Table Of ContentA quantitative analysis of MRI images using commercial
software for the assessment of radiotherapy-induced
anatomical changes of parotid glands
Gerlinde Logghe
Supervisors: Prof. Dirk Verellen, Prof. Giovanna Rizzo (University of
Milano-Bicocca, Italy)
Counsellor: Prof. Claudio Fiorino (Servizio Fisica Sanitaria - Ospedale San Raffaele
IRCCS)
Master's dissertation submitted in order to obtain the academic degree of
Master of Science in Biomedical Engineering
Faculty of Engineering and Architecture
Academic year 2014-2015
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master
dissertation”
Gerlinde
Logghe
21/05/2015
i
Preface
Writing
this
thesis
is
the
final
chapter
of
my
life
as
a
student
and
I
would
like
to
thank
some
people
that
have
made
this
experience
possible
for
me.
My
parents,
who
gave
me
the
opportunity
to
study
for
all
these
years
and
who
supported
me
in
all
my
decisions.
My
brother
Barteld,
who
has
always
believed
in
me.
Professor
Verellen,
who
has
helped
me
finding
a
thesis
subject
abroad
and
who
agreed
to
be
my
supervisor.
Claudio
Fiorino
and
dr.
Giovanna
Rizzo
for
guiding
and
helping
me
to
write
this
thesis
and
for
welcoming
me
in
Milan.
Maria-‐Luisa
Belli
and
Sara
Broggi
for
helping
me
with
the
project
and
answering
my
many
questions.
My
colleagues
in
the
San
Raffaele
Hospital
and
LITA.
You
made
my
stay
in
Milan
unforgettable.
ii
Abstract
A
quantitative
analysis
of
MRI
images
using
commercial
software
for
the
assessment
of
radiotherapy-‐induced
anatomical
changes
of
parotid
glands
Gerlinde
Logghe
Supervisors:
Prof.
Dirk
Verellen,
Prof.
Giovanna
Rizzo
(University
of
Milano-‐Bicocca,
Italy)
Counsellors:
Prof.
Claudio
Fiorino
(Servizio
Fisica
Sanitaria
–
Ospedale
San
Raffaele
IRCCS)
Master's
dissertation
submitted
in
order
to
obtain
the
academic
degree
of
Master
of
Science
in
Biomedical
Engineering
Faculty
of
Engineering
and
Architecture,
Academic
year
2014
-‐
1015
Summary
Radiotherapy
is
one
of
the
main
therapies
to
treat
head
and
neck
cancer
(HNC).
However,
one
of
the
consequences
of
radiation
therapy
is
the
radiation-‐induced
damage
to
normal
tissue
and
cells.
In
HNC
patients,
one
of
the
main
side
effects
is
xerostomia,
which
is
the
result
of
a
change
of
saliva
composition
or
reduced
saliva
flow.
Image
analysis,
and
in
particular
deformable
image
registration
(DIR),
is
used
to
investigate
parotid
shrinkage,
which
can
lead
to
xerostomia,
and
can
be
used
to
investigate
certain
clinical
and
dosimetric
parameters
that
could
predict
this
shrinkage.
In
this
Masters
dissertation,
MIM
software,
will
be
used
for
MRI/MRI
monomodality
deformable
registration
and
contour
propagation.
After
the
accuracy
of
the
deformable
registration
and
contour
propagation
is
validated
(correct
for
all
but
one
parotid
gland),
MIM
software
is
used
for
a
clinical
application:
the
determination
of
radiation-‐induced
parotid
shrinkage
and
correlation
with
clinical
and
dosimetric
parameters.
Significant
changes
in
parotid
gland
volume
in
the
acute
(2-‐3
months)
and
late
phase
(6-‐18
months),
compared
with
the
pre-‐RT
scan
are
noticed
and
initial
volume
seems
to
be
correlated
with
volume
loss
in
the
acute
phase.
Also
2
subpopulations
were
found
to
be
present,
which
could
be
explained
by
a
difference
in
mean
planned
dose
to
the
parotid.
Mean
planned
dose
seems
to
be
correlated
with
volume
loss
in
the
late
phase,
especially
for
the
high-‐dose
group.
The
contour-‐propagation
tool
included
in
MIM
software
reduces
the
contouring
time
with
50
%
iii
A quantitative analysis of MRI images using
commercial software for the assessment of
radiotherapy-induced anatomical changes
of parotid glands
Gerlinde Logghe
Supervisor(s): Giovanna Rizzo, Claudio Fiorino
the region of the oropharynx, 5 in the nasopharynx. In 7 of
Abstract In this research, the use of MIM software for these patients, the tumour was located bilaterally, while in 5
MRI/MRI deformable registration and contour propagation is of them the tumour was located at the right side, and in other
investigated and validated. As an application of MIM software, 2 patients at the left side. There were 8 males and 6 female
the predictive value of some clinical and anatomical parameters patients. The PTV1 – dose ranged from 61,5 Gy to 67 Gy with
for parotid shrinkage is investigated.
2,05 to 2,3 Gy per fraction (30 fractions) and the PTV2- from
Keywords MIM software, MRI, DIR, parotid gland shrinkage 54 Gy to 56 Gy with 1,8 to 1,9 Gy per fraction (30 fractions).
The mean dose to the parotid glands was 32,6 Gy and ranged
from 21,8 Gy to 51,6 Gy.
I. INTRODUCTION The MRI scans are performed with a THRIVE sequence
Cancer of the head and neck region (HNC) is the seventh using a Philips machine (Achieva 1.5 and Philips Interna for
leading cancer worldwide. Radiotherapy is one of the main patient 5). This is T1-weighted high-resolution isotropic
therapies to treat HNC; Ionizing radiation is used to introduce volume examination sequence (THRIVE) with 3D ultra-fast
damage in the DNA, which will lead to cell death and spoiled gradient, useful for soft-tissue imaging as it provides
impaired cell division. However, one of the consequences of more detailed anatomical information while retaining a good
radiation therapy is the radiation-induced damage to normal spatial resolution and having an acceptable acquisition time.
tissue. In HNC patients, one of the main side effects is dryness
of the mouth, also known as xerostomia, which is the result of B. MIM Software
a change of saliva composition or reduced saliva flow. The Version 6.3 of MIM software (Cleveland, Ohio) is used in
parotid glands are the mayor contributor to the saliva this thesis project. MIM offers a great flexibility and
production, and shrinkage has been suggested to be an efficiency for its users and its design philosophy was based on
indicator of xerostomia. Image analysis, and in particular offering the user an intuitive and friendly interface. However,
deformable image registration (DIR), is used to investigate details regarding the implementation of the algorithms behind
parotid shrinkage and certain clinical and dosimetric these tools are not available to users.
parameters that could predict this shrinkage in the parotid Rigid and deformable registration in combination with
glands. contour propagation, are the main tools used in this thesis
project. Contour propagation is linked to registration by using
MIM software has been used extensively for CT/CT DIR, the registration field to propagate the contours from one image
but there is not much information available on MRI/MRI DIR. to the other. DICE Coefficients and Hausdorff distance values
Therefore the aim of this thesis is also to find a protocol in will be used to evaluate the propagation/registration. Several
MIM software for MRI/MRI DIR of HNC patients that will settings are possible for registration (rigid and deformable),
give adequate and acceptable results in terms of accuracy. and the most optimal setting will be investigated and
In a second part, selected parameters that could be validated. For this step a subset of 10 patients is used.
correlated with parotid gland shrinkage are investigated by the
use of MIM software. C. Statistical Tests
SPSS (IBM ® SPSS ® Statistics) Version 21 is used for
II. EXPERIMENTAL RESEARCH statistical analysis. The Wilcoxon signed-rank test is used for
the comparison of means in repeated measurements (pre-RT
A. Patient Data-set vs. acute/late phase scan). The independent-Samples Mann-
Whitney U test is used for the comparison of means in two
14 patients were selected from a database containing HNC
patients. These 14 patients all had a pre-treatment MRI scan, independent samples.
an acute phase MRI scan (2-3 months after treatments) and a
late phase MRI scan (6-18 months later).
The ages of the patients ranged from 33 to 78 years with a
median value of 55,4 years. 9 of them had a tumour located in
III. RESULTS smaller group (group 2), consisting of only 6 parotid glands,
shows a decline in the acute phase (from ± 23 ml to ± 20ml),
followed by a further decline in the late phase (to ±16,5 ml).
A. Parameter settings and validation in MIM Software
The volume changes in the second group are smaller when
The combination of a rigid registration with a region that
compared to the first group as well as the pre-RT volume.
includes the parotid glands (‘Box Based Assisted Alignment’)
The correlation between volume loss and certain parameters
together with a deformable registration that focuses on the
(initial volume, mean planned dose, %overlap between PTV
whole image, gave the best results (maximum DICE
and parotid gland, age, and gender) was investigated, see
coefficient and minimum Hausdorff distance values).
Table I.
However, the differences with the other registration
approaches are small and no statistical significance is Table I Correlation between certain parameters and volume loss of
determined. parotid glands in acute an late phase
It was found that a deformable smoothness factor (DSF) of
Total Group 1 Group 2
0,5 is the optimal setting when working with MRI/MRI image
registration. However, in the cases where the images are Para-
Acute Late Acute Late Acute Late
subjected to some degree of artefacts and/or noise or where meters:
the volumes differ too much between the 2 images, it is better
to use a deformable smoothness factor of 2. When these 2
Initial 0,669
deformable smoothness factors are being considered, it can be volume ** 0,267 0,711
concluded that all patients (with the exception of one parotid
in patient 7) have a median error (Hausdorff distance median)
that falls within the voxel size, see Figure I This means that Mean
the registration protocol can be used for further MRI/MRI planned -0,054 0,365 0,241 0,249 -0,257 0,429
dose
registrations.
%
overlap
-0,031 0,112 0,139 0,132 -0,329 0,188
with
PTV
Age 0,034- 0,132
There is a difference in volume between man and female patients.
Gender However, this does not translate into a significant difference in relative
volume loss between man and female.
Figure I Validation results
C. Reduction in contouring time
B. Clinical and dosimetric parameters that can predict From the volume extraction experiment, it was concluded
parotid shrinkage that the deformable registration process/contour propagation
tool in MIM is not sufficient enough to produce propagated
It was found that there are significant changes in parotid
contours that don’t need manual adjustment. However, it was
gland volume when going from the pre-treatment to the acute
noticed that when the propagation tool was used, the
(2-3 months) and late phase (6-18 months). Two
contouring phase goes much faster. In order to assess the gain
subpopulations were found to be present, see Figure II.
in time due to the combination of propagation+manual
adjustment vs. manual contouring, the last 4 patients of the
volume extraction protocol were used, together with 5 other
patients that only had an acute or late phase scan (and thus
were not included in the volume extraction experiment).
The average time needed for manually contouring both
parotid glands is about 62,11 minutes, while when the contour
propagation tool is used there is a reduction to 31,63 min in
acute phase and 31,40 min in late phase, which equals a
reduction of about 50%, see table Table II
Table II Time reduction for contouring
Figure II Volume changes for 2 subpopulations Contouring time (in minutes)
Acute Scan Late Scan
The large majority of parotids (n=22 parotid glands, group Pre- (propagated (propagated
treatment
1) are characterized by an initial decline of volume in the contours + contours +
scan
acute phase (from ± 28 ml to ±20 ml), followed by a plateau adjustment) adjustment)
1 1 73 40 29
or even an increase in the late phase (from ±20 ml to ± 23,5
12 53 25 27
ml). However, the original volume is never reached again. A
13 67 35 35 V. CONCLUSION
14 68 34 32
15 54 30 / It was found that MIM software is able perform a MRI/MRI
16 57 25 / deformable registration and contour propagation with enough
17 61 / 34 accuracy (less than max. voxel error). However, the
18 61 30 /
performance of MIM software should be compared with open-
19 65 34 /
source software programs that already have been used to
Average 62,11 31,63 31,40
Average/gland 31,06 15,81 15,70 explore and optimize MRI/MRI registration, such as Elastix.
%reduction 49,08 49,45 As these programs are open-source software systems and the
user itself creates the algorithm, it is expected that these
results will be more accurate but will be more time-
IV. DISCUSSION consuming. It was shown in this thesis, that the DIR tool of
MIM has enough accuracy to be used, so it has to be
A. Parameter settings and validation in MIM Software investigated whether a higher accuracy will result in
noticeably better clinical and practical outcome.
For the analysis of MRI images, it was found that the best
Concerning the found correlations between volume loss and
deformable registration is obtained when using ‘Box Based
certain clinical and dosimetric parameters, it needs to be
Assisted Alignment’ focused on the parotid glands, a
investigated if the conclusions from this research still hold in
deformable registration without focusing on a specific ROI
a larger population. If so, it should also be investigated
and a deformable smoothness of 0,5 and 2.
whether or not a linear regression model can be build with
The observations about the DSF were later confirmed
these parameters. This model could than be used as a
during a webinar organized by Jonathan W. Piper (MIM
predictive model for parotid shrinkage.
software) about ‘Deformable Image Registration and Quality
Also data about toxicity and xerostomia in the patients are
Assurance’ using MIM software [1].
necessary to draw any valid conclusion about radiation-
By comparing the Hausdorff distances between the manual
induced xerostomia.
and propagated contours with the maximum voxel size, the
accuracy of the deformable registration and contour
propagation in MIM software was validated.
REFERENCES
B. Clinical and dosimetric parameters that can predict
parotid shrinkage
[1] J. (MIM software I. . Piper, “Deformable Image Registration and
A large, positive and significant correlation was found Quality Assurance,” 2015.
between the initial parotid gland volume and the volume loss
[2] S. Broggi, C. Fiorino, I. Dell’Oca, N. Dinapoli, M. Paiusco, A.
after 2-3 months. The same conclusion was also reached in
Muraglia, E. Maggiulli, F. Ricchetti, V. Valentini, G. Sanguineti, G.
research performed by Broggi et al. (2010) [2]. In the same M. Cattaneo, N. Di Muzio, and R. Calandrino, “A two-variable
study other parameters predicting the parotid shrinkage in linear model of parotid shrinkage during IMRT for head and neck
acute phase are: mean planned dose to parotid gland and age. cancer,” Radiother. Oncol., vol. 94, no. 2, pp. 206–212, 2010.
In this thesis however, no correlation between age and relative
volume loss in acute phase is found. In terms of planned mean
dose to the parotid glands, there seems to be no correlation
with the acute phase relative volume loss and a positive
correlation with the late phase relative volume loss.
Correlation between mean dose and absolute volume loss,
gives the same conclusion.
It was also found that there was a significant difference
between the planned mean doses in the 2 subpopulations; this
could be one of the reasons for the existence of the 2
subpopulations as the correlation of group 2 (higher mean
planned dose) with the relative late phase volume loss is
larger than the correlation with group 1.
It was found that gender and subpopulation are independent
from each other.
From the data it was also concluded that there was a
significant difference in age between the man (64,9 years) and
woman (46,6 years); the women are younger than the man.
Furthermore, parotid glands of female patients seem to be
more ‘rigid’: there is less initial volume loss, but also less
recovery later on. However, no significant differences are
found between volume losses in man vs. women.
C. Reduction in contouring time
The use of the contour propagation tool will reduce the time
needed for contouring with about 50%. This saves a lot of
time, which can be an important factor in clinical practice.
Table of contents
PERMISSION
FOR
USAGE
I
PREFACE
II
ABSTRACT
III
EXTENDED
ABSTRACT
IV
TABLE
OF
CONTENTS
VII
LIST
OF
FIGURES
X
LIST
OF
TABLES
XII
LIST
OF
ABBREVIATIONS
XIII
CHAPTER
1
1
INTRODUCTION
1
1
BACKGROUND
1
2
GOAL
OF
THIS
THESIS
2
3
OUTLINE
OF
THIS
THESIS
2
CHAPTER
2
4
LITERATURE
STUDY
4
1
ONCOLOGY
4
1.1
Oncology:
facts
and
figures
4
1.2
Tumour
development
and
progression
5
1.3
Prevention
and
treatment
of
cancers
6
1.3.1
Types
of
treatment
therapies
7
1.4
Cancers
of
the
head
and
neck
region
9
1.4.1
Head
and
neck
cancer
9
1.4.2
Treatment
of
HNC
10
2
RADIATION
ONCOLOGY
12
2.1
Ionizing
radiation
12
2.2
Interactions
with
matter
13
2.3
The
use
of
radiation
therapy
in
clinical
practice
18
2.3.1
Internal
radiation
therapy
18
2.3.2
External
beam
therapy
18
vii
2.4
Side-‐effects
of
radiation
therapy
25
2.4.1
Stochastic
effects
vs.
tissue
reactions
25
2.4.2
Early
vs.
late
responding
tissues
25
2.4.3
Effects
in
HNC
26
3
IMAGING
TECHNIQUES
29
3.1
Overview
and
incentive
29
3.1.1
X-‐ray
imaging
and
CT
29
3.1.2
PET
and
SPECT
30
3.1.3
Ultrasound
31
3.2
MRI
31
3.2.1
Principle
32
3.2.2
Use
in
radiotherapy
35
3.3
Image
analysis
in
radiotherapy
36
3.3.1
Registration
36
3.3.2
Contour
propagation
39
CHAPTER
3
41
SOFTWARE
FOR
REGISTRATION
41
1
USER-‐DEPENDENT
SOFTWARE
42
2
COMMERCIAL
SOFTWARE
43
2.1
About
MIM
43
2.2
Registration
Algorithms
in
MIM
43
2.2.1
Rigid
Registration
44
2.2.2
Deformable
registration
46
2.2.3
Contour
propagation
49
2.3
Evaluation
tools
in
MIM
49
2.3.1
Evaluation
tools
for
registration
49
2.3.2
Evaluation
tools
for
contour
propagation
50
CHAPTER
4
53
EXPERIMENTAL
RESEARCH
53
1
INTRODUCTION
53
2
PATIENT-‐DATABASE
54
3
MIM
SOFTWARE
56
3.1
Determination
of
useful
parameters
56
3.1.1
Patient
subset
56
3.1.2
Rigid
Registration
57
3.1.3
Deformable
registration
59
3.1.4
Conclusions
67
3.2
Validation
of
parameter
setting
68
viii
Description:radiotherapy-induced anatomical changes of parotid glands. Gerlinde Logghe. Supervisor(s): Giovanna Rizzo, Claudio Fiorino. Abstract In this research, the use of MIM software for. MRI/MRI deformable registration and contour propagation is investigated and validated. As an application of MIM softwar
