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Machine Learning in Healthcare

Fundamentals and Recent Applications

Bikesh Kumar Singh

G.R. Sinha
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First edition published 2022

by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-​2742
and by CRC Press
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor & Francis Group, LLC
© 2022 Bikesh Kumar Singh and G.R. Sinha
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Library of Congress Cataloging‑in‑Publication Data
Names: Singh, Bikesh Kumar, author. | Sinha, G. R., 1975– author.
Title: Machine learning in healthcare : fundamentals and recent applications /
Bikesh Kumar Singh, G.R. Sinha.
Description: First edition. | Boca Raton : CRC Press, 2022. |
Includes bibliographical references and index.
Identifiers: LCCN 2021042203 (print) | LCCN 2021042204 (ebook) |
ISBN 9780367564421 (hardback) | ISBN 9780367564438 (paperback) |
ISBN 9781003097808 (ebook)
Subjects: MESH: Machine Learning | Delivery of Health Care
Classification: LCC R855.3 (print) | LCC R855.3 (ebook) |
NLM W 26.55.A7 | DDC 610.285–dc23
LC record available at https://lccn.loc.gov/2021042203
LC ebook record available at https://lccn.loc.gov/2021042204
ISBN: 978-​0-​367-​56442-​1 (hbk)
ISBN: 978-​0-​367-​56443-​8 (pbk)
ISBN: 978-​1-​003-​09780-​8 (ebk)
DOI: 10.1201/​9781003097808
Typeset in Times
by Newgen Publishing UK
v

Dedicated to my late father, Shri R. S. Singh Ji, and my PhD

joint supervisor, the late Dr. Kesari Verma
Bikesh Kumar Singh

Dedicated to my late grandparents, my teachers and Revered

Swami Vivekananda
G. R. Sinha
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Contents
List of Figures..........................................................................................................xiii
List of Tables...........................................................................................................xvii
Preface......................................................................................................................xix
Acknowledgments..................................................................................................xxiii
Author Bio.............................................................................................................. xxv

Chapter 1 Biostatistics........................................................................................... 1
1.1 Data and Variables......................................................................1
1.2 Types of Research Studies.......................................................... 2
1.3 Sources of Medical Data............................................................. 2
1.4 Measures of Central Tendency.................................................... 3
1.5 Data Sampling and Its Types...................................................... 5
1.5.1 Probability Sampling Methods...................................... 5
1.5.2 Non-​probability Sampling Methods.............................. 6
1.6 Statistical Significance Analysis................................................. 6
1.7 Skewness................................................................................... 10
1.8 Kurtosis..................................................................................... 11
1.8.1 Mesokurtic................................................................... 13
1.8.2 Leptokurtic.................................................................. 13
1.8.3 Platykurtic................................................................... 14
1.9 Curve Fitting............................................................................. 14
1.9.1 Linear and Non-​linear Relationship............................ 14
1.9.2 Use of Curve-​Fitting Method...................................... 14
1.10 Correlation................................................................................ 14
1.10.1 Pearson Correlation (PC)............................................15
1.10.2 Spearman Rank Correlation (SRC)............................. 16
1.11 Regression................................................................................. 18
1.11.1 Linear Regression........................................................ 18
1.11.2 Estimation of Regression Coefficients........................ 19

Chapter 2 Probability Theory............................................................................... 23

2.1 Basic Concept of Probability.................................................... 23
2.2 Random Experiment................................................................. 24
2.3 Conditional Probability............................................................. 24
2.3.1 Types of Events........................................................... 25
2.4 Bayes Theorem......................................................................... 26
2.5 Random Variable....................................................................... 28
2.6 Distribution Functions..............................................................28
2.6.1 Binomial Distribution.................................................. 29
2.6.2 Poisson Distribution.................................................... 30

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2.6.3 Normal Distribution.................................................... 30

2.7 Estimation................................................................................. 31
2.8 Standard Error........................................................................... 32
2.9 Probability of Error................................................................... 32

Chapter 3 Medical Data Acquisition and Pre-​processing.................................... 35

3.1 Medical Data Formats............................................................... 35
3.1.1 Data Formats for Medical Images............................... 35
3.1.1.1 DICOM (Digital Imaging and
Communications in Medicine)..................... 36
3.1.1.2 Analyse......................................................... 36
3.1.1.3 NIfTI (Neuroimaging Informatics
Technology Initiative).................................. 36
3.1.1.4 MINC (Medical Imaging NetCDF).............. 36
3.1.2 Medical Data Formats for Signals............................... 37
3.1.2.1 EDF (European Data Format)...................... 37
3.1.2.2 BDF (BioSemi Data Format)....................... 37
3.1.2.3 GDF (General Data Format)........................ 38
3.2 Data Augmentation and Generation.......................................... 38
3.3 Data Labelling........................................................................... 38
3.4 Data Cleaning............................................................................ 39
3.4.1 Statistical Approach..................................................... 40
3.4.1.1 Listwise Deletion......................................... 40
3.4.1.2 Pairwise Deletion......................................... 40
3.4.1.3 Multiple Imputation..................................... 40
3.4.1.4 Maximum Likelihood Imputation................ 41
3.4.2 Machine Learning for Data Imputation....................... 41
3.4.2.1 K-​Nearest Neighbour (KNN)....................... 41
3.4.2.2 Bayesian Network (BN)............................... 41
3.5 Data Normalization................................................................... 42

Chapter 4 Medical Image Processing..................................................................45

4.1 Medical Image Modalities, Their Applications,
Advantages and Limitations.....................................................45
4.1.1 Radiography................................................................ 46
4.1.2 Nuclear Medicine........................................................ 46
4.1.2.1 Positron Emission Tomography (PET)........ 46
4.1.3 Elastography................................................................ 46
4.1.4 Photoacoustic Imaging................................................ 47
4.1.5 Tomography................................................................. 47
4.1.6 Magnetic Resonance Imaging (MRI).......................... 47
4.1.7 Ultrasound Imaging Techniques.................................. 48
4.2 Medical Image Enhancement.................................................... 49
4.3 Basics of Histogram.................................................................. 51
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4.4 Medical Image De-​noising........................................................ 56

4.4.1 Spatial Filtering........................................................... 56
4.4.1.1 Linear Filters............................................... 56
4.4.1.2 Non-​linear Filters......................................... 58
4.4.2 Transform Domain Filtering.......................................58
4.4.2.1 Non-​data Adaptive Transform...................... 58
4.4.2.2 Data-​Adaptive Transforms........................... 59
4.5 Segmentation............................................................................. 59
4.6 Region-​Based Methods............................................................. 59
4.6.1 Region-​Growing Segmentation................................... 61

Chapter 5 Bio-​signals........................................................................................... 65
5.1 Origin of Bio-​signals................................................................. 65
5.2 Different Types of Bio-​signals.................................................. 65
5.2.1 Electrocardiogram....................................................... 65
5.2.2 Electroencephalogram (EEG).....................................68
5.2.3 Electroocculogram (EOG)........................................... 69
5.2.4 Electromyogram (EMG).............................................69
5.3 Noise and Artefacts................................................................... 72
5.4 Filtering of Bio-​signals............................................................. 73
5.5 Applications of Bio-​signals....................................................... 74

Chapter 6 Feature Extraction............................................................................... 77

6.1 Feature Extraction..................................................................... 77
6.2 Echographic Characteristics of Breast Tumours in
Ultrasound Imaging.................................................................. 78
6.3 Texture Feature Extraction........................................................ 78
6.3.1 First-​Order Statistical Features.................................... 78
6.3.2 Grey-​Level Co-​occurrence Matrices........................... 82
6.3.3 Grey-​Level Difference Statistics................................. 87
6.3.4 Neighbourhood Grey-​Tone Difference Matrix............ 88
6.3.5 Statistical Feature Matrix............................................ 91
6.3.6 Texture Energy Measures............................................ 92
6.3.7 Fractal Dimension Texture Analysis........................... 93
6.3.8 Spectral Measures of Texture...................................... 95
6.3.9 Run-​Length Texture Features...................................... 96
6.4 Shape Feature Extraction........................................................ 100
6.4.1 Region Properties...................................................... 100
6.4.2 Moment Invariants..................................................... 100
6.5 Feature Normalization............................................................ 102
6.5.1 Brief Overview of Feature Normalization
Techniques................................................................. 102
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Chapter 7 Introduction to Machine Learning..................................................... 107

7.1 Introduction: What Is Machine Learning?.............................. 107
7.2 Classification of Machine Learning (ML) Methods............... 108
7.3 Steps in Implementation of Machine Learning....................... 109
7.4 Training, Testing and Validation............................................. 113
7.5 Machine Learning Methods.................................................... 114
7.5.1 Supervised Learning.................................................. 114
7.5.2 Unsupervised Learning.............................................125
7.6 Performance Evaluation of Machine Learning Model............ 130

Chapter 8 Cancer Detection: Breast Cancer Detection Using

Mammography, Ultrasound and Magnetic Resonance
Imaging (MRI).................................................................................. 135
8.1 Introduction............................................................................. 135
8.2 Different Imaging Modalities.................................................136
8.2.1 Mammography (MG)................................................ 136
8.2.2 Ultrasound (US)........................................................ 137
8.2.3 Magnetic Resonance Imaging (MRI)........................ 140
8.3 Breast Imaging Reporting and Data System
(BI-​RADS).............................................................................. 141
8.4 Usefulness of Machine Learning (ML)................................... 141
8.4.1 Image Pre-​processing................................................ 142
8.4.2 Image Segmentation.................................................. 143
8.4.3 Feature Extraction..................................................... 143
8.4.4 Feature Selection....................................................... 145
8.4.5 Classification............................................................. 146
8.4.6 Performance Evaluation............................................ 147
8.5 Issues and Challenges............................................................. 147
8.6 Conclusion.............................................................................. 149

Chapter 9 Sickle Cell Disease Management: A Machine Learning

Approach........................................................................................... 153
9.1 Introduction............................................................................. 153
9.2 Severity Detection of Sickle Cell Disease.............................. 155
9.2.1 Analysis of Clinical Complications........................... 156
9.2.2 Analysis of Clinical Attributes.................................. 156
9.2.3 Analysis of Microscopic Images of RBC.................. 158
9.3 Hydroxyurea Dosage Prediction for SCD Patients................. 159
9.4 Patient Response to Medications through
Hydroxyurea (HU).................................................................. 165
9.5 SCD Management Proposed Model........................................ 168
9.6 Conclusions............................................................................. 168
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Chapter 10 Detection of Pulmonary Disease....................................................... 171

10.1 Introduction to Pulmonary Disorders...................................... 171
10.2 Restrictive and Obstructive Lung Diseases............................. 172
10.2.1 Obstructive Lung Disease.......................................... 172
10.2.2 Restrictive Lung Disease........................................... 173
10.3 Diagnosis of Disease and Disorder......................................... 174
10.4 Chest X-​ray........................................................................... 175
10.5 CT Scan................................................................................ 176
10.6 SPO2 Level............................................................................. 179
10.7 Arterial Blood Gas Analysis................................................. 180
10.8 Laboratory Tests................................................................... 180
10.9 Bronchoscopy....................................................................... 181
10.10 Sputum Test.......................................................................... 182
10.11 Pulmonary Function Test...................................................... 183
10.12 Challenges and Issues........................................................... 185
10.13 Application of Machine Learning in Diagnosis of
Pulmonary Disorder.............................................................. 186
10.14 Conclusion............................................................................ 188

Chapter 11 Mental Illness and Neurodevelopmental Disorders.......................... 191

11.1 Neurodevelopmental Disorders............................................... 191
11.2 Developmental Dyslexia......................................................... 191
11.2.1 Diagnostic Methods................................................... 192
11.2.2 Behavioural Method.................................................. 192
11.2.3 Brain Imaging Modalities.......................................... 193
11.2.4 Recent Advancement in Diagnostic
Techniques................................................................. 193
11.3 Attention-​Deficit/​Hyperactivity Disorder (ADHD)................ 195
11.3.1 Types......................................................................... 195
11.3.2 Symptoms.................................................................. 195
11.3.3 ADHD Screening...................................................... 196
11.3.4 Diagnosis Based on Brain Imaging and
Machine Learning Methods......................................196
11.3.5 Treatment for ADHD................................................. 197
11.4 Parkinson’s Disease................................................................ 198
11.4.1 Parkinson’s Disease Prognosis and Measurement
Rating Scales............................................................. 199
11.4.1.1 HY Scale.................................................. 199
11.4.1.2 UPDRS Scale........................................... 199
11.4.2 Involvement of Digital Technologies for
Detection and Monitoring of PD............................... 200
11.5 Epilepsy................................................................................... 203
11.5.1 Recent Literatures on Epilepsy Detection................. 203
11.5.2 Generalized Machine Learning Model for
Epilepsy Detection System........................................ 204
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11.6 Schizophrenia.......................................................................... 205

11.6.1 Recent Research........................................................ 206
11.6.2 A Machine Learning Model for Schizophrenia
Detection................................................................... 206

Chapter 12 Applications and Challenges............................................................. 213

12.1 Role of Machine Learning in Healthcare Research................ 213
12.2 Efficient Diagnosis of Diabetes..............................................214
12.3 Neuropathy.............................................................................. 215
12.4 Drug Monitoring..................................................................... 216
12.5 Bioinformatics......................................................................... 217
12.6 DNA Analysis......................................................................... 219
12.7 Digital Health Records............................................................ 220
12.8 Future Research Challenges.................................................... 221

Index....................................................................................................................... 225
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Figures
1.1 Steps involved in statistical analysis of data................................................... 7
1.2 Illustration of skewness................................................................................. 11
1.3 Illustration of skewness. (a) Negative skewed, (b) Normal (symmetric)
and (c) Positive skewed................................................................................. 12
1.4 Illustration of kurtosis................................................................................... 13
1.5 An example of curve fitting.......................................................................... 15
1.6 Scatter plots between variables “A” and “B”................................................ 16
1.7 Regression plot for variables x (independent) and y (dependent)................. 20
1.8 Severity of cancer patients’ disease.............................................................. 20
2.1 Venn diagram representation of various types of events............................... 26
2.2 Bayes theorem............................................................................................... 27
2.3 Normal distribution bell curve...................................................................... 31
3.1 File formats for medical imaging.................................................................. 36
3.2 File formats for medical signals.................................................................... 37
3.3 Labelling process for supervised learning model......................................... 39
4.1 A typical block diagram of an ultrasound imaging system........................... 48
4.2 Classification of image enhancement methods............................................. 49
4.3 Point processing of image enhancement....................................................... 50
4.4 Masking operation........................................................................................ 50
4.5 Image complement of a mammogram.......................................................... 51
4.6 Logarithmic transformation.......................................................................... 51
4.7 Contrast enhancement................................................................................... 52
4.8 A typical histogram and histograms of images having different
values of contrast.......................................................................................... 52
4.9 Histogram of input image............................................................................. 53
4.10 Histogram of output image after histogram equalization............................. 54
4.11 An example of histogram equalization......................................................... 54
4.12 Frequency domain operations....................................................................... 55
4.13 Various de-​noising techniques used in medical image processing............... 57
4.14 Different segmentation techniques used in Image processing...................... 60
4.15 Region-growing segmentation...................................................................... 61
4.16 (a) Original ultrasound image of benign breast, (b) Result of
segmentation using FCM.............................................................................. 62
4.17 (a) Original ultrasound image of benign breast, (b) Result of
segmentation using k-​means......................................................................... 62
5.1 A typical ECG waveform.............................................................................. 66
5.2 ECG leads and Einthoven triangle................................................................ 67
5.3 EEG 10–​20 electrode placement................................................................... 68
5.4 EEG bands.................................................................................................... 70
5.5 EOG signal [9]‌.............................................................................................. 71
5.6 EMG signal................................................................................................... 72

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xiv List of Figures

6.1 Breast ultrasound image containing (a) malignant tumour and

(b) benign tumour......................................................................................... 79
6.2 Illustration of skewness. (a) Negative skewed, (b) Normal
(symmetric) and (c) Positive skewed............................................................ 81
6.3 Illustration of kurtosis. (a) Leptokurtic and (b) Platykurtic.......................... 82
6.4 The four orientations used to construct co-​occurrence matrices.................. 83
7.1 Different steps of machine learning............................................................ 110
7.2 Division of labelled dataset......................................................................... 113
7.3 A support vector machine classifier............................................................ 115
7.4 Non-​linear support vector machine............................................................. 116
7.5 Schematic of K-​NN classifier for K =​3 and K =​5..................................... 117
7.6 Decision tree classifier (a) for binary data and (b) for numeric data.......... 119
7.7 A random forest classifier with bagging..................................................... 122
7.8 An artificial neural network model............................................................. 123
7.9 Node function of an artificial neural network............................................. 124
7.10 (a) Scatter plot of data. (b) Data clusters.................................................... 126
7.11 Confusion matrix representation................................................................. 131
7.12 Representation of ROC-​AUC curve............................................................ 132
8.1 Different views used in mammography [6, 7]............................................ 136
8.2 Breast ultrasound images showing (a) Benign tumour
(b) Malignant tumour [17].......................................................................... 138
8.3 Typical block diagram highlighting steps for breast cancer
detection...................................................................................................... 142
8.4 Different types of image segmentation techniques..................................... 144
8.5 Commonly extracted type of features......................................................... 145
8.6 Types of feature selection techniques......................................................... 145
8.7 Different types of classifiers used in machine learning.............................. 146
8.8 Block diagram of implementation of the machine learning
approach...................................................................................................... 148
9.1 ROC curve for different methods................................................................ 157
9.2 Microscopic image of red blood cell.......................................................... 158
9.3 Circle Hough Transform method based normal and abnormal
cell counting................................................................................................ 159
9.4 Essential steps for Watershed segmentation............................................... 160
9.5 Experimental setup for dosage prediction................................................... 162
9.6 Experimental set-​up and result for LSTM model....................................... 164
9.7 Experimental set-​up for prediction of response for HU therapy................. 167
9.8 Proposed experimental setup for SCD management using
machine learning......................................................................................... 169
10.1 Types of pulmonary diseases...................................................................... 173
10.2 X-​ray machine............................................................................................. 176
10.3 Computer tomography machine.................................................................. 178
10.4 Pulmonary function test.............................................................................. 184
10.5 Machine learning and image processing for diagnosis result
of disorder................................................................................................... 186