thermal effects of prenatal doppler ultrasound on …

THERMAL EFFECTS OF PRENATAL DOPPLER

ULTRASOUND ON NEWBORNS OF ORYCTOLAGUS

CUNICULUS

BY

UMI NADRAH BINTI AMRAN

A thesis submitted in fulfilment of the requirement for the

Master of Health Sciences (Medical Imaging)

Kulliyyah of Allied Health Sciences

International Islamic University Malaysia

MARCH 2020

http://www.google.com.my/url?url=http://www.iium.edu.my/educ&rct=j&frm=1&q=&esrc=s&sa=U&ei=KHqFVJaTIZKyuATNwoGoBw&ved=0CBMQFjAA&usg=AFQjCNH8CPBB4-yr6XSF1EeEZS5f3iT02w

1

ABSTRACT

Despite the usefulness of Doppler ultrasound in complementing prenatal care, its usage

had also been reported to increase the temperature of tissues. Prolonged exposure to

Doppler ultrasound may increase the risk of bioeffects. Therefore, the aim of this study

was to investigate the influence of Doppler ultrasound on the body weight, brain size

and bone mineral density (BMD) of newborn Oryctolagus cuniculus throughout three

gestational ages (GA). The study utilised twelve (12) pregnant Oryctolagus cuniculus

or New Zealand white rabbits (NZWR) (Control Group = 3; Exposed Group = 9). By

utilizing Siemens Model ACUSON X150 ultrasound machine, linear array transducer

VF10-5 (5.0 to 10.0 MHz) the exposed group was exposed once to Doppler ultrasound

at a stipulated gestational day (GD) of their GAs (1st GA, GD 8-9; 2nd GA, GD 18-19;

3rd GA, GD 29-30). They were exposed to three different Doppler ultrasound exposure

durations (ED) (30, 60 and 90 minutes). Acoustic output parameters such as frequency

= 5.2 MHz, focal distance = 4.5 cm, Db/DR = 55/50 and mechanical index = 0.7 - 1.0

were kept constant. A total of 64 newborns (control, n = 17; 30 minutes ED, n = 17; 60

minutes ED, n = 12; 90 minutes ED, n = 18) were analysed for body weight, brain size

and BMD measurements. The data were statistically analysed using Statistical Package

for Social Sciences (SPSS) version 20. In the newborn’s body weight, significant

differences were perceived for 1st GA (p = <0.01) and 2nd GA (p = 0.02). No significant

correlations were found for all GAs. For the newborn’s brain size, significant

correlation was found for 1st GA (brain surface, r = -0.44; brain volume, r = -0.42) and

2nd GA (brain surface, r = -0.57; brain volume, r = -0.52) only. Significant differences

were also found for 1st GA (brain surface, p = <0.01; brain volume, p = <0.01 and 2nd

GA (brain surface, p = <0.01; brain volume, p = 0.01). In terms of BMD, significant

correlation was found for all GAs (1st, r = 0.47; 2nd, r = -0.64; 3rd, r = 0.50) but significant

differences were only found in BMD for 2nd GA (p = 0.01), and 3rd GA (p = 0.02). In

conclusion, the results highlighted the heating effects of Doppler ultrasound on

Oryctolagus cuniculus newborns with respect to body weight and brain size in early

GAs (1st & 2nd), whereas BMD in later GAs (2nd & 3rd). The study could suggest that

Doppler ultrasound ED should be limited to 30 minutes as significant results were

observed in all GAs in order to reduce the potential heating effects on the newborns.

The findings presented in this thesis fortified the understanding on the heating effects

of Doppler ultrasound besides facilitating the establishment of guidelines on using

Doppler ultrasound safely in the future.

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خلاصة البحث

ABSTRACT IN ARABIC

بلق ما الرعاية استكمال في تخطيط صدى القلب الدوبلري فوق الموجات فائدة من الرغم وعلى

فتراتل التعرض يزيد وقد. الأنسجة حرارة درجة لزيادة أيضًا استخدامه عن الإبلاغ تم فقد الولادة،

لهدفا كان الحيوية. لذلك، الآثار خطر تخطيط صدى القلب الدوبلري من فوق الموجات إلى طويلة

لجسما وزن على تخطيط صدى القلب الدوبلري فوق الموجات تأثير من التحقق هو الدراسة هذه من

عمر ثةثلا الولادة أوريكتولاغوس كونيكلس طوال لحديثي للعظام المعدنية والكثافة الدماغ وحجم

البيضاء الأرانب كونيكلس أو لأوريكتولاغوس حامل( 12) عشر اثني راسةالد الحمل. واستخدمت

جهاز استخدام خلال ومن (.9= المكشوفة المجموعة ؛ 3= الضابطة المجموعة) النيوزيلندية

VF10-5 (5.0 الخطي الصفيف من سيمنز، محول ACUSON X150الصوتية فوق الموجات

تخطيط صدى فوق الموجات إلى واحدة مرة المكشوفة المجموعة ، تعرضت(MHz 10.0 إلى

GD الأولى، GA) بهم الخاصة GA من( GD) عليه المنصوص الحمل يوم في القلب الدوبلري

من مختلفة فترات لثلاث وتعرض (.GA 2nd ، GD 18-19 rd3 GA ، GD 29-30 ؛ 8-9

الحفاظ وتم(. دقيقة 90 و 60 و 30) (ED) تخطيط صدى القلب الدوبلري فوق بالموجات التعرض

Db سم، 4.5= البؤرية والمسافة ميجاهرتز، 5.2= التردد مثل الصوتي الإخراج معلمات على

/ DR = 55/50 جديداً مولوداً 64 مجموعه ما تحليل وتم .ثابت 1.0 - 0.7= الميكانيكي والمؤشر

ED ، n دقيقة 90 ؛ ED ، n = 12 دقيقة 60 ؛ ED ، n = 17 دقيقة 30 ؛ n = 17 ، التحكم)

ياناتالب تحليل وتم .للعظام المعدنية وقياسات الكثافة الدماغ وحجم الجسم وزن لتحليل( 18 =

جسم وزن وفي. 20 الإصدار( SPSS) الاجتماعية للعلوم الإحصائية الحزمة باستخدام إحصائياً

(.p = 0.02) الثاني GA و( p = <0.01) الأول GA لـ كبيرة اختلافات إدراك تم الجديد، المولود

على ورالعث تم الوليد، دماغ لحجم لجميع عمر الحمل. وبالنسبة مهمة ارتباطات على العثور يتم ولم

الثاني GA و( r = -0.42 ، الدماغ حجم ؛ r = -0.44 ، الدماغ سطح) الأول GA لـ كبير ارتباط

اختلافات على أيضًا العثور فقط. وتم (r = -0.52 ، الدماغ حجم ؛ r = -0.57 الدماغ، سطح)

الثاني GA و p = <0.01 الدماغ، حجم ؛ p = <0.01 ، الدماغ سطح) الأول GA لـ كبيرة

للعظام المعدنية ومن حيث الكثافة (.p = 0.01 الدماغ، حجم ؛p = <0.01 ، الدماغ سطح)

r = -0.64 ، الثاني ؛ r = 0.47 ، 1)لجميع عمر الحمل كبير ارتباط على العثور )بي.ايم.دي(، تم

عظام لل المعدنية الكثافة في فقط كبيرة اختلافات على العثور تم ولكن( 0.50= ص الثالث، ؛

الضوء النتائج سلطت الختام، . وفيGA 3 (p = 0.02) و ،GA 2 (p = 0.01 ) )بي.ايم.دي(

ة الولاد حديثي على تخطيط صدى القلب الدوبلري فوق بالموجات التسخين تأثيرات على

في جميع عمر الحمل )الأول الدماغ وحجم الجسم بوزن يتعلق أوريكتولاغوس كونيكلس فيما

لدراسةا تقترح أن أن بي.ايم.دي في عمر الحمل لاحقا )الثاني والثالث(. ويمكن حين والثاني(، في

نتائج لوحظت حيث دقيقة 30 على يقتصر أن أن تخطيط صدى القلب الدوبلري )اي.دي( يجب

لولادة. ا حديثي الأطفال على المحتملة التسخين تأثيرات تقليل أجل جميع عمر الحمل من في مهمة

يط تخط فوق بالموجات التسخين تأثيرات حول الفهم الأطروحة هذه في المقدمة النتائج وعززت

لقلب اتخطيط صدى فوق الموجات استخدام حول إرشادات وضع تسهيل إلى صدى القلب بالإضافة

.المستقبل في بسلام

3

APPROVAL PAGE

I certify that I have supervised and read this study and that in my opinion, it conforms

to acceptable standards of scholarly presentation and is fully adequate, in scope and

quality, as a thesis for the Master of Health Sciences (Medical Imaging)

…………………………………..

Asst. Prof. Dr. Farah Wahida

Ahmad Zaiki

Supervisor

…………………………………..

Assoc. Prof. Dr. Hj. Sulaiman Md

Dom

Co-Supervisor

I certify that I have read this study and that in my opinion it conforms to acceptable

standards of scholarly presentation and is fully adequate, in scope and quality, as a thesis

for the Master of Health Sciences (Medical Imaging)

…………………………………..

Assoc. Prof. Dr. Sayed Inayatullah

Shah

Internal Examiner

4

…………………………………..

Asst. Prof. Dr. Noor Shafini

Mohamad

External Examiner

This thesis was submitted to the Department of Diagnostic Imaging and Radiotherapy

and is accepted as a fulfilment of the requirement for the Master of Health Sciences

(Medical Imaging)

…………………………………..

Assoc. Prof. Dr. Sayed Inayatullah

Shah

Head, Department of Diagnostic

Imaging and Radiotherapy

This thesis was submitted to the Kulliyyah of Allied Health Sciences and is accepted as

a fulfilment of the requirement for the Master of Health Sciences (Medical Imaging)

…………………………………..

Prof. Dr. Suzanah Abdul Rahman

Dean, Kulliyyah of Allied of

Health Sciences

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DECLARATION

I hereby declare that this thesis is the result of my own investigations, except where

otherwise stated. I also declare that it has not been previously or concurrently submitted

as a whole for any other degrees at IIUM or other institutions.

Umi Nadrah binti Amran

Signature........................................................... Date.........................................

6

INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA

DECLARATION OF COPYRIGHT AND AFFIRMATION OF

FAIR USE OF UNPUBLISHED RESEARCH

THERMAL EFFECTS OF PRENATAL DOPPLER ULTRASOUND

ON NEWBORNS OF ORYCTOLAGUS CUNICULUS

I declare that the copyright holders of this thesis are jointly owned by the student

and IIUM.

Copyright © 2020 Umi Nadrah binti Amran and International Islamic University Malaysia. All

rights reserved.

No part of this unpublished research may be reproduced, stored in a retrieval system,

or transmitted, in any form or by any means, electronic, mechanical, photocopying,

recording or otherwise without prior written permission of the copyright holder

except as provided below

1. Any material contained in or derived from this unpublished research

may be used by others in their writing with due acknowledgement.

2. IIUM or its library will have the right to make and transmit copies (print

or electronic) for institutional and academic purposes.

3. The IIUM library will have the right to make, store in a retrieved system

and supply copies of this unpublished research if requested by other

universities and research libraries.

By signing this form, I acknowledged that I have read and understand the IIUM

Intellectual Property Right and Commercialization policy.

Affirmed by Umi Nadrah binti Amran

……..…………………….. ………………………..

Signature Date

7

DEDICATIONS

I dedicated this thesis to myself for being brave, patience and strong enough to complete

this unexpected master’s journey. This is for the sacrifices, tears, blood, and sweat that

accompany me all along.

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ACKNOWLEDGEMENTS

Bismillahirrahmannirrahim. In the name of Allah the most Benevolent and the most

Merciful. First and foremost, praise to Allah S. W. T, with His blessings, I able to finish

this study after a few ups and downs throughout my master’s journey. I would like to

express my countless gratitude to my supervisor, Asst. Prof. Dr. Farah Wahida Ahmad

Zaiki and co-supervisor, Assoc. Prof. Dr. Hj. Sulaiman Md Dom for their advice,

beneficial critics, patience, and kindness through this whole time guiding me without

fail.

I shall thank all the lecturers, staffs from Diagnostic Imaging and Radiotherapy

Department (DDIR), as well as other lecturers and staffs from Kulliyyah Allied Health

Sciences (KAHS) IIUM, Department of Orthopaedics from Jalan Hospital Campus

(JHC) and Centre of Medical Imaging, Faculty of Health Sciences, UiTM Puncak Alam

for their unconditional assistance and suggestions. Not forgotten to my lab partner,

Nadzirah Mohamad Radzi and fellow friends who walk by my sides, together holding

me up, always reminding me to stay strong and never once failed to offer help whenever

I need to have one.

Lastly, my special appreciation would be to my both parents, Amran bin Zakaria and

Siti Rohana binti Asmuni, my fiancé, Engku Fathul Shah Nor Haqim bin E Shahrunizad

and my families for always believe and being thoughtful for every single thing I have

done to complete this journey. I would not be able to put my two legs at where I stand

today if there are no prayers from them. Thank you for always have faith in this one

human, unwearyingly waited for her to complete her long study journey and for every

penny you spent for her educational fees and well-being. May each and every single

person who involves in this journey, directly or indirectly, is granted with His blessings

for this life and hereafter.

Thank you.

Umi Nadrah binti Amran

9

TABLE OF CONTENTS

Abstract ....................................................................................................... 1

Abstract in Arabic .................................................................................................. 2

Approval Page ....................................................................................................... 3

Declaration ....................................................................................................... 5

Copyright ....................................................................................................... 6

Dedications ....................................................................................................... 7

Acknowledgements ................................................................................................ 8

Table of Contents ................................................................................................... 9

List of Tables ....................................................................................................... 12

List of Figures ....................................................................................................... 14

List of Equations .................................................................................................... 15

List of Symbols / SI Units ...................................................................................... 16

List of Abbreviations ............................................................................................. 18

CHAPTER ONE: INTRODUCTION .................................................................. 20

Background of the Study ........................................................................ 20

Statement of the Problem........................................................................ 22

Purpose of the Study ............................................................................... 24

Research Objectives................................................................................ 24

Research Questions ................................................................................. 25

Significance of the Study ........................................................................ 25

Limitations of the Study ......................................................................... 26

Outline of the Thesis ............................................................................... 30

Chapter Summary ................................................................................... 31

CHAPTER TWO: LITERATURE REVIEW .................................................... 32

Introduction............................................................................................. 32

A Brief History on Human Embryology ................................................ 32

Oryctolagus cuniculus ............................................................................ 35

The Similarity of Features Between Human and Oryctolagus

Cuniculus ................................................................................................ 36

Micro-Computed Tomography (Micro-CT) ........................................... 37

Ultrasound Physics ................................................................................. 39

2.6.1 Sound Waves................................................................................. 39

2.6.2 Relationship between Acoustic Variables ..................................... 41

2.6.3 Transducer ..................................................................................... 43

Interaction of Ultrasound with Tissue .................................................... 44

2.7.1 Attenuation of Ultrasound in Tissue ............................................. 45

2.7.1.1 Absorption ........................................................................ 45

2.7.1.2 Reflection.......................................................................... 46

2.7.1.3 Scattering .......................................................................... 46

2.7.1.4 Refraction ......................................................................... 47

2.7.1.5 Divergence of Beam ......................................................... 47

2.7.2 Mechanism of Ultrasound Interaction with Tissue ....................... 49

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2.7.2.1 Thermal (Heat) Mechanism .............................................. 49

2.7.2.2 Mechanical (Non-Thermal) Mechanism .......................... 50

Prenatal Ultrasound Imaging .................................................................. 52

2.8.1 Thermal Effect of Ultrasound on Pregnancy ................................ 53

Doppler Ultrasound in Pregnancy .......................................................... 55

2.9.1 Doppler Principle .......................................................................... 56

2.9.2 Doppler Ultrasound Bioeffects on Human .................................... 57

2.9.3 Doppler Bioeffects in Animal Studies .......................................... 59

Chapter Summary ................................................................................. 61

CHAPTER THREE: RESEARCH METHODOLOGY ................................... 62

Introduction............................................................................................. 62

Instrumentation and Research Tools ...................................................... 62

3.2.1 The Subject ................................................................................... 62

3.2.2 Subject Acclimatisation, Housing and Husbandry ....................... 63

3.2.3 Subject Impregnation (Mating) ..................................................... 65

3.2.4 Ultrasound Equipment .................................................................. 66

3.2.5 Measurement of Fetal Weight ....................................................... 67

3.2.6 Euthanisation ................................................................................. 67

3.2.7 Fixation and Stain ......................................................................... 67

3.2.8 Micro-CT Scanner, Reconstruction, and Analyser ....................... 68

Methodology ........................................................................................... 71

3.3.1 Randomized Assignment of Groups ............................................. 71

3.3.2 Pre-Scanning Preparation .............................................................. 72

3.3.3 Exposure Duration ........................................................................ 73

3.3.4 Doppler Acoustic Output Parameters ........................................... 74

3.3.5 Maternal Rectal Temperature Measurement ................................. 76

3.3.6 Number of Samples (n) ................................................................. 76

3.3.7 Newborn Weighing and Analysis ................................................. 77

3.3.8 Newborn Wet Sampling and Analysis .......................................... 77

3.3.8.1 Euthanization Procedure ................................................... 78

3.3.8.2 Fixing and Staining Procedure ......................................... 78

3.3.8.3 Micro-CT Scanning Procedure ......................................... 81

3.3.8.4 Image Reconstruction, Brain Size Measurement and BMD

Calculation ....................................................................... 82

Data Analysis .......................................................................................... 84

3.4.1 Normality Assumption .................................................................. 85

3.4.1.1 Kolmogorov-Smirnov Statistic ......................................... 85

3.4.1.2 Histogram ......................................................................... 85

3.4.1.3 Normal Q-Q Plot .............................................................. 85

3.4.2 Correlation Analysis ..................................................................... 85

3.4.2.1 Pearson Correlation Coefficient (r) .................................. 86

3.4.2.2 Coefficient of Determination ............................................ 86

3.4.2.3 Significant Difference Level (p-value) ............................. 87

3.4.3 One-Way Between-Groups ANOVA with Post-Hoc Tests .......... 87

3.4.3.1 Levene’s Test For Homogeneity of Variance ................... 87

3.4.3.2 Analysis of Variance (ANOVA) ...................................... 88

3.4.3.3 Post-Hoc Test (Tukey HSD)............................................. 88

3.4.3.4 The Effect Size Statistics .................................................. 88

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3.4.4 Kruskal-Wallis Test With Mann-Whitney U Test ........................ 89

Flow Chart of the Study .......................................................................... 89

Chapter Summary ................................................................................... 91

CHAPTER FOUR: RESULTS ............................................................................ 92

Introduction............................................................................................. 92

Maternal Temperature Results ................................................................ 92

Part I: Newborns Body Weight Analysis................................................ 93


4.3.2 Descriptive Analysis ..................................................................... 94


4.3.4 One-Way ANOVA with Post-Hoc Test ........................................ 97

Part II: Newborns Brain Size Analysis ................................................... 100



4.4.2.1 Newborns Brain Surface Area .......................................... 102

4.4.2.2 Newborns Brain Volume .................................................. 103




4.4.4 One-Way ANOVA with Post-Hoc Test and Kruskal-Wallis

With Mann-Whitney U Test ......................................................... 107



Part III: Newborns Bone Mineral Density (BMD) Analysis .................. 113




4.5.4 One-Way ANOVA with Post-Hoc Test and Kruskal-Wallis

with Mann-Whitney U Test .......................................................... 116

Chapter Summary ................................................................................... 120

CHAPTER FIVE: DISCUSSION AND CONCLUSION .................................. 121

Introduction............................................................................................. 121

Maternal Temperature ............................................................................ 121

Part I: Newborns Body Weight............................................................... 122

Part II: Newborns Brain Size .................................................................. 126

Part III: Newborns Bone Mineral Density (BMD) ................................. 130

Conclusion and Implications .................................................................. 133

Future Recommendation ......................................................................... 135

Chapter Summary ................................................................................... 136

REFERENCES ....................................................................................................... 137

APPENDIX A: STATISTICAL RESULTS ............................................................ 146

APPENDIX B: ETHICAL CLEARANCE BY IIUM I-ACUC .............................. 166

APPENDIX C: PUBLISHED ARTICLES / MANUSCRIPTS /

PROCEEDINGS / ABSTRACTS ................................................. 167

APPENDIX D: CERTIFICATES ............................................................................ 180

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LIST OF TABLES

Table 2.1 Acoustic variables 41

Table 2.2 Acoustic output during the ultrasound studies 58

Table 3.1 10% buffered formalin recipe 68

Table 3.2 Skyscan 1176 technical specification 69

Table 3.3 Acoustic parameters 75

Table 3.4 Number of samples (n) used in the study 77

Table 3.5 Micro-CT scanning parameters for brain 82

Table 3.6 Micro-CT scanning parameters for femur 82

Table 4.1 Maternal rectal temperature range and mean 93

Table 4.2 Normality assumption for newborns body weight 94

Table 4.3 Correlation between newborns body weight and exposure durations

at different gestational ages 96

Table 4.4 Summary of ANOVA and Post-Hoc test on newborns body weight 98

Table 4.5 Normality assumption for newborns brain surface area 100

Table 4.6 Normality assumption for newborns brain volume 101

Table 4.7 Correlation between newborns brain surface area and exposure

durations at different gestational ages 104

Table 4.8 Correlation between newborns brain volume and exposure durations


Table 4.9 Summary of ANOVA and Post-Hoc test on newborns brain surface

area 108

Table 4.10 Summary of ANOVA and Post-Hoc test on newborns brain volume 110

Table 4.11 Summary of Kruskal-Wallis and Mann-Whitney U test on

newborns brain volume 111

Table 4.12 Normality assumption for newborns left femur BMD 113

13

Table 4.13 Correlation between newborns left femur BMD and exposure


Table 4.14 Summary of ANOVA and Post-Hoc test for newborns left femur

BMD 117

Table 4.15 Summary of Kruskal-Wallis and Mann-Whitney U test for

newborns left femur BMD 118

14

LIST OF FIGURES

Figure 2.1 Human prenatal development 34

Figure 2.2 Categories of sound 40

Figure 2.3 Phase of sound waves 42

Figure 3.1 NZWR in an iron steel cage 63

Figure 3.2 Skyscan 1176 Micro-CT 70

Figure 3.3 Randomized assignment of groups 72

Figure 3.4 Ultrasound images produced using selected acoustic output 75

Figure 3.5 Wet samples in 10% buffered formalin 79

Figure 3.6 Wet sampling and analysis workflow 80

Figure 3.7 Placement of wet sample inside the Micro-CT scanner 81

Figure 3.8 Reconstruction of the newborn’s brain and left femur using NRecon

software 83

Figure 3.9 Measurement of newborn’s brain size and BMD of left femur using

CTan software 84

Figure 3.10 Research workflow 90

Figure 4.1 Mean comparison of newborns body weight and exposure durations


Figure 4.2 Mean comparison of newborns brain surface area and exposure


Figure 4.3 Mean/median comparison of newborns brain volume and exposure


Figure 4.4 Mean comparison of newborns left femur BMD and exposure


15

LIST OF EQUATIONS

Equation 2.1 Period versus frequency 42

Equation 2.2 Wavelength equation 43

Equation 2.3 Acoustic impedence 48

Equation 3.1 Dilution equation 68

Equation 3.2 Coefficient of determination 87

Equation 3.3 The effect size 88

16

LIST OF SYMBOLS / SI UNITS

% Percent

” Inch

± Precision of an approximation

° Degree

µm Micrometre

µm2 Micrometre squared

µm2 Square micrometre

µm3 Cube micrometre

µm3 Micrometre cubed

µs Microsecond

A Amplitude

℃ Degree Celsius

c Velocity

cm Centimetre

df Doppler shift

f Frequency

g Gram

g.cm3 Gram per cubic centimetre

h Hour

Hz Hertz

kg Kilogram

kV Kilovoltage

M Mean value

m/s Metre per second

17

M1 Molarity of concentrated solution

M2 Molarity of diluted solution

Md Median value

MHz Megahertz

ml Millilitre

ml/kg Millilitre per kilogram

mm Millimetre

ms Millisecond

mW/cm Milliwatt per centimetre

n Number of samples

Na2HPO4 Diphasic sodium phosphate

NaCL Sodium chloride

p P-value

r Pearson correlation coefficient

T Period (time)

U Mann-Whitney U value

V1 Volume of concentrated solution

V2 Volume of diluted solution

W/kg Watt per kilogram

z Z-value

λ Wavelength

𝑥̅ Mean

18

LIST OF ABBREVIATIONS

2D Two dimensional

3D Three dimensional

3Rs Replacement, reduction and refinement

AIUM American Institute of Ultrasound in Medicine

ALARA As low as reasonably achievable

ANOVA Analysis of variance

BMD Bone mineral density

B-mode Brightness mode

BMUS British Medical Ultrasound Safety

CE Conformité Européene / European Conformity

CPU Central Processing Unit

CT Computed tomography

CTAn Computed tomography analyser

ED Exposure duration

FDA Food and Drug Administration

GA Gestational age

GD Gestational day

I-ACUC Animal Care and Use Committee

IBM International Business Machine Corporation

IIUM International Islamic University Malaysia

IPCC Intergovernmental Panel on Climate Change

ISPTA Spatial-pulse-temporal-average intensities

KAHS Kulliyyah of Allied Health Sciences

LCD Liquid Crystal Display

19

MI Mechanical index

Micro-CT Micro-computed tomography

M-mode Motion mode

MRI Magnetic resonance imaging

MRM Magnetic resonance microscopy

mRNA Messenger-ribonucleic acid

NIR Non-ionizing radiation

NRecon NReconstruction software

NZWR New Zealand white rabbit

PET Positron emission tomography

PTA Phosphotungstic acid

ROI Region of interest

SAR Specific absorption rate

SD Standard deviation

SPECT Single photon emission computed tomography

SPSS Statistical Package for Social Sciences

TI Thermal index

TPC Tenderness, pamper and care

UiTM Universiti Teknologi MARA

20

CHAPTER ONE

INTRODUCTION

BACKGROUND OF THE STUDY

Ultrasound has been long known as the safest imaging modality as it involves no

ionising radiation and is used frequently in prenatal care for decades. Doppler

ultrasound plays a role in the obstetrics and gynaecology field to serve as a

complementary mode in a standard prenatal scan (Chau, 2002). It aids in investigating

foetus blood flow in expectant mothers’ wombs, which is usually for those who come

with pregnancy complications (Alfirevic, Stampalija, & Dowswell, 2017; Schellpfeffer,

2013).

After the invention of ultrasound in the late 1950s, it has continued to develop

throughout these decades (Chau, 2002). Today, Doppler ultrasound has been

commercially applied by private companies and healthcare institution for prenatal care.

Doppler ultrasound’s technology advancement has improved the service of standard

prenatal ultrasound scanning. The practicality of Doppler effects by the motion or

direction of blood flow helps practitioners to evaluate and estimate blood circulation

abnormalities of the foetus in a better view (Oglat et al., 2018).

21

As of current practice, only an expectant mother with high potential for

complication gets the privilege of having Doppler ultrasound to check on her foetus

(Hill, 2016). As reported by Hill (2016), the percentage of stillborn rate can be reduced

if Doppler ultrasound is implemented as one of the standard prenatal scanning

procedure. In an interview conducted, a mother who had lost her unborn child believed

that her child could be saved if Doppler ultrasound has been made as a standard practice

in the health institution. She said Doppler ultrasound should be done on every pregnant

woman since standard prenatal ultrasound could not give any information whether the

foetus had gotten enough oxygen, nutrients and blood supply from the placenta to grow

healthy in the womb.

In contrary to the conventional two dimensional (2D) ultrasound, the Doppler

ultrasound beam is focused at only one point. This may lead to heat accumulation in the

area, thus increasing the temperature. Therefore, concerns arise regarding the safety of

Doppler ultrasound mode’s prolonged use on the foetus. It is proven that temperature

elevations on both mother and foetus contributed to numerous adverse outcomes

(Strand, Barnett, & Tong, 2011). These include low birth weight, spontaneous abortion,

stillbirth and premature contraction (Goldenberg, Culhane, Iams, & Romero, 2008;

Salvesen et al., 2011).

The possible harm of ultrasound including Doppler is uncertain since it is well-

known to be the safest imaging modalities among others (Barnett & Maulik, 2001).

Nonetheless, ultrasound still has quite a number of possibilities to cause heat (thermal)

and mechanical (non-thermal) effects. The bioeffect risk increases as the technology of

Doppler ultrasound advances through the decades. It has been reported that potential

cavitation can happen when Doppler is used together with three dimensional (3D)

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ultrasound (Pooh et al., 2016). Other literature has also stated that the Doppler’s

acoustic outputs are relatively sufficient to result in obvious biological effects when

maximum operating settings are used (Barnett & Maulik, 2001).

STATEMENT OF THE PROBLEM

Years before the trend set, USA Today (2004) has reported that the American Institute

of Ultrasound in Medicine (AIUM) notifies expecting parents about possible harms in

having an unregulated ultrasound for entertainment purposes (“Parents ignoring FDA

warning against prenatal portraits,” 2004). Even though there are no confirmed

biological effects from the regulated prenatal ultrasound, unregulated prenatal

ultrasound takes longer time and uses more energy compared to regulated ones. Food

and Drug Administration (FDA) has made a statement concerning the unknown long-

term effects of tissue heating by frequent visits and prolonged examination time

(Pawlowski, 2014; Romm, 2014). Therefore, experts have stated that ultrasound using

Doppler should only be done on expectant mothers when there is a medical purpose to

perform it. If it is performed on an expectant mother without any diagnostic purpose, it

begs the question of whether it is safe and justified for the foetus.

In recent years, there are increasing interests in exploring the bioeffects of

Doppler ultrasound. Previous studies have reported several results on Doppler

ultrasound bioeffects in various animals. Jia et al. (2005) have found that the

insonification fetal group has a higher significant difference in myocardial apoptosis

compared to the control group. Later in 2009, the finding of Schneider-Kolsky et al.

(2009) confirmed that exposure to Doppler ultrasound may result in an impairment

towards a mammal’s cognitive function. They found significant memory impairment

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after 2 days post-hatch following the Doppler exposure to the foetal chick for several

minutes on day 19 of the incubation period.

In 2011, a study on the effect of pulse Doppler examination on ductus venosus

in rat foetuses showed a positive result where there was a positive linear correlation

between Doppler exposure time and apoptotic activities of exposed liver tissues

(Pellicer et al., 2011). Helmy, Bader, Koch, Tiringer, and Kollmann (2015) have

undertaken an in-vitro study in measuring the thermal output of Doppler ultrasound.

The energy output of the ultrasound transducer was investigated using the water bath

model. In the study, they found that the activation of Doppler ultrasound in water bath

increased the temperature of water in one minute. Thus, they come into a conclusion

that Doppler ultrasound can induce a thermal effect to the foetuses, especially in early

pregnancy.

In spite of several new findings of the bioeffects of the Doppler ultrasound,

several other studies have been done to investigate the heating effects of prenatal

ultrasound without using Doppler mode as well. In 2013, a study of fluctuations in

haematological analysis and foetal weight was statistically found a significant

difference in the newborn of Oryctolagus cuniculus after being exposed to prenatal

ultrasound (Zaiki, Dom, Razak, & Hassan, 2013; Zaiki & Dom, 2014). Zaiki and Dom

(2016) later found the heating effect during prenatal scanning does interfere with the

foetal neuro-development. In 2016, Isa and Dom (2016) found that the lowermost

Oryctolagus cuniculus growth is recorded when they are exposed to 2D ultrasound for

90 minutes long at the 2nd gestational age.

thermal effects of prenatal doppler ultrasound on …

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