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    FacultyofComputersandInformationComputerScienceDepartment

    ArtificialIntelligenceTechniquesforOcular

    PatternClassification

    Amr

    Ahmed

    Sabry

    Abdel

    Rahman

    Ghoneim

    Supervisedby:ProfessorAtefZakiGhalwash

    ProfessorofComputerScience,TheFacultyofComputers&Information,Helwan

    University,

    Cairo,

    Egypt.

    AssociateProfessorAliaaAbdelHaleimAbdelRazikYoussif

    AssociateProfessorofComputerScience,TheFacultyOfComputers&Information,HelwanUniversity,Cairo,Egypt.

    AssistantProfessorHosamElDeanMahmoudBakeir

    AssistantProfessorofOphthalmology,TheFacultyofMedicine,Cairo

    University,

    Cairo,

    Egypt.

    A thesissubmitted toHelwanUniversity inaccordancewith therequirements forthedegreeofMasterofScienceinComputerScienceattheFacultyofComputers&Information,DepartmentofComputerScience.

    May2007

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    References2

    Thispageisleftblankintentionally

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    )285(

    ))286

    InthenameofAllah,MostGracious,MostMercifulTheMessengerbelieveth inwhathathbeenrevealed tohimfromhisLord,asdo

    themenoffaith.Eachone(ofthem)believethinAllah,Hisangels,HisBooks,and

    His Messengers. Wemake nodistinction (they say)between one andanotherof

    HisMessengers. Andtheysay: Wehear,andweobey,(weseek)Thyforgiveness,

    ourLord,andtoTheeistheendofalljourneys. (285)OnnosouldothAllahplace

    aburden greater than it canbear. It gets every good that it earns, and it suffers

    everyill

    that

    it

    earns.

    (Pray:) Our

    Lord!

    Condemn

    us

    not

    if

    we

    forget

    or

    fall

    into

    error;ourLord!Laynotonusaburden like thatwhichThoudidst layon those

    beforeus;ourLord!laynotonusaburdengreaterthanwehavestrengthtobear.

    Blot out our sins, and grant us forgiveness. Have mercy on us. Thou art our

    Protector;helpusagainstthosewhostandagainstFaith.(286)TheholyQuran:Chapter2AlBaqarah285:286

    : : .

    AbuHuraira(Allahbepleasedwithhim)reportedAllahsMessenger(Maypeaceandblessingsbeuponhim)assaying:Whenamandies,hisactscometoanend,butthree,recurringcharity,orknowledge(bywhichpeople)benefit,orapiousson,whopraysforhim(forthedeceased).

    SahihMuslim

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    References2

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    To

    thememoryofmycolleagues

    IbraheimArafat,

    MustaphaGamal,

    &

    KhaledAbdelMoneim

    Andtomybelovedcity,Cairo,acitythatnever

    failsto

    make

    an

    impression,

    an

    everlasting,

    unique

    impression

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    Theresearch

    described

    in

    this

    thesis

    was

    carried

    out

    at

    the

    Faculty

    of

    Computers

    &

    Information HelwanUniversity,Cairo,TheArabRepublicofEgypt.

    Copyright 2007 by Amr S. Ghoneim. All rights reserved. No part of this

    publication may be reproduced or transmitted in any form or by any means,

    electronic or mechanical, including photocopy, recording, or any information

    storageandretrievalsystem,withoutpermission inwriting from theauthor.Any

    trademarksinthispublicationarepropertyoftheirrespectiveowners.

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    Contents vii

    C o n t e n t s

    Abstract & Keywords. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiv

    Acknowledgment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

    Declaration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xx

    List of Publications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi

    List of Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxii

    List of Tables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxviii

    Awards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxix

    Medical Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxx

    1 Introduction 1

    1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

    1.2 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

    1.3 Thesis Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

    1.4 Thesis Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

    1.5 Eye Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

    1.6 Fundus Photography and Eye Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

    1.6.1 Diabetic Retinopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

    1.6.2 Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

    1.6.3 Detecting Retina Landmarks . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

    1.6.4 Fundus Photography Datasets . . . . . . . . . . . . . . . . . . . . . . . . . . 12

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    Contents

    viii

    2 Preprocessing 13

    2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

    2.2 Fundamentals of Retinal Digital Image Representation . . . . . . . . . . . . . . 13

    2.3 Mask Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

    2.4 Illumination Equalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

    2.5 Contrast Enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

    2.5.1 Green Band Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

    2.5.2 Histogram Equalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

    2.5.3 Local Contrast Enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . 21

    2.5.4 Adaptive Histogram Equalization . . . . . . . . . . . . . . . . . . . . . . 23

    2.5.5 Background Subtraction of Retinal Blood Vessels (BSRBV)

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

    2.5.6 Estimation of Background Luminosity and Contrast

    Variability (EBLCV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

    2.6 Color Normalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

    2.6.1 Gray-World Normalization . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

    2.6.2 Comprehensive Normalization . . . . . . . . . . . . . . . . . . . . . . . . . 27

    2.6.3 Histogram Equalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

    2.6.4 Histogram Specification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

    2.7 Image Quality Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

    2.7.1 Convolution of Global Intensity Histograms . . . . . . . . . . . . . . 32

    2.7.2 Edge Magnitude and Local Pixel Intensity Distributions . . . . . 33

    2.7.3 Asymmetry of Histograms Derived from Edge Maps . . . . . . . 34

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    2.7.4 Chromaticity Values Distribution . . . . . . . . . . . . . . . . . . . . . . 37

    2.7.5 Clarity and Field Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

    2.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

    3 Automatic Localization of the Optic Disc 43

    3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

    3.2 Properties of the Optic Disc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

    3.3 Automatic Optic Disc Localization: A Literature Review . . . . . . . . . . . . . 46

    3.3.1 Optic Disc Localization versus Disc Boundary Detection . . . . 46

    3.3.2 Existing Automatic OD-Localization Algorithms Review . . . . 46

    3.3.3 Alternative OD-Localization Algorithms . . . . . . . . . . . . . . . . . 58

    3.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

    4 Automatic Segmentation of the Retinal Vasculature 61

    4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

    4.2 Properties of the Retinal Vasculature . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

    4.3 Automatic Retinal Vasculature Segmentation: A Literature Review . . . . 62

    4.3.1 Detection of Blood Vessels in Retinal Images using TwoDimensional Matched Filters . . . . . . . . . . . . . . . . . . . . . . . . . .

    63

    4.3.2 Existing Automatic Retinal Vasculature Segmentation

    Algorithms Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    66

    4.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

    5 Automatic Detection of Hard Exudates 75

    5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

    5.2 Properties of the Diabetic Retinopathy Lesions . . . . . . . . . . . . . . . . . . . . 76

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    5.3 Automatic Diabetic Retinopathy Lesions Detection: A Literature Review

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .78

    5.3.1 Existing Automatic Bright Lesions Detection Algorithms

    Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79

    5.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

    6 Comparative Studies 85

    6.1 A Comparative Study of Mask Generation Methods . . . . . . . . . . . . . . . . . 85

    6.1.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

    6.1.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

    6.1.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

    6.1.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 86

    6.2 A Comparative Study of Illumination Equalization Methods . . . . . . . . . . 88

    6.2.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

    6.2.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

    6.2.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

    6.2.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 89

    6.3 A Comparative Study of Contrast Enhancement Methods . . . . . . . . . . . . 90

    6.3.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

    6.3.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

    6.3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

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    6.3.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 91

    6.4 A Comparative Study of Color Normalization Methods . . . . . . . . . . . . . . 95

    6.4.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

    6.4.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

    6.4.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

    6.4.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 96

    7 The Developed Automatic DR Screening System Components 100

    7.1 Optic Disc Localization by Means of a Vessels Direction Matched Filter

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100

    7.1.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

    7.1.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

    7.1.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

    7.1.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 106

    7.2 Retinal Vasculature Segmentation using a Large-Scale Support Vector

    Machine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109

    7.2.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

    7.2.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

    7.2.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

    7.2.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 114

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    7.3 Hard Exudates Detection using a Large-Scale Support Vector Machine .

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .118

    7.3.1 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

    7.3.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

    7.3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

    7.3.4 Observations and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 123

    8 Conclusions & Future Work 125

    8.1 Preprocessing of Digital Retinal Fundus Images . . . . . . . . . . . . . . . . . . . . 125

    8.2 Retinal Landmarks Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

    8.3 Diabetic Retinopathies Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

    Appendix A Eye-Related Images 129

    A.1 Fundus Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

    A.2 Fluorescein Angiograms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

    A.3 Indocyanine Green Dye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

    A.4 Hartmann-Shack Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

    A.5 Iris Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

    Appendix B Diabetes, Diabetic Retinopathy and their Prevalence in Egypt 135

    B.1 Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

    B.2 Diabetes in Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

    B.3 Diabetic Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

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    Contents xiii

    B.4 Diabetic Retinopathy in Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

    Appendix C Fundus Photography Datasets 142

    C.1 DRIVE Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

    C.2 STARE Project Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

    Appendix D Color Models 147

    D.1 HSI Color Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

    D.1.1 Converting Colors from RGB to HIS . . . . . . . . . . . . . . . . . . . . 148

    D.1.2 Converting Colors from HSI to RGB . . . . . . . . . . . . . . . . . . . . 148

    D.2 Chromaticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

    Appendix E A Threshold Selection Method from Gray-Level Histograms 151

    References 154

    (Abstract & Keywords in Arabic) (Cover page in Arabic)

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    Abstract & Keywordsxiv

    Abstract

    Diabetes is a disease that affects about 5.5% of the global population. In

    Egypt, nearly 9 million (over 13% of the population 20 years) will have

    diabetes by the year 2025, while recent surveys from Oman and Pakistan

    suggest that this may be a regional phenomenon. Consequently, about 10%

    of all diabetic patients have diabetic retinopathy (DR); one of the most

    prevalent complications of diabetes and which is the primary cause of

    blindness in the Western World, and this is likely to be true in Hong Kong,

    and Egypt. Moreover, diabetic population is expected to have a 25 times

    greater risk of going blind than non-diabetic. Due to the growing number of

    patients, and with insufficient ophthalmologists to screen them all, automatic

    screening can reduce the threat of blindness by 50%, provide considerable

    cost savings, and decrease the pressure on available infrastructures and

    resources.

    Retinal photography is significantly more effective than direct

    ophthalmoscopy in detecting DR. Digital fundus images do not require

    injecting the body by fluorescein or indocyanine green dye, thus not

    requiring a trained personnel. Digital fundus images are routinely analyzed

    by screening systems, and owing to the acquisition process, these images are

    very often of poor quality that hinders further analysis. State-of-the-art

    studies still struggle with the issue of preprocessing in retinal images, mainly

    due to the lack of literature reviews and comparative studies. Furthermore,

    available preprocessing methods are not being evaluated on large benchmark

    publicly-available datasets.

    The first part of this dissertation discusses four major preprocessing

    methodologies described in literature (mask generation, illumination

    equalization, contrast enhancement, and color normalization), and their

    effect on detecting retinal anatomy. In each methodology, a comparative

    performance measure based on proposed appropriate metrics is

    accomplished among available methods, using two publicly available fundus

    datasets. In addition, we proposed the comprehensive normalizationand a

    local contrast enhancement proceeded by illumination equalizationwhich

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    Abstract & Keywordsxv

    recorded acceptable results when applied for color normalization and

    contrast enhancement respectively.

    Detecting retinal landmarks (the vasculature, optic disc, and macula)

    give a framework from which automatedanalysis and human interpretation

    of the retina proceed.And therefore, it will highly aid the future detection

    and hence quantification of diseases in the mentioned regions. In addition,

    recognizing main components can be used for criteria that allow the

    discarding of images that have a too bad quality for assessment of

    retinopathy.

    The second part of the dissertation deals with the Optic Disc (OD)detection as a main step while developing automated screening systems for

    diabetic retinopathy. We present in this study a method to automatically

    detect the position of the OD in digital retinal fundus images based on

    matching the expected directional pattern of the retinal blood vessels. Hence,

    a simple matched filter is proposed to roughly match the direction of the

    vessels at the OD vicinity. The proposed method was evaluated using a

    subset of the STARE project's dataset, containing 81fundus images of both

    normal and diseased retinas, and initially used by literature OD detection

    methods. The OD-center was detected correctly in 80 out of the 81 images(98.77%). In addition, the OD-center was detected correctly in all of the 40

    images (100%) using the publicly available DRIVE dataset.

    The third part of the dissertation deals with the Retinal vasculature

    (RV) segmentation as another basic foundation while developing retinal

    screening systems, since the RV acts as the main landmark for further

    analysis. Recently, supervised classification proved to be more efficient and

    accurate for the segmentation process. Moreover, novel features have been

    used in literature methods, showing high separability between vessels/non-vessels classes. This work utilizes the large-scale support vector machine for

    automatic segmentation of RV, using for the pixel features a mixture of the

    2D-Gabor wavelet, Top-hat, and Hessian-based enhancements. The

    presented method noticeably reduces the number of training pixels since

    2000 instead of 1 million pixels, as presented in recent literature studies, are

    only needed for training. As a result, the average training time drops to 3.75

    seconds instead of the 9 hours that was previously recorded in literature. For

    classifying an image, 30 seconds were only needed. Small training sets and

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    Abstract & Keywordsxvi

    efficient training time are critical for systems that always need readjustment

    and tuning with various datasets. The publicly available benchmark DRIVE

    dataset was used for evaluating the performance of the presented method.Experiments reveal that the area under the receiver operating characteristic

    curve (AUC) reached a value 0.9537 which is highly comparable to

    previously reported AUCs that range from 0.7878 to 0.9614.

    Finally, the fourth part of the presented work deals with the

    automated detection of hard exudates, as a main manifestation of diabetic

    retinopathies. Methods dealing with the detection of retinal bright-lesions in

    general were reviewed. Then, a method based on the response of the large-

    scale support vector machine for the RV segmentation was proposed. Themethod uses to a closed inverted version of the large-scale support vector

    machine response to determine the potential exudates regions according to

    the properties of each region. The response image was segmented into

    regions using the watersheds algorithm. The proposed method achieved and

    accuracy of 100% for detecting hard exudates, an accuracy of 90% for

    indicating images not including any form of bright-lesions.

    Keywords Medical Image Processing, Artificial Intelligence,

    Preprocessing, Retinal/Fundus Image Analysis, Optic Disc Localization,

    Vessels Segmentation, Exudates Detection, Diabetic Retinopathies

    Detection.

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    Acknowledgment xvii

    Acknowledgment

    For their tireless support, I thankMom,Dad,my sisterGhada,and

    mybrotherAyman. Iamsure thesuccessof thisworkwouldmake

    themdelighted.

    Formany years of priceless advice andwisdomwhich shapedmy

    development as a researcher, I thankmy supervisors Prof.AtefZ.

    Ghalwashand

    Prof.

    Aliaa

    A.

    Youssif.

    Iowe

    them

    much

    for

    their

    assistance in all aspects of my work, providing me great help on

    varioustopics,exchangingideasonbothacademicandnonacademic

    matters,andforawonderfulfriendship.Thankyouverymuch!

    Special thanks are given to the consultant ophthalmologist Dr.

    HosamElDeanBakeirforhiskindsupervisionofmedicalexpertise.

    For taking the time tobelieve inmeand investing theirmindsand

    hearts into teaching me how to be a better person, I thank my

    teachers Lecturers & Assistants at the Faculty of Computers &

    Information(FCI),HelwanUniversitywhohaveshapedmymindand

    madeathoughtfulimpactonmydevelopmentovertheyears.Andof

    them, I wish to express my gratitude to Dr. Mohamed A. Belal

    (currently at the Faculty of Science and Information Technology, Al

    Zaytoonah

    University,Amman,

    Jordan)

    for

    supporting

    me

    in

    ComputationalIntelligence.AndIwishalsotoexpressmygratitude

    toDr.WaleedA.YousefwhosupportedmeinLinearAlgebra.

    IwouldliketothankmanyofmycolleaguestheTeachingAssistants

    at both departments in my faculty for their support and

    understanding.

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    Acknowledgmentxviii

    I would like to deeply thank my true friends from all grades,

    especiallymy

    class

    (the

    2002

    graduates),

    and

    both

    the

    2005

    and

    2006

    graduates, always givingme support, encouragement, and helping

    mekeepmyspiritsup.AndIshallneverforgetmystudents(hopefully

    the2007and2008graduates) forbeingsopatient,understandingand

    loving. I acknowledge thatwithout allmyFCIHelwan friends,my

    lifeisempty.Youkeptmegoingonguys!!

    I am also indebted to many researchers who supported me with

    variousresources

    during

    all

    stages

    of

    writing,

    and

    so

    Special

    thanks

    aredueto:

    Ayman S.Ghoneim; a TeachingAssistant at the Operations

    Research Dept., the Faculty of Computers & Information

    Cairo Univ. (now aM.Sc. student at the School of Information

    Technology & Electrical Engineering (ITEE), Australian Defense

    Force Academy (ADFA), the University of New South Wales

    (UNSW),

    Canberra,

    Australia.)

    Amany AbdelHaleim & Bassam Morsy; both are Teaching

    Assistants at the Information Systems/Computer Science

    Departments respectively, the Faculty of Computers &

    Information Helwan Univ. (currently students at the

    DepartmentofElectricalandComputerEngineering,Universityof

    Victoria,Victoria,BritishColumbia,Canada.)

    GhadaKhoriba&AymanEzzat;bothareTeachingAssistants

    atthe

    Computer

    Science

    Department,

    the

    Faculty

    of

    Computers & Information Helwan Univ. (currently PhD.

    students at the Graduate School of Systems and Information

    Engineering,TsukubaUniversity,Tsukuba,Japan.)

    Mohamed Ali; a Teaching Assistant at the Bioengineering

    Dept.,theFacultyofEngineering HelwanUniversity.

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    Acknowledgment xix

    Theworkofmanyresearchers inthisfieldmade thisworkpossible,

    butmydirectcontactswithsomeofthemwhokindlyansweredsome

    technicalquestions

    pertaining

    to

    their

    work

    have

    influenced

    my

    thinkingagreatdeal,andsoIwishtoexpressmysincerethanksto:

    Chanjira Sinthanayothin; the National Electronics and

    ComputerTechnologyCentre(NECTEC),Thailand.

    Subhasis Chaudhuri; Professor & Head, Dept. of Electrical

    Engineering, Indian Institute of Technology (IIT), Powai,

    Bombay,India.

    SarahA. Barman; Senior Lecturer,Digital Imaging Research

    Centre,Kingston

    University,

    London,

    UK.

    NormanKatz;CEO of the IPConsulting (a custom enterprise

    softwarecompany),SanDiego,California,USA.

    LangisGagnon;AssociateProfessor,DepartmentofComputer

    andElectricalEngineering,UniversitLaval,Quebec,Canada.

    Meindert Niemeijer; Ph.D. Student, Image Sciences Institute

    (ISI), University Medical Center Utrecht, Utrecht, the

    Netherlands.

    Andfinally,StephenR.Aylward;Anassistantprofessorinthe

    DepartmentofRadiologyandanadjunctassistantprofessorin

    the Department of Computer Science, College of Arts &

    Sciences at theUniversity ofNorthCarolina atChapelHill,

    USA.HewastheAssociateEditorresponsibleforcoordinating

    thereviewofmy first IEEETransactionsonMedical Imaging

    paper.

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    Chapter 1 Introductionxx

    Declaration

    I declare that the work in this dissertation was carried out inaccordancewith theRegulationsofHelwanUniversity.Thework isoriginalexceptwhereindicatedbyspecialreferenceinthetextandnopartofthedissertationhasbeensubmittedforanyotherdegree.Thedissertationhasnotbeenpresented toanyotherUniversity forexamination

    either

    in

    the

    Arab

    Republic

    of

    Egypt

    or

    abroad.

    AmrS.Ghoneim

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    List of Publications xxi

    ListofPublicationsInpeerreviewedjournals:[1] Aliaa A. A. Youssif, Atef Z. Ghalwash, and Amr S. Ghoneim, Optic

    Disc Detection from Normalized Digital Fundus Images by Means of a

    Vessels Direction Matched Filter,IEEETransactions on Medical Imaging,

    accepted for publication (in press).

    [2] Aliaa A. A. Youssif, Atef Z. Ghalwash, and Amr S. Ghoneim,

    Automatic Segmentation of the Retinal Vasculature using a Large-Scale

    Support Vector Machine, IEEE Transactions on Medical Imaging,

    Submitted for publication.

    Ininternationalconferenceproceedings:[3] Aliaa A. A. Youssif, Atef Z. Ghalwash, and Amr S. Ghoneim,

    Comparative Study of Contrast Enhancement and Illumination Equalization

    Methods for Retinal Vasculature Segmentation, in: Proceedings of the

    Third CairoInternational Biomedical Engineering Conf. (CIBEC06), Cairo

    Egypt, December 21-24, 2006.

    [4] Aliaa A. A. Youssif, Atef Z. Ghalwash, and Amr S. Ghoneim, A

    Comparative Evaluation of Preprocessing Methods for Automatic Detection

    of Retinal Anatomy, in: Proceedings of the fifth International Conference

    on Informatics and Systems (INFOS2007), Cairo Egypt, pp. 24-31, March

    24-26, 2007.

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    List of Figuresxxii

    L i s t o f F i g u r e s

    Figure 1.1

    A typical generic automatic eye screening system, the figure

    highlights the modules that will be included in our research (the light

    grey-blocks point out modules that are out of the scope of this work.)

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    5

    Figure 1.2Simplified diagram of a horizontal cross section of the human eye.

    [4] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7

    Figure 1.3(a) A typical retinal image from the right eye. (b) Diagram of the

    retina. [1] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

    Figure 1.4 (a) A normal optic disc. (b) Glaucomatous optic disc. [15] . . . . . . . . 11

    Figure 2.1

    (a) The area of the retina captured in the photograph with respect tothe different FOV's. (b) The computation of scale according the

    FOV-geometry. [19] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    15

    Figure 2.2 A typical mask for a fundus image. [24] . . . . . . . . . . . . . . . . . . . . . . . 15

    Figure 2.3

    (a) Typical retinal image. [24] (b) The green image (green band)of

    'a'. (c) The smoothed local average intensity image of 'b'using a 40 40window. (d) Illumination equalized version of 'b'usingEq. 2.1.

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    17

    Figure 2.4(a) A typical RGB colored fundus image. (b) Red component image.

    (c) Green component. (d) Blue component. [27] . . . . . . . . . . . . . . . .19

    Figure 2.5

    (a) Typical retinal image. [24] (b) Contrast enhanced version of 'a'

    by applying histogram equalization to eachR, G, B bandseparately.

    (c) Histogram equalization applied to theIntensitycomponent of 'a'.

    (d) Color local contrast enhancement of each R, G, B band of 'a'

    separately. (e) Color local contrast enhancement of the Intensity

    component of 'a'. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    22

    Figure 2.6

    (a) The inverted green channel of the retinal image shown in '2.3(a)'.

    (b) Illumination equalized version of 'a'. (c) Adaptive histogram

    equalization applied to the image 'b'usingEq. 2.9. . . . . . . . . . . . . . .

    23

    Figure 2.7

    (a) The background subtraction of retinal blood vessels and (b) the

    estimation of background luminosity and contrast variability

    enhancements, both methods are applied to the retinal image shown

    in '2.3(a)'. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    25

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    List of Figures xxiii

    Figure 2.8

    The gray-world (a, c)and comprehensive (b, d)normalizations of

    2.5(a) and 2.3(a) respectively. The normalization process was

    repeated for 5 iterations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    28

    Figure 2.9

    The summarized procedure shown in blue for applying

    histogram specification to a given input image using the histogram

    of a reference image. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    30

    Figure 2.10

    (a) Reference image. [24] (b) Typical retinal image. (c) Colornormalized version of 'b' using the histogram of 'a' by applying

    histogram specification separately using each R, G, B bandof both

    images. (d) Histogram specification applied using the Intensitycomponent of both images. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    31

    Figure 2.11Scatter plot showing the separability of the three classes "Good

    image", "Fair image" and "Bad image". [37] . . . . . . . . . . . . . . . . . . .35

    Figure 2.12

    The Rayleigh distribution, which is a continuous probability

    distribution that usually arises when a two dimensional vector (e.g.

    wind velocity) has its two orthogonal components normally and

    independently distributed. The absolute value (e.g. wind speed)will

    then have a Rayleigh distribution. [40] . . . . . . . . . . . . . . . . . . . . . . . .

    36

    Figure 2.13Chromaticity space (r and g values)plots. (a) No normalization (b)

    Histogram specification. [22] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

    Figure 2.14

    (a) The method of macular vessel length detection. (b) The filed

    definition metrics [41]. Constraints are expressed in multiples of

    disc diameters DD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    40

    Figure 3.1

    (a) Swollen nerve, showing a distorted size and shape. (b) Nerve that

    is completely obscured by hemorrhaging. (c) Bright circular lesion

    that looks similar to an optic nerve. (d) Retina containing lesions of

    the same brightness as the nerve. [18, 27] . . . . . . . . . . . . . . . . . . . . . .

    44

    Figure 3.2A fundus diagnosed of having high severity retinal/sub-retinal

    exudates. [27] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45

    Figure 3.3A typical healthy fundus image, it shows the properties of a normal

    optic disc. [24] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45

    Figure 3.4

    (a) Adaptive local contrast enhancement applied to the intensityimage of the retinal fundus in figure 3.3. (b) The variance image of

    'a'. (c) The average variances of 'b'. (d) The OD location (white

    cross) determined as the area of highest average variation in

    intensity values. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    47

    Figure 3.5

    An example for the training set of images. Ten intensity images,

    manually cropped around the OD from the DRIVE-dataset [24], &

    can be used to create the OD model. . . . . . . . . . . . . . . . . . . . . . . . . . .

    49

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    List of Figuresxxiv

    Figure 3.6 The OD template image used by Alireza Osareh [1, 10]. . . . . . . . . . . 50

    Figure 3.7 Five-level pyramidal decomposition applied to the green band of thefundus image in Figure 3.3. (a) (e) Image at the first, second, third,

    fourth and fifth level correspondingly. . . . . . . . . . . . . . . . . . . . . . . . .

    51

    Figure 3.8Closing applied to the green band of the fundus image in Figure 3.3

    in order to suppress the blood vessels. . . . . . . . . . . . . . . . . . . . . . . . .52

    Figure 3.9 The fuzzy convergence image of a retinal blood vasculature. [18] . . . 54

    Figure 3.10 A schematic drawing of the vessel orientations. [19] . . . . . . . . . . . . . 55

    Figure 3.11

    Complete model of vessels direction. For sake of clarity, directions

    (gray segments)are shown only on an arbitrary grid of points. [53] .

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    56

    Figure 3.12 The OD localization filter (template)used by [43]. . . . . . . . . . . . . . . 57

    Figure 4.1One of the 12 different kernels that have been used to detect vessel

    segments along the vertical direction. [30] . . . . . . . . . . . . . . . . . . . . .65

    Figure 4.2

    (a) The maximum responses after applying the 12 kernels proposed

    by Chaudhuri et al.[30] to the retinal image shown in 2.6(c). (b)

    The corresponding binarized image using the threshold selection

    method proposed by Otsu [63]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    66

    Figure 4.3 The eight impulse response arrays of Kirschs method. [12] . . . . . . . 67

    Figure 4.4

    (a) A typical fundus image from the STARE dataset. (b) The first

    manual RV segmentation by Adam Hoover. (c) The second manualRV segmentation by Valentina Kouznetsova. (d) The results of

    applying thepiecewise threshold probing of a MFR. [27] . . . . . . . . .

    68

    Figure 4.5

    The first (a) and second (b) manual segmentations for the retinal

    image in 2.5(a), and the corresponding results of the RVsegmentation methods by Chaudhuri et al.[30] (c), Zana and Klein

    [65] (d), Niemeijer et al.[50] (e), and Staal et al.[7] (f). . . . . . . . . . .

    70

    Figure 4.6

    (a)(d) The maximum 2D-Gabor wavelet response for scales a= 2,

    3, 4, and 5 pixels respectively, applied to the retinal image in2.5(a). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    72

    Figure 4.7(a) Top-hat and (b) Top-hat Hessian-based enhancements, both

    applied to the retinal image in 2.5(a). . . . . . . . . . . . . . . . . . . . . . . . .73

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    List of Figures xxv

    Figure 5.1

    (a)(d) STARE images showing different symptoms of DR.

    (e) Drusen, a macular degeneration disease usually confused with

    bright DR lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    77

    Figure 5.2Manual image segmentation. (a) An abnormal image. (b) Manually

    segmented exudates (in green). (c) Close-up view of exudates. [1] . .80

    Figure 5.3 Tissue layers within the ocular fundus. [85] . . . . . . . . . . . . . . . . . . . . 83

    Figure 6.1

    Results of comparing Mask Generation methods using the STARE.

    (1st row) three typical images from the STARE, (2nd, 3rd, and 4th

    rows) are the results of applying the mask generation methods of

    Gagnon et al. [23], Goatman et al. [22], and Frank ter Haar [19]respectively. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    87

    Figure 6.2

    Results of comparing Illumination Equalization methods using theDRIVE. Top row images are typical gray-scale images, while the

    bottom images represent the highest 2% intensity pixels per image.(a) green-band of a typical DRIVE image. (b) and (c) are

    illumination equalized by [19] and [25] respectively. . . . . . . . . . . . . .

    89

    Figure 6.3

    Reviewed normalizations of a typical fundus image. (a) Intensity

    image. (b) Green-band image. (c) Histogram equalization.(d) Adaptive local contrast enhancement. (e) Adaptive histogram

    equalization. (f) Desired average intensity. (g) Division by an over-

    smoothed version. (h) Background subtraction of retinal bloodvessels. (i) Estimation of background luminosity and contrast

    variability. (j) Adaptive local contrast enhancement applied to g

    instead of a. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    92

    Figure 6.4

    (a)(j) are the results of applying a RV segmentation method to theimages Fig. 6.3 (a)(j) respectively. (k) A manual segmentation of

    Fig. 6.3(a)(used as a gold-standard). . . . . . . . . . . . . . . . . . . . . . . . . .

    93

    Figure 6.5 ROC curves of the compared contrast enhancements methods. . . . . . 94

    Figure 6.6

    Color normalization chromaticity plots. (a) Before applying any

    normalization methods. (b) Gray-world normalization.

    (c) Comprehensive normalization. (d) Histogram equalization.(e) Histogram specification (matching). Red ellipse and elements

    plots represent the non-vessels cluster, while the blue represent the

    vessels cluster.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    97

    Figure 7.1The proposed vessels direction at the OD vicinity matched filter. .

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103

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    List of Figuresxxvi

    Figure 7.2

    The proposed method applied to the fundus image in 6.8(i). (a) ROI

    mask generated. (b) Green-band image. (c) Illumination equalized

    image. (d) Adaptive histogram equalization. (e) Binary vessel/non-

    vessel image. (f) Thinned version of the preceding binary image.(g) The intensity mask. (h) Final OD-center candidates. (i) OD

    detected successfully using the proposed method (White cross, right-

    hand side). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    104

    Figure 7.3

    Results of the proposed method using the STARE dataset (white

    cross represents the estimated OD center). (a) The only case where

    the OD detection method failed. (b)(h) The results of the proposed

    method on the images shown in [53]. . . . . . . . . . . . . . . . . . . . . . . . . .

    105

    Figure 7.4Results of the proposed method using the DRIVE dataset (white

    cross represents the estimated OD center). . . . . . . . . . . . . . . . . . . . . .106

    Figure 7.5

    The pixels features. (a) A typical digital fundus image from the

    DRIVE. (b) The inverted green-channel of a padded using [66].

    (c)(f) The maximum 2D-Gabor wavelet response for scales a = 2,

    3, 4, and 5 pixels respectively. (g) Top-hat enhancement. (h) Top-hat

    Hessian-based enhancement. (i) Green-band Hessian-basedenhancement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    113

    Figure 7.6

    (1strow) Using three typical retinal images from the DRIVE, results

    of the LS-SVM classifier trained using 2000 pixels with the final set

    of features. (2nd row) The corresponding ground-truth manualsegmentation. (3rdrow) Another manual segmentation available for

    the DRIVE images. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    115

    Figure 7.7

    ROC curve for classification on the DRIVE dataset using the LS-

    SVM classifier trained using 2000 pixels with the final set of

    features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    116

    Figure 7.8

    The first steps while detecting Exudates. (1st row) Typical STARE

    images containing exudates. (2nd row) The LS-SVM RV

    segmentation soft-responses for the 1st row images. (3rd row) The

    binarization hard-responses of the RV segmentation outputs inthe 2ndrow. (4throw) The effect of the morphological closing when

    applied to inverted versions of the images in the 2ndrow. . . . . . . . . .

    120

    Figure 7.9

    The final steps while detecting Exudates. (1st row) The watersheds

    segmentation results of the images in Figure 6.14 (4th row). (2ndrow) A binary mask showing the regions finally selected as exudates

    according to their properties. (3rd row) The identified exudates

    shown in blue superimposed on the original images of Figure6.14 (1strow). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    121

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    List of Figures xxvii

    Figure 7.10

    STARE images diagnosed manually as not containing any form of

    bright-lesions, and indicated as free of any bright-lesions by our

    proposed approach (a message indicating so is superimposed on the

    upper-left most corner). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    123

    Figure 7.11

    STARE images manually diagnosed as having forms of bright-

    lesions other than hard exudates, and indicated as having brightlesions by our proposed approach. The identified bright lesions are

    shown in blue (follow the white arrows), and superimposed on the

    original images. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    123

    Figure A.1 Front view of a healthy retina. [97] . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

    Figure A.2

    (a) An example fundus image shows "Puckering the macula" a

    macular disease were an opaque membrane obscures the visibilityof the macula and drags the para-macular vessels. (b) The dragged

    vessels are shown better in fluorescein angiogram. [98] . . . . . . . . . . .

    130

    Figure A.3

    (a) Typical Hartmann-Shack spot pattern (inverted) from a human

    eyes measurement. (b) Hartmann-Shack wavefront sensor with

    micro-lens array and image sensor in the focal plane. [101] . . . . . . . .

    132

    Figure A.4 A typical iris image. [105] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

    Figure B.1Diabetic retinopathy effect on the vision (a) Without retinopathy. (b)

    With retinopathy. [1] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .138

    Figure B.2Diabetic retinopathy syndromes as categorized by [1] (the light grey-

    blocks point out DR forms that are not detected by this work.). . . . .140

    Figure D.1

    Chromaticity Diagram, by the CIE (Commission Internationale de

    l'Eclairage the international Commission on Illumination). [112] .

    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    150

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    List of Tables

    xxviii

    L i s t o f T a b l e s

    Table 2.1 Image-Clarity grading scheme. [41] . . . . . . . . . . . . . . . . . . . . . . . . . . 40

    Table 2.2 Field definition grading scheme. [41] . . . . . . . . . . . . . . . . . . . . . . . . . 41

    Table 2.3 The sensitivity and specificity of inadequate detection. [41] . . . . . . . 41

    Table 6.1 Results of comparing Mask Generation methods using the DRIVE. . 86

    Table 6.2Area under curve (AUC) measured per contrast enhancementmethod. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    94

    Table 7.1OD detection results for the proposed and literature reviewed

    methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107

    Table 7.2

    Results for the performance evaluation experiments made for our

    presented method, and compared to different literature segmentationmethods (for the DRIVE dataset). . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    117

    Table 7.3Results of detecting Hard Exudates using the STARE. . . . . . . . . . . . 122

    Table B.1Projected counts and prevalence of diabetes in Egypt (population 20 years),1995 to 2025. [8] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    137

    Table B.2Distribution of the 300 diabetic patients by their seeking of medical

    care. [110] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141

    Table C.1

    The total STARE publicly available 82 images used by [52]

    and/or [18], together with the ground truth diagnoses of each image.

    [27] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    146

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    Awards xxix

    A w a r d s

    November

    2007

    The 1stPlace Winning Postgraduate in the MIA Made-In-the-Arab-

    worldCompetition Organized by the Arab League & the Arab

    Academy for Science and Technology (ASTF) Cairo, Egypt.

    July 2007

    The 1stPlace Winning Postgraduate in the MIE Made-In-Egypt

    Competition Organized by the IEEE-Egypt Gold Section Cairo,

    Egypt.

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    Medical Glossaryxxx

    M e d i c a l G l o s s a r y

    Agerelated macular degeneration (AMD, ARMD); (MAKyulur).Group of conditions that include

    deteriorationofthemacula,resultinginlossofsharpcentralvision.Twogeneraltypes: dry, whichis

    morecommon,and wet, inwhichabnormalnewbloodvesselsgrowundertheretinaand leakfluid

    andblood(neovascularization),furtherdisturbingmacularfunction.Mostcommoncauseofdecreased

    visionafterage60.Anteriorchamber;Portionoftheeyebetweenthecorneaandtheiris.

    Blindspot;Sightlessareawithinthevisualfieldofanormaleye.Causedbyabsenceof lightsensitive

    photoreceptorswheretheopticnerveenterstheeye.

    Choroid;Thevascularmiddlecoatoftheeyelocatedbehindtheretinaandinfrontofthesclera.Ciliary

    body;Theportionoftheuvealtractbetweenthe irisand thechoroid;composedofciliarymuscleand

    processes. Cone; Lightsensitive retinal receptor cell that provides sharp visual acuity and color

    discrimination.Cornea;Transparentportionoftheoutercoatoftheeyeballformingtheanteriorwallof

    the anterior chamber. Cottonwool

    spots; Infarction of the opticnerve fiber layer of the retina, as in

    hypertension.

    Diabetic retinopathy; (retinAHPuhthee).Spectrumof retinal changesaccompanying longstanding

    diabetesmellitus.Early stage is background retinopathy.May advance toproliferative retinopathy,whichincludes the growth of abnormal newblood vessels (neovascularization) and fibrous tissue. Dilated

    pupil;Enlargedpupil,resultingfromcontractionofthedilatormuscleorrelaxationoftheirissphincter.

    Occursnormallyindimillumination,ormaybeproducedbycertaindrugs(mydriatics,cycloplegics)or

    resultfromblunttrauma.Drusen;(DRUzin).Tiny,whitehyalinedepositsonBruchsmembrane(ofthe

    retinalpigmentepithelium).Commonafterage60;sometimesanearlysignofmaculardegeneration.

    Fluorescein angiography; (FLORuhseen anjeeAHgruhfee). Technique used for visualizing andrecording location and sizeofbloodvessels and any eyeproblems affecting them; fluoresceindye is

    injectedinto

    an

    arm

    vein,

    then

    rapid,

    sequential

    photographs

    are

    taken

    of

    the

    eye

    as

    the

    dye

    circulates.

    Fovea;Thethinnedcentreofthemacula,responsibleforfineacuity.Fundus;Interiorposteriorsurfaceof

    theeyeball;includesretina,opticdisc,macula,posteriorpole.Canbeseenwithanophthalmoscope.

    Glaucoma;Progressiveopticneuropathywithcharacteristicnerveandvisualfieldchanges.

    Intraocularpressure(IOP);Pressurewithintheglobe(Nrrange=8 21mmHg).Iris;Pigmentedtissue

    lyingbehindthecorneathatgivescolortotheeye(e.g.,blueeyes)andcontrolsamountoflightentering

    theeyebyvaryingthesizeofthepupillaryopening.

    Macula;Thesmallavascularareaoftheretinasurroundingthefovea.Mydriasis;Dilationofthepupil.

    Neovascularization; (neeohVASkyulurihZAYshun). Abnormal formation of new blood vessels,

    usuallyinorundertheretinaorontheirissurface.Maydevelopindiabeticretinopathy,blockageofthe

    centralretinalvein,ormaculardegeneration.

    Ophthalmologist; (ahfthalMAHlohjist).Physician (MD) specializing indiagnosis and treatment of

    refractive,medicalandsurgicalproblemsrelatedtoeyediseasesanddisorders.Ophthalmoscope;(ahfTHALmuhskohp).Illuminatedinstrumentforvisualizingtheinterioroftheeye(especiallythefundus).

    Opticdisc,Opticnervehead;Ocularendoftheopticnerve.Denotestheexitofretinalnervefibersfrom

    theeyeandentranceofbloodvesselstotheeye.Opticnerve;Largestsensorynerveoftheeye;carries

    impulsesforsightfromtheretinatothebrain.

    Peripheralvision;Sidevision;visionelicitedbystimulifallingonretinalareasdistantfromthemacula.

    Pupil;Variablesizedblackcircularopening in thecenterof the iris thatregulates theamountof light

    thatenterstheeye.

    Retina;Theinnermostlayeroftheeyecomprisedoftenlayers.

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    Chapter 1 Introduction 1

    C h a p t e r 1

    Introduction1.1 Motivation

    The classification of various ocular/ophthalmic eye related patterns is

    an essential step in many fields. Whether in medical diagnosis medical

    image processing or security, analyzing and classifying ocular images can

    aid significantly in automating and improving real-time systems.

    Consequently, that leads to a practical and sensible reduction in time and

    costs, and prevents in case of medical diagnosis people from suffering

    due to various forms of pathologies, with blindness at the forefront.

    Medical image processing can be considered recently as one the mostattractive research areas due to the considerable achievements that

    significantly improved the type of medical care available to patients,

    although it's a multidisciplinary that requires comprehensive knowledge in

    many areas such as medicine, pattern recognition, machine learning, and

    image processing. Medical image analysis can highly assist physicians in

    diagnosing, treating, and monitoring changes of various diseases; hence, a

    physician can obtain decision support [1].

    Diabetes severe progression is one of the greatest immediate challenges

    to the current worldwide health system [1]. Diabetic retinopathy (DR),

    beside others, is a common complication of diabetes, and a leading cause of

    blindness in Egypt, the Middle-East, and in the working-age population of

    western countries. Glaucoma is also a leading cause of blindness worldwide.

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    Chapter 1Introduction

    2

    In general, threats to vision and blinding complications of DR and glaucoma

    give little or no warning, but can be moderated if detected early enough for

    treatment. Thus, annual screening(s) that employs direct examination with an

    ophthalmoscope especially for diabetic patients is highly recommended.

    Automatic screening has been shown to be cost effective compared to the

    high cost of conventional examination. Insufficient ophthalmologists

    especially in rural areas also hinders patients from obtaining regular

    examinations. Thus, an automatic system for analyzing the retinal fundus

    images would be more practical, efficient, and cost effective.

    Artificial Intelligence (AI) may be defined as the branch of computer

    science that is concerned with the automation of intelligent behavior. It is

    still a young discipline, and its structure, concerns, and methods are less

    clearly defined than those of a more mature science such as physics [2],

    although it has always been more concerned with expanding the capabilities

    of computer science than with defining its limits. AI can be broadly

    classified into two major directions:

    Logic-Based Traditional AI which includes symbolic processing,

    And, Computational Intelligence (CI) which is relatively new and

    encompasses approaches primarily based on the bio-inspired artificial

    neural networks and evolutionary algorithms, besides fuzzy logic rules,

    support vector machines, and also hybrid approaches.

    CI approaches can be trained to learn patterns, a property that must be a partof any system that would claim to possess general intelligence [2], and hence

    the so-called Machine Learning is one major branch of AI. CI techniques

    are increasingly being used in biomedical areas because of the complexity of

    the biological systems as well as the limitations of the existing quantitative

    techniques in modeling [3]. Even though just stated, performed researches

    concerning the analysis and classification of ocular images are mainly based

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    Chapter 1 Introduction 3

    on other approaches; for example, statistical methods, geometrical models,

    and convolutional kernels.

    Finally, many of the researches and methods conducted, especially for

    medical diagnosis, lack the evaluation on large benchmark datasets. As a

    result, carrying out comparative studies is durable and inflexible.

    1.2 Objectives

    The main objective of this research is to aid in developing automatic

    screening systems for retinopathies (especially DR). Such systems will

    significantly help ophthalmologists while diagnosing and treating patients.

    Automated screening systems promise with more efficient and costless

    medical services, in addition to delivering health-care services to rural areas.

    Over and above, automated screening systems will lend a hand to hold back

    the personal and social costs of DR as one of the most prevalent

    complications of diabetes and one of the leading causes of blindness.

    To develop any automatic ocular screening system, firstly we have toanalyze the anatomical structure of the retinal fundus image, which consists

    mainly of the Retinal Blood Vessels (RBV), Optic Disc (OD), and Macula.

    Detecting the previously mentioned structures will further help in detecting

    and quantizing several retinopathies. Then, to detect the presence of DR, we

    have to detect a DR manifestation such as exudates, or microaneurysms.

    The presence of AI approaches has to be investigated through this

    research, since these approaches have proven great effectiveness in pattern

    classification and image processing. Employing CI approaches while dealing

    with retinal fundus images may highly improve the results achieved. Finally,

    all the methods that will be selected for a comparative study or for being

    employed in the final proposed system should be compared against the

    appropriate benchmark dataset(s) to realize a practical evaluation.

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    Chapter 1Introduction

    4

    1.3 Thesis Overview

    This thesis mainly presents a literature review and a comparative studyfor some of the basic tasks employed while developing an automated ocular

    screening system for detecting DR. These main tasks and the overall scope

    of this work are shown in Figure 1.1.

    The thesis starts with exploring various phases used for preprocessing a

    retinal fundus image; which includes mask generation, color normalization,

    contrast enhancement, and illumination equalization. Preprocessing a fundus

    image is vital step that prepares the image to be effectively analyzed.

    Selected preprocessing methods are compared and evaluated using a

    standard dataset. The thesis then moves on by exploring various approaches

    used for detecting retinal fundus images' landmarks (retinal blood vessels,

    optic disc)which are considered the most important anatomical structures in

    fundus images. Then new methods are proposed, compared and evaluated on

    somehow large, benchmark, and publicly available datasets.

    The thesis continues by surveying some researches that aim to detect and

    somehow aid the quantification of bright forms manifestations of DR,

    and especially the hard exudates. The later researches basically depend on

    using the retinal structures previously segmented. Finally, the thesis

    summarizes the contribution achieved, and brings together all different

    modules of the automated screening system which will be able at this point

    to identify diabetic patients who need further examination.

    1.4 Thesis Outline

    Chapter 1continues on by furnishing basics required to understand the

    presented work, and introduces the medical background. Chapter 2

    describes different methodologies used to preprocess fundus images and

    prepare them for further analysis.

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    Chapter 1 Introduction 5

    Figure 1.1A typical generic automatic eye screening system, the figure highlights

    the modules that will be included in our research (the light grey-blocks point out

    modules that are out of the scope of this work.)

    Diabetic Retinopathy

    Bright Lesions (mainlyHard Exudates)

    Dark (Red)Lesions

    Pre-Processing

    Mask GenerationColor Normalization

    Contrast Enhancement Illumination Equalization

    Analyzing Retinal Landmarks

    Optic Disc Localization

    Retinal Blood Vessels

    Segmentation

    Fovea Localization

    Detecting Retinopathies

    Glaucoma

    Data Acquisition

    Distinguishing the Central

    Retinal Artery and Vein

    A typical digitized retinal fundus image

    acquired for medical diagnoses through a

    non-mydriatic fundus camera.

    Differentiate Exudates

    from Cottonwool Spots

    Boundary Detection

    Type-of-Eye (left/right)

    Detection

    Differentiate

    Haemorrhages from

    Microaneurysms

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    Chapter 1Introduction

    6

    Chapters 3 and 4provide an overview of previous work, and describe in

    some details the implementation for automatically segmenting the optic disc,

    and the retinal blood vessels respectively. Chapter 5 describes the

    approaches used to automatically extract Exudates, as main bright DR

    manifestation of non-proliferative background diabetic retinopathy.

    Chapters 6 and 7 present our prototyped system for preprocessing

    fundal images, automatically segmenting retinal landmarks, and

    automatically detecting exudates. Both chapters also include the comparative

    studies carried out to evaluate the system, and provide the results of

    experiments that test the capabilities/limitations of the presented methods.

    Chapter 8ends this thesis with a summary of the main achievements of the

    research, a discussion of possible improvements, proposing possible areas

    for future research, as well as concluding remarks.

    1.5 Eye Anatomy

    Developing a basic understanding of the human eye anatomy (Figure 1.2)

    is an appropriate step before going on with this thesis. The eye is nearly a

    sphere, with an average diameter of approximately 20 mm [4], enclosed by

    three membranes: the cornea and sclera compose the outer cover, the

    choroid, and the retina. The cornea is a tough, transparent tissue that covers

    the frontal surface, and continuous with it, the sclera is an opaque membrane

    that encloses the remainder of the optic globe.

    The choroid lies directly below the sclera and it contains a network ofblood vessels that serve as the major source of nutrition. Even superficial

    injury to the choroid, often not deemed serious, can lead to severe eye

    damage as a result of inflammation that restricts blood flow [4]. The choroid

    coat is heavily pigmented and so helps to reduce the amount of extraneous

    light entering the eye and the backscatter within the optical globe. At its

    anterior extreme, the choroid is divided into the ciliary body and the iris

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    Chapter 1 Introduction 7

    diaphragm. The central opening of the iris (the pupil) varies in diameter

    from approximately 2 to 8 mm. The front of the iris contains the visible pig-

    ment of the eye, whereas the back contains a black pigment.

    Retina is the innermost membrane, which lines the inside of the walls

    entire posterior portion. When the eye is properly focused, light from an

    object outside the eye is imaged on the retina. Pattern vision is afforded by

    the distribution of discrete light receptors photoreceptors over the

    surface of the retina. These receptors are responsible for receiving light

    beams, exchanging them into electrical impulses and then transmitting these

    impulses information to the brain where they are turned into images [1].

    Figure 1.2

    Simplified diagram

    of a horizontal cross

    section of the human

    eye. [4]

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    Chapter 1Introduction

    8

    There are two classes of receptors: cones and rods. The cones in each eye

    number between 6 and 7 million, are highly sensitive to color, and are

    located primarily in the central portion of the retina, called the fovea a

    circular indentation of 1.5 mm in diameter.Rods are distributed over the

    retinal surface and number from 75 to 150 million. The absence of receptors

    in the region of emergence of the optic nerve fibers and the blood vessels

    from the eye results in the so-called blind spotor the optic disc [4]. Detailed

    description of the optic disc, retinal blood vessels, and the fovea are found in

    sections 3.2, 4.2 and D.2 respectively, while figure 1.3 shows an example of

    a right fundus image including the main anatomical structures.

    Figure 1.3(a) A typical retinal image from the right eye. (b) Diagram of the

    retina. [1]

    The main retinal components numbered in Figure 1.3 are as follows:1- Superior temporal blood vessels

    2- Superior nasal blood vessels

    3- Fovea / Macula

    4- Optic nerve head / Optic disc

    5- Inferior temporal blood vessels

    6- Inferior nasal blood vessels

    a b

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    Chapter 1 Introduction 9

    1.6 Fundus Photography and Eye Diseases

    Currently, the majority of screenings are carried out by fundalexamination performed by medical staff, which is expensive, and has been

    shown to be inaccurate [5]. Using digital fundus photography provides us

    with digitized data that could be exploited for computerized detection of

    diseases. Fully automated approaches involving fundus image analysis by a

    computer could provide an immediate classification of retinopathy without

    the need for specialist opinions. Thus, it is more cost-effective, ideal for

    those who are unable or unwilling to travel to hospital clinics (especiallythose who live in rural areas), and greatly facilitating the management of

    certain diseases.

    Automated retinopathy screening systems lately depend on fundus

    images taken by a non-mydriatic fundus camera which mainly does not

    require pupillary dilatation, and its operator does not need to be skilled at

    ophthalmoscopy [5]. In addition, fundus photography surpassed fluorescein

    angiography and infrared fluorescence spectrum since no dye need to be

    injected into the bloodstream. See Appendix A for more details about the

    various forms of eye-related images.

    The objective of an automatic screening of fundus images is to improve

    the image appearance, interpretation of the main retinal components and

    analysis of the image in order to detect and quantify retinopathies such as

    microaneurysms, haemorrhages and exudates [5]. In this thesis, we are

    mainly concerned with diabetic retinopathies, and somehow glaucoma,due

    to their impact on society, and were both should be included among the

    avoidable major causes of blindness as some forms of treatment are

    available. Among patients presenting to the Alexandria Specialized Medical

    Committee for Eye Diseases (Alexandria, Egypt), glaucoma was responsible

    for 19.7% of blindness, and diabetic retinopathy for 9% [6].

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    Chapter 1 Introduction 11

    they do not require the injection of fluorescein or indocyanine green dye into

    the body. In general, a screening method that does not require trained

    personnel would be of a great benefit to screening services by decreasing

    their costs, also by decreasing the pressure on available infrastructures and

    resources [14]. The pressure is due to the growing numbers of diabetic

    patients, with insufficient ophthalmologists to screen them all [5],specially

    while World Health Organization (WHO) advices yearly ocular screening of

    patients [7].

    1.6.2 Glaucoma

    Glaucoma is also one of the major causes of preventable blindness. It

    induces nerve damage to the optic nerve head (Figure 1.3) via increased

    pressure in the ocular fluid (Figure 1.4). In most cases the damage occurs

    asymptotically, i.e. before the patient notices any changes to his or her

    vision. And this damage is irreversible; treatment can only reduce or prevent

    further damage [15]. Age is the most constant risk factor for glaucoma, and a

    family history of glaucoma is also a risk factor [6].

    Figure 1.4(a) A normal optic disc. (b) Glaucomatous optic disc. [15]a b

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    Chapter 1Introduction

    12

    Glaucoma is presently detected either by regular inspection of the retina,

    measurement of the intra ocular pressure (IOP) or by a loss of vision. It has

    been observed that nerve head damage precedes that latter two events and

    that direct observation of the nerve head could therefore be a better method

    of detecting glaucoma [16]. In [15], fundus images were used to detect and

    characterize the abnormal optic disc in glaucoma.

    1.6.3 Detecting Retina Landmarks

    Detecting retinal landmarks (Figure 1.3) give a framework from which

    automated analysis and human interpretation of the retina proceed [17].Identifying these landmarks in the retinal image will highly aid the future

    detection and hence quantification of diseases in the mentioned regions. As

    an example, in diabetic retinopathy, after detecting retinal main components

    an image could be analyzed for sight-threatening complications such as disc

    neovascularisation, vascular changes or foveal exudation. Besides just

    mentioned, recognizing main components can be used for criteria that allow

    the discarding of images that have a too bad quality for assessment ofretinopathy [5]. Methods for detecting the optic disc, and retinal blood

    vessels are described in Chapters 3, and 4 respectively.

    1.6.4 Fundus Photography Datasets

    In this work we used a number of publicly available datasets of retinal

    images as a benchmark to evaluate our work, and to compare the

    performance of some selected methods. These datasets include a somehowlarge number of healthy retinas images and others with various diseases, it

    may include also the field-of-view (FOV) mask of each image, the gold

    standard (manual segmentation) used by some algorithms, and the results of

    applying specific algorithms to each image (for details seeAppendix C).

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    Chapter 2

    Preprocessing

    13

    C h a p t e r 2

    Preprocessing2.1 Introduction

    A significant percentage of fundus images are of poor quality that

    hinders analysis due to many factors such as patient movement, poor focus,

    bad positioning, reflections, disease opacity, or uneven/inadequate

    illumination. The sphericity of the eye is a significant determinant in the

    intensity of reflections from the retinal tissues, in addition, the interface

    between the anterior and posterior ocular chambers may cause compound

    artifacts such as circular and crescent-shaped low-frequency contrast and

    intensity changes [17]. The improper focusing of light may radially decreasethe brightness of the image outward from the center, leading to sort of

    uneven illumination known as vignetting [18], and which consequently

    results in the optic disc appearing darker than other areas of the image [19].

    These artifacts are significant enough to impede human grading in about

    10% of retinal images [17], and it can reach 15% in some retinal images sets

    [20]. A similar amount is assumed to be of inadequate quality for automated

    analysis. Preprocessing of the fundus images can wilt or even remove the

    mentioned interferences. This chapter is a literature review that starts with

    describing automatic methods for mask generation, proceeds on by

    discussing various methods for the preprocessing of a fundus image, and

    ends up by describing methods for automatically assessing the quality of

    retinal images.

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    Chapter 2 Preprocessing14

    2.2 Fundamentals of Retinal Digital Image Representation

    Digital images in general may be defined as a two-dimensional lightintensity function,f( x, y),wherexandyare spatial (plane)coordinates, and

    the amplitude (value)offat any point of coordinates ( x, y)is proportional to

    the intensity (brightness, or gray-level)at that point [4]. Digital images are

    images whose spatial coordinates and brightness values are selected in

    discrete increments, not in a continuous range. Thus a digital image is

    composed of a finite number of picture elements (pixels), each of which has

    a particular location and value in case of a monochrome 'grayscale' imageor values three values, usually red, green, and blue, in case of a colored

    image. In a typical retinal true colored image, the value of each pixel is

    usually represented by 24 bits of memory, giving 256 (28) different shades

    for each of the three color bands, thus the total of approximately 16.7 million

    possible colors.

    Generally, the retinal images of the publicly available databases used

    through this work were about 685 rows and 640 columns, for a total of

    about 440,000 pixels. Although digital retinal images must be of size 2-3000

    pixels (2-3 mega-pixels) to match ordinary film resolution [21], digital

    retinal images are a practical alternative to ordinary filming.

    The extent scope of the captured scene of the retina is called the field

    of view (FOV), and is measured in degrees of arc (Figure 2.1(a)). A typical

    retina has a FOV that is somewhat more than 180 degrees of arc, but it's not

    all captured. The images that were used in this work have a 35 or 45 degrees

    of FOV depending on the type and settings of the retinal fundus cameras

    used. Since cameras using a 35-FOV show a smaller area of the retina

    compared to 45-FOV cameras, 35-FOV images are comparatively

    magnified and need to be subsampled before processing [19]. Figure 2.1(b)

    shows the subsampling factor calculated according to the FOV-geometry.

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    Chapter 2 Preprocessing16

    (4-sigma threshold with a free parameter) value was automatically

    calculated using pixel value statistics (mean and standard deviation)outside

    the ROI for each color band. Then logical operators (AND/OR) together with

    region connectivity test are used to combine the binary results of all bands in

    order to identify the largest common connected mask (due to the different

    color response of the camera, ROI size is not always the same for each

    band)[23].

    In [19], the ROI was detected by applying a threshold t to the red color

    band (empirically, 35=t ), and then the morphological operators opening,

    closing, and erosion were applied respectively (to the result of the

    preceding step)using a 33 square kernel to give the final ROI mask. For

    more details on the mentioned logical and morphological operators (i.e.

    AND, OR, opening, closing, and erosion), see [4].

    2.4 Illumination Equalization

    The illumination in a retinal image is non-uniform (uneven) due to the

    variation of the retina response or the non-uniformity of the imaging system

    (e.g. vignetting, and varying the eye position relative to the camera).

    Vignetting and other forms of uneven illumination make the typical analysis

    of retinal images impractical and useless. For instance, the optic disc (OD) is

    characterized as the brightest anatomical structure in a retinal image, hence

    applying a simple threshold or grouping the high intensity pixels should

    localize the OD successfully. Yet, due to uneven illumination vignetting in

    particular the OD may appear darker than other retinal regions, especially

    when retinal images are often captured with the fovea appearing in the

    middle of the image and the OD to one side [18]. Once the OD loses its

    distinct appearance due to the non-uniform illumination or pathologies,

    localizing the OD won't be straightforward, especially for methods based on

    intensity variation or just on intensity values [19].

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    Figure 2.3

    (a) Typical retinal image. [24] (b) The green image (green band)of 'a'

    (c) The smoothed local average intensity image of 'b'using a 40 40window.

    (d) Illumination equalized version of 'b'usingEq. 2.1.

    In order to overcome the non-uniform illumination, illumination

    equalization is applied to the image, where each pixel ),( crI is adjusted

    using the following equation [18, 19]:

    ),(),(),( crImcrIcrI Weq += (Eq. 2.1)

    where m is the desired average intensity (128 in an 8-bit grayscale image)

    and ),( crIW is the mean intensity value (i.e. local average intensity). The

    a bdc

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    mean intensity value is computed independently for each pixel as the

    average intensity of the pixels within a window Wof sizeNN. The local

    average intensities are smoothed using the same windowing (Fig. 2.3). The

    window sizeNapplied in [18] is variable, in order to use the same number of

    pixels (between 30 and 50) every time while computing the average in the

    center or near the border of the image.

    In [19], a running window of only one size (40 40) and pixels inside

    the ROI were used to calculate the mean intensity value, therefore the

    amount of pixels used while calculating the local average intensity in the

    center is more than the amount of pixels used near the border where the

    running window overlaps background pixels. Although the resulting images

    look very similar to those using the variable running window, the ROI of the

    retinal images is shrunk by five pixels to discard the pixels near the border

    where the chances of erroneous values are higher [19].

    In [25], correcting the non-uniform illumination in retinal images is

    achieved by dividing the image by an over-smoothed version of it using aspatially large median filter. Usually, the illumination equalization process is

    applied to the green band (green image)of the retina [18, 19, 25].

    2.5 Contrast Enhancement

    Enhancement is processing an image so that the result is more

    appropriate than the original appearance for a specific application. Contrast

    enhancement refers to any process that expands the range of the significantintensities. The various possible processes differ in how the significant range

    is identified and how the expansion is performed [5].

    2.5.1 Green Band Processing

    In order to simply enhance the contrast of the retinal fundus images,

    some information is commonly discarded before processing, such as the red

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    so-called red-free images and blue components of the image.

    Consequently, only the green band (green image)is extensively used in the

    processing (Figure 2.4) as it displays the best vessels/background contrast

    [26], and the greatest contrast between the optic disc and the retinal tissue

    [15]. In addition, micro-aneurysms a diabetic retinopathy early symptom

    are more distinguishable from the background in the green band although

    they normally appear as small reddish spots on the retina [25].

    Conversely, the red band tends to be highly saturated, thus it's hardly

    used by any automated application that uses intensity information alone.

    Besides, the blue band tends to be empty, and therefore discarded. Therefore,

    many vessel detection and optic disc localization methods are based on the

    green component/channel of the color fundus image [15, 25, 26, 28-30].

    a b

    c d

    Figure 2.4

    (a) A typical

    RGB colored

    fundus image.

    (b) Red

    component

    image.(c) Green

    component.

    (d) Blue

    component. [27]

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    2.5.2 Histogram Equalization

    A typical well-known technique for contrast enhancement is the

    histogram (gray-level) equalization [4], which spans the histogram of an

    image to a fuller range of the gray scale. The histogram of a digital image

    withLtotal possible intensity levels in the range ]1,0[ L is defined as the

    discrete function:

    1,,2,1,0)( == Lknrh kk K (Eq. 2.2)

    where kr is the kth intensity level in the given interval and kn is the number

    of pixels in the image whose intensity level is kr [31]. The probability of

    occurrence of gray level kr in an image (i.e. the probability density function

    'PDF')is approximated by:

    1,,2,1,0/)( == Lknnrp kkr K (Eq. 2.3)

    where n is the total number of pixels in the image. Thus, a histogram

    equalized image is obtained by mapping each pixel with level kr in the input

    image to a corresponding pixel with level ks in the output image using the

    following equation (based on the cumulative distribution function 'CDF'):

    1,,2,1,0/)()(00

    ==== ==

    LknnrprTsk

    j

    j

    k

    j

    jrkk K

    (Eq. 2.4)

    Although histogram equalization is a standard technique, it has some

    drawbacks since it depends on the global statistics of the image (i.e. pixels

    are modified by a transformation function based on the gray-level content of

    an entire image). For example, a washed-out appearance can be seen in some

    parts of the image due to over enhancement, while other parts need more

    enhancing such as the peripheral region (Figure 2.5) [4, 5].

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    2.5.3 Local Contrast Enhancement

    As a result of the histogram equalization drawbacks, a local contrast

    enhancement technique was invented by Sinthanayothin et al. [5, 32] in

    which it doesn't depend on the global statistics of an image, and so it's not

    applied to the entire image. Instead, it's applied to local areas depending on

    the mean and variance in that area. Considering a small running window or a

    sub-image, W, with the size , and centered on the pixel ),( ji , the

    mean of the intensity within Wcan be defined as:

    =>< ),(),(),( ),(/1

    jiWlk

    jiW lkfMf (Eq. 2.5)

    while the standard deviation of the intensity within Wis:

    >

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    The local contrast enhancement of a colored image is applied