Technology and Health Care 22 (2014) 867–875 DOI 10.3233/THC-140868 IOS Press

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Design and analysis of finite element based sensors for diagnosis of liver disorders using biocompatible metals K. Arunachalama , Lijin V. Jacobb and K. Kamalanandb,∗ a Department

b Department

of Automobile Engineering, MIT Campus, Anna University, Chennai, India of Instrumentation Engineering, MIT Campus, Anna University, Chennai, India

Received 8 August 2014 Accepted 13 October 2014 Abstract. BACKGROUND: Analysis of liver tissue in normal and abnormal conditions is essential for disease research, medical device design and treatment planning. Currently cirrhosis and malignancies of liver are among the major causes of mortality, worldwide. OBJECTIVE: The objective of this work is to design an efficient capacitive sensor using Finite Element Methods (FEM), for diagnosis of cirrhotic and malignant liver. METHODS: In this work, 3D geometric FEM models (N = 120) of normal, cirrhotic and malignant liver were generated using Comsol 3.5a. A set of ‘E’ shaped metallic plates, each with a dimension of 1 × 1 × 1 mm were modeled and mounted on the developed liver models. Four different bio-compatible metals namely Gold, Silver, Palladium and Platinum were used for analysis. Further, the observed capacitance values were converted into voltage using a De Sauty’s bridge circuit implemented using Proteus 8. Finally, the statistical significance of the results was analyzed using the ANOVA test. RESULTS: Results demonstrate that the observed voltages show significant variations between different liver pathologies. The developed sensor characteristic was found to be linear and the sensitivity of the sensor was found to be high when platinum electrodes were used. The diagnostic ability of the developed sensors for the adopted biocompatible metals was found to be highly statistically significant (P < 0.001). CONCLUSIONS: The proposed sensor design is compact with small dimensions and can be placed in contact with the human liver using endoscopic techniques. Hence, the developed sensor may provide a minimally invasive technique for liver diagnosis. This study appears to be of high clinical relevance since modelling of normal and abnormal liver, as well as design of suitable sensors for identification of liver abnormalities is required for improving the present diagnostic techniques. Keywords: Liver, finite element method, malignancy, cirrhosis, biocompatible metals, capacitive sensor

1. Introduction The liver is a vital organ present in humans, in the upper right quadrant of the abdomen. The liver has a wide range of functions, including detoxification of various metabolites, protein synthesis, and the production of biochemical’s necessary for digestion [1]. However, the liver is commonly affected ∗ Corresponding author: K. Kamalanand, Department of Instrumentation Engineering, MIT Campus, Anna University, Chennai, India. E-mail: [email protected].

c 2014 – IOS Press and the authors. All rights reserved 0928-7329/14/$27.50 

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K. Arunachalam et al. / Design and analysis of finite element based sensors for diagnosis of liver disorders Table 1 The typical electrical properties of normal and abnormal liver tissue used for development of the finite element model Material Normal liver Cirrhotic liver Malignant liver Blood

Average permittivity [range] 44.14 [41.53–48] 51.03 [48.9–53.47] 57.61 [53.05–64.25] 61.314

Conductivity (S/m) 1.16 1.38 1.34 1.54

by different pathologies such as malignancies and cirrhosis. Cirrhosis is scarring of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcohol abuse. Furthermore, auto and diesel exhaust contain dozens of liver damaging poisons such as lead, sulfur, nitrogen oxides, acetaldehyde, cadmium and peroxyacetylnitrile, which may cause cirrhosis and malignancies [2]. For most patients, cirrhosis is associated with short survival, and liver transplantation is often offered as the only effective therapy [3]. Patients with cirrhosis are also at much higher risk of developing hepatocellular carcinoma. Currently, cirrhosis and hepatocellular carcinoma are among the top ten causes of death worldwide, and in many developed countries liver disease is now one of the top five causes of death in middle-age group [4]. The liver is a common site for both primary and secondary malignancies. Colorectal (the most common secondary tumours) and hepatocellular cancers are the third and fifth most common cancers worldwide, respectively, combined causing a million deaths annually [5,6]. Measurement of physical properties of liver tissue is important for classification and diagnosis of various liver abnormalities. Fundamentally, the dielectric properties of soft tissues determine how the electromagnetic fields will interact with and propagate within the tissues [7,8]. Further, malignancies are generally considered to have elevated water content when compared to normal tissue because of the increased hydration associated with the rapid metabolism of cancer cells, causing a significant variation in dielectric properties [9]. O’Rourke et al. [10] characterized the dielectric properties of normal, malignant and cirrhotic human liver tissues and have reported that there is a significant variation in the dielectric permittivity of normal and abnormal liver tissues. Liver biopsy is considered as the gold-standard method for the diagnosis and assessment of liver abnormalities. Due to the invasive nature of liver biopsy, a great deal of effort has been directed toward developing non invasive methods of evaluating liver disease. Imaging techniques, such as measuring the elasticity of the liver using transient elastography, may assess fibrosis more directly. However, the use of such techniques in routine clinical practice has not been well defined. Sonography is often the first imaging procedure performed for the evaluation of individuals with suspected liver disease, but this technique suffers from imperfect sensitivity and specificity [11]. The Computerized Tomography (CT) offers good spatial resolution, but requires high radiation dose and iodinated contrast media for imaging of the liver. Also, the Magnetic Resonance Imaging (MRI) has emerged as the best imaging test for liver lesion detection and characterization, because this modality provides high lesion-to-liver contrast and does not use ionizing radiation. However, the drawbacks of MRI include its high cost, a long procedure time, and the need for the patient to hold his breath for longer periods [12]. Given the invasive nature of liver biopsy, and the need for simple and non-invasive methods to assess liver abnormalities, it is likely that alternative tests will continue to emerge and will likely be utilized more widely in clinical practice [10,13–15]. Hence, the design and development of a compact capacitive sensor for minimally invasive diagnosis of liver disorders is highly useful as a replacement for liver biopsy. The objective of this work is to design an efficient diagnostic sensor for the analysis of normal, cirrhotic and malignant liver conditions.

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Table 2 The material properties of the adopted biocompatible metals Property Conductivity (S/m) Density (Kg/m3 ) Poisson’s Ratio Young’s Modulus (Pa)

Silver (Ag) 61.6 × 106 10500 0.37 83 × 109

Gold (Au) 45.6 × 106 19300 0.44 70 × 109

Fig. 1. The developed 3D geometric model of adult liver (length across the widest points = 21 cm and the greatest vertical height = 16 cm).

Platinum (Pt) 8.9 × 106 21450 0.38 168 × 109

Palladium (Pd) 10 × 106 12020 0.44 73 × 109

Fig. 2. 3D geometric model of parallel plate capacitive sensor with a dimension of 1 × 1 × 1 mm, surrounded by region of blood.

2. Methodology 2.1. Generation of 3D geometric models of various biocompatible capacitive sensors mounted on normal, cirrhotic and malignant liver The approximate 3D geometric FEM models of normal, cirrhotic and malignant liver were generated using Comsol 3.5a software, as shown in Fig. 1. Further, a set of ‘E’ shaped metallic plates, each with a dimension of 1 × 1 × 1 mm were modeled, as presented in Fig. 2, and mounted on the developed liver models. The ‘E’ shaped design is used because it exhibits increased sensitivity. Four different biocompatible metals namely Gold, Silver, Platinum and Palladium were used for analysis. The material properties [10] of normal and abnormal liver, as well as the materials used for the capacitive plate design, were incorporated into the developed models. The typical values of material properties of a generated liver model and the properties of biocompatible metals are presented in Tables 1 and 2 respectively. 2.2. Mesh generation of developed models The meshing of the developed FEM models was performed using Delaunay triangulation method. Triangulation is a subdivision of a geometric object into simplices or triangles. Delaunay triangulation for a set P of points in the plane is a triangulation DT(P) such that no point in P is inside the circumcircle of any triangle in DT(P). The circumcircle always passes through all three vertices of a triangle. Its centre is at the point where all the perpendicular bisectors of triangles sides meet. Delaunay triangulations maximize the minimum angle of all the angles of the triangles in the triangulation for avoiding skinny triangles [16–20]. The meshed 3D geometric models of parallel plate capacitive sensor surrounded by

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K. Arunachalam et al. / Design and analysis of finite element based sensors for diagnosis of liver disorders

(a)

(b) Fig. 3. (a) Meshed 3D geometric model of parallel plate capacitive sensor surrounded by blood layer mounted on normal liver (b) Magnified image of meshed parallel plate capacitor mounted on normal liver.

Fig. 4. Circuit for converting measured capacitance into voltage.

blood layer mounted on liver is shown in Fig. 3(a). The magnified images of meshed parallel plates mounted on liver is shown in Fig. 3(b). The number of tetrahedral mesh elements of the developed model is 15959. 2.3. Design of capacitance to voltage conversion circuit The variation in average capacitance values obtained for normal, cirrhotic and malignant liver was found to be in the third decimal point, which was converted to a significant voltage range using a capacitance to voltage conversion circuit known as the De Sauty’s bridge circuit, as shown in Fig. 4. The circuit was developed using Proteus software and contains two fixed resistors, one fixed capacitor and a variable capacitor. Parallel plates mounted on liver surrounded by region of blood will act as the variable capacitor. The values of fixed resistors are taken as 10 MΩ, and the value of fixed capacitor is taken as 0.2135 pF to obtain the bridge balance condition. The amplitude and frequency of the excitation signal was set to a value of 10 Volts and 1 KHz respectively. Further, any changes in the measured capacitance values of liver (in case of abnormal states) leads to unbalance condition and the change in capacitance reflects as voltage variations. The changes in voltage can be measured using an AC voltmeter, as shown in Fig. 4. 3. Results and discussion Based on the analysis performed on the FEM solver, it is observed that error converges to a minimum value of 10−6 after 18 iterations, in all the cases. Convergence refers to the point in the iterative process when the desired accuracy is obtained. Typical convergence plot for normal liver when gold is used as parallel plate, is shown in Fig. 5.

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Fig. 5. Convergence plot of FEM solver for normal liver when gold is used as metal. 0.219

Capacitance (pF)

0.218 0.217 0.216

GOLD

0.215

SILVER

0.214

PALLADIUM PLATINUM

0.213 0.212 0.211 NORMAL LIVER

CIRRHOTIC LIVER

MALIGNANT LIVER

Fig. 6. Variation in average capacitance value for normal, cirrhotic and malignant liver with different metals. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/THC-140868)

Variations in average capacitance values for normal, cirrhotic and malignant liver with different metals are shown in Fig. 6. The variation in capacitance values obtained using different conductors appears to be low. The variation of capacitance in (pF) between different liver states is in third decimal point, which is amplified to a significant voltage range by using capacitance to voltage conversion circuit. It is observed that, in case of normal liver, gold shows maximum sensitivity followed by platinum. In case of cirrhotic liver, palladium shows maximum sensitivity followed by gold. In case of malignant liver, platinum shows maximum sensitivity followed by palladium.

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K. Arunachalam et al. / Design and analysis of finite element based sensors for diagnosis of liver disorders Table 3 The average voltage values obtained for normal, cirrhotic and malignant liver using different biocompatible metals Voltage (mV) Cirrhotic liver 10.567 10.198 10.725 10.414

Normal liver 2.119 1.904 1.841 2.009

Gold Silver Palladium Platinum

Malignant liver 18.10 17.73 18.86 19.28

30

Voltage (mV)

25 20 15 10 Normal Cirrhotic Malignant

5 0 0.213

0.214

0.215

0.216

0.217

0.218

0.219

0.22

0.221

Capacitance (pF) Fig. 7. Variation of output voltage shown as a function of measured capacitance for normal, cirrhotic and malignant liver, when Gold is used as parallel plate metal. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/ THC-140868) 30 25

Voltage (mV)

20 15 10 Normal Cirrhotic Malignant

5 0 0.213

0.214

0.215

0.216

0.217

0.218

0.219

0.22

0.221

Capacitance (pF) Fig. 8. Variation of output voltage shown as a function of measured capacitance for normal, cirrhotic and malignant liver, when Silver is used as parallel plate metal. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/ THC-140868)

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30

Voltage (mV)

25 20 15 10 Normal Cirrhotic Malignant

5 0 0.213

0.214

0.215

0.216

0.217

0.218

0.219

0.22

0.221

Capacitance (pF) Fig. 9. Variation of output voltage shown as a function of measured capacitance for normal, cirrhotic and malignant liver, when Palladium is used as parallel plate metal. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/ THC-140868) 30

Voltage (mV)

25 20 15 10 Normal Cirrhotic Malignant

5 0 0.213

0.214

0.215

0.216

0.217

0.218

0.219

0.22

0.221

Capacitance (pF) Fig. 10. Variation of output voltage shown as a function of measured capacitance for normal, cirrhotic and malignant liver, when Platinum is used as parallel plate metal. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/ THC-140868)

The variation in observed capacitance is very small which is further amplified to a significant voltage range by using a De Sauty’s bridge circuit. Variations in average voltage value for normal, cirrhotic and malignant liver with different metals are presented in Table 3. It is observed that in case of normal liver, Gold shows maximum sensitivity followed by Platinum. For cirrhotic liver Palladium shows maximum sensitivity followed by Gold, and for malignant liver Platinum shows maximum sensitivity followed by Palladium and Gold. However in case of palladium there is a 6 fold variation and 10 fold variation in voltage value for cirrhotic and malignant liver respectively with respect to normal liver, whereas in case of platinum there is a 5 fold variation and 9 fold variation in voltage for cirrhotic and malignant liver respectively with respect to normal liver.

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The variation of observed voltage for Normal, Cirrhotic and Malignant Liver with different biocompatible metals is shown as a function of capacitance, in Figs 7 to 10. It is observed that sensor characteristic is linear for normal, cirrhotic and malignant liver when gold, silver, palladium and platinum are used as parallel plates. It is observed that voltage increases linearly as capacitance increases. Sensitivity of bridge circuit when gold is used as parallel plates is found to be 4296.296 mV/pF. Similar sensitivity value was observed when silver electrodes were used. However sensitivity of bridge circuit when palladium is used as parallel plates is found to be 4275.862 mV/pF. Whereas sensitivity of bridge circuit when platinum is used as parallel plates is found to be 4310.344 mV/pF. The statistical significance of the capacitance value was analyzed based on the ANOVA test. It is observed that the difference in the Mean value of voltage for different biocompatible metals is highly statistically significant (P < 0.001). Hence, from the statistical significance test performed, it is seen that the developed capacitive sensor and capacitance to voltage circuit are useful for diagnosis of normal, cirrhotic and malignant liver. 4. Conclusions In order to prevent liver failure, diagnosis of liver is essential. Liver biopsy is considered as the goldstandard method for the diagnosis and assessment of liver abnormalities. Due to the invasive nature of liver biopsy, a great deal of effort has been directed toward developing non invasive methods of evaluating liver disease. Further, the physical properties of liver tissue changes with the type of abnormalities [21]. In this work, 3D geometric models of normal, cirrhotic and malignant liver were developed using Comsol 3.5a, an efficient capacitive sensor surrounded by blood layer were also mounted on developed liver models. Suitable biocompatible metals for design of parallel plates were identified. Entire 3D geometry of the capacitive plate mounted on the liver, surrounded by blood was developed. Physical properties of biocompatible noble metals like Gold, Silver, Platinum and Palladium were studied and it is identified from the literature that as nobility increases, reactivity decreases. The identified properties of the materials used were incorporated into the developed models for further analysis. Since the variation in capacitance generated by the sensor for normal, cirrhotic and malignant condition is very small, a De Sauty’s bridge was designed to convert low sensor output to a significant voltage range. The significance of the result was analysed by using ANOVA test. It is observed that P value is less than 0.001 for all the metals used. Results demonstrate that the developed capacitive sensor is efficient in classification of normal, cirrhotic and malignant liver. Also, the designed sensor is highly compact with small dimensions and can be used as an endoscopic probe. Hence, the developed sensor may provide a minimally invasive solution for diagnosis of liver disorders. Furthermore, using the proposed sensor, diagnosis can be performed in vivo unlike the classical liver biopsy. This study appears to be of high clinical relevance since the design of suitable sensors for identification of liver abnormalities is required for improving the present diagnostic techniques. Acknowledgement The Authors would like to thank, Dr. George Varghese Kurien, Senior Resident Surgeon, Postgraduate Institute of Technology, Chattisgarh, India, for his help in development of the model.

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Design and analysis of finite element based sensors for diagnosis of liver disorders using biocompatible metals.

Analysis of liver tissue in normal and abnormal conditions is essential for disease research, medical device design and treatment planning. Currently ...
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