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Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial

tactile sensing in conjunction with artificial neural network

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2016 J. Phys. D: Appl. Phys. 49 075404

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Journal of Physics D: Applied Physics

J. Phys. D: Appl. Phys. 49 (2016) 075404 (16pp) doi:10.1088/0022-3727/49/7/075404

Parameter estimation of brain tumors using


intraoperative thermal imaging based on
artificial tactile sensing in conjunction with
artificial neural network
M Sadeghi-Goughari1, A Mojra1 and S Sadeghi2
1
Faculty of Mechanical Engineering, K. N. Toosi University of Technology, P. O. Box: 19395-1999
Tehran, Iran
2
Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

E-mail: mojra@kntu.ac.ir, ms.sadeghi@mail.kntu.ac.ir and sohrab.sadeghi9@ymail.com

Received 1 September 2015, revised 5 December 2015


Accepted for publication 18 December 2015
Published 25 January 2016

Abstract
Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that
can potentially locate margins of brain tumor in order to achieve maximum tumor resection
with least morbidity. This study introduces a new approach to ITI based on artificial tactile
sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility
and applicability of this method in diagnosis and localization of brain tumors is investigated.
In order to analyze validity and reliability of the proposed method, two simulations were
performed. (i) An in vitro experimental setup was designed and fabricated using a resistance
heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in
the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented
to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor
geometries were constructed from MRI data and tumor temperature and depth of location were
estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the
tissue phantom surface to measure temperature variations and ANN was trained to estimate
the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive
method which can be useful to detect, localize and characterize brain tumors.

Keywords: brain tissue, intraoperative thermal imaging, assisted robotic surgery, finite element
analysis, artificial neural network, artificial tactile sensing

(Some figures may appear in colour only in the online journal)

1. Introduction and size of the tumor (Scoccianti and Ricardi 2012). Whether
the tumor is benign or malignant, surgery is the cornerstone in
The central nervous system (CNS) tumor is the second most the treatment of brain tumors.
common cancer among children. More than 4 000 brain and Today’s medical advancements offer revolutionary sur-
spinal cord tumors are diagnosed each year in children and gical treatment technique called Minimally Invasive Surgery
teens (www.cancer.org). The American Cancer Society statis- (MIS), to minimize both blood loss and trauma to the normal
tics state that about 22 850 new cases (including both adults tissues including the muscular elements supporting the
and children) with malignant tumors will be diagnosed in nervous system and of course nerves themselves (Proctor
2015 in the United States while an estimated 15 320 people and McL 2005, Jinglong 2013). Minimally invasive neuro-
will die from CNS tumors (www.cancer.org). Treatment of a surgery is colloquially thought to be surgery through small
brain tumor depends on many factors, including type, location opening in the scalp or the skull bone. However, there is

0022-3727/16/075404+16$33.00 1 © 2016 IOP Publishing Ltd Printed in the UK


J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

another interpretation. The goal is to implement MIS in order The loss of haptic feedback and inability to palpate during
to perform maximum tumor resection procedure with suffi- MIS can result in accidental tissue damage (Demi et al 2005).
cient precision to leave surrounding neural tissue unharmed During recent years, haptic feedback was achieved by meas-
(Proctor and McL 2005). Positioning accuracy in diagnosis urement of mechanical parameters by a new non-invasive
and tumor ablation accuracy in treatment have long been chal- technology which is called ‘artificial tactile sensing (ATS)’
lenging tasks in the applicability of MIS in brain tumor sur- during MIS (Liu et al 2010). ATS can detect abnormalities in
gery (Hermes et al 2011, Jinglong 2013). the tissue by examining the tissue surface (Tiwana et al 2012).
In a general manner, imaging techniques including com- The use of tactile sensing for tissue abnormalities detection
puted tomography (CT) and magnetic resonance imaging is significant for safe, fast and accurate interaction with the
(MRI) have been used to determine the surgical target in MIS. environment (Tiwana et al 2012).
The most important drawback of preoperative imaging falls Estimation of tumor’s characteristics including tumor
into a well-known phenomenon which is referred as ‘brain temper­ature, location, depth and size plays a significant role in
shift’ (Reinertsen et al 2014). The opening of the skull and safe tumor surgery. Hosseini et al (2007) considered stiffness
of dura mater, the loss of cerebrospinal fluid, the reduction features to demonstrate the existence of an embedded abnor-
of intracranial pressure and placing surgical apparatus during mality in an elastic tissue and developed a three-layer feed
neurosurgery can often contribute to an intraoperative brain forward neuron network (FFNN) as an inverse analysis for
deformation, known as ‘brain shift’ (Hartkens et al 2003, estimation of tumor properties.. Mitra and Balaji (2010) used
Kateb et al 2009). Brain shift often makes intraoperative the temperatures obtained on the surface of the breast tissue
tumor delineation difficult as its preoperative data can no through a breast thermogram in conjunction with artificial
longer be entirely relied on. neural network to estimate the position and size of a spherical
Intraoperative imaging is a revolutionary tool in modern tumor in a human breast. Keshavarz and Mojra (2015) imple-
minimally invasive neurosurgery (Proctor and McL 2005). mented the imperialist competitive algorithm to optimize a
Intraoperative imaging techniques especially intraopera- FFNN outputs in estimating tumor’s geometrical parameters
tive MRI (iMRI), help neurosurgeons to achieve the goal of embedded in a liver tissue.
maximum tumor resection with least morbidity (Schulder There are a number of experimental investigations on
and Carmel 2003). In addition, iMRI allows neurosurgeons to thermal analysis of an in vitro tissue. In thermal examination,
compensate for the effects of brain shift (Kateb et al 2009). agar phantom was utilized to simulate the soft tissue. Mital
Despite all advances made in the field of brain imaging in the and Scott (2007) used a resistance heater that was embedded
last decades, imaging techniques are still classified in the group in agar in order to simulate the heat produced by a tumor in
of invasive methods, since the body is exposed to harmful the breast tissue. Sadeghi-Goughari and Mojra (2015) devel-
effects of using magnetic field and x-ray (Yegingil 2009). oped a novel haptic-thermal robot having a Cartesian mech­
Furthermore, iMRI is really expensive and time-consuming as anism to palpate the brain tissue for tumor localization during
each scan prolongs about 20 min (Fahlbusch and Samii 2007). minimally invasive diagnosis in the neurosurgery. The exper­
Thermography is a new non-invasive developing technique imental examinations were conducted on an agar phantom
based on the temperature measurement in the soft tissue which simulating the brain tissue which contains a resistance heater
has been successfully used in diagnosis and detection of breast as the tumor.
cancers (Song et al 2005, Shi et al 2014, Saniei et al 2015), In the present study, a forward analysis using the ITI tech-
skin cancers (Cholewka et al 2013, Bhowmik et al 2015) and nique based on ATS is proposed and feasibility and capability
eye diseases (Tan et al 2009, Gonnermann et al 2011). Initial of this methodin detection and localization of brain tumors is
studies using intraoperative imaging of brain tumors revealed investigated. Tumor’s related features were estimated by an
a significant temperature difference between the tumor tissue inverse analysis in order to optimize tumor resection in the
and the surrounding neural tissue (Kateb et al 2009), while brain tumor surgery. In the forward analysis, a finite element
depending on the type of the tumor, the temperature difference approach based on commercial software ABAQUS was used to
is varied (Jayasundar and Singh 2002, Gorbach et al 2004). simulate conduction heat transfer in the brain tissue including
Intraoperative Thermal Imaging (ITI) is a novel neuro- a tumor. For a realistic simulation, 3D real geometries of the
imaging technique that can potentially localize brain tumors brain and the tumor were constructed by implementing MRI
for optimized surgical resection. Gorbach et al (2004) used images. In the inverse problem, a FFNN was utilized to esti-
an infrared camera to measure the tumor temperature during mate tumor’s features including tumor temperature and its
cranial surgery and showed that brain tumors of glial origin depth. In order to validate and analyze the applicability of
generally have 0.5–2.0 °C temperature difference compared the proposed estimation procedure, an experimental setup
to normal surrounding tissue. Kateb et al (2009) performed using agar tissue phantom was fabricated which contained an
ITI on a patient with a metastatic intracortical melanoma and embedded heat source to simulate the brain tumor. The agar
showed that ITI is a novel neuroimaging technique that can be phantom was examined by a robot-assisted device which was
used to provide a rapid, non-invasive, and real-time intraoper- equipped with a tactile temperature sensor. The haptic-thermal
ative imaging. Several research groups investigated the appli- robot palpated the tissue phantom and output was temperature
cability and accuracy of ITI in the neurosurgical procedures, distribution on the top surface of the tissue called the thermal
e.g. the studies done by Hollmach et al (2013), Hoffmann image. The aim is to implement thermography technique as
et al (2014) and Kastek et al (2014). a non-invasive high precision intraoperative tool instead of

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 1. Flowchart of forward and inverse approaches. Figure 2. Schematic of cuboid tissue model containing a
cylindrical heat source.
common imaging methods. By the aid of the FFNN, results
interpretation of the proposed method became independent Table 1. Heat source parameters in the cuboid tissue model.
of the surgeon’s skills and tumor’s related features including Parameter Range of variation Increment
temperature and depth would be straightly extracted.
Power (P) 0.45 − 1 W 0.05 W
Depth (H) 8 − 24.5 mm 1.5 mm
2. Numerical modeling

Estimation of brain tumor’s features including tumor temper­ cylinder were compatible with the experimental set-up which
ature and depth is a necessity in making suitable therapeutic will be described later. For tumor characterization, variations
decisions. In the preset study, a forward and an inverse analysis of heat source parameters (power and depth) are listed in
based on Artificial Neural Network (ANN) are proposed to table 1.
estimate tumor’s features using brain thermogram (figure 1). In order to obtain the precise information on the brain
The first part of the work involves the forward analysis of and tumor geometries, MRI of a patient was utilized. We are
heat conduction in a cancerous brain tissue by employing a reporting a 41 year-old female patient who was presented
Finite Element Method (FEM). The achieved tissue surface with a long history of brain tumor. According to the Helsinki
temperatures were trained against the tumor parameters by agreement, the whole study was thoroughly explained for the
using ANN. A feed-forward neural network (FFNN) could be patient. She was referred to our team neurosurgeon to treat her
then utilized to retrieve tumor’s related parameters with high brain tumor. MRI with and without contrast were performed
accuracy. on the patient in the ‘Iran Gamma Knife Center’ in Tehran,
Iran. A 61 mm × 44 mm large heterogeneous ill defined
residual posterior parafalcine meningioma was noted with
2.1. Finite element method
peri-lesional edema (figure 3).
2.1.1. Tumor’s geometrical and thermal features. The trans- 3D solid models of the brain and tumor were obtained
port of thermal energy in biological tissues is a complex pro- from MRI data and are presented in figure 4. Based on the
cess involving multiple phenomenological mechanisms such solid models, the volume fraction of the tumor relative to
as conduction, convection, metabolism, evaporation phase the normal tissue was about 6.7%. The tumor had uncertain
change and radiation (Yang et al 2005). A finite element anal- margins and was located at about 35 mm from the top sur-
ysis using ABAQUS software (version 6.10) was carried out face of the brain tissue. As mentioned earlier, the aim is to
to simulate heat conduction and convection procedures during implement ANN to estimate tumor’s temperature and depth
Intraoperative Thermal Imaging (ITI). of location. For the forward analysis and training of ANN,
For simulation of brain intraoperative imaging, the thermal real sizes of brain and tumor were utilized while the tumor
examination process was considered for two geometries: first, temper­ature and depth were varied. After training of ANN
a simplified geometry of the tissue was constructed to exper­ with different tumor temperatures and depths, capability of
imentally validate capability of the thermography method in ANN in estimation of tumor characteristics of the case report
brain tumor localization; and second, a 3D real geometry of was investigated. Range of variations of tumor’s depth and its
the brain was constructed from MRI data to overcome the sen- temperature (related to the tumor type) are listed in tables 2
sitivity of the ITI to the heterogeneous geometry of the brain and 3, respectively.
and also to investigate the applicability of estimation proce-
dure with clinical examination. 2.1.2. Finite element mesh and boundary condition. For ther-
A simplified cuboid model was developed to simulate the mal finite element analysis in ABAQUS, the tetrahedra ele-
normal tissue and a cylindrical heat source was considered to ment type was selected for both cuboid model and real brain
represent the tumor (figure 2). Dimensions of the cube and the model which is well suited to irregular meshes. Steady-state

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Table 2. Variations of tumor depth for the 3D real brain model.

Parameter Range of variation Increment


Tumor depth (H) 30 − 75 mm 5 mm

Table 3. Temperature in different brain tumors (Jayasundar and


Singh, 2002).

Tumor types Temperature (°C)


Meningioma 31
Grade IV astrocytoma 33.9
Recurrent gliomas with radionecrosis 34.3
Low grade astrocytoma 35.3
Oligoastrocytoma 36.9
Metastasis 38
Craniopharyngioma 38.3
Anaplastic astrocytoma 39.2
Glioma 43
Ependymoma 43.4

Figure 3. (a) Axial MRI, (b) Sagittal MRI, (c) Coronal MRI images
of brain; please note the view of tumor in left pictures.

Figure 5. Three surfaces of brain tissue for definition of boundary


conditions.

thermal analysis was applied by the step named ‘HEAT


TRANSFER’.
For applying the boundary conditions to the simplified
tissue model, the cube was considered insulated on all sides
except the top surface, which was exposed to convection heat
transfer. Since the convection from top surface is the only
means of heat transfer, the effect of convection coefficient
is much more pronounced than it would be otherwise. For
applying a close simulation of the mentioned experimental
tests, the values of ambient convection coefficient and air
W
temper­ature were assumed to be 40 m2 °C and 22.5 °C respec-
tively. The cylinder was selected as a heat generator to simu-
late the heat produced by a tumor inside the brain. Since the
agar phantom utilized in the experimental test was made of
98% water, the value of its thermal conductivity was taken to
W
be 0.6 m °C , same as the thermal conductivity of water.
In the 3D real brain model (figure 5), constant physiological
temperature was considered for the tumor surface. The ther-
mally insulated condition was assumed for the lower surface
of the brain tissue which was in contact with the skull bone.
The upper surface of brain was exposed to convection, so its
Figure 4. 3D solid models of brain and tumor, please note the surface temperature was sensitive to the heat transfer coef-
concept of tumor depth. ficient and the ambient temperature. For optimal measurment
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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 6. Meshing dependency of (a) the cuboid model with 32492 elements, (b) the 3D brain model with 158004 elements.

of the brain surface temperature, cold environment and good requires 524 s and the brain model with 15 8004 elements
thermally insulated conditions near the brain surface are required 1752 s comutational times
suggested and considered in the FEM simulation. In a cold
environ­ment, the blood vessels of the brain tissue constrict, so
the brain surface doesn’t waste the heat which this phenom­ 2.2. Artificial neural networks
enon is known as themoregulation. For considering the FEM Artificial neural networks are a family of computational
simulation close to the operating room conditions, the ambient learning models inspired by the human brain. ANN is gener-
air temperature and convection coefficient were assumed to ally formed as a system of interconnected ‘neurons’ which
W
be 18 °C and 10 m2 °C , respectively. For thermal analysis, send messages to each other. ANN can be defined as a math-
thermal conductivity of the brain tissue was considered equal ematical model which consists of many nonlinear artificial
W
to 0.6 m °C (Elwassif et al 2006, Farah et al 2013). neurons generated as one layered or multiple layered which
About mesh dependency, temperature distribution on the can be utilized to approximate functions that can depend on a
path passes through center of the tissue’s upper surface is large number of inputs. The ANN has to be trained to adjust
compared for three stages of mesh refinement and the max- the connection weights and biases in order to produce the
imum difference is reported. Mesh dependency was exam- desired mapping (Hornik et al 1989).
ined in the simplified cuboid model contained a tumor having In this study, a three layer FFNN with back propagation
11 mm depth and power of 0.5 W. The maximum difference learning algorithm was developed for solving the inverse
was less than 1%, so the computational mesh with 32 492 ele- problem. The internal weights and biases of FFNN were
ments and 6441 nodes was selected. (figure 6(a)). Similarly, calculated from training dataset. Also, testing dataset was
mesh independency was checked for the real 3D brain model performed to evaluate the neural network performance. The
of the reported patient and a maximum error less than 3.7% FEM outputs achieved from a forward analysis were divided
was achieved. So, a computational mesh with 15 8004 tetra- into two major groups involving training and testing datasets.
hedral elements and 29 679 nodes was adapted. (figure 6(b)). Thermal parameters extracted from tissue surface temper­ature
The required computational time increases with the number profiles were used as the input of ANN, while ANN was going
of mesh elements. The cuboid model with 32 492 elements to estimate tumor’s related features. For simplified cuboid

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Table 4. Artificial Neural network’s properties.

Number of Number of Number of


Training Performance Number of Number of Transfer neurons in neurons in neurons in Number
function function inputs out puts Function 1st layer 2nd layer 3rd layer of epochs
Trainbr MSE 5 2 Tansig 3 5 2 1000

3. Experimental setup

3.1. Haptic-thermal robot specifications

Based on artificial tactile sensing method, a haptic-thermal


robot with Cartesian mechanism was developed to precisely
palpate the tissue surface with attempts to provide a compre-
hensive haptic feedback during Minimally Invasive Surgery
(figure 7). The ability of Cartesian robots in multiple linear
motions, makes them great for applications that require a great
deal of precision and repeatability, like robot-assisted surgery
(Funda et al 1996).
The haptic-thermal robot mainly consists of three DC
motors (24 V; 110 RPM; Buhler 1.61.070.324, Germany) to
generate rotary motion and three perpendicular ball screws
(Lead size: 5 mm / round, HIWIN, Taiwan) to convert rotary
motion to linear motion. It contains three incremental rotary
encoders (200 Pulse / Round) to convert the angular position
to a digital code. According to the type of the encoders (200
pulse per round) and the ball screws pitch (5 mm/round),
the accuracy of position measurements can be found 25 µ m.
Figure 7. The haptic-thermal robot developed for in vitro The end-effector of robot can move in a cuboid pattern with
examination tests.
400 mm length, 400 mm width and 160 mm height. The probe
of the end-effector consists of a tactile temperature sensor
tissue model, the training and testing dataset consisted of (SHT 11, Sensirion, Switzerland) which is fully calibrated
115 and 29 samples, respectively. For the real brain model, and the calibration coefficients were programmed into an OTP
80 samples were used for training, while the remaining 20 memory on the sensor chip. The tactile sensor can measure the
samples were considered for testing procedure. Details of the temperature in an operating rang of −40 °C to 123.8 °C with
proposed FFNN properties can be found in table 4. resolution of 0.01 °C and accuracy of 0.4 °C.
The performances of the ANN for both training and testing
data were evaluated according to two statistical parameters
3.2. Experimental protocol
which were Efficiency (E) and root mean square error (RMSE)
(equations (1) and (2)): Several in vitro thermal experiments were performed to ana-
⎡ N
lyze the capability of the haptic thermography method and

RMSE = ⎢
(Xd − Xs )2 ⎥ estimation procedure to accurately predict the power and depth
(1)

⎣ i=1 N ⎥

∑ of an embedded tumor simulated by a heat source. For in vitro
test systems, agar tissue phantoms were utilized to simulate
the brain tissue. The agar tissue phantom consisted of a 2.0%
N N
solution of agar and water. The agar solution was cooled in a
∑(Xd − Xs )2 − ∑(Xd − Xs )2 plexiglass cube with dimensions 110 mm × 60 mm × 50 mm.
E = i=1
(2) N
i=1
In order to simulate the thermal conditions of the brain during
∑(Xd − Xs )2 the neurosurgical procedures, the cube was insulated with
i=1 2 mm thick natural cork strip on all sides except the top sur-
Where Xd is the desired variable, Xs is the estimated variable, face. A 39 Ohm cylindrical resistance heater having 15 mm
Xd is the average of the desired variable and Xs is the average radius and 25 mm length was used to model the brain tumor.
of the estimated variable. The resistance heater was then connected to a 0 – 30 V dc
Efficiency (E) evaluates ANN’s performance while the power supply to simulate heat generation phenomenon by
RMSE calculates residual between estimated and desired the tumor (figure 8). In a clinical setting, the room was main-
values of the embedded tumor features. Theoretically, values tained between 18 − 22 °C while illumination, sunlight, and
of E close to 1.0 point out good model performance. In order humidity of the room were carefully controlled.
to have a perfect fit to the model, it is desirable that the value The haptic-thermal robot was utilized for thermal imaging
of RMSE equals to zero. as shown in figure 9. A total number of four experiments were

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 8. Experimental setup for modeling of tissue and tumor.

performed, grouped into experimental sets A and B (table 5).


For each experiment, the setup was kept at undisturbed con-
dition for about 4 h after turning on the dc power supply to
ensure a steady-state temperature distribution in the specimen.
The range of tumor power was selected based on assuming
W
that a tumor is unlikely to generate more than 25 000 m3 of heat
W
while a heat generation rate of a healthy tissue is about 700 m3
(Mital and Scott 2007).
Surface temperature could be measured on many spots
based on the position accuracy of the robotic system. For the
developed tissue phantoms, the distance between two con-
secutive spots was selected 10 mm, so totally 84 spots were
considered for extracting surface temperature distribution.
The robot was programmed to measure the spot temperature
after 10 s of surface touching and end effector needed 2 s to
pass from one point to next point. Consequently, the thermal Figure 9. Photograph of the experimental setup and the tissue
imaging process rapidly prolonged 1008 s or 16.8 min. phantom under test.

Table 5. Experimental test number for different values of heat


4. Results source power and depth.
RUN Depth (mm) Power (W)
4.1. Forward analysis and extracting thermal parameters
A1 10.5 0.6
In forward analysis, thermal imaging technique was per- A2 10.5 0.915
formed to demonstrate tumor existence. Two specific results B1 19.5 0.6
were extracted from the forward thermal analysis: B2 19.5 0.915

(a) Temperature distribution on the top surface of the tissue


called ‘thermogram’
temperature distribution for heat source with low power
(b) Temperature distribution on a path defined over the tumor
located at deep regions relative to the superficial heat source
and located on the brain’s top surface called ‘thermal
is noticeable.
diagram’
In order to compare the experimental examinations with
The haptic-thermal robot was utilized to capture tissue their corresponding numerical simulations, all experimental
phantom thermograms of experimental sets A & B and the sets were also simulated numerically and the thermal dia-
results are provided in figure 10. The peak in the surface grams are displayed in figure 11. Diagrams show that exper­
temper­ature profile clearly shows existence of the abnor- imental and numerical results are in good agreement.
mality embedded in the tissue phantom. It can be seen that The brain thermogram of the reported patient is presented
the temper­ature approaches to the highest level at some point in figure 12. Thermal results are clearly indicative of an
located above the heat source and that the level varies versus abnormality in the left posterior region of the brain. It can
the simulated tumor’s power and depth of location. Smoother be seen that, there is a marked temperature increase in the

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 10. Tissue phantom thermograms for experimental sets A and B.

vicinity of the tumor region. Moreover, the overshoot in sur- • Confined area between the thermal diagram and the
face temperature profile is not only indicative of the tumor horizontal line passes through the point having minimum
existence but also provides a good suggestion of tumor’s temperature (Q1)
margins. • Difference between the maximum and minimum surface
Effects of tumor’s features were individually investigated temperatures (Q2)
on the surface temperature distribution. The achieved thermal • Slope of the line passes through the points having
diagrams are presented in figure 13. It can be perceived that as maximum and minimum temperatures (Q3)
the tumor recedes further inside the brain tissue, the corresp­ • Difference between temperature of a constant arbitrary
onding surface temperature decreases. The opposite would point located on the tissue surface on the region having
occur if there is an elevation in the temperature of the simu- temperature difference relative to the normal tissue and
lated tumor. minimum temperature (Q4)
We are seeking for a unique algorithm which can well • Slope of thermal diagram at the specified point (Q5)
predict surface temperature variations versus variations of
tumor’s geometrical and thermal properties. A suitable inverse 4.2. Inverse analysis and performance evaluation
analysis would provide such an algorithm. In order to connect
forward results to the inverse analysis, a set of thermal para­ Although, the existence of tumor could be demonstrated by
meters were extracted from the achieved thermal diagrams forward analysis, thermal images do not provide the neuro-
which are shown in figure 13 and are listed as follows: surgeons with detailed information on the tumor features and

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 11. Thermal diagrams plotted for experimental sets A & B and the corresponding numerical simulations.

Figure 12. Brain thermogram of the reported patient; MRI images are provided in figure 3.

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 13. Thermal diagram response to the variations of tumor feature and thermal parameters extracted from numerical modeling;
(a) simplified cuboid tissue, (b) 3D real brain.

Table 6. The statistical variables implemented as the neural network’s input dataset for the simplified cuboid model.

Training dataset Testing dataset


Variables x x min x max x x min x max

Q1 144.9195 50.8958 347.0129 173.9425 61.7738 365.2728


Q2 3.5655 1.0773 9.7544 4.4450 1.3337 10.2677
Q3 0.0648 0.0196 0.1774 0.0808 0.0242 0.1867
Q4 2.7732 0.8938 7.3241 3.4272 1.0891 7.7096
Q5 0.1523 0.0309 0.6270 0.2194 0.0400 0.6600

characteristics. To this end, an inverse approach using a feed ill-conditioning was avoided in the neural network. The box-
forward neural network was carried out to estimate the men- plots (figure 14) show the minimum, maximum, percentile
tioned properties. Thermal parameters extracted form FEM and median values of the normalized thermal parameters. On
outputs were utilized as the ANN’s inputs. each box, the central mark is the median, the edges of the box
are the 25th and 75th percentiles, the whiskers extend to the
4.2.1. Simplified cuboid model. For simplified cuboid model, most extreme data points not considered outliers and outliers
ANN was trained to estimate heat source power and its depth are plotted individually. The boxplots show that distribution of
of location. Then 144 samples of the tissue phantom including all normalized thermal parameters for 144 samples are quite
a heat source with different depths and powers were modeled. loose and normal. Among thermal parameters, Q5 has the most
Among all dataset, 115 samples were used for training the compact and least normal distribution.
network and 29 remaining samples were considered for the Figure 15 shows estimated values of the heat source depth
testing procedure. of location and its power calculated by the ANN and their
Three statistical variables including mean (x ), minimum corresponding desired values for the selected testing data-
(x min ), and maximum (x max ) of the extracted thermal para­ sets. Tumor features are stated via the related test number.
meters related to simplified cuboid model are listed in table 6. Comparsion between the estimated and the desired values
It can be seen that range of variations of the network input confirms the applicability of the neural network in estimation
parameters is quite wide. Since the ‘tansig’ was the neural of the simulated tumor’s features and characteristics.
transfer function and it takes values only between  −1 and Variations of the estimated values of heat source power and
1, each of the neural network’s variable was normalized in depth against the desired values are displayed in figure 16. It
an appropriate manner. With normalization of the dataset, can be elicited that all estimated values are located on or very

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 14. Boxplots of the proposed normalized thermal parameters for simplified cuboid model.

Figure 15. Comparison of heat source characteristics calculated by the ANN with the desired values; (a) depth of heat source, (b) power of
heat source.

close to the diagonal line. table 7 lists slopes and intercepts Real and estimated values of depth and power of the
of the fitted lines to the estimated values by the FFNN. These embedded heat source simulating the tumor are listed in
parameters are known as the linear regression coefficients. table 9 for the four experiments A1, A2, B1 and B2. These
Statistical analysis was carried out over estimated values by results show good agreement between the actual and the pre-
FFNN by reporting RMSE and efficiency (table 8). Efficiency and dicted parameters, with maximum absolute error in depth
RMSE values are very close to one and zero, respectively. From within 0.2939 mm and in power within 0.0277 W. Note that
data afforded by table 8, accuracy of the proposed ANN is appar- better agreement was achieved for the cases with lower depth
ently higher in depth estimation rather than power assessment. of the embedded heat source.

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 16. Regression analysis performed over the heat source depth and power estimations calculated by the proposed ANN.

Table 7. Linear regression coefficients for the proposed FFNN model for simplified cuboid model; Output value  =  a  ×  Desired value  +  b.

Training dataset Test dataset All dataset


Output a b a B a b
Depth 0.9941 0.0871 0.9993 −0.0035 0.9955 0.0619
Power 0.9849 0.0109 0.9735 0.0179 0.9821 0.0126

Table 8. Performance of FFNN models for estimations of power Table 9. Actual and estimated values of depth and power of the
and depth on the simplified cuboid model. embedded heat sourcefrom experimental examination of cases A1,
A2, B1 and B2.
Training dataset Test dataset
Actual Estimated
Output RMSE E RMSE E
Depth Power Depth Power
Depth 0.1113 0.9995 0.1256 0.9975 Experiment (mm) (W) (mm) (W)
Power 0.0102 0.9964 0.0156 0.9923
A1 19.5 0.6 19.2473 0.5894
A2 19.5 0.915 19.2061 0.9164
4.2.2. 3D real brain model. Intraoperative brain tumor’s B1 10.5 0.6 10.4164 0.5838
features and characteristics estimation helps neurosurgeons to B2 10.5 0.915 10.4928 0.8873
resect tumor with minimum trauma to the normal tissue. Ther-
mal parameters extracted from intraoperative thermal imaging Q2 and Q3 have the highest normal distribution, Q4 and Q5
of brain surface were used to train a FFNN to estimates brain have the least. Meanwhile, distributions of Q1 and Q4 are quite
tumor temperature and depth of location. For an inverse analy- loose while distributions of Q2 and Q3 are more compact.
sis, 100 generated samples were divided into 80 samples as In order to investigate performance of the estimation algo-
training datasets and 20 remaining samples as testing datasets. rithm, estimated values of tumor temperature and depth were
Mean, minimum and maximum values of the employed compared with corresponding desired values for the testing
thermal parameters are presented in table 10. Boxplots datasets in figure 18. The highlighted test number refers to
related to the normalized thermal parameters are displayed in the tumor features of case report patient. Related actual and
figure 17. According to the boxplots, distributions of thermal estimated values are listed in table 11 which affirms a very
parameters of 100 samples are quite loose. Moreover, while good agreement.

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Table 10. Statistical parameters for neural network’s input dataset for real brain model.

Training dataset Testing dataset


Variables x xmin xmax x xmin xmax

Q1 678.2782 217.6749 1501 668.9241 312.5285 1525


Q2 11.1381 6.0842 17.1961 10.7150 7.7281 17.4712
Q3 0.0771 0.0402 0.1394 0.0738 0.0511 0.1416
Q4 3.7801 0.6883 10.8192 3.7423 1.0590 10.9922
Q5 0.0978 0.0080 0.4028 0.0942 0.0123 0.4092

Figure 17. Boxplots of the proposed normalized thermal parameters for 3D real brain model.

Regression plot of the training and testing datasets via the tumor. For ITI of in vitro test system, a haptic-thermal robot
tumor features are shown in figure 19. Related linear regres- was developed to palpate the tissue surface for temperature
sion coefficients are listed in table 12. Results verify that out- measurment.
puts of the proposed ANN agreed well with the desired values. The appearance of overshoot in the temperature level on
Performance evaluation of the ANN model for tumor temper­ the tissue surface is the most fundamental result that con-
ature and depth estimations was accomplished by calculation of firms the applicability of ITI in tumor detection (figures 10
efficiency and RMSE. Table 13 presents these statistical para­ and 12). Thermal results prove that temperature distribution
meters calculated for both training and testing datasets. on the brain surface (brain thermogram) can be an appropriate
outcome of ITI for the superficial tumors while by increasing
5. Discussion tumor depth, the symptoms of tumor existence on temperature
distribution of brain top surface would fade out.
Intraoperative Thermal Imaging (ITI) is a novel neuroimaging Furthermore, the surface temperatures obtained from FEM
technique that can potentially localize brain tumor for the goal analysis were used as the input of FFNN. By using five thermal
of maximum tumor resection with least morbidity. For simu- parameters, the surface temperature graphs were reduced and
lation purposes, the ITI process was divided into two parts: converted into more effective quantitative values, which can
first, the detection of brain tumor; and second, the estimation be used as the inputs of the neural network.It is worth to men-
of the tumor’s features including tumor temperature and its tion that selection of these parameters is not restricted to Q1 to
depth of location. A finite element approach was employed Q5. The only criterion that needs to take into consideration is
to localize brain tumor while the temperature distribution that values of the selected parameter should have a wide range
on tissue surface was proposed as the indicative factor of of variation versus tumor’s different geometrical and thermal
tumor existence. For reliable simulation of ITI process, real characteristics (tumor temperature and its depth). Such a wide
geometries of the brain and the tumor were developed from range provides much effective information for better training
brain MRI images of a sample patient referred to the ‘Iran of the network.. The box plots are presented (figures 14 and
Gamma Knife Center’. Then a three layer FFNN with back 17) to show the range of the employed para­meters and affirm
propagation learning algorithm was adapted for the estimation the applicability of them in training the ANN. Based on the
procedure. The estimation procedure was also analyzed and plots, variations of 5 thermal parameters with tumor features
validated experimentally. The experiments were conducted on were acceptable. However, the boxplots show that the men-
an agar phantom which contained a heat source as the brain tioned parameters do not have the same credit in the estimation

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 18. Comparison of tumor parameters calculated by the ANN with the desired values for test data; (a) tumor depth (b) tumor
temperature.

Table 11. Results from parameter estimation procedure to procedure using ITI in brain tumor surgery. Thermal para­
determine tumor temperature and depth of the reported patient. meters extracted from ITI process were utilized to train the
Actual Estimated proposed FFNN to estimate tumor temperature and depth.
Temperature of tumor and its depth were estimated with error
Depth Tumor Tumor equal 0.0627 °C and 0.7015 mm, respectively.
(mm) Temperature (°C) Depth (mm) Temperature (°C)
The intraoperative brain thermogram provides the real
35 31 (Meningioma) 35.7015 31.0627 time information on the brain temperature distribtion which
may be a surgical assist tool to help neurosurgeons. First,
neurosurgeon can use the data related to maximum temper­
procedure. In fact figures 14 and 17 show that for both simpli- ature to specify the area on the brain where resection can be
fied and real brain models, the thermal parameter Q1 has more originated. The maximum temperature sensed on the tissue
contribution in training of the network. Implementation of surface is located at a region or a point that a tumor has the
thermal inputs by a FFNN was performed, and ANN’s outputs least distance from the tissue top surface. Besides, the esti-
were compared with desired values and good performance is mation of tumor depth allows neurosurgeons to compensate
reported (figures 15, 16, 18 and 19). for the effects of the brain shift and provides the real time
For the experimental cases, the FFNN’s applicability and information of tumor location to achieve near total resec-
accuracy in estimation of heat source power and depth of tion through a more objective detection. Finally, estimation
location was investigated (table 9). The proposed estimation of tumor temperature provides the additional real-time ana-
procedure using thermal imaging could estimate heat source tomical information of brain tumor such as blood flow per-
depth and power with absolute error less than 0.2939 mm and fusion and chemical composition. The data related to tumor
0.0277 W, respectively. temperature significantly contributes to an improved extent
A case report patient with a parafalcine meningioma of tumor resection by updating delineation of the tumor
was presented to evaluate the usefulness of the estimation margins.

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

Figure 19. Regression analysis performed over the tumor temperature and depth estimations calculated by the proposed ANN.

Table 12. Linear regression coefficients for the proposed ANN model for the real brain model; Output value  =  a  ×  Desired value  +  b.

Training dataset Test dataset All dataset


Output a b A b a b
Tumor depth 0.9915 0.4045 0.9953 0.3112 0.9920 0.3972
Tumor temperature 1.0000 0.0160 0.9721 0.9734 0.9961 0.1484

Table 13. Performance of ANN models for tumor temperature and a patient was implemented to estimate the embedded tumor
depth estimations in real brain model. temperature and depth. Such estimation can be adapted for
Training dataset Test dataset improvement of the brain tumor surgery. The FEM analysis
was performed over a wide range of tumor temperatures and
Output RMSE E RMSE E
depths of location and the resultant thermal diagrams of the
Tumor depth 0.4594 0.9990 0.4748 0.9987 brain surface was reported.
Tumor temperature 0.1145 0.9991 0.1564 0.9978 It was elicited that appearance of overshoot in the tissue
surface temperature is the symptom of tumor existence mean-
6. Conclusion while it provides information about tumor temper­ature and
depth of location. Thermal results showed that by increasing
In the present study, intraoperative thermal imaging coupled the tumor temperatuer or decreasing the depth, an elevation
with artificial tactile sensing and artificial neural network was appears in the maximum temperature sensed on the tissue
employed to study the feasibility and applicability of the the surface.
proposed method in the diagnosis and localization of brain Five thermal parameters were extracted from FEM thermal
tumors and estimating geometrical and thermal properties of results to train a FFNN for the estimation of tumor features
the detected tumor. In order to investigate the applicability of and characteristics. Training of the ANN was performed by a
the estimation procedure in estimating and predicting depth back propagation algorithm. Comparsion between estimated
of location and type of the tumor, a cuboid in vitro sample values of tumor related features and the desired expected
made of agar gel with an embeded heat source was modeled values confirms the applicability of thermography coupled
numerically and experimentally. For the experimental anal- with ATS and ANN in estimation of tumor’s features and
ysis, a haptic-thermal robotic device was developed to pre- characteristics. It can be stated that ITI based on ATS is a new
cisely measure the surface temperature during brain phantom developing non-invasive technique that can potentially detect
examinations. Moreover for a realistic simulation and estima- and localize brain tissue abnormalities which may greatly
tion, real geometry of the brain constructed from MRI data of facilitate the neurosurgeon’s task during MIS.

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J. Phys. D: Appl. Phys. 49 (2016) 075404 M Sadeghi-Goughari et al

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