Gerlinde Logghe anatomical changes of parotid glands software for the assessment of ...

139 Pages·2015·9.21 MB·English

by  Gerlinde Logghe

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)
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

Permission  for  usage  

“The
  author(s)
  gives
  (give)
  permission
  to
  make
  this
  master
  dissertation
  available
  for

consultation
 and
 to
 copy
 parts
 of
 this
 master
 dissertation
 for
 personal
 use.

In
 the
 case
 of
 any
 other
 use,
 the
 copyright
 terms
 have
 to
 be
 respected,
 in
 particular
 with

regard
 to
 the
 obligation
 to
 state
 expressly
 the
 source
 when
 quoting
 results
 from
 this
 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