vii TABLE OF CONTENTS CHAPTER TITLE DECLARATION ii DEDICATION iii ACKNOWLENGEMENT iv ABSTRACT v ABSTRAK vi TABLE OF CONTENTS vii LIST OF TABLES xi LIST OF FIGURES xiii LIST OF ABBREVIATIONS xviii LIST OF SYMBOLS LIST OF APPENDICES 1 2 PAGE xx xxiii INTRODUCTION 1 1.1 Research Background 1 1.2 Problem Statement 4 1.3 Objectives 4 1.4 Scope of Research 5 1.5 Thesis Organization 6 1.6 Contribution of Research 6 LITERATURE REVIEW 8 2.1 Anatomy of Normal Kidney 8 2.2 Review of Kidney Test and Diagnosis Techniques 9 2.2.1 10 Blood Test viii 2.3 2.2.2 Urine Test 12 2.2.3 Kidney Biopsy 13 2.2.4 Imaging Tests 14 Ultrasound Imaging for Kidney Diagnosis 16 2.3.1 Review of Ultrasound 17 2.3.2 Kidney Risks, Abnormalities and Diseases 20 2.3.3 Ultrasound Image Features 27 2.3.4 Kidney Ultrasound Diagnosis: Variation and Misdiagnosis 2.4 Kidney Ultrasound Image Processing and Analysis 2.4.1 3 29 32 Image Enhancement and Speckle Reduction 33 2.4.2 Image Segmentation 34 2.4.3 Vector Graphic Image 37 2.4.4 Automatic Kidney Region of Interest Generation 41 2.4.5 Feature Extraction of Kidney US Images 42 2.4.6 Computer Aided Diagnosis (CAD) 43 2.5 Artificial Neural Network (ANN) 46 2.6 Summary 48 EXPERIMENTAL DESIGN AND IMPLEMENTATION 50 3.1 Introduction 50 3.2 Data Acquisition 52 3.3 Vector Graphic Image Formation 54 3.4 Automatic Region of Interest Generation of 3.5 Kidney Ultrasound Images 63 3.4.1 Seed Region Selection 65 3.4.2 Active Contour Rough Segmentation 67 Automatic Detection and Segmentation of Kidney Cysts in Ultrasound Images 68 ix 3.6 4 Feature Extraction, Selection and Kidney Ultrasound Image Classification 72 3.6.1 Image Pre-Processing 74 3.6.2 Feature Extraction 77 3.6.3 Feature Selection 81 3.6.4 Image Classification 81 RESULT AND DISCUSSION 86 4.1 Introduction 86 4.2 Vector Graphic Image Formation 86 4.2.1 89 4.3 Parameter Optimization Experiment Result of Automatic Kidney ROI Generation 4.4 4.5 4.6 5 92 Experiment Result of Automatic Detection and Segmentation of Kidney Cysts 95 4.4.1 Evaluation Metrics 98 4.4.2 Comparison with Other Segmentation Methods 100 4.4.3 Multiple Cysts Detection 104 4.4.4 Statistical Tests 106 4.4.5 Sensitivity Analysis 111 4.4.6 Limitations 113 Experiment Result of Feature Extraction, Selection and ANN-based Classification 114 4.5.1 Result of Feature Extraction 115 4.5.2 Feature Selection 118 4.5.3 ANN-based Classification 119 Summary 124 4.6.1 126 Usefulness Index CONCLUSION AND RECOMMENDATION 128 5.1 Conclusion 128 5.2 Recommendation 130 x REFERENCES Appendices A – E 133 148-176 xi LIST OF TABLES TABLE NO. TITLE PAGE 2.1 Classification of CKD 11 2.2 Kidney diseases affecting kidney size 21 2.3 Comparison of detection of renal stones using ultrasound and CT 30 The interrater reliability for antenatal hydronephrosis diagnosis of 50 anteroposterior renal pelvis diameter measurements [174] 31 Summary of segmentation approach for kidney ultrasound images 36 2.6 Comparison of available vector graphic software 39 2.7 Performance levels of CAD schemes for differential diagnosis 44 2.8 Tests for Kidney Diagnosis 48 3.1 MSE and PSNR value of three different filters applied to kidney ultrasound images 59 3.2 ANN data sampling 83 4.1 Vector graphic image of different values of Ncolor and respective execution time 91 4.2 Validation of automatic ROI generation 94 4.3 Comparison of error metrics of the active contour method by Chan and Vese [168], level set method by Li et al. [170], and the proposed method 103 2.4 2.5 4.4 Comparison of time complexity of the Active Contour method [168], Level-Set method [170], and the xii proposed method 103 Determination of TP, FP, FN and TN during cysts detection 106 Performance evaluation of developed algorithm for single cyst detection 108 4.7 Algorithm testing to 25 multicysts kidney images 110 4.8 Summary findings of Ncolor and R value for detection of cysts in different organs 113 Manual assessment of three image classes (NR, BI and CD) by experts 115 Mean and standard deviation value of all features for three classes of kidney ultrasound images 116 4.11 Student t-test results for NR, BI and CD 118 4.12 Classification result of the neural network using significant features 124 Classification result of the neural network using vector graphic features 124 4.5 4.6 4.9 4.10 4.13 xiii LIST OF FIGURES FIGURE NO. TITLE PAGE 2.1 Anatomy structure of a normal kidney 9 2.2 Healthy and damaged kidney during albumin filteration 12 2.3 Real time kidney biopsy using ultrasound 13 2.4 Kidney images of (a) IVP, (b) CT, (c) MRI, and (d) Ultrasound 15 Measurement of kidney length (A), width (B) as well as volume (C) using Toshiba Aplio MX ultrasound machine 16 2.6 Doppler ultrasound showing normal resistive index 17 2.7 Frequency of sound waves for ultrasound system (adapted from [49]) 18 2.8 Nomenclature related to ultrasound resolution 19 2.9 An example of ectopic kidney (arrow); smaller in size and abnormally rotated [68] 22 Example of ADPKD [18]; (a) Illustration of polycystic kidney, (b) White line shows US calipers used for measuring purpose (cyst and size) while black line shows some of the cysts detected 23 An example of mutiple cysts image, with clear visualization of cysts, renal pyramids as well as calyces 25 2.5 2.10 2.11 2.12 Example of acute pyelonephritis kidney image [73]. Left image is 2-dimensional image while right image is Doppler ultrasound image. Yellow arrows in both left and right images show the infected area. xiv For Doppler US image, red and blue colors indicate the blood flow of the area where blue is when the blood flow away from the transducer while red is when the blood flow towards the transducer. 26 Ultrasound image of kidney with stones. White arrow shows the kidney stone 27 2.14 A normal kidney ultrasound images 28 2.15 Example of vector graphic transformation using market software (a), (c), (e) and (g) Original bitmap image (b) Vectorization using Adobe Illustrator [154], (d) Vectorization using CorelDRAW [155] (f) Vectorization using Vector Magic [113], and (h) Vectorization using AutoTrace [140] 40 An overall system for breast cancer screening using ultrasound images, consists of an ultrasound imaging device, a whole-breast scanning device and CAD system [162] 45 Basic diagram of an artificial neural network with one input layer, 2 hidden layers and one output layer. The hidden layers employ a sigmoid and linear transfer function to adjust weight (W) and biases (b) [132] 47 3.1 Workflow design for the study 51 3.2 Sample US images of (a) Normal kidney, (b) Abnormal kidney with infection, and (c) Abnormal kidney with cysts 53 3.3 Flowchart of vector graphic image formation 54 3.4 Formation of vector graphic image with different value of Ncolor 55 3.5 RGB Color Cube for uint8 Images [63] 56 3.6 Minimum variance quantization on a slice of the RGB color cube [63] 57 Kidney ultrasound, (a) Original image, (b) Wavelet filtering output, (c) Median filtering output, and (d) Wiener filtering output 59 3 layers of black and white image for Ncolor =3, (a) Layer 1, (b) Layer 2, (c) Layer 3 60 2.13 2.16 2.17 3.7 3.8 xv 3.9 3.10 3.11 3.12 Shapes plotting of P = [0; 0; 1; 1], T = [0; 1; 1; 0], and C = 1 62 Vector graphic image of kidney ultrasound using Ncolor = 3 62 Flowchart for generation 63 automatic region of interest Ultrasound Image of (a) normal kidney. Normal kidney always have clear and separate regions of sinus and cortex (b) cystic kidney. Appearance of cyst in kidney leads to unclear separate regions of sinus and cortex 64 (a) Black and white image after thresholding, (b) output of filtered image that intersect with center window 65 (a) Image with two remaining regions (region 1 and region 2), (b) region 1 was selected as winning region, (c) Image with three remaining regions (region 1, region 2, and region 3), (b) region 1 was selected as winning region 67 Kidney ultrasound image with, (a) single cyst, and (b) multiple cysts 69 Steps for kidney cysts automatic detection and segmentation 70 Roundness test for both kidney ultrasound image of single and multiple cysts 72 3.18 Steps for kidney ultrasound image classification 73 3.19 Edge detection of kidney in ultrasound image (black contour) 74 Rotation to zero degree (a) Orientation before rotation, (b) Position of Ymin, Ymax, Xmin and Xmax, (c) Orientation after rotation 75 3.21 Image rotation to zero degree 75 3.22 Output image after cropping 76 3.23 An image with removed background 76 3.24 Development of GLCM from input, I image, with 3.13 3.14 3.15 3.16 3.17 3.20 xvi different orientation (0, 45, 90, and 135) ; adapted from [63] 78 Kidney vector graphic images for different class (NR, BI and CD) for different value of Ncolor (1,2,3,4,5) 80 3.26 Overall ANN development process 82 4.1 (a) Input image of real kidney, (b) Input image of kidney ultrasound, (c) Output image of (a) after vectorization using Vector Magic, (d) Output image of (b) after vectorization using Vector Magic, (e) Output image of (a) after vectorization using proposed algorithm, and (f) Output image of (b) after vectorization using proposed algorithm 88 Vector graphic image of different value of Ncolor (Ncolor = 1 to Ncolor = 12) 90 (a) Input and (b) Vector graphic image with Ncolor = 3, (c) Winning seed region, (d) Active contour rough segmentation result, and (e) Output image of automatic region of interest generation 93 4.4 Example of false positive ROI generation 94 4.5 Kidney images with manually detected cysts boundary by group of experts for (a) single cyst, and (b) multiple cysts 96 (a) Input image of kidney with single cyst, (b) vector graphic image, (c) Image after binarization, (d) Image after filtering, (e) Cyst detection and segmentation 97 Areas of TP, FP and FN in image with manual and automatic contours 99 Segmentation result of (a) manual contour by sonographer, (b) proposed method, (c) active contour method by Chan and Vese [168], (d) levelset method by Li et al. [170] 102 (a) Input image of kidney with multiple cysts, (b) vector graphic image, (c) Image after binarization, (d) Image after filtering, and (e) Cyst detection and segmentation 105 3.25 4.2 4.3 4.6 4.7 4.8 4.9 4.10 Example of mutiple cysts kidney images; (a) Cyst xvii 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 detection by experts (white borders), (b) Cyst detection by developed algorithm (red borders), with true positive cyst regions (red), false negative cyst region (yellow) and false positive cyst region (blue) (TP = 8, FP = 1, and FN = 1) 109 (a) Input, and (b) output image of segmentation of liver cyst (R = 0.55) 112 (a) Input and (b) output images of segmentation of thyroid cyst (R = 0.61) 112 (a) Input and (b) output images of segmentation of multiple cysts in ovary (0.55 ≤ R ≤ 1) 112 Output image of multile cysts kidney with unsuccessful (yellow circle) and wrong (blue circle) detection of cysts. 114 Mean value for three classes of kidney ultrasound images for (a) Intensity histogram features, (b) GLCM features, and (c) Vector graphic features 117 MSE and testing performance for different neuron number in the hidden layer 120 MSE and testing performance for different value of learning rate 121 MSE and testing performance for different value of iteration rate 122 MSE and testing performance for different value of momentum constant 123 xviii LIST OF ABBREVIATIONS 3D - Three dimensional AC - Active contour ADPKD - Autosomal dominant polycystic kidney disease AI - Adobe Illustrator ANN - Artificial neural network ARPKD - Autosomal recessive polycystic kidney disease BI - Bacterial Infection BUN - Blood urea nitrogen CAD - Computer aided diagnosis CBIR - Content-based image retrieval CC - Cortical cyst CD - Cystic disease CKD - Chronic kidney disease CT - Computed tomography DICOM - Digital imaging and communication in medicine ESRD - End stage renal disease FBME - Faculty of Biosciences and Medical Engineering FN - False negative FP - False Positive GFR - Glomerular filtration rate GLCM - Gray level co-occurrence matrix GUI - Graphical user interface HD - Hausdorff distance IVP - Intravenous pyelogram MDRD - Modification of diet in renal disease MLP - Multilayer perception xix MRD - Medical renal disease MRI - Magnetic resonance imaging MRF - Markov random field MSE - Mean squared error NR - Normal PCA - Principal component analysis PDF - Portable document format PSNR - Peak signal to noise ratio RGB - RGB image RI - Resistive index ROC - Receiver operating characteristic ROI - Region of interest RRT - Renal replacement therapy SI - Similarity index SPL - Spatial pulse length SVG - Support vector graphics SVM - Support vector machine TP - True positive US - Ultrasound VBA - Visual basic for application VUR - Vesicoulateral reflux WV - Weight vector xx LIST OF SYMBOLS A - Area Am - Pixel set of manual outline Aa - Pixel set of automatic outline Az - Average ROC curve area b - Biases BW - Body weight cm - Centimeter Cn - Contrast Cr - Correlation dB - Decibel dl - Deciliter d(pj, Q) - Shortest distance of pj to contour Q E - Energy EQ - Equality test F - Number of cycle GLCM(i,j) - GLCM image gm - Gram H - Homogeneity IIN - Input image ILAYERED(i) - Layered image IORI - Original image IVG - Vector graphic image IWF(i,j) - Wiener filtered image kHz - Kilohertz K(m,n) - Kurtosis m - Meter xxi MAP - Array mg - Milligram MHz - Megahertz min - Minute ml - Milliliter n - Number of bits MN - Size of image Ncolor - Number of colors Npixel - Number of pixel NR - Number of pixel in region Nshape - Number of shape p - Perimeter R - Roundness test Rrank - Region rank $ - US Dollar Scr - Serum creatinine S(m,n) - Skewness TC - Threshold TT - Threshold u(i,j) - Discrete image v - Speed v2 - Noise variance VG2R - Vector graphic ratio in 2nd layer VG3R - Vector graphic ratio in 3rd layer VG4R - Vector graphic ratio in 4th layer w - Weight x(i,j) - Original image Xmax - Maximum value of X Xmin - Minimum value of X y(i,j) - Output Image Ymax - Maximum value of Y Ymin - Minimum value of Y z - Axial resolution xxii - Local mean - Mean σ2 - Local variance σ2(m,n) - Variance θ0 - Angle - Wavelength (m,n) xxiii LIST OF APPENDICES APPENDIX TITLE PAGE A Data, Machines and Operators 148 B Ultrasound Scanning Procedure 151 C Source Code for Image Segmentation 169 D Gantt Chart 174 E List of Publications 175