ANATOMICAL AND PHYSIOLOGICAL BASES
OF BONE MARROW OEDEMA-LIKE STRUCTURES
IN MAGNETIC RESONANCE IMAGING:
AN IN-VITRO MACRO- AND MICROSCOPIC STUDY
Submitted by Christine Jane Heales, to the University of Exeter as a thesis for the
degree of Doctor of Philosophy by Research in Physics, April 2009.
This thesis is available for Library use on the understanding that it is copyright
material and that no quotation from the thesis may be published without proper
acknowledgement.
I certify that all material in this thesis which is not my own work has been identified
and that no material has previously been submitted and approved for the award of
a degree by this or any other University.
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Abstract
ABSTRACT
Bone marrow oedema is a term used to define the appearance of regions of low signal on T1
weighted and high signal on T2 weighted fat-suppressed magnetic resonance images. The
potential association between bone marrow oedema and prognosis in pathologies such as
osteoarthritis is becoming increasingly recognised through clinical studies. A limited number of
clinical studies have linked bone marrow oedema to altered bone density or altered bone
marrow perfusion. The principal aims of this study were to investigate these findings in vitro,
using the equine forelimb.
The presence of bone marrow oedema within the equine forelimb was initially confirmed by
undertaking magnetic resonance imaging scans. Bone samples were selected from 10 animals,
5 exhibiting the presence of bone marrow oedema-type abnormalities (BMOA) at the distal
metacarpal. Raman microspectroscopy was used to determine the chemical composition of
bone and projection radiography to provide a measure of bone density. Micro computed x-ray
tomography was undertaken on a subset of three bone samples exhibiting BMOA. A second
component of the study utilised contrast enhanced magnetic resonance imaging to enable
comparison of perfusion to bone marrow with and without evidence of oedema. A saline flushing
agent containing Evan’s blue was used so that subsequent sectioning of the bone would enable
visualisation of the distribution of contrast agent as part of a histological examination of the
oedematous region.
An initial observation was that the majority of bone marrow oedema that was observed in the
distal metacarpal appeared in a consistent location, namely the postero-inferior aspect of the
bone, corresponding to the point of greatest load thereby suggesting a potential relationship to
forces upon the joint. The principal observations were that there appears to be increased bone
volume densities in those bone samples with evidence of bone marrow oedema. The Raman
microspectroscopy did not demonstrate any statistically significant differences in the chemical
composition of bone. Hence the overall impression is that bone marrow oedema is associated
with a greater volume of bone, although of similar maturity and composition. There was limited
evidence of increased perfusion (suggestive of increased vascularity and / or hyperpermeability)
in those samples with bone marrow oedema.
This work suggests that these particular bone marrow oedema lesions are associated with bone
changes and potentially vascular changes although the aetiology is currently unclear. Further
work is needed to determine the clinical significance and prognosis associated with these
particular lesions, and whether these findings can be replicated for bone marrow oedema
demonstrated at other anatomical locations.
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Acknowledgements
ACKNOWLEDGEMENTS
Advisor:
Professor Winlove1
Supervisors:
Dr Ian Summers1
Dr Karen Knapp1
Technical Advice:
Dick Ellis1
Ellen Green1
Dave Colridge1
Dr Charlotte Moger1
MRI Advice:
Dr Malek Benyattallah1
Dr Jon Fulford2
Bruno Notarberardino3 (data collection)
Micro-CT
Dr Philippe Young3
Abattoir ‘Buddies’
Sophie Willis1
Rachel Palfrey1
General Support:
Dr Kenton Arkill1
The Medical Imaging Programme Team1
Friends and Family
1School
of Physics, University of Exeter
2Peninsula
3School
Medical School, Universities of Plymouth and Exeter
of Engineering, Computing and Mathematics, University of Exeter
Page 3 of 6
List of Chapters
LIST OF CHAPTERS
1
Introduction--------------------------------------------------------------------------------- 20
2
Materials and Methods ------------------------------------------------------------------ 54
3
Results - MR Imaging ------------------------------------------------------------------ 131
4
Results - X-ray Imaging ---------------------------------------------------------------- 172
5
Results - Raman Microspectroscopy ----------------------------------------------- 188
6
Results – Histology---------------------------------------------------------------------- 226
7
Summary and Suggestions for Further Work ------------------------------------ 260
8
References -------------------------------------------------------------------------------- 271
9
Appendix A -------------------------------------------------------------------------------- 281
10 Appendix B -------------------------------------------------------------------------------- 288
11 Appendix C -------------------------------------------------------------------------------- 291
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Table of Abbreviations
ABBREVIATIONS
BMO
Bone marrow oedema
BMOA
Bone marrow oedema-type appearance
BMU
Basic multicellular unit
CT
Computed tomography
DR
Normalised dynamic range
DV
Display value
DXA
Dual-energy x-ray absorptiometry
FFD
Focus to film (image receptor) distance
FFE
Fast field echo
FP
Floating point
FSE
Fast spin echo
Micro-CT
Micro-computed tomography
MR
Magnetic resonance
MRI
Magnetic resonance imaging
PV
Pixel value
RANK
Receptor activator of nuclear factor kappa B
RI
Rescale intercept
RS
Rescale slope
S(TI)
Signal intensity for a given inversion time
SID
Source to image receptor distance
SNR
Signal to noise ratio
SS
Scale slope
STIR
Short tau inversion recovery
TE
Echo time
TI
Inversion delay
TR
Repetition time
WSR
Within slice ratio
w/v
Weight by volume
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Table of Symbols
SYMBOLS
Al
Aluminium
ωo
Angular precessional frequency
b
Bone
LAl
Calculated equivalent thickness in mm of aluminium
E
Elastic modulus
Bo
Field strength of the static magnetic field
α
Flip angle
m
Ground state
γ
Gyromagnetic ratio
R
Image intensity
µ
Linear attenuation co-efficient
F
Magnitude of force
L
Measured thickness of bone
Mo
Net magnetisation
σ
Normal stress
ν
Raman shift
Sα
Signal intensity for flip angle α
t
Soft tissue
A
Surface area
L
Thickness of bone
µ
Total linear attenuation co-efficient
i
Transmitted intensity
n
Vibrationally excited state
λ
Wavelength
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