Assessment of placental and fetal oxygenation in normal and abnormal pregnancy using magnetic ...

222 Pages·2014·2.03 MB·English

Assessment of placental and
fetal oxygenation in normal and
abnormal pregnancy using
magnetic resonance imaging

A thesis submitted to the University of Manchester for the Degree of
Doctor of Philosophy in the Faculty of Medical and Human Sciences

2013

Isaac Kwong-Ping Huen

School of Medicine, Faculty of Medical and Human Sciences
List of Contents

List of Figures .................................................................................... 7
List of Tables.................................................................................... 10
List of Abbreviations ......................................................................... 11
Abstract ............................................................................................ 13
Declaration ....................................................................................... 14
Copyright ......................................................................................... 15
Acknowledgements .......................................................................... 16
The Alternative Format Thesis ......................................................... 17
1 Introduction ............................................................................... 18
1.1 Introduction ......................................................................... 18
1.2 Aims and Objectives ........................................................... 19
1.3 Summary ............................................................................ 20
2 Background ............................................................................... 21
2.1 Introduction ......................................................................... 21
2.2 FGR .................................................................................... 21
2.2.1 Symptoms .................................................................... 21
2.2.2 Aetiology ...................................................................... 24
2.2.3 Investigating the placental oxygen environment ........... 27
2.3 Introduction to MRI ............................................................. 30
2.3.1 Fundamentals of MRI ................................................... 30
2.3.2 Gradient-Echo Sequence ............................................. 37
2.3.3 Spin-Echo Sequence .................................................... 41
2.3.4 Inversion Recovery ....................................................... 44
2
2.4 MRI methods ...................................................................... 50
2.4.1 Hyperoxic challenge paradigm ..................................... 50
2.4.2 OE-MRI ........................................................................ 53
2.4.3 BOLD ........................................................................... 54
2.4.4 ASL .............................................................................. 55
2.4.5 Motion compensation ................................................... 59
2.4.6 Safety of MRI in pregnancy .......................................... 61
2.5 Summary ............................................................................ 62
3 Optimization of MRI techniques ................................................ 65
3.1 Introduction ......................................................................... 65
3.2 Evaluation of respiratory triggering ..................................... 66
3.2.1 Choice of respiratory triggering scheme for T mapping
1
in non-pregnant volunteers ....................................................... 66
3.2.2 Comparison of freebreathing and respiratory-triggered
dynamic in placental scanning .................................................. 83
3.3 Evaluation of OE-MRI and BOLD sequences under
hyperoxic challenge ...................................................................... 89
3.3.1 Introduction .................................................................. 89
3.3.2 Method ......................................................................... 89
3.3.3 Results ......................................................................... 93
3.3.4 Discussion .................................................................... 98
3.4 Table of final sequence parameters .................................. 100

4 R and R * changes in the human placenta in response to
1 2
maternal oxygen challenge ............................................................ 101
4.1 Abstract ................................................................................. 4
3
4.2 Introduction ........................................................................... 5
4.3 Methods ................................................................................ 8
4.3.1 Study population............................................................. 8
4.3.2 Data acquisition .............................................................. 8
4.3.3 Sequence parameters .................................................. 11
4.3.4 Image Analysis ............................................................. 13
4.4 Results ................................................................................ 16
4.4.1 OE-MRI ........................................................................ 16
4.4.2 OE-MRI dynamic .......................................................... 19
4.4.3 BOLD ........................................................................... 21
4.5 Discussion .......................................................................... 23
4.6 Conclusions ........................................................................ 27
4.7 Acknowledgements ............................................................. 29

5 R and R * in human placentas from normal and fetal growth
1 2
restricted pregnancies in response to maternal hyperoxia ............. 102
5.1 Abstract ................................................................................. 4
5.2 Introduction ........................................................................... 6
5.3 Methods ................................................................................ 8
5.3.1 Subjects ......................................................................... 8
5.3.2 Data acquisition ............................................................ 11
5.3.3 Sequence parameters .................................................. 13
5.3.4 Image Analysis ............................................................. 15
5.3.5 Statistical Analysis ........................................................ 16
5.4 Results ................................................................................ 16
4
5.5 Discussion .......................................................................... 23
5.6 Acknowledgement .............................................................. 26

6 Absence of pO change in fetal brain despite pO increase in
2 2
placenta in response to maternal oxygen challenge ...................... 102
6.1 Abstract ................................................................................. 3
6.2 Introduction ........................................................................... 5
6.3 Materials and Methods.......................................................... 7
6.3.1 Fetal brain & placenta .................................................... 7
6.3.2 Adult brain ...................................................................... 9
6.3.3 Image Analysis ............................................................. 10
6.4 Results ................................................................................ 12
6.4.1 Fetal brain & placenta .................................................. 12
6.4.2 Adult brains .................................................................. 14
6.5 Discussion .......................................................................... 16
6.5.1 Main Findings ............................................................... 16
6.5.2 Strengths and limitations .............................................. 16
6.5.3 Interpretation ................................................................ 17
6.6 Conclusion .......................................................................... 19
6.7 Acknowledgement .............................................................. 20

7 Preliminary study of effect of maternal hyperoxia on placental
perfusion using arterial spin labelling ............................................. 103
7.1 Abstract ................................................................................. 4
7.2 Introduction ........................................................................... 5
5
7.3 Methods ................................................................................ 8
7.3.1 Subjects ......................................................................... 8
7.3.2 MRI acquisitions ........................................................... 10
7.3.3 Image analysis ............................................................. 12
7.3.4 Effect of reducing number of repetitions ....................... 13
7.4 Results ................................................................................ 15
7.5 Discussion .......................................................................... 19
7.6 Acknowledgement .............................................................. 21

8 Conclusions and Future Work ................................................. 104
9 Appendix ................................................................................. 112
References..................................................................................... 113

Word count: 38,231

6
List of Figures
Figure 2.1. Schematic of the placenta. ...................................................... 24
Figure 2.2. Excitation pulse. ...................................................................... 31
Figure 2.3. Formation of a gradient-recalled echo. .................................... 33
Figure 2.4. k-space. .................................................................................. 35
Figure 2.5. GE sequence. ......................................................................... 38
Figure 2.6. Example mGRE sequence. ..................................................... 39
Figure 2.7. Example FLASH sequence. .................................................... 40
Figure 2.8. Formation of spin-echo. .......................................................... 41
Figure 2.9. SE sequence. ......................................................................... 42
Figure 2.10. Example TSE sequence. ....................................................... 43
Figure 2.11. Inversion recovery. ................................................................ 45
Figure 2.12. Example IR-SE sequence. .................................................... 46
Figure 2.13. Fitting of inversion recovery curve to magnitude-reconstructed
signal. ....................................................................................................... 48
Figure 2.14. Oxygen haemoglobin dissociation curve. .............................. 51
Figure 2.15. STAR and FAIR labelling strategies. ..................................... 58

Figure 3.1. Protocol of example IR T mapping sequence. ........................ 67
1
Figure 3.2. Spleen T maps from 1 (top) and 5 (bottom) repeats............... 68
1
Figure 3.3. Acquisition delay in terms of trigger delay and TI. ................... 70
Figure 3.4. Long-delay (top) and short-delay (bottom) triggering schemes
showing TI (light gray boxes), TD (white boxes) and minimum TR (dark
gray boxes). .............................................................................................. 72
Figure 3.5. T -weighted HASTE structural image of spleen in coronal
2
orientation. ................................................................................................ 75
7
Figure 3.6. TI-specific COV maps with ROI (red border) for all TIs in an
example short-delay triggering scheme. ................................................... 78
Figure 3.7. COV distribution inside ROI of example COV map. ................. 79
Figure 3.8. COV (top) and RSS (bottom) maps in a representative subject
obtained with long-delay triggering (left) and short-delay triggering (right). 80
Figure 3.9. COV maps under freebreathing (left) and triggering (right) with
ROI shown (red border). ........................................................................... 87
Figure 3.10. Scanning protocol, showing the T -weighted dynamic
1
acquisition between T and T * mapping acquisitions. .............................. 90
1 2
Figure 3.11. R dynamics in subjects 1-3 (top, middle, bottom). ................ 95
1
Figure 3.12. Respiratory motion in the dynamic of subject 3. .................... 99

Figure 4.1 Protocol for acquisition of OE-MRI and BOLD data under oxygen
challenge. ................................................................................................... 9
Figure 4.2. Coronal in-plane view (A) and sagittal through-plane view (B).
ROI marked by solid black lines. IR-TSE acquisition at TI=300 ms. .......... 10
Figure 4.3 Placental T maps obtained in an in-plane view under air-
1
breathing (left) and oxygen-breathing (right) superimposed onto a T -
2
weighted structural image. ........................................................................ 17
Figure 4.4 ∆R derived from static T maps (A) and ΔR derived from the
1s 1 1d
T -weighted dynamic acquisition (B) as a function of gestational age at
1
scan. ......................................................................................................... 18
Figure 4.5 Example ΔR dynamic time-courses shown from the point of
1d
oxygen administration. .............................................................................. 20
Figure 4.6 ∆R * plotted against gestational age at time of scan. ............... 22
2

Figure 5.1 Example coronal view of maternal abdomen containing in-plane
(top) and through-plane (bottom) views of placenta (black line). ............... 12
Figure 5.2 Acquisition of ΔR and ΔR * data under oxygen challenge. ...... 14
1 2
Figure 5.3 Relationship between baseline R and IBC in all subjects. ....... 19
1
8
Figure 5.4 Relationship between ∆R and gestational age at scan in normal
1
and SGA subjects under oxygen breathing. .............................................. 20
Figure 5.5 Relationship between baseline R * and IBC in all subjects. ..... 21
2
Figure 5.6 Relationship between ∆R * and gestational age in normal and
2
SGA subjects under oxygen breathing. ..................................................... 22

Figure 6.1 Sagittal view of maternal abdomen containing fetal brain and
placenta. ................................................................................................... 11
Figure 6.2. ΔR (mean ± SD) between maternal oxygen administration of
1
21% and 100% for all subjects in fetal brain (grey dashed line) and placenta
(black line). ............................................................................................... 13
Figure 6.3. ΔR (mean ± SD) between oxygen administration of 21% and
1
100% in adult brain (line). ......................................................................... 15

Figure 7.1. Example imaging slice. ........................................................... 11
Figure 7.2. Mean (top) and standard deviation (bottom) of f fitted for
increasing numbers of repetitions n averaged across 9 normal pregnant
volunteers. ................................................................................................ 14
Figure 7.3. f measured under air-breathing (light grey bars) and oxygen-
breathing (dark grey bars) in 4 subjects. ................................................... 16
Figure 7.4 ASL signal (circles), standard error (vertical lines) and fit (curve)
against TI under air-breathing (left column) and oxygen-breathing (right
column) for all subjects. ............................................................................ 18

Figure 9.1. Relationship between ∆R and days delivered after scan in
1
normal subjects from published paper included in Chapter 4. ................. 112

9
List of Tables
Table 3.1. Comparison of T between schemes. ....................................... 81
1
Table 3.2. Comparison of reproducibility (COV) and fit quality (RSS)
between long-delay and short-delay triggering schemes. .......................... 81
Table 3.3. Comparison of reproducibility (coefficient of variation) between
schemes in dynamic acquisition under air-breathing. ................................ 88
Table 3.4. Comparison of mapped and dynamic T data obtained under air
1
and oxygen breathing. .............................................................................. 93
Table 3.5. Comparison of T * map data obtained under air and oxygen
2
breathing. ................................................................................................. 96
Table 3.6. Comparison of T and T * data with other studies. Medians and
1 2
range shown for this study, means and SD shown for others. ................... 97

Table 5.1 Demographics of study population. ........................................... 10
Table 5.2 Correlation of parameters with IBC and gestational age. ........... 18

Table 6.1 Demographics of pregnant study population. .............................. 8

Table 7.1. Demographics of study population. ............................................ 9

10