of materials some energy is dissipated, but some energy is stored. It is
characterized as viscoelasticity: the stored energy is elastic behaviour and the dissipated energy is
viscous behaviour of material.

Hoyt et al [18] used Kelvin-Voight Fractional Derivative viscoelastic model to compare the elasticity
parameters between normal and cancerous prostate tissues. The outcome of the research revealed
that elasticity parameters of cancerous tissue were greater than healthy tissue.

As we can see from the Fig. 19 the material with cancerous properties has bigger time constant
comparing to one with healthy tissue properties. The elasticity modulus of the material has a great
affect to the time constant value. Consequently, the material with higher elasticity modulus has
greater time constants. Furthermore, when the applied strain to the material is increased the
differences between time constant of both materials become smaller.

3.5. Effect of cyclic loading


It has been described that soft biological tissues exhibit viscoelastic effects that require
preconditioning for an accurate characterization [19]. The next experiment was conducted to examine
the magnitude of strain the material can sustain. By exploring the damage mechanics of material it is
possible to obtain further information about the mechanical behaviour, also the failure of material.

The uniaxial cyclic stress relaxation test is available in “Mach-1 Motion” software (Biomomentum Inc.)
as “Ramp--release” function. The “Ramp-release” function were executed to investigate if there was
any damage on the material after given load cycles. During a “Ramp-release” test a displacement was
executed at velocity 0.5 mm/s, followed by a relaxation of duration 60 seconds and a return to the
original position at the same velocity.

For this experiment 2 different samples with the same concentration (normal tissue properties) were
prepared. The first sample was compressed until 10% strain and 25 cycles. The recorded data was
used to inspect force-displacement characteristics of gelatine material. From Fig. 20 it observed that
the each following compressive load was smaller than previous load. The red arrows shows the force
respond trend line at different load cycles periods (Fig. 20). At first 10 cycles the force drops intensely
as time increasing, then at next 10 cycles the force is still decreasing, but slower than previous load
cycle period. Eventually, after 20 cycles the force value tends to be linear as time goes to infinity. It
can be explained as Mullins effect. Mullins effect states that under cyclic force conditions, material
losses of stiffness leading to cyclic stress softening and stress hysteresis [20].

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Figure 20 Cyclic loading with 10% strain rate

Following, the second sample was compressed until 20% strain, with 25 loops of force cycles. When
20% strain load cycles was applied to the material its force response trend line was similar as 10%
strain load cycles (Fig. 21). However, at 20% strain load cycles the trend line arrows tend to be more
inclined towards vertical downward direction comparing to 10% strain load cycles. Furthermore, at
20% strain load cycles the difference between respond forces for first 10 cycles was 1.6 N greater than
when 10% strain load cycles were applied. This number was reduced to 0.4 N from 10th to 20th load
cycles. It wasn’t possible to compare last 5 load cycles, since at 20% strain load cycles the material was
damaged and broke after 23 cycles.

Figure 21. Cyclic loading with 20% strain rate

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3.6. Sweeping indentation experiment
The objective of the experiment was to locate the tissue anomalies by sweeping indentation method.
For this purpose the phantom with healthy tissue properties was prepared which contains the
cancerous material inside (Fig. 22). The length, width and height of cancerous nodule were 20 mm, 12
mm and 12 mm respectively (Fig 23). The tumour material was placed vertically 10 mm from the top
surface of the material where 𝑥 and 𝑦 centrelines intersect.

Figure 22. Phantom with tumour Figure 23. Side view of diseased phantom

Initially, 7 points were marked to conduct the sweeping intonation test, but when the spherical
intender with 10 mm diameter moved toward the sample the deformation affected other testing
points due to the closeness. Therefore, the distance between the testing points were increased and
number of them reduced from 7 to 5. As can be seen from Fig 24 for the indentation test 5 positions
were marked on the surface of the material. The testing points are placed 20 mm distance between
each other and the space from the edge of sample to the closest testing point was 10 mm.

Figure 24. The setup of sweeping indentation test

15
Before conducting the sweeping indentation experiment on the phantom with abnormalities,
2 different samples with healthy and cancerous tissue properties were prepared. The sweeping
indentation test was executed for both materials to obtain the material parameters. These material
parameters will be used to observe the changes at mechanical properties of material when the
cancerous tissue was located inside the healthy tissue.

The stress relaxation function was executed at each marked point by moving sample on linear stage
from left side to the right side. The spherical indenter with 10 mm diameter was moved toward the
sample at velocity 0.5 mm/s and amplitude 2mm, followed by 150 seconds relaxation time. The
number of ramps was 3 until indenter reaches to 6mm depth. After the end of relaxation time at
6 mm depth the next marked position was indented with similar method.

Theoretically, at sweeping indentation experiment the force recordings by varying testing positions
have to be symmetrical track due to the boundary conditions of material. For material with healthy
tissue properties the force readings almost symmetrical at each given depth (Fig 25 (a)). The force
readings of position 4 at the 2, 4 and 6 mm depth are respectively 3.2%, 1.9% and 1.5% lesser than
force values at position 2. Experimentally, it was not possible to obtain the ideal symmetry due to the
temperature effect and the friction between the indenter and the material surface.

2 mm 2 mm
2 (a) Healthy tissue 4 mm
3
(b) Cancer tissue 4 mm
6 mm 6 mm

2.5
1.5
2
Force (N)
Force (N)

1 1.5
1
0.5
0.5

0 0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Position Position
Figure 25. Sweeping indentation test for (a) healthy and (b) cancer tissues

2 mm
Healthy vs tumour 4 mm
2
6 mm
Tumour

1.5
Force (N)

0.5

0
0 1 2 3 4 5 6
Position
Figure 26. Comparison of healthy and unhealthy tissue properties

16
Fig. 26 shows the comparison of force readings for healthy tissue and tissue with abnormalities at
different 3 depths. It was observed that as indenter moves deeper the difference between the reaction
forces of healthy and diseased phantoms became larger. At the testing point of tumour (position 3)
the force readings for material with tumour at 6 mm and 4 mm depth are respectively 2.7% and 1.5%
higher than healthy tissue. However, against the expectations at the 2 mm depth the reaction force
of diseased tissue was 3.2% smaller than normal tissue. For detecting the exact location of a sample
surface and to place an indenter in contact with a sample “Mach-1 Motion” software (Biomomentum
Inc.) executes “Find-contact” function. The “Find Contact” function requires “Stage velocity” and “Stop
criteria” inputs. The “Stop criteria” corresponds to the variation of the load and the stage moves until
the load cell reads user specified force value. However, the initial acceleration of the stage causes a
high force reading which enough to trigger the stop criteria. The reason of that is that when the stage
moves toward the sample the machine is not considering the weight of the indenter.

4. Conclusion and Future Work


In this paper Gelatine powder (Dr. Oetker Ltd., UK) was used to mimic a biological soft tissue. The
different concentrations of water and gelatine were prepared and tested to obtain the material with
close mechanical properties as healthy and cancerous tissues. It was observed that by increasing the
gelatine powder the material became stiffer, conversely increased amount of water made the sample
softer. The effect of evaporation was examined and it was found out that the gelatine samples with
healthy and cancerous tissue properties lost respectively 5.3 g (3%) and 5.75 g (3.6%) of their weights
during the 4 hours of experiment period. By carrying out uniaxial compression test the strain-stress
curves of the material was compared in three coordinate axes’ directions. From here, 3-5% differences
were detected which characterises sample as an isotropic material. Further experiment was
conducted to compare the mechanical properties of the top and bottom surfaces of the samples for
both normal and cancerous tissues. The difference between the stiffness of the top and bottom
surfaces for normal and cancerous tissues were respectively 3% and 7% at 20% strain. Stress relaxation
test was conducted to compare the viscoelastic properties of phantoms with healthy and cancerous
tissue properties. It was determined that cancerous sample’s tangent modulus is (45.1 kPa) 36% higher
than healthy tissue sample (28.7 kPa) when 20% strain applied. The stress relaxation curves of normal
and cancerous tissues at different strain rates were fitted into the equation of 𝑦 = 𝑎𝑒 −𝑡/𝑏 + 𝑐 to
compare the time constant - 𝑏. It was revealed that the time constant parameter of cancerous tissue
is higher than healthy tissue as published literature data [18]. Uniaxial cyclic stress relaxation test was
performed by using 2 different samples with the same concentration. When the first sample was
compressed until 10% strain with 25 cycles, the reaction force decayed faster at the first 10 cycles and
slowed down gradually. Eventually, after 20 cycles the force value tends to be linear as time goes to
infinity. It is explained as Mullins effect which states that under cyclic force conditions, material losses
of stiffness leading to cyclic stress softening and stress hysteresis [20]. Following, the second sample
was compressed until 20% strain, with 25 loops of force cycles.

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When 20% strain load cycles was applied to the material, its force response trend line was similar as
10% strain load cycles, however it was not possible to complete the test, since the material was
damaged and broke after 23 cycles.

Finally, the sweeping indentation test was carried out to determine the location of the tumour within
healthy tissue. It was found that at 6 mm and 4 mm depth the stiffness of material with tumour are
respectively 2.7% and 1.5% higher than normal tissue. However, at the 2 mm depth the stiffness of
diseased tissue was 3.2% smaller than normal tissue. The main sources of this error is the difficulty of
finding the contact point due to the initial acceleration of the stage. When the stage moves toward
the sample the machine is not considering the weight of the indenter which causes high force reading
miss the stop criteria.

The main objective was to find bio mimicking materials which can mimic the real healthy and diseased
coronary arteries. That was achieved by using the stress relaxation, material homogeneity and fatigue
experiments. The sweeping indentation technique was used to localize tumour in soft tissues including
depth and size characterization. However to improve the material characterization and approach the
present technique to the high standards of clinical practice further research is required.

For future work:

 The experimental data from sweeping indentation test will be used to perform FE simulation
By using the findings from the comparison of finite element modelling and experiment data
the potential sources of errors might be determined and eliminated
 The stress relaxation time can be increased from 150 s to 300 s to obtain more accurate results
 Thermocouples can be used to determine the effect of the temperature in the mechanical
properties of the material
 S-N curve determination, which can be used to further investigate the material damage
 Alternative bio mimicking materials can be used to compare the results with gelatine samples

Acknowledgments
I would like to thank my project supervisor, Dr Yuhang Chen, for his patience, encouragement,
guidance and motivation throughout the project. Dr Yuhang found always time for listening to the
problems and gave valuable advices. Also, I would like to thank my postgraduate project advisor, PhD
candidate, Javier Palacio Torralba for his comments that improved the presentation and contents of
this paper. Javier always answered my questions with great enthusiasm and provided me with all
necessary codes to process the experimental data.

18
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