L UDWIG -M AXIMILIANS -U NIVERSITÄT M ÜNCHEN

FACULTY OF P HYSICS
C HAIR OF M EDICAL P HYSICS

M ASTER T HESIS

Optimization of LINAC beam modeling

and clinical translation of a novel
EPID-based QA Tool

Author: Supervisor:
Rangoli Saxena Prof. Dr. Katia Parodi
M.Sc. Juliana Martins

Submitted on
December 3, 2018
L UDWIG -M AXIMILIANS -U NIVERSITÄT M ÜNCHEN
FACULTY OF P HYSICS
C HAIR OF M EDICAL P HYSICS

M ASTER T HESIS

Optimierung eines LINAC Strahlmodelle

und klinische Einführung eines neuartige
EPID-basiert QA Verfahren

Author: Supervisor:
Rangoli Saxena Prof. Dr. Katia Parodi
M.Sc. Juliana Martins

Submitted on
December 3, 2018
 iii

Abstract
Monte Carlo simulations offer powerful techniques in the field of radiotherapy for
estimating precisely and efficiently the dose delivered to the patient. Accurate Monte
Carlo models of medical linear accelerators (linacs), based on these techniques can be
utilized in creating treatment plans. To implement such a model, detailed technical
information of almost all the internal components of the linac is needed. This infor-
mation is often a commercial secret and is not disclosed by vendors. Optionally, a
commissioned Phase Space (PhSp) file available on the International Atomic Energy
Agency (IAEA) portal can be used as the photon beam source instead of modeling
the entire linac. These PhSps are characteristic to the linac model they were gen-
erated for. In the event of an unavailability of the PhSp of a specific linac, which
is intended to be modeled, this study offers an alternative approach. An available
PhSp of a linac model is optimized for a different linac model. Initially, the informa-
tion in the PhSp is perturbed randomly, and is then simulated iteratively to identify
correlations of this information with the simulated dose profiles. Once a correlation
has been identified, the PhSp is optimized under supervision, aiming at reducing
the quantified discrepancy, referred to as cost values, between the simulated and
measured dose profiles. This optimization requires several iterations, each involv-
ing numerous simulations depending on the parameter being optimized. In this
study, the energy and momentum of the particles were optimized. The optimal fix
for energy was identified and the full PhSp was validated. Considerable reduction in
cost values was observed for percentage depth dose, as well as, inline lateral profile.
The optimization of momentum was relatively more challenging. Promising results
were obtained when the momentum optimization was performed for crossline and
inline profiles individually. The merging of the two optimal momentum fix in the
same PhSp proved to be a challenge. Multiple approaches were formulated, imple-
mented and analyzed. Three such approaches are presented in this work. The best
performing approach was used to determine the optimal perturbation factors which
produced the lowest cost values. These factors were then used to perturb the full
PhSp and the corresponding cost values of the lateral profiles were determined for
all considered field sizes. The optimization of momentum secured a collective gain
in improving the lateral profiles to a considerable degree. Further improvement can
be achieved by acquiring additional measured lateral dose profiles in different lat-
eral directions between crossline and inline.
The second part of this thesis is in the realm of dosimetric validations using Elec-
tronic Portal Imaging Device (EPID). EPID is a flat panel 2D detector attached at the
bottom of the linac gantry. Although traditionally employed for only fast verifica-
tion of patient position, it poses exciting usability in determining the 3D dose distri-
bution as part of pre-treatment patient specific treatment plan verification. For this
purpose, a clinical tool, Novel EPID-based Audit Tool (NEAT), was implemented to
audit a reconstruction algorithm, which had produced promising initial results. The
tool offers a compact interface for the complete reconstruction of a 3D dose distri-
bution from frames acquisition to generation of DICOM files. 22 VMAT treatment
plans were audited using the tool. These reconstructions were then compared with
the ones computed by the Treatment Planning System, using gamma index evalu-
ation with a criteria of (3 mm, 3%). The results show that 13 out of the 22 recon-
structions passed with passing rates higher than 95%. The passing rates of the other
9 failing reconstructions improve considerably when further correction factors are
employed.
 v

Acknowledgements
I would first like to thank Prof. Dr. Katia Parodi who gave me the opportunity to
work on this project at the Chair of Medical Physics. Throughout the course of work-
ing on my Master Thesis she was supportive and understanding of the problems we
were facing. Despite of her busy routine, she responded very quickly to all queries
and kept track of the thesis progress. I felt very secure under her guidance. I am also
grateful to her for giving us the chance to present a summary of this project at the
DGMP Jahrestagung and in European Congress of Medical Physics. Thank you!
Next, I would like to extend a huge thanks to Juliana Cristina Martins. She
helped me at every step. Each time I was stuck with a complex problem I would
just turn back and call for her assistance. Be it late night or early morning, she re-
sponded almost instantly. A proper researcher with incredible writing skills. She
guided me greatly while I was writing this thesis. Without her support, guidance
and a myriad of comments, this thesis would never have been in the form as it is
now. She taught me from scratch how to write scientifically, a skill I would use from
now and forever. She is an amazing teacher. I would miss her dearly in my next
projects.
A huge thanks to Sebastian Neppl, whom I nagged a lot in the last weeks of the
project. I am forever indebted to his patience and helpful nature. I am grateful for
his assistance with the linac and also for setting up my workstation at least 15 times
in the past months. Thank you for everything.
I would also like to thank Abdulaziz Alhazmi, without whose support I would
never have been able to finish the second part of my thesis. I am grateful to him for
guiding me with the complete back-end code and for always being supportive.
Thank you Carmen Seller Oria, a colleague and a great friend, who listened to
all my cribbing over project problems and dead-ends. She has been a great support
throughout my Masters.
Neha Das and Sumit Dugar! My friends from India who are now pursuing mas-
ters at TUM. Thank you for feeding me countless dinners and lunches when I was
too busy to cook anything decent! I could always count on you guys shamelessly.
Masters would have very lonely without the both of you.
Lastly, I would like to thank my parents who supported me in all ways. They are
the biggest support in my life and my loudest cheerleaders who believe in me more
than I believe in a photon being the fastest (even in vacuum).
 vii

Contents

Abstract iii

Acknowledgements v

1 Introduction 1
1.1 External Beam Therapy in Cancer Treatment . . . . . . . . . . . . . . . 2
1.2 MC Techniques in External Beam Therapy . . . . . . . . . . . . . . . . . 3
1.2.1 Complications with Linac MC modeling . . . . . . . . . . . . . 3
1.2.2 Optimization of PhSp . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 EPID Dosimetry in External Beam Therapy . . . . . . . . . . . . . . . . 5
1.3.1 Novel EPID-based Audit Tool . . . . . . . . . . . . . . . . . . . 5

2 Scientific Background 7
2.1 Introduction to Radiation Therapy . . . . . . . . . . . . . . . . . . . . . 7
2.1.1 Discovery of X-rays . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.1.2 Origin of Dosimetry . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.1.3 Biological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.2 X-rays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2.1 Production of X rays . . . . . . . . . . . . . . . . . . . . . . . . . 10
A historical perspective of X-rays production for Radiation
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.2.2 Interaction of X-ray photons with matter . . . . . . . . . . . . . 15
Compton effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Photoelectric effect . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Pair production . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Rayleigh scattering . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Photonuclear interactions . . . . . . . . . . . . . . . . . . . . . . 21
2.2.3 X-ray beam attenuation . . . . . . . . . . . . . . . . . . . . . . . 22
2.2.4 Brief Overview of Dosimetric Quantities . . . . . . . . . . . . . 25
2.3 Modern Linear Accelerators . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.3.1 Linac Waveguide . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.3.2 Linac Head . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
The X-ray target . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Beam Collimators . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Flattening filter . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Ion Chamber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Wedge Filter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3.3 Electronic Portal Imaging Devices (EPID) . . . . . . . . . . . . . 30
2.3.4 Clinical Workflow in Conformal Radiotherapy . . . . . . . . . . 30
2.4 Monte Carlo Simulation . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.4.1 The Monte Carlo Linac Model . . . . . . . . . . . . . . . . . . . 32
2.4.2 Geant4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
viii

3 Optimization of Phase Space File 35

3.1 Measurements and Modeling . . . . . . . . . . . . . . . . . . . . . . . . 35
3.2 Cropping the PhSp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
3.3 Optimization Of Energy . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.3.1 The Cost Function . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.3.2 Acceptable Cropping for PDD . . . . . . . . . . . . . . . . . . . 41
3.3.3 Small Energy Perturbations . . . . . . . . . . . . . . . . . . . . . 44
3.3.4 Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.3.5 Final Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.4 Optimization of Momentum . . . . . . . . . . . . . . . . . . . . . . . . . 49
3.4.1 The Momentum Direction and the Geometric Penumbra . . . . 49
3.4.2 The Cost Function . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Rationale for using Sigmoid . . . . . . . . . . . . . . . . . . . . . 52
3.4.3 Correlation between the Divergence and Penumbra . . . . . . . 53
The Slope perturbation factor : µ and its identities . . . . . . . . 54
Sigmoid Fitting Parameters for Varying µ . . . . . . . . . . . . . 57
3.4.4 Statistical Uncertainties among Simulations . . . . . . . . . . . . 58
3.4.5 Acceptable Cropping for Lateral Profiles . . . . . . . . . . . . . 59
3.4.6 Finding the Optimal Slope Perturbation Factor for Crossline
(µcr ) or Inline (µin ) . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.4.7 Merging µcr and µin : Approaches and Results . . . . . . . . . . 63
The φ2 approach . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
The compensated φ2 approach . . . . . . . . . . . . . . . . . . . 67
The compensated φ6 approach . . . . . . . . . . . . . . . . . . . 69
3.4.8 Final Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

4 EPID-based QA Tool 75
4.1 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.1.1 Frame Acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . 76
3D Dose Reconstruction . . . . . . . . . . . . . . . . . . . . . . . 76
Gamma Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.2 Final Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

5 Conclusion and Outlook 87

5.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Optimization of PhSp . . . . . . . . . . . . . . . . . . . . . . . . 87
EPID-based QA Tool . . . . . . . . . . . . . . . . . . . . . . . . . 88
5.2 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Additional measurements, extensive validations and further
approaches . . . . . . . . . . . . . . . . . . . . . . . . . 88
Automated engine . . . . . . . . . . . . . . . . . . . . . . . . . . 89
GitHub repository : phaselab . . . . . . . . . . . . . . . . . . . . 89
Virtual Source Models . . . . . . . . . . . . . . . . . . . . . . . . 89
Machine Learning Kernels . . . . . . . . . . . . . . . . . . . . . . 89
NEAT 2.0 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Bibliography 91

Declaration of Authorship 97
 ix

List of Figures

1.1 A schematic representation of an image classification CNN model. A

and B are multi-dimensional matrices, collectively called the convolu-
tion module. C, D, E and F are non linear functions, collectively called
the classification module. The output for a cat image as an input is 1,
a positive identification of the image. The output for a dog image as
an input is 0, a negative identification of the image. . . . . . . . . . . . 5
1.2 The start interface of NEAT: a clinical tool for EPID-based dosimetry
as part of pre-treatment patient specific QA. . . . . . . . . . . . . . . . . 6

2.1 (A) The first X-ray radiograph: a picture of Anna Bertha Roentgen’s
hand (Deutsches Röntgen-Museum, Remscheid, Germany, Mould, 1995).
(B) Photograph in The Windsor Magazine of April 1896 of a lecture
demonstrating the production of an X-ray radiograph at The Royal
Photographic Society, London, UK (Mould, 1995). . . . . . . . . . . . . 8
2.2 The top plot indicates the behavior of tumor cure or control and nor-
mal tissue necrosis (tissue death) with increasing radiation dose. The
bottom plot indicates a rough estimate of the therapeutic window
which represents the probability of complication free control of dis-
ease (Easson and Pointon, 1985; Steel, 2007). . . . . . . . . . . . . . . . . 9
2.3 A typical X-ray energy spectrum produced in an X-ray tube. The
different curves represent the spectrum produced by varying peak
operating voltage of the X-ray tube, with added filtration of 1-mm
aluminum. The dashed line represents the corresponding unfiltered
energy spectrum. The sudden peaks in the curves are representative
of the characteristic radiation, possessing discrete energies depending
on the orbital transition (Khan and Gibbons, 2014). . . . . . . . . . . . . 11
2.4 X-ray therapy in 1900 using an X-ray tube (Widder, 2014). . . . . . . . 12
2.5 The 8 MeV linear accelerator at Hammersmith hospital, London, UK
with the angle of the beam outlet adjusted to produce a beam directed
vertically downwards. The first linear accelerator to be built specially
for medical use (Howard-Flanders, 1954) . . . . . . . . . . . . . . . . . 13
2.6 (A) The IMRT technique of delivering intensity modulated radiation
from different direction to get a resultant conformal dose at the tumor
volume, as explained in the paper by Brahme, 1988. (B) Multi leaf
collimator manufactured using high attenuation material like tung-
sten. These leaves can be programmed to collimate the beam differ-
entially in different directions, thus making it possible to deliver com-
plex shapes (Bortfeld, 2006). . . . . . . . . . . . . . . . . . . . . . . . . . 14
x

2.7 A picture of an Elekta Synergy R

model installed at Klinikum der
Universität München - Campus Großhadern, Munich, Germany. The
linac head rotates around the patient, forming an arc while deliver-
ing the radiation using advanced modulation techniques. The couch
has multiple degrees of freedom which aids in maximizing the dose
conformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.8 A schematic diagram of Compton effect. An incoming photon of ini-
tial energy hν collides with a stationary electron scattering it at an
angle θ. The photon is deflected by an angle φ in the same plane and
loses a part of its energy to the electron, resulting in a decreased en-
ergy hν0 . The final kinetic energy of the electron is T (Attix, 1986). . . . 16
2.9 (A) The variation of e σtr and e σ with respect to the initial photon en-
ergy hν. (B) The variation of the mean fraction of the total photon en-
ergy transferred to the electron for all scattering angles with respect
to the initial photon energy hν (Attix, 1986). . . . . . . . . . . . . . . . . 17
2.10 A schematic diagram of photoelectric effect. A photon of initial en-
ergy hν on interaction with a bound electron transfers all of its energy
to it. The electron is then ejected out from the atom at an arbitrary
angle (shown here as θ) and the atom, essentially the nucleus, absorbs
the recoil momentum. (Attix, 1986). The final kinetic energy of the
electron is the difference in its binding energy, Eb , and the initial pho-
ton energy. The recoil kinetic energy of the nucleus can be neglected
owing to its high mass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.11 The different atomic cross-sections (in barn) of photoelectric effect for
varying photon energy. Different curves refers to material with dif-
ferent atomic number, lead (Pb) being the highest and hydrogen (H)
being the lowest Z material. The non-differentiable points denoted by
’K’, ’L’ and ’M’ are the peaks of the shell absorption edges. (Podgor-
sak, 2010). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.12 A high energy photon disintegrates into an electron and a positron,
scattered at distinct angles and with possibly distinct kinetic ener-
gies, in the presence of a strong Coulomb force field such as that of
an atomic nucleus. The recoil kinetic energy imparted to the nucleus
is negligible owing to its high mass (Attix, 1986). . . . . . . . . . . . . . 20
2.13 A comparison of triplet to pair production ratios for different gaseous
medium. The ratio decreases with increasing atomic number. The
atomic number of the gases are increasing from top to bottom with
Methane (CH4 ) having the smallest Z, 8 and Argon the highest at 18.
(Evans, 1955). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.14 (A) Regions of relative predominance of the three main forms of pho-
ton interaction with matter in X-ray therapy. The left curve represents
the locus where the probability of an occurrence of photoelectric effect
is equal to that of the Compton effect; the right curve represents the lo-
cus where the probability of an occurrence of Compton effect is equal
to that of the pair production (Podgorsak, 2005). (B) The energy his-
togram, also called energy spectrum, of the X-ray beam used in this
study. The maximum energy is around 6 MeV. . . . . . . . . . . . . . . 23
 xi

2.15 The dependence of mass attenuation coefficient of Compton (µc /ρ),

photoelectric (τ/ρ) and pair production (κ/ρ) on varying photon en-
ergies in lead. The total mass attenuation coefficient is labeled as
(µ/ρ). The peaks labeled ’K’ and ’L’ represent the shell absorption
edges (Podgorsak, 2005). . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.16 A visualization of the internal components of a linac. The magnetron
pumps RF waves into the waveguide which accelerates the electrons
before they hit the target and produces high energy X-rays (How a
Linear Accelerator Works, Elekta 2010). . . . . . . . . . . . . . . . . . . . . 26
2.17 A visualization of the linac waveguide. The inner walls of the cavi-
ties are induced with a current which establishes intense EM fields in
them, accelerating the electron in the forward direction synchronously.
The steering coils control the direction of the beam ensuring that it re-
mains parallel along the guide axis. The focusing coils further define
the beam, focusing it into a very small focal spot (Loverock, 2007; How
a Linear Accelerator Works, Elekta 2010). . . . . . . . . . . . . . . . . . . . 27
2.18 A visualization of the linac head and the patient table. The X-ray
beam (yellow rays) is modified in the linac head. The linac head or
the gantry can rotate around the patient table delivering the beam in
an arc like movement. The patient table also has multiple degrees
of freedom to further aid in the conformity of the dose (How a Linear
Accelerator Works, Elekta 2010). (The X-ray beam is represented as a
yellow radiation only for illustration purposes). The Electronic Portal
Imaging Device, EPID, will be explained in the next section. . . . . . . 28
2.19 Schematic representation of major components of a typical linac (Love-
rock, 2007). Not drawn to scale. . . . . . . . . . . . . . . . . . . . . . . . 29
2.20 The profile of a beam is essentially flattened using a flattening filter. A
beam with a low profile (left) at the edge, relative to the central region,
has a flattened profile in the center after the application of a flattening
filter (right) (Loverock, 2007). . . . . . . . . . . . . . . . . . . . . . . . . 29
2.21 Graphical User Interface of Monaco displaying prostrate treatment
plans. The plots on the top right are dose volume histograms (DVHs).
The different colors are associated to the dose delivered to different
target volumes. The other three plots represent the dose distribution
for different treatment plans for the same patient. The dose level in
different anatomical regions is represented by different colors. Red
represents the region with the highest dose delivery. The DVH can
represent up to three plans by using solid, dashed and dotted lines
(Monaco 2018). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.22 A schematic representation of the major linac components modeled in
MC. Adapted from Seco and Verhaegen, 2016. . . . . . . . . . . . . . . 33
2.23 The mirror is part of an optical system used for reflecting the informa-
tion received from the reflectors on the leaves as a verification mea-
sure. Mylar is a highly reflective material (Loverock, 2007). . . . . . . . 34
2.24 Visualizing the setup model using OpenGl. The interface comes with
a dialog box which can be used to edit the model and run the simula-
tions in real-time. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
xii

3.1 (A) Visual construction of the MC Model used for PDD profiles. (B)
Visual construction of the MC Model used for lateral profiles. The
labeled components in both the models: (a) Detector; (b) Water Phan-
tom; (c) Inline Diaphragm; (d) Crossline MLC; (e) Photon Beam Di-
rection. The model is not drawn to scale. . . . . . . . . . . . . . . . . . . 36
3.2 An example of cropping the original PhSp (on the left) to generate a
cropped PhSp (on the right). The cropping radius is 20 mm which
reduces the simulation time by a factor of 20. . . . . . . . . . . . . . . . 37
3.3 The blue histogram represents the energy spectrum of the original
PhSp. The green histogram represents the energy spectrum of the
manipulated PhSp for which the energy of all the particles has been
increased by 0.2 MeV. The annihilation peak at ∼0.511 MeV remains
undisturbed. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.4 The measured depth dose profiles for all field sizes. All measurements
were performed using a 6 MeV Elekta Synergy R
linac coupled to
Elekta Agility TM collimator (Elekta, Stoockholm, Sweden) in a Blue
Phantom (IBA Dosimetry, Schwarzenbruck, Germany), installed at
Klinikum der Universität München - Campus Großhadern, Munich,
Germany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.5 Well fitted curve using the formula given by Eq. 3.4 (left). The same
plot was erroneously fitted +on using the formula given by Eq. 3.5
(right). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.6 The effect of large energy perturbation to the energy of the particles
within distinct radially symmetric regions of the PhSp is presented.
The PDD profile simulated using a perturbed PhSp is represented by
the purple curve. The PDD profile simulated using the original full
PhSp is represented by the orange curve. Different plots signify the
different radially symmetric regions within which the energy of the
particles was increased by 3 MeV. These regions are: (A) 0 to 5 mm, (B)
5 to 10 mm, (C) 10 to 15 mm, (D) 15 to 20 mm, (E) 20 to 40 mm and for
(F) 40 to 60 mm. The corresponding cost (%) consistently decreased
from ∼466% in (A) to ∼0.73% in (F). . . . . . . . . . . . . . . . . . . . . 43
3.7 Comparison of the PDD profile generated using a cropped PhSp (drawn
in purple) to the PDD profile generated using the full PhSp (drawn in
orange). The cropping radius was 20 mm and the field size used was
10x10 cm 2 . The final cost (%) is determined to be 0.82%. . . . . . . . . 44
3.8 The PDD profiles generated using cropped PhSps with different en-
ergy perturbations. The corresponding cost values (%) between the
measured PDD profile (green curve) and the simulated PDD profile
(red curve) is presented. . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.9 Comparison of the measured PDD profiles to simulated PDD profiles
using the original unperturbed PhSp (left) and the optimized PhSp
(right), for field sizes of 2x2, 5x5, 10x10 and 20x20cm2 . The corre-
sponding cost values (%) are presented together with the curves. All
profiles have been generated using the full PhSp for validation. . . . . 48
3.10 3D visualization of the photon beam. The blue plane represents the
PhSp in the XZ plane. A random particle is located at A on the PhSp
with the total momentum in the direction AB making an angle α with
the beam direction. The beam is traveling in the -Y direction. . . . . . . 49
3.11 Measured inline lateral profiles for field size 10x10 cm2 . The fitting
function used is a sigmoid which will be explained in section 3.4.2. . . 50
 xiii

3.12 A schematic visualization of the geometric penumbra, AB and CD.

These regions receive partial shielding from the collimator assembly.
SCD is the distance of the collimator from the source. The geometri-
cal edge is the ideal edge of the radiation limit for a point source at
the source position along the central axis. f is the distance of the pro-
file plane from the source. The geometric penumbra decreases with
increasing SCD, increasing f and/or decreasing source size. . . . . . . . 50
3.13 A schematic visualization of changing focal spot of the electron beam
size with the change in divergence of the photon beam. Here the focal
spot is in reference to the electron spot. . . . . . . . . . . . . . . . . . . . 51
3.14 Two cases of sigmoid fitting with different fitting periods. The corre-
sponding cost values for k and x0 are shown. . . . . . . . . . . . . . . . 53
3.15 The slope of the beam divergence line, shown in green, is perturbed
by a factor of µ, transforming it to the beam divergence line shown in
red. The Y-intercept value is maintained at c. . . . . . . . . . . . . . . . 54
3.16 The sigmoid fitting parameter, k, for different slope perturbation fac-
tors (blue dots). The red line represents the linear fit to the data. . . . . 58
3.17 The sigmoid fitting parameter, x0 , for different slope perturbation fac-
tors (blue dots). The red line represents the linear fit to the data. . . . . 58
3.18 Fitting Parameter k determined by multiple instances of the same sim-
ulation for different field sizes. . . . . . . . . . . . . . . . . . . . . . . . 59
3.19 Median of the varying fitting parameter k plotted against sets with
different number of instances of the same simulation. . . . . . . . . . . 59
3.20 The spatial configuration of the setup for simulating the lateral pro-
files. The isocenter is at a distance of 1000 mm from the surface. The
medium is a Blue (Water) Phantom (IBA Dosimetry, Schwarzenbruck,
Germany). The source to surface distance is 900 mm. The LMU PhSp
is placed at a distance of 300 mm from the source. The detector for the
lateral profiles is placed at a depth of 15 mm from the surface. (Not
drawn to scale). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.21 The linear correlation of the slope perturbation factor and the sig-
moid fitting parameters are represented by the diagonal red lines.
The green horizontal lines represent the fitting parameters of the mea-
sured crossline profile. The green dot represents the intersection of
both lines, which gives the optimal perturbation factor in the crossline
direction for the field size 10x10 cm2 . The optimized fitting param-
eters are represented by the boxplots in the middle. The final cost
values are mentioned in the bottom left of the plots. . . . . . . . . . . . 63
3.22 (A) A schematic representation of the PhSp plane (the blue circle). The
angular position of a particle on the PhSp is denoted by φ. The pink
shaded region is a visual representation of the degree of relevance
of the particles for the crossline dose profile, as explained in the text
(not shaded to scale). (B) The variation of µop with increasing angular
distance, φ as presented in this section, represented by the thick blue
line. The green and the red horizontal lines are the individual flat
perturbation factors, µcr and µin respectively. . . . . . . . . . . . . . . . 66
3.23 The variation of µop with increasing angular distance, φ as presented
in this section, represented by the thick blue line. . . . . . . . . . . . . . 67
xiv

3.24 The variation of absolute cost with different combinations of µ0cr and
0 . Iteration sequence are just integers denoted to every such combi-
µin
nation. A trade-off between the crossline and the inline cost values is
evident. Iteration sequence 3 represents the last combination enumer-
ated in Table 3.12. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.25 The variation of µop with increasing angular distance, φ as presented
in this section, represented by the thick blue line. The thick pink line is
the variation of µop with increasing angular distance, φ, as presented
in section 3.4.7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3.26 (A) Inline dose profile for a field size 2x2 cm2 before the optimization
of energy. (B) Inline dose profile for a field size 2x2 cm2 after the opti-
mization of energy and momentum. The profile after the optimization
of energy has a lower cost value. . . . . . . . . . . . . . . . . . . . . . . 72
3.27 (A) Percentage Depth Dose profile for a field size 10x10 cm2 before the
optimization of momentum. (B) Percentage Depth Dose profile for a
field size 10x10 cm2 after the optimization of momentum. . . . . . . . . 73

4.1 The accurate positioning of the EPID before the treatment plan is per-
formed as required. The center of the EPID is positioned along the
isocenter axis at a depth of 160 cm from the X-ray source. The green
field is the laser guide which assists in estimating the photon beam
field position. The isocenter axis passes through the intersecting point
of the faint red cross. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.2 (A) The Elekta iViewGT computer, enclosed in the blue rectangle, re-
ceives the frames during the treatment. (B) The frame acquisition ca-
ble is redirected to the EPID computer, shown in the picture, from the
Elekta iViewGT computer, thus effectively redirecting the acquired
frames to the self-contained EPID computer. . . . . . . . . . . . . . . . 78
4.3 The start interface of NEAT. . . . . . . . . . . . . . . . . . . . . . . . . . 78
4.4 Once the reconstruction is complete the DICOM file can be viewed by
clicking on Show Reconstruction. . . . . . . . . . . . . . . . . . . . . . . . 79
4.5 Once the reconstruction is complete the DICOM file can be saved by
clicking on Save DICOM. . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.6 Comparison of the TPS calculated and a NEAT reconstructed dose
distribution of an exemplary treatment plan. The top left and bot-
tom left plots are the coronal plane of the TPS calculated and NEAT
reconstructed dose distributions, respectively. The differently colored
contours stand for different dose percentages. The top right plot is the
1D lateral profile of the corresponding vertical central line in the top
left plot. The bottom right plot is the visual plot of gamma passing
rates for the coronal plane. The red colored regions stand for failing
points with dose values higher than the reference dose values. Here
reference dose value is the TPS calculated dose distribution. The blue
colored regions (not present in the plot) stand for failing points with
dose values lower than the reference dose values. . . . . . . . . . . . . 81
 xv

4.7 (A) A comparison of the 1D dose profile of the TPS calculation (drawn
in orange) and the reconstruction (drawn in blue) in the coronal plane
for an exemplary treatment plan. (B) A misalignment in the TG direc-
tion is corrected and the blue plot shifts to the right by 3.6 mm. This
represents the TG factor. (C) The misalignment in the absolute dose
values is corrected and the blue plot is raised by 3%. This represents
the NF. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
 xvii

List of Tables

1.1 A study carried out by International Agency for Research on Can-

cer in 2015 revealed that malignant neoplasms (cancerous tumor) was
the second leading cause of death in high income countries and third
leading in low and middle income countries in 2012 (Global Cancer
Facts & Figures 3rd Edition. 2015). . . . . . . . . . . . . . . . . . . . . . . 1
1.2 The results of a study performed by Delaney et al., 2005 which enu-
merates the proportion of patients receiving radiotherapy as com-
pared to the location of the tumor. The proportion of all cancer pa-
tients for whom radiotherapy is preferred has been estimated to be at
least 52%. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

2.1 A survey done in 1986 recording the number of radiation therapy

units in United States and worldwide (Robison, 1995). . . . . . . . . . . 12
2.2 Information stored in the PhSp . . . . . . . . . . . . . . . . . . . . . . . 33

3.1 The initial and final cost values for the optimization of energy. The
simulated PDD profiles were generated using the full PhSp. . . . . . . 46
3.2 The initial and final cost values for the inline lateral profile after the
optimization of energy for field size of 2x2, 5x5, 10x10 and 20x20 cm2 . . 46
3.3 The initial and final cost values for the crossline lateral profile before
and after the optimization of energy for field size of 2x2, 5x5, 10x10
and 20x20 cm2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.4 The Sigmoid Fitting Parameters . . . . . . . . . . . . . . . . . . . . . . . 52
3.5 The Linear Fitting Parameters . . . . . . . . . . . . . . . . . . . . . . . . 52
3.6 The arithmetic progression of the perturbation factor with respect to
the sequence of simulation. . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.7 Comparing the inline fitting parameters determined using a cropped
PhSp and the full PhSp. . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.8 Comparing the crossline fitting parameters determined using a cropped
PhSp and the full PhSp. . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.9 Results of the crossline profile (corresponding to fitting parameter k)
following the methodology, explained in the previous section 3.4.6.
∆Cost written in green represents a drop in cost and in red represents
a gain in cost . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.10 Initial cost values for inline and crossline profiles as reference. . . . . . 64
3.11 Results of the crossline profile for φ2 approach. ∆Cost written in green
represents a drop in cost and in red represents a gain in cost. . . . . . . 65
3.12 Cost values for different combinations of µ0cr and µin 0 . ∆Cost written

in green represents a drop in cost and in red represents a gain in cost. . 68

3.13 Final cost values of the best performing approach, compensated φ6 ,
for field sizes 2x2, 5x5, 10x10 and 20x20 cm2 using the full PhSp. ∆Cost
written in green represents a drop in cost and in red represents a gain
in cost. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
xviii

3.14 Final cost values of the crossline profiles for the best performing ap-
proach, compensated φ6 , generated for field sizes 2x2, 5x5, 10x10 and
20x20 cm2 using the full PhSp as compared to the initial cost values
before the optimization of energy and momentum. The initial cost
values before the optimization of energy can be obtained from Table
3.3. ∆Cost written in green represents a drop in cost and in red repre-
sents a gain in cost. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.15 Final cost values of the inline profiles for the best performing ap-
proach, compensated φ6 , generated for field sizes 2x2, 5x5, 10x10 and
20x20 cm2 using the full PhSp as compared to the initial cost values
before the optimization of energy and momentum. The initial cost
values before the optimization of energy can be obtained from Table
3.2. ∆Cost written in green represents a drop in cost and in red repre-
sents a gain in cost. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.16 Optimal perturbation factors determined using PhSp cropped with
different cropping radii. . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

4.1 (3%, 3 mm) gamma index evaluation for the NEAT reconstructed dose
distribution for 22 treatment plans. NF stands for normalization fac-
tor. TG corrected implies that the reconstruction has been shifted by
3.6 mm in the -Z direction to correct for the EPID positioning discrep-
ancy. Passing rates highlighted in green represent values greater than
95%. Yellow represents passing rates between 80% and 95%. Red
represents passing rates below 80%. TP stands for Treatment Plan.
The reconstructions which had achieved a passing rate higher than
the threshold was not corrected further using NF 8%, as a higher NF
produced a worse passing rate. . . . . . . . . . . . . . . . . . . . . . . . 83
4.2 (2%, 2 mm) and (1%, 1 mm) gamma index evaluation for the NEAT
reconstructed dose distribution for the the 5 best performing recon-
structions. Passing rates highlighted in green represent values greater
than 95%. Yellow represents passing rates between 80% and 95%. Red
represents passing rates below 80%. . . . . . . . . . . . . . . . . . . . . 84
 xix

Physical Constants

Speed of Light c = 2.997 924 58 × 108 m s−1 (approx)

Electron rest mass mo = 9.109 × 10−31 kg (approx)
Planck’s constant h = 6.626 070 04 × 10−34 m2 kg/s (approx)
 1

Chapter 1

Introduction

Cancer is the uncontrolled growth and spread of cells that arises from a gene muta-
tion. This mutation may have been caused by dietary habits, genetic factors and/or
environmental factors. The transformation of a healthy cell into a cancerous cell can
eventually lead to tumors which can metastasize to other parts of the body (Cassidy
et al., 2015). Such an abnormal growth if not controlled can lead to death. A study
performed by the International Agency for Research on Cancer (Global Cancer Facts
& Figures 3rd Edition. 2015) reveals that cancer is the second leading cause of death
in high income countries and the third leading in low and middle income countries,
as can be seen in Table 1.1. There will be an estimated 18.1 million new cancer cases
and 9.6 million cancer deaths in 2018 (Bray et al., 2018). Globally, about 1 in 6 deaths
has been due to cancer (Cancer, Key facts 2018). Thus, cancer treatment has become
the focus of many growing areas of research.

TABLE 1.1: A study carried out by International Agency for Research

on Cancer in 2015 revealed that malignant neoplasms (cancerous tu-
mor) was the second leading cause of death in high income countries
and third leading in low and middle income countries in 2012 (Global
Cancer Facts & Figures 3rd Edition. 2015).
2 Chapter 1. Introduction

1.1 External Beam Therapy in Cancer Treatment

According to a study performed by Delaney et al., 2005, the ideal proportion of can-
cer patients that should be treated using external beam therapy, at least once during
the entire course of their illness, based on the available statistical data is presented
in Table 1.2. It suggests that the proportion of cancer patients for whom external
beam therapy is preferred is at least 52%. These optimal proportions depend on the
type and location of cancer which can be as high as 92% in few cases, such as a tumor
located in the central nervous system. This indicates the high demand of external ra-
diotherapy in the field of cancer treatment and the growing need of improved dose
delivery with high accuracy and efficiency.

TABLE 1.2: The results of a study performed by Delaney et al., 2005

which enumerates the proportion of patients receiving radiotherapy
as compared to the location of the tumor. The proportion of all cancer
patients for whom radiotherapy is preferred has been estimated to be
at least 52%.
1.2. MC Techniques in External Beam Therapy 3

1.2 MC Techniques in External Beam Therapy

Monte Carlo (MC) techniques offer powerful numerical solutions to problems with
a high number of parameters. These techniques have been proven mathematically
to be far more accurate than analytical algorithms (Seco and Verhaegen, 2016) and
have thus gained immense popularity in radiotherapy.
The earliest works of applying MC simulations to optimize photon beams for
the improvement of linear accelerator (linac) design include the pioneering paper by
McCall, McIntyre, and Turnbull, 1978. Eventually these simulations were employed
to optimize the electron target model responsible for the production of bremsstrahlung
photons (Bielajew, 1989; Faddegon et al., 1990). A crucial realization in this study
was the correlation between the spot size of the electron beam and the correspond-
ing dose distributions (Munro, Rawlinson, and Fenster, 1988; Jaffray et al., 1993). The
rest of the model in the beam downstream was also studied to analyze its influence
on the photon beam. The flattening filter and the backscatter into the monitor-ion
chamber had a major influence on the machine output and was studied extensively
by Mohan, Chui, and Lidofsky, 1985 and Liu, Mackie, and McCullough, 1997 re-
spectively. The complete linac modeling was then implemented by Bednarz and Xu,
2009; Rodriguez et al., 2015 and Lin, Chu, and Lin, 2001 among many others. Fur-
thermore, with the increase in computation power the calculation times taken in the
assessment of absorbed dose greatly improved as presented in a study performed
by Chetty et al., 2007.
An assessment of their applicability in dosimetry and imaging has been compre-
hensively presented in Sarrut et al., 2014. Thus, MC simulations have proven to be
exceptionally useful in determining the absorbed dose in the patient accurately and
efficiently.

1.2.1 Complications with Linac MC modeling

The objective of the complete project, of which this study is a part of, was to model
a 6 MeV Elekta Synergy R
linac coupled to Elekta AgilityTM collimator installed at
Klinikum der Universität München - Campus Großhadern, Munich, Germany using
the MC simulation toolkit, Geant4.
The accurate modeling of linacs in MC requires detailed knowledge of almost all
of its components. This includes the exact spatial positions and motion along with
their dimensions, material densities and alloy compositions. However, these details
are often commercial secrets and are not disclosed by vendors, in most cases. Thus,
a faithful MC model of a linac is difficult to implement.
The validation of such models is extensive and a myriad of simulated profiles
in different directions and positions are compared with the corresponding measure-
ments. Such a validation procedure has been presented in published papers like
Chaney, Cullip, and Gabriel, 1994, Ding, 2002 and Bencheikh et al., 2017. Once a
MC model of a specific linac has been validated, it can be used to generate PhSp files
positioned anywhere along the beam. Optionally, these files can be submitted to
IAEA for commissioning. Once commissioned, they can be published on the IAEA
website (Capote, 2011).
These PhSp files are used as a surrogate in the modeling of different linac models.
The PhSp file of 6 MeV Elekta Synergy R
is not available on the IAEA website and
thus the modeling of the entire linac is needed.
4 Chapter 1. Introduction

1.2.2 Optimization of PhSp

As the PhSp file of 6 MeV Elekta Synergy R
is not available on the IAEA website, a
second approach could be manipulating an available PhSp and optimizing it for the
Synergy model.
The goal of this study was to manipulate the information in the commissioned
PhSp file of a 6 Mev Elekta Precise, as available on the IAEA website, and optimize
it for a 6 MeV Elekta Synergy R
. The study has since evolved into an investiga-
tory work to create generalized methodologies for manipulation of commissioned
PhSp file of one linac model to optimize it for another model. The basic approach
was to find statistical correlations between the information held by the PhSp and the
corresponding simulation results. This was done by manipulating this information
first randomly and observing the changes reflected in the simulation results. Once
a correlation had been identified, the information was then manipulated under su-
pervision to bring these results closer to the measurements.
The initial hypothesis was that these statistical correlations existed. The inspi-
ration behind forming such a hypothesis was the impressive success of convolution
neural networks (CNN) in image classification as presented in innumerable pub-
lished works (Krizhevsky, Sutskever, and Hinton, 2012; Cireşan et al., 2011).
CNN is an ongoing research in the field of Artificial Intelligence. It is inspired by
the functioning of neurons in the brain and how learning happens in living beings
(Koushik, 2016). A basic example of an image classification CNN model has been
explained in Fig.1.1. A and B are multi dimensional matrices. The input image of
the cat is converted into a 2D matrix of its pixel values. This is then convolved with
A. The output is convolved with B and the resulting values are fed into C, D and
E. These circles represent non linear functions. The final function F gives a binary
output thus classifying the image as a cat. A, B, C, D, E and F collectively form
the CNN model. These models can be much more complex with multiple convo-
lution and classification layers with different network architectures. They are first
trained using a collection of already classified images. During the training process,
the values in the matrices are adjusted using gradient descent and back propagation
(Cui, 2018). Such a mathematical model has produced impressive results in recent
years (Yu, Jia, and Xu, 2017; Gao et al., 2017). Achieving similar results employing
analytical algorithms is incomprehensible.
Manipulating the information inside the PhSp is analogous to manipulating the
values in the matrices of the CNN model. Furthermore, an image classification prob-
lem is mathematically much more complex because of weak correlations between
the final result (the output from F in Fig. 1.1) and the input. Whereas, it was con-
ceivable that much stronger correlations between the PhSp and the dose distribu-
tions existed and hence was an interesting field of inquiry.
1.3. EPID Dosimetry in External Beam Therapy 5

F IGURE 1.1: A schematic representation of an image classification

CNN model. A and B are multi-dimensional matrices, collectively
called the convolution module. C, D, E and F are non linear func-
tions, collectively called the classification module. The output for a
cat image as an input is 1, a positive identification of the image. The
output for a dog image as an input is 0, a negative identification of
the image.

1.3 EPID Dosimetry in External Beam Therapy

During the dose delivery in external beam therapy, it is crucial that the correct
anatomical site of the patient is radiated to ensure maximal conformity. Tradition-
ally, radiographic films were used to verify the patient position. This process was
time consuming and the information on the film was only useful for a short period
of time as the position of the patient is not truly static. Electronic Portal Imaging
Devices (EPIDs) were developed to provide instantaneous verification of the patient
position. They are essentially flat panel detectors with sub-mm resolution, attached
at the bottom of the linac gantry which receives the radiation transmitting through
the patient. This radiation is acquired in the form of images, hereon referred to as
EPID frames. These frames are used to verify the patient position before the dose is
delivered (Mubata, 2007).
Owing to the high pixel resolution of EPID and fast frame response, its capability
in pre-treatment dosimetric verifications was also investigated. The past decade has
seen a growing interest in reconstructing 3D dose distribution at the patient position
using the information stored in the EPID frames, as presented in Alhazmi et al.,
2018; Han et al., 2017 and Nijsten et al., 2007. These reconstructed dose distributions
can be compared to the planned dose distribution as a pre-treatment patient specific
plan verification. In this study a Graphical User Interface (GUI) was created, as a
clinical tool, to reconstruct 3D dose distribution as imparted to a water equivalent
medium using the reconstruction algorithm developed by Alhazmi et al., 2018.

1.3.1 Novel EPID-based Audit Tool

For the purpose of creating a clinical tool to verify the planned dose distributions of
treatment plans, a compact GUI, Novel EPID-based Audit Tool (NEAT) was devel-
oped. The start interface of NEAT is shown in Fig. 1.2. This tool is intended to be a
part of the pre-treatment Quality Assurance (QA) procedure routinely performed in
6 Chapter 1. Introduction

clinical practices. The reconstruction algorithm used in NEAT has been provided by
Alhazmi et al., 2018.
In this study 22 Volumetric Arc Therapy (VMAT) treatment plans were per-
formed on a 6 MeV Elekta Synergy R Linac coupled to Elekta AgilityTM collima-
tor (Elekta, Stoockholm, Sweden) installed at Klinikum der Universität München -
Campus Großhadern, Munich, Germany. A PerkinElmer XRD 1640 AL5 P aSi EPID
(Elekta iVewGT) mounted at source to surface distance of 160 cm was used for in air
frame acquisitions of the treatment plans. The frames acquired were then used to
reconstruct 3D dose distributions as imparted to a water equivalent medium. These
reconstructions were compared to the planned dose distributions, calculated by the
Treatment Planning System using a gamma evaluation with a (3%, 3 mm) criteria for
the purpose of testing the tool and auditing the reconstruction algorithm.

F IGURE 1.2: The start interface of NEAT: a clinical tool for EPID-
based dosimetry as part of pre-treatment patient specific QA.
 7

Chapter 2

Scientific Background

2.1 Introduction to Radiation Therapy

Radiological physics is the science of ionizing radiation and its interaction with mat-
ter, the prime interest being the energy thus absorbed in the interacting medium
(Attix, 1986). Radiation therapy is primarily the application of radiological physics
in the field of cancer treatment to destroy cancerous cells (Baskar et al., 2012). The
birth of radiation therapy can probably be traced back to a singular event in history,
the discovery of X-rays.

2.1.1 Discovery of X-rays

The discovery of X-rays by Wilhelm Conrad Röntgen in November 1895 marked the
onset of Radiological Physics (Attix, 1986). He was working with a cathode-ray tube
in his laboratory at Würzburg University, Germany, when he observed the presence
of a green fluorescent light being generated by a material a few feet away from the
tube, despite the tube being covered by a black paper. He then deduced that a ra-
diation was being emitted from inside the tube itself and was exciting the material
which was then producing the green fluorescent light. He discovered that this ra-
diation could pass through many objects. However, it was not able to transverse
through some objects like bone or metal. His first experiment in 1895 was the fa-
mous X-ray photograph of his wife’s hand as shown in Fig. 2.1 (A). In December
1895, Röntgen submitted his findings to the Würzburg’s Physical-Medical Society
journal in which he referred to the radiation as X. These radiations were eventually
coined as X-rays. Lectures and demonstrations to spread the knowledge of X-rays
were held in Europe and United States (Fig. 2.1 (B)). Within an year of this discovery,
physicians in the two continents were using it routinely in diagnostic radiography.
For this significant contribution to science, Röntgen was awarded the 1901 Nobel
Prize for Physics (Reed, 2011; Mould, 1995).

2.1.2 Origin of Dosimetry

In the subsequent years two significant discoveries were made. Radioactivity was
discovered by Henri Becquerel in 1896, and Marie Sklodowska Curie and Pierre
Curie discovered Radium in 1898. For their respective discoveries, Becquerel, Marie
Curie and Pierre Curie collectively received the 1903 Nobel Prize for Physics (Reed,
2011). Their work contributed to the rate at which the use of radiation in biologi-
cal treatments was increasing. However, without adequate radiation protection the
harmful effects of the radiation, like skin erythema and epilation were beginning to
be recognized (Lederman, 1981). The effect of ionizing radiation on human skin was
8 Chapter 2. Scientific Background

(A) (B)

F IGURE 2.1: (A) The first X-ray radiograph: a picture of Anna

Bertha Roentgen’s hand (Deutsches Röntgen-Museum, Remscheid,
Germany, Mould, 1995). (B) Photograph in The Windsor Magazine
of April 1896 of a lecture demonstrating the production of an X-ray
radiograph at The Royal Photographic Society, London, UK (Mould,
1995).

also documented when Bequerel carried a tube of pure radium in his pocket. Af-
ter 15 days, a severe burn underneath this particular pocket developed which was
deduced to be due to the effect of radium. These events indicated the need of analyz-
ing the biological effects of the radiation in human tissue. Radiation dose was thus
defined as the quantified energy deposited by radiation to matter. Dosimetry deals
with formation and validation of methods and procedures to measure the radiation
dose and its correlation with biological effectiveness. Over the years, efforts were
made to introduce suitable dosimetric concepts and conventions associated to strict
physical definitions. The current SI dosimetric quantity for dose is Gray, abbreviated
as Gy. Its equivalent relationship in energy units is Joules per kilogram (Ma, 2014;
Parodi, 2017). This is directly correlated to the biological effectiveness of ionizing
radiation.

2.1.3 Biological Effects

The main goal of radiation therapy is to kill cancerous cells, while preserving sur-
rounding healthy cells. A cell can be killed by ionizing radiation via two distinct
mechanisms. The first is interphase cell death, also called apoptis, caused due to
direct radiation damage. This involves the perishing of the cell within few hours
of irradiation as a programmed cell death or during a mitotic (to undergo division)
attempt (Eriksson and Stigbrand, 2010). The second mechanism is a damage to the
DNA caused by the radiation which renders the cell incapable of undergoing mi-
tosis. A cell damaged by such a mechanism dies naturally after completing its life
cycle. Moreover, as it does not proliferate, its occurrence is controlled (Little, 2003).
Biological effect is characterized by the cell survival rate, which decreases with
increasing radiation dose. Correspondingly, the probability of cell damage, regard-
less of its health, increases with increasing radiation dose. This relationship follows
a sigmoid as can be seen in the top plot of Fig. 2.2. The healthy cells do not en-
tirely escape from radiation damage. However, a higher radiation dose is needed to
produce the same biological effect in a healthy cell as compared to a cancerous one.
2.2. X-rays 9

This difference creates a therapeutic window as presented in the bottom plot of Fig.
2.2. It is a bell-shaped curve which represents the probability of complication free
control of disease. This therapeutic window enables the use of ionizing radiations
in cancer treatment (Steel, 2007).

F IGURE 2.2: The top plot indicates the behavior of tumor cure or con-
trol and normal tissue necrosis (tissue death) with increasing radia-
tion dose. The bottom plot indicates a rough estimate of the thera-
peutic window which represents the probability of complication free
control of disease (Easson and Pointon, 1985; Steel, 2007).

2.2 X-rays
The term radiation is referred to the propagation of energy through space or a medium.
Radiations which are characterized by their pronounced capability of ionizing the
atoms of the interacting medium are referred to as ionizing radiation. The ICRU (In-
ternational Commission on Radiation Units and Measurements, 1971) recommends
two broad classifications of ionizing radiation, on account of the grossly distinct in-
teractions of charged and uncharged particles with matter (Attix, 1986):
10 Chapter 2. Scientific Background

• Directly Ionizing Radiation: This includes radiation composed of charged par-

ticles like electrons, protons or heavy ions. They deliver their energy to the
interacting medium via direct interactions.
• Indirectly Ionizing Radiation: This includes radiation composed of electrically
neutral particles, like photons or neutrons, which transfer their energy to the
medium in a two step process. They first transfer their energy to charged par-
ticles which then eventually transfer it to the medium. X-rays belong to this
classification.

2.2.1 Production of X rays

The practical generation of X-ray for radiotherapy involves accelerating an electron
beam and letting it strike a metallic target (Attix, 1986). The basic setup includes
a cathode and an anode in a sealed vacuum tube. The cathode is usually a tung-
sten filament, that when heated by passing a current through it, emits electrons via
thermionic emission. The electrons thus produced are then accelerated towards the
anode, composed of a high atomic number metal. This energetic beam of electrons
strikes the anode, also called the X-ray target, and produces two known types of X-
rays, Bremsstrahlung and Characteristic (Greener, 2007; Khan and Gibbons, 2014).
A more detailed explanation of this setup involving modern techniques is explained
in section 2.3.
The two types of radiations are briefly explained as follows:

• Bremsstrahlung X-rays, also called braking radiation, are produced when an

energetic electron is deflected from its path, upon Coulomb interactions with
the nuclei of the atoms of the target (anode). This interaction results in a loss
of the electron energy which is radiated as Bremsstrahlung X-rays (Podgorsak,
2010; Khan and Gibbons, 2014).
• Characteristic radiation is produced when an electron, with energy above a
threshold, collides inelastically with a bound electron and ejects it out from
the atom. This threshold energy level depends on the atomic number of the
interacting nuclei and the shell from which the ejected electron is removed.
The created vacancy in the orbit is filled by the fall of an outer shell electron.
When this electron transitions from an outer shell to an inner shell, it loses
energy in form of radiation, called characteristic radiation. These radiations
are characteristic to the orbital transition of the electron and are emitted at
discrete energies. This implies that the energy of the emitted photon strictly
depends on the difference in the binding energies of the shell it falls down
from and the shell it falls into (Podgorsak, 2010; Khan and Gibbons, 2014).

The energy spectrum of the X-rays produced is heterogeneous and continuous,

as presented in Fig. 2.3. This spectrum is a superposition of the individual energy
spectrum of the two radiations. The peaks in the continuous curves are representa-
tive of the characteristic radiation energy. As mentioned before, the energy of this
radiation is in discrete form depending strictly on the shell transition.
The radiation thus produced is usually filtered using a metal layer. The most
common choices for this layer are lead, tin, copper, and aluminum, which may be
used individually or in combination (Attix, 1986) depending on the desired resulting
spectrum. The primary purpose of adding filtration is to enrich the beam by absorb-
ing the low energy photons. This hardens the beam and increases its penetration
depth (Khan and Gibbons, 2014).
2.2. X-rays 11

If no filtration is added in the path of the generated beam, the energy spectrum
for the bremsstrahlung radiation will be a continuous straight line, as represented
by the dotted line in Fig. 2.3. It is given by the Kramer’s equation, Eq.(2.1).

IE = KZ ( Em − E) (2.1)

Here, IE is the intensity of the photon with energy E, Z is the atomic number of
the target, Em is the maximum photon energy and K is a constant. The maximum
possible energy a photon can acquire is equal to the energy of the incident electron
which indirectly or directly produces it. The maximum energy of the electron is
determined by the peak operating voltage of the X-ray tube. Thus, on increasing
the potential difference between the two electrodes, the energy of the electron beam
can be increased, effectively increasing the energies of the photons produced. This
changes the shape of the spectrum as can be seen in Fig. 2.3. The upper curves cor-
respond to the X-ray energy spectrum produced by a relatively higher peak voltage,
or excitation voltage, applied to the electrodes of the X-ray tube (Khan and Gibbons,
2014).

F IGURE 2.3: A typical X-ray energy spectrum produced in an X-ray

tube. The different curves represent the spectrum produced by vary-
ing peak operating voltage of the X-ray tube, with added filtration of
1-mm aluminum. The dashed line represents the corresponding un-
filtered energy spectrum. The sudden peaks in the curves are repre-
sentative of the characteristic radiation, possessing discrete energies
depending on the orbital transition (Khan and Gibbons, 2014).

A historical perspective of X-rays production for Radiation Therapy

The original apparatus used in the production of X-rays was essentially composed
of a glass tube with two metal electrodes on each side. The treatment was done by
keeping such a device in proximity to the area being treated without any radiation
protection as demonstrated in Fig. 2.4 (Nascimento, 2014).
The first linear accelerator (linac) was conceptualized by Gustaf Ising, a Swedish
physicist in 1924 and then later implemented as a ’proof of principle’ by Rolf Wideröe,
a Norwegian physicist in 1928 (Bryant, 1994). The electron accelerators were trans-
formed into 600-900 KV X-ray therapy machine, later achieving 1 MV by 1937-1939.
12 Chapter 2. Scientific Background

F IGURE 2.4: X-ray therapy in 1900 using an X-ray tube (Widder,

2014).

It also marked a transitional period when giant particle accelerators were beginning
to be constructed (Slater, 2012; Robison, 1995; Hefner, 1996).
One of the earliest recorded treatment using a 1 MV X-ray beam was performed
in 1937. It was delivered by a 1 MV tube and a Van De Graaff generator unit, which
was available for treatment at the Collis P. Huntington Memorial Hospital in Boston.
A Van de Graaff generator is based on the concept of accumulating charge on the in-
side of a hollow metal sphere, insulated from the surroundings, using a moving belt.
This was capable of generating very high potentials which then produced high en-
ergy X-rays (Graaff et al., 1933). The patient who was treated with the generator was
recorded to have outlived the Boston hospital, which closed in 1941 (Robison, 1995).
Although, treatments with a Megavoltage X-ray beam was principally possible us-
ing such generators, it escalated with the advent of Cobalt 60 (Co-60) as a radiation
source which was comparatively much more stable than the other isotopes of Co and
had a long half-life of approximately 5.3 years. It produces γ-rays in the range of 1 to
1.3 MV. In 1951 the first clinical treatment using Co-60 γ-rays was performed, at the
Victoria Hospital in London, Ontario, Canada (Robison, 1995; London Health Sciences
Centre 2011). A survey done in 1986 by the American College of Radiology shows
the notable presence of Co-60 therapy units in cancer treatment (Robison, 1995), as
presented in Table 2.1.

TABLE 2.1: A survey done in 1986 recording the number of radiation

therapy units in United States and worldwide (Robison, 1995).
2.2. X-rays 13

The first clinical linac was installed for the Medical Research Council at Ham-
mersmith Hospital, London, UK. It was an 8 MeV machine attached to the ceiling
with exceedingly limited degree of freedom as can be seen in Fig. 2.5.

F IGURE 2.5: The 8 MeV linear accelerator at Hammersmith hospital,

London, UK with the angle of the beam outlet adjusted to produce
a beam directed vertically downwards. The first linear accelerator to
be built specially for medical use (Howard-Flanders, 1954)

By mid 1950s, high energy X-rays were routinely employed in clinical treatments
for deep seated tumors owing to their increased penetration depth. However, as
high energy meant a higher dose delivery, the need of conforming the radiation to
the site of the tumor while sparing the surrounding healthy tissues emerged. This
brought the advent of three dimensional conformal radiation therapy techniques
(3D CRT). In this technique the radiation dose was delivered from multiple beam
angles, using stationary collimators to produce different beam shapes, thus deliver-
ing a relatively more conformal dose at the site of the tumor. The paper by Brahme,
Roos, and Lax, 1982 proved to be a cornerstone for Intensity Modulated Radiation
Therapy (IMRT), an advanced 3D CRT technique. The paper presented a mathemat-
ical solution of an integral, which resulted in the absorbed dose distribution during
a single 360-degree rotation of the beam delivery angle.
The IMRT technique uses multiple beams in different directions. The intensity
of the beam is modulated during the irradiation of the tumor thus delivering a very
conformal dose at the tumor volume as presented in Fig. 2.6 (A). The intensity is
14 Chapter 2. Scientific Background

modulated using a Multi Leaf Collimator (MLC) as shown in Fig. 2.6 (B) which
collimates it into complex shapes (Bortfeld, 2006).

(A) (B)

F IGURE 2.6: (A) The IMRT technique of delivering intensity mod-

ulated radiation from different direction to get a resultant conformal
dose at the tumor volume, as explained in the paper by Brahme, 1988.
(B) Multi leaf collimator manufactured using high attenuation mate-
rial like tungsten. These leaves can be programmed to collimate the
beam differentially in different directions, thus making it possible to
deliver complex shapes (Bortfeld, 2006).

By 2000, IMRT was considered to be one of the most advanced radiation tech-
niques for high energy X-ray photon therapy. Around 2008, Volumetric Arc Ther-
apy (VMAT), a novel delivery technique, was introduced. This technique was an
improvement over IMRT delivering the radiation with a 360-degree continuous ro-
tation of the gantry around the patient. The conventional IMRT treatments, how-
ever required the rotation of the gantry several times and/or with repeated starts
and stops, thus increasing the delivery time. One of the earliest study using VMAT
was done by Palma et al., 2008. In this study, the conformity of the treatment plans
of a VMAT was compared to that of an IMRT and a conventional 3D CRT. The re-
sults showed that IMRT and VMAT were significantly much more conformal in their
dose deliveries as compared to 3D CRT. The work published in the paper by Teoh
et al., 2011 compares two dose distributions achieved using VMAT and conventional
IMRT showing that VMAT has a superior conformity. Fig. 2.7 shows a commercial
Elekta Synergy R
linear accelerator, installed at Klinikum der Universität München -
Campus Großhadern, Munich, Germany. It is capable of performing treatment using
advanced delivery techniques including IMRT and VMAT.
2.2. X-rays 15

F IGURE 2.7: A picture of an Elekta Synergy R

model installed at
Klinikum der Universität München - Campus Großhadern, Munich,
Germany. The linac head rotates around the patient, forming an
arc while delivering the radiation using advanced modulation tech-
niques. The couch has multiple degrees of freedom which aids in
maximizing the dose conformity.

2.2.2 Interaction of X-ray photons with matter

There are five types of X-ray photon interactions with matter which are of prime
interest in radiotherapy:

1. Compton effect

2. Photoelectric effect

3. Pair production

4. Rayleigh scattering

5. Photonuclear interactions

The photon first transfers energy to secondary particles, electrons, of the medium
with which they are interacting via any of the first three interactions. These electrons
then deposit some or all of its energy to the medium via Coulomb force interactions
along their path of travel. The first three interactions are thus crucial for the use of
X-ray in therapy. In Rayleigh interaction, a photon trajectory is deflected without
any change in its energy, therefore, no energy is release in the material. Photonu-
clear interactions are observed for photons with energy above few MeV and are not
relevant for the photon energies dealt in this study. In such interactions, the high
energy photon is absorbed by the nucleus and a proton or a neutron is emitted. The
resulting nucleus is radioactive (Attix, 1986).

Compton effect
In Compton effect, an unbound electron is struck by an incoming photon, scattering
it at an angle. The photon transfers some of its energy to the electron and is deflected
by an angle from its initial path. The scattering angles and the final energies of the
electron and the photon can be solved using the kinematic law of conservation of
energy and momentum. These final quantities are dependent on the initial energy of
16 Chapter 2. Scientific Background

F IGURE 2.8: A schematic diagram of Compton effect. An incoming

photon of initial energy hν collides with a stationary electron scatter-
ing it at an angle θ. The photon is deflected by an angle φ in the same
plane and loses a part of its energy to the electron, resulting in a de-
creased energy hν0 . The final kinetic energy of the electron is T (Attix,
1986).

the photon. The resulting solutions are presented in Eq. (2.2), (2.3) and (2.4), where
hν and hν’ is the initial and final energy of the photon respectively and T is the final
kinetic energy of the scattered electron. θ and φ are the scattering angles for the
electron and the photon respectively. mo c2 is the electron rest energy. A schematic of
the Compton interaction is depicted in Fig. 2.8.

hν
hν0 = (2.2)
1 + ( mhνc2 )(1 − cosφ)
0
0
T = hν − hν (2.3)
hν φ
cotθ = (1 + 2
)tan (2.4)
m0 c 2

There are two quantities of interest. The first is the probability of the occurrence
of a Compton interaction which is given by the scattering cross section. The second
is the average fraction of the incident energy transferred to the electron. The dif-
ferential cross-section for an interaction between a photon and a single free electron
de σ
per unit solid angle ( dΩ φ
) is given by the Klein-Nishina (K-N) formula, as can be
referred from Eq. (2.5). Here, hν is the initial photon energy, φ is the scattering angle
of the photon, r0 is the classical electron radius, which is equal to 2.818 × 10−13 cm
(Attix, 1986; Podgorsak, 2010) and dΩφ is the differential solid angle for the photon
scattering angle φ.

2 
r2 hν0 hν0
 
de σ hν
= 0 0
+ − sin2 φ (2.5)
dΩφ 2 hν hν hν

The total electronic cross-section, e σ, for the photon interaction with a single elec-
tron is calculated by integrating this differential equation for all photon scattering
angles. The final value is dependent on the initial energy of the photon hν. The
variation of the cross-section with respect to different photon energies is presented
2.2. X-rays 17

graphically as the upper curve in Fig. 2.9 (A). Furthermore, this cross-section is in-
dependent of Z, thus, the total atomic cross-section is proportional to the atomic
number, Z, of the interacting matter.

aσ ∝Z (2.6)

The proportionality presented in Eq. 2.6 will be revisited later in this chapter when
X-ray beam attenuation is explained (section 2.2.3).
The fraction of the photon energy transferred to the electron is of prime interest
as it indirectly effects the amount of dose deposited in the medium. For a single
T
electron, this fraction can be written as hν . Thus, the differential cross-section for
energy transfer is given by Eq. (2.7). The total cross-section for energy transfer to a
single electron (e σtr ) is then calculated by integrating it over all scattering angles. It
is graphically shown as the bottom curve in Fig. 2.9 (A). Finally the average fraction
of the total photon energy imparted to the electrons is calculated by using eq. (2.8).
The variation of this fraction with respect to different hν values is shown in Fig. 2.9
(B).

de σtr de σ T
= · (2.7)
dΩφ dΩφ hν
T̄ e σtr
= (2.8)
hν eσ

(A) (B)

F IGURE 2.9: (A) The variation of e σtr and e σ with respect to the initial
photon energy hν. (B) The variation of the mean fraction of the total
photon energy transferred to the electron for all scattering angles with
respect to the initial photon energy hν (Attix, 1986).

Thus, it can be observed that the fraction of the energy imparted to the electrons
increases with increasing initial photon energy, hν for given cross-sections, e σtr and
e σ.

Photoelectric effect
The photoelectric effect is essentially an absorption of a photon by a bound electron.
The photon instead of transferring only a part of its energy, like in Compton effect,
imparts all of its energy to a bound electron and ceases to exist. The electron is then
ejected from the atom at an angle and the nucleus absorbs the recoil momentum as
18 Chapter 2. Scientific Background

shown in Fig. 2.10 (Attix, 1986). The final kinetic energy of the nucleus is negligible
owing to its higher mass.
The photoelectric effect only occurs if the energy of the incoming photon, hν, is
greater than the binding energy of the electron, Eb . The difference of the two energies
is the resultant kinetic energy, T, of the ejected electron.

F IGURE 2.10: A schematic diagram of photoelectric effect. A photon

of initial energy hν on interaction with a bound electron transfers all
of its energy to it. The electron is then ejected out from the atom
at an arbitrary angle (shown here as θ) and the atom, essentially the
nucleus, absorbs the recoil momentum. (Attix, 1986). The final kinetic
energy of the electron is the difference in its binding energy, Eb , and
the initial photon energy. The recoil kinetic energy of the nucleus can
be neglected owing to its high mass.

The probability or the atomic cross-section of photoelectric effect depends on the

atomic number, Z, of the matter it is interacting with and on the photon’s initial
energy hν. It is given by the proportionality (2.9). Here a σph is the atomic cross-
section, n ≈ 4, for photon energy less than 0.1 MeV and gradually rising to about
4.6 at photon energy 3 MeV, and m ≈ 3 for photon energy less than 0.1 MeV, grad-
ually decreasing to about 1 at photon energy 5 MeV (Attix, 1986). Thus, it can be
inferred that photoelectric effect is predominant for relatively low photon energies
and a high Z material medium. This dependence of the atomic cross-section on Z
for different photon energy is shown in the form of different curves in Fig. 2.11. It
can be seen from the figure that lead (Pb) has comparatively a higher relative atomic
cross-section for any energy when compared to the atomic cross-sections of the dif-
ferent materials plotted. Thus, lead is a routine choice of shielding material for high
energy X-rays (Rezaei-Ochbelagh and Azimkhani, 2012).

Zn
a σph ∝ (2.9)
hνm
The sudden surge in the cross-section, as can been seen in the curves in Fig. 2.11
(denoted by the letters ’K’, ’L’ and ’M’), occurs when the photon energy is very close
to the binding energy of an atomic shell. In such cases, resonance occurs and the
probability of the absorption of the photon by an electron from that specific shell
escalates abruptly (Khan and Gibbons, 2014). These effects are referred to as shell
absorption edges in the plot and is denoted by ’K’, ’L’ and ’M’ for their respective
shells.
2.2. X-rays 19

F IGURE 2.11: The different atomic cross-sections (in barn) of photo-

electric effect for varying photon energy. Different curves refers to
material with different atomic number, lead (Pb) being the highest
and hydrogen (H) being the lowest Z material. The non-differentiable
points denoted by ’K’, ’L’ and ’M’ are the peaks of the shell absorption
edges. (Podgorsak, 2010).

A vacancy in an inner shell of the atom, caused by any process such as the pho-
toelectric effect or shell transition effect, can produce fluorescence X-rays. These
X-rays are emitted when this vacancy is filled by an electron from a higher shell.
Furthermore, the fluorescence X-rays can be absorbed by another bound electron
of the same atom subjecting it to an ejection. Such an effect is classified in the cat-
egory of Auger emission which contributes to the final dose deposited in the sur-
rounding matter. Under Auger emission, the electrons can also be emitted by other
mechanisms such as the Coster-Kronig effect or the super Coster-Kronig effect. In
these mechanisms the electron transitions to a sub-shell with a higher binding en-
ergy within the same shell. The emitted radiation is then absorbed by either an
electron from a higher shell (Coster-Kronig effect) or an electron in the same shell
with a lower binding energy (super Coster-Kronig effect) (Podgorsak, 2010).
Photoelectric effect is the dominant interaction for X-ray imaging and is not of
much consequence in the therapeutic energy range. This will be reviewed later,
along with sufficient explanations, in X-ray beam attenuation, section 2.2.3.

Pair production
When a photon with energy higher than 1.02 MeV is in the vicinity of a Coulomb
force field, there is a reasonable probability of it getting absorbed giving rise to an
electron and a positron. Such an absorption process is called a pair production, the
electron and the positron being the pair produced (Fig. 2.12). This Coulomb force
field, which triggers such an event, is generally that of an atomic nucleus. However,
a similar event can also occur near the Coulomb force field of an atomic electron for
even higher photon energies. The photon is absorbed giving rise to two electrons
and a positron at the site of absorption. Such an event is called a triplet production
and will be discussed briefly later in this section (Attix, 1986).
The relationship for conservation of energy in a pair production can be given by
Eq. (2.10). Here the initial energy of the photon is hν, the final energies of the electron
and the positron are T− and T+ respectively, and the rest mass energy of an electron
20 Chapter 2. Scientific Background

F IGURE 2.12: A high energy photon disintegrates into an electron

and a positron, scattered at distinct angles and with possibly distinct
kinetic energies, in the presence of a strong Coulomb force field such
as that of an atomic nucleus. The recoil kinetic energy imparted to the
nucleus is negligible owing to its high mass (Attix, 1986).

is mo c2 which is approximately 0.51 MeV. The average kinetic energy received by the
electron and the positron is given by Eq. (2.11). It is not necessary that they receive
equal energy.

hν = ( T− + mo c2 ) + ( T+ + m0 c2 ) (2.10)
hν − 2m0 c2
T̄ = (2.11)
2
The differential atomic cross-section of nuclear pair production for the creation of
a positron of energy T+ (and a corresponding electron of energy of hv − 2m0 c2 − T+ ),
is derived by the Bethe-Heitler theory as presented in Bethe and Maximon, 1954. On
integrating the differential atomic cross-section over all values of T+ , the total atomic
cross-section, a σn , is given by the proportionality (2.12).

a σn ∝ Z2 (2.12)

The atomic cross-section for a triplet production is relatively small when com-
pared to the atomic cross-section of pair production. The ratio of the two cross-
sections is given by Eq. (2.13). Here, a σe is the atomic cross-section of a triplet pro-
duction and a σn is the atomic cross-section of a pair production. C is a parameter
dependent entirely on hν, which increases as the photon energy decreases. Thus
for lower energies the probability of a triplet production decreases for a specific Z.
The threshold energy below which triplet production does not occur is 4m0 c2 . The
different values of the aforementioned ratio for different gaseous medium has been
presented in the work by Evans, 1955 as can be referred from Fig. 2.13. The photon
energy used was ranging from 6-7 MeV. It can be inferred from the same that even
at such a high energy the number of pairs produced are much higher than the num-
ber of triplets produced. Triplet production is not a dominant event for the photon
energies dealt in this study.

a σe 1
= (2.13)
a σn CZ
2.2. X-rays 21

F IGURE 2.13: A comparison of triplet to pair production ratios for dif-

ferent gaseous medium. The ratio decreases with increasing atomic
number. The atomic number of the gases are increasing from top to
bottom with Methane (CH4 ) having the smallest Z, 8 and Argon the
highest at 18. (Evans, 1955).

Rayleigh scattering
Rayleigh scattering is a coherent elastic scattering where, coherent means that the
photon interacts with the entire atom as a whole, and elastic means that the photon
does not lose any of its energy in the process. It is merely deflected by an angle from
its original path.
The Rayleigh scattering atomic cross-section is dependent on the Z and hν ac-
cording to the proportionality (2.14).

 2
Z
a σR ∝ (2.14)
hν

Rayleigh scattering is of little importance in high energy X-ray therapy as the

contribution of this scattering to the final attenuation is small. This fact will be uti-
lized later in this chapter when the X-ray beam attenuation is discussed.

Photonuclear interactions
In photonuclear interactions, an energetic photon, with energy higher than a few
MeV, enters an atomic nucleus. The excited nucleus then emits either a neutron or a
proton.
The emitted proton contributes directly to the dose imparted to the surround-
ing matter. Although, the relative contribution is less than 5% because of the high
probability that the photon undergoes pair production instead, being in the close
proximity of the nucleus (Attix, 1986).
The emitted neutron generates a need of better radiation protection. Neutrons
are hard to shield as they are neutral and can pass through dense materials unat-
tenuated. Furthermore, the resultant daughter nuclei may be radioactive adding to
the radiation hazard. The threshold energy, which denotes the binding energy of a
neutron with the nucleus, is of the order of 8 MeV or higher for most nuclei, except
for Deuteron and Beryllium-9 where it is 2.22 MeV and 1.66 MeV, respectively (Pod-
gorsak, 2010). Thus, it is a concern for facilities in which machines are capable of
producing photon beams of 8 MeV or higher. The beam energy used in this study is
around 6 MeV and hence such an interaction is not a concern.
22 Chapter 2. Scientific Background

2.2.3 X-ray beam attenuation

When an X-ray beam enters matter, there is a certain probability of its photons un-
dergoing scattering or absorption like Compton effect, photoelectric effect or pair
production. For each photon, the probability of such an event occurring depends
on its energy and the atomic number, Z, of the matter it is traveling through. These
individual events contribute to the collective attenuation of the X-ray beam. Thus,
the attenuation depends on these individual probabilities of interactions. This is pre-
sented in Fig. 2.14 (A) in which the curves represent the loci where the two neigh-
boring interactions are equally probable. The energy spectrum of the X-ray beam
concerning this study is presented in Fig. 2.14 (B). The contribution of Rayleigh
scattering is exceedingly small at such energies. Photonuclear interactions are not
relevant for the range of photon energies dealt with in this study. Thus, from hereon
only the attenuation due to the Compton effect, pair production and photoelectric
effect will be considered (Evans, 1955).
The probability of a photon transversing a matter of thickness x without under-
going Compton scattering is exp(−µc x ) where µc is the linear attenuation coefficient
for Compton effect. Similarly, the probability of no photoelectric absorption and pair
production is exp(−τx ) and exp(−κx ) respectively. These probabilities are multi-
plied for an uninterrupted travel, hence the total linear attenuation coefficient can
be given as Eq. (2.15) (Evans, 1955). The attenuated intensity I thus can be given Eq.
(2.16) where I0 is the initial intensity of the beam.

µo = µc + τ + κ (2.15)
I = I0 exp(−µc x − τx − κx ) (2.16)

Mass attenuation coefficient for any type of interaction is the linear attenuation
coefficient divided by the density of the material. It is fundamentally more valu-
able than the linear coefficient because of its independence from the density and the
physical state of the medium material. The mass attenuation coefficients for differ-
ent interactions are related to the corresponding atomic cross-sections by Eq. (2.17).
Here µ is the linear attenuation coefficient, ρ is the density of the material, a σ is the
atomic cross-section of the interaction, NA is Avogadro’s constant,
  Z is the atomic
Z
number and A is the atomic mass of the material. The ratio A written separately
in the parenthesis is roughly constant, equal to 0.45 ± 0.05 (Evans, 1955).

 
µ N Z
=a σ · A (2.17)
ρ Z A

The dependence of the mass attenuation coefficient for the different interactions
can now be given as Eq. (2.18), (2.19) and (2.20).

µc
∝ Z0 (2.18)
ρ
τ
∝ Z3 (2.19)
ρ
κ
∝ Z1 (2.20)
ρ
2.2. X-rays 23

(A)

(B)

F IGURE 2.14: (A) Regions of relative predominance of the three main

forms of photon interaction with matter in X-ray therapy. The left
curve represents the locus where the probability of an occurrence of
photoelectric effect is equal to that of the Compton effect; the right
curve represents the locus where the probability of an occurrence of
Compton effect is equal to that of the pair production (Podgorsak,
2005). (B) The energy histogram, also called energy spectrum, of the
X-ray beam used in this study. The maximum energy is around 6
MeV.
24 Chapter 2. Scientific Background

The proportionality of the respective cross-sections to Z can be referred from

(2.6), (2.9) and (2.12) as explained in the previous sections. The dependence of these
mass attenuation coefficients, for lead, with varying photon energy is shown in Fig.
2.15 where mass attenuation coefficient of Compton is (µc /ρ), photoelectric is (τ/ρ)
and pair production is (κ/ρ). The peaks labeled ’K’ and ’L’ represent the shell ab-
sorption edges. σR /ρ represents the mass attenuation coefficient of Rayleigh scat-
tering which can be seen to decrease sharply with increasing photon energy and
reaches negligible values at the onset of therapeutic energy range.

F IGURE 2.15: The dependence of mass attenuation coefficient of

Compton (µc /ρ), photoelectric (τ/ρ) and pair production (κ/ρ) on
varying photon energies in lead. The total mass attenuation coeffi-
cient is labeled as (µ/ρ). The peaks labeled ’K’ and ’L’ represent the
shell absorption edges (Podgorsak, 2005).
2.3. Modern Linear Accelerators 25

2.2.4 Brief Overview of Dosimetric Quantities

Radiation dosimetry is the study of quantitatively determining the amount of energy
deposited by an ionizing radiation in the interacting medium. This involves defining
several dosimetric quantities and units dedicated to radiation measurement. The
quantities which are often used in dose measurements utilizing a photon beam are
explained below.
The particle fluence is the ratio of the number of particles, dN, incident on a
sphere to the cross-sectional area of that sphere, dA, and is given by (2.21) (Seuntjens,
Strydom, and Shortt, 2005).

dN
Φ= (2.21)
dA
The energy fluence is the ratio of the amount of radiant energy, dR, incident on
a sphere to the cross-sectional area of that sphere, dA and is defined by (2.22). It is
related to the particle fluence by (2.23) where E is the energy of the monoenergetic
photons. (Seuntjens, Strydom, and Shortt, 2005).

dR
Ψ= (2.22)
dA
Ψ = ΦE (2.23)

Kinetic energy released per unit mass, also known as kerma, is defined as the
mean energy, Ētr , transferred by the electrically neutral radiation to charged parti-
cles in the medium per unit mass, m. This quantity is only applicable to indirectly
ionizing radiations and is defined by (2.24). The unit of kerma is joule per kilogram
(J/kg) and is called as the gray (Gy) (Seuntjens, Strydom, and Shortt, 2005) .

d Ētr
K= (2.24)
dm
In an indirectly ionizing radiation the energy is deposited in the medium in a two
step process. In the first step, the energy is imparted to the charged particles of the
medium as kinetic energy. The charged particles then transfer some of this kinetic
energy to the medium. This absorbed energy is the dose imparted to the medium.
It is defined as the mean energy, ē deposited in a finite volume of the material, with
mass m and is given by (2.25). The unit of absorbed dose is joule per kilogram (J/kg)
and is called as the gray (Gy) (Seuntjens, Strydom, and Shortt, 2005).

dē
D= (2.25)
dm

2.3 Modern Linear Accelerators

Linear Accelerators or linac is the device most commonly used to perform external
beam therapy using high energy X-ray beams. With the aid of advanced compu-
tation, the treatment delivery has seen large advancements and has significantly in-
creased in its complexity as well. Historically, the delivered beam was not collimated
26 Chapter 2. Scientific Background

F IGURE 2.16: A visualization of the internal components of a linac.

The magnetron pumps RF waves into the waveguide which acceler-
ates the electrons before they hit the target and produces high energy
X-rays (How a Linear Accelerator Works, Elekta 2010).

into complex shapes but rather had simple rectangular collimation. In modern tech-
nologies, emphasis is on shaping the beam using Multi Leaf Collimator (MLC). MLC
modulates the intensity of the beam in different directions thus conforming the dose
at the site of the tumor while minimizing the dose to the healthy tissues surrounding
it. This requires complex programming and sophisticated computational models to
solve for the inverse treatment plans.

2.3.1 Linac Waveguide

In linear accelerators designed for the purpose of radiation therapy, electrons are
accelerated using a radio frequency (RF) waveguide. The accelerating waveguide
component of a linac is essentially a copper tube with internal cavities as can be
seen in Fig. 2.16. Radio frequency waves are pumped into the guide through a mag-
netron or a klystron. This is synchronized with the injection of electrons into the
waveguide by the electron gun which produces electrons by heating up a tungsten
filament, acting as the cathode, to high temperatures. The RF waves pumped into
the wave induce current in the cavity walls. This induced current then establishes
intense electromagnetic (EM) field in the cavities throughout the length of the guide.
The electrons are then accelerated to a speed approaching the speed of light by these
EM fields. Furthermore, a vacuum is created inside the waveguide to ensure that the
electron beam does not interfere with other particles. Two sets of quadrapole mag-
nets, called steering coils, control the path of the electron beam and steer it along the
guide. Another two sets of focusing coils assist in the focusing of the electron beam,
as can be seen in Fig. 2.17. Thus, an extremely small focus spot can be achieved
when the electron beam hits the target (Loverock, 2007).

2.3.2 Linac Head

The part of the linac which is responsible for the complete spatial tailoring of the
X-ray beam is collectively called the linac head, or the gantry, as can be seen in Fig.
2.3. Modern Linear Accelerators 27

F IGURE 2.17: A visualization of the linac waveguide. The inner walls

of the cavities are induced with a current which establishes intense
EM fields in them, accelerating the electron in the forward direction
synchronously. The steering coils control the direction of the beam
ensuring that it remains parallel along the guide axis. The focusing
coils further define the beam, focusing it into a very small focal spot
(Loverock, 2007; How a Linear Accelerator Works, Elekta 2010).

2.18. It can rotate around the patient table thus delivering the beam from any di-
rection in the rotation plane. Modern techniques of delivering the beam like VMAT
(as introduced in section 2.2.1) utilizes the gantry’s capability of achieving variable
rotational speed along with a continuous delivery unlike conventional delivery tech-
niques. The linac in Fig. 2.18 depicts an Elekta Synergy R
linac (Elekta 2018).

The X-ray target

The focused and accelerated electron beam hits a high atomic number metal target at
a speed approaching the speed of light. X-rays are produced in this interaction. The
physics behind such an interaction has been explained in section 2.2.1. The energy
of the X-ray beam thus produced can be altered by manipulating the energy of the
electron beam (Loverock, 2007).

Beam Collimators
In Elekta Synergy R
, the beam is collimated at several steps, the first of which is
done by the primary collimator. It is a cone shaped collimator positioned close to
the target (X-ray source) to limit the field to a circular shape (as can been in Fig.
2.19). Afterwards, the beam is collimated by further collimating devices. The con-
ventional collimators can only shape the radiation in rectangular fields, which offers
a limited conformity. With the development of Multi Leaf Collimator (MLC) it be-
came possible to produce highly complex radiation fields, as they are composed
of many thin leaves which move independent from one another. In the present
study, an Elekta Synergy R
linac coupled to an Elekta AgilityTM collimator are used.
The Agility MLC is composed by 80 pairs of inter-digitating leaves and two block-
diaphragms that move perpendicular to the leaves. The leaves can move indepen-
dently. This movement is controlled by miniature direct current motors according
to a pre-uploaded MLC plan. Each leaf is fitted with a reflector illuminated by an
28 Chapter 2. Scientific Background

F IGURE 2.18: A visualization of the linac head and the patient table.
The X-ray beam (yellow rays) is modified in the linac head. The linac
head or the gantry can rotate around the patient table delivering the
beam in an arc like movement. The patient table also has multiple
degrees of freedom to further aid in the conformity of the dose (How a
Linear Accelerator Works, Elekta 2010). (The X-ray beam is represented
as a yellow radiation only for illustration purposes). The Electronic
Portal Imaging Device, EPID, will be explained in the next section.

optical beam. The reflection from them are captured by a video camera. This infor-
mation is used to continuously estimate and validate the position of the leaf. In case
of an error, the delivery is stopped (Loverock, 2007).

Flattening filter
The X-ray beam produced via Bremsstrahlung is primarily directed forward. This
produces a beam which has a lower profile in the edges, in comparison to the central
part of the profile as shown in Fig. 2.20 (left). The filter is designed in a way that it
flattens the beam profile as shown in Fig. 2.20 (right). It is usually radially symmetric
(Loverock, 2007).

Ion Chamber
A transmission ionization chamber is placed right above the MLC, which is the clos-
est practical position to the patient. Its primary purpose is monitoring the delivered
dose and the dose rate along with the beam uniformity and flatness. It also auto-
matically terminates treatment if any of the mentioned quantities are outside the
acceptable tolerances (Loverock, 2007).

Wedge Filter
In cases where a wedge-shaped beam profile is needed instead of a uniform one, the
wedge filter is employed. This filter can be placed either above or below the moving
collimator assembly. It changes the beam profile according to the length, the time
and the position of its insertion into the beam during the delivery (Loverock, 2007).
2.3. Modern Linear Accelerators 29

F IGURE 2.19: Schematic representation of major components of a typ-

ical linac (Loverock, 2007). Not drawn to scale.

F IGURE 2.20: The profile of a beam is essentially flattened using a

flattening filter. A beam with a low profile (left) at the edge, relative
to the central region, has a flattened profile in the center after the ap-
plication of a flattening filter (right) (Loverock, 2007).
30 Chapter 2. Scientific Background

2.3.3 Electronic Portal Imaging Devices (EPID)

In radiotherapy it is crucial that the dose is delivered at the planned anatomical
site so that the precise treatment is delivered to the patient. The importance of this
positional accuracy has further increased with the advent of modern radiotherapy
techniques such as IMRT and VMAT. For this purpose, Electronic Portal Imaging
Devices (EPIDs) are attached to the bottom of the gantry (as can be seen in Fig. 2.18),
which receive the radiation exiting from the patient. The information in the radiation
received is acquired in the form of images, from hereon referred to as frames. These
give an instantaneous verification of the patient position with high accuracy.
Unlike the traditional radiographic film based methods for patient position ver-
ification, the frames from the EPID can be acquired and displayed online in real
time. Moreover, multiple frames can be acquired without entering the treatment
room. One advantage of such a verification is that the frames acquired are digitally
available which can be shared, processed, filtered and archived without much effort
(Mubata, 2007).
EPIDs are essentially a flat panel detector. In this study, a PerkinElmer XRD 1640
AL5 P aSi EPID (ELEKTA iVewGT) is used. It is based on 16 inches (approximately
40 cm) amorphous silicon sensors operating as two-dimensional photodiode arrays.
It contains more than 1 million pixels with a 400 µm pixel pitch and produces live
images at a speed of 3.5 frames per second (PerkinElmer 2005).
Although traditionally EPIDs were used solely for patient position verification,
their high pixel resolution and fast acquisition time have led to the investigation of
employing EPIDs for other validations, like verification of individual leaf positions
and verification of IMRT fields to name a few. The past decade has also seen a grow-
ing interest in using the information being received by the EPID and to reconstruct it
into a three dimensional dose deposited as imparted to a water equivalent medium
at the patient position (Alhazmi et al., 2018; Low et al., 2011; Nijsten et al., 2007).

2.3.4 Clinical Workflow in Conformal Radiotherapy

The goal of conformal radiotherapy is straightforward. It aims to achieve a high-
dose volume at the site of the tumor wrapped closely around the planning target
volume (PTV), while minimizing the dose delivery to organs at risk (OAR) to pre-
vent any complications. Furthermore, to achieve a high tumor control probability
(TCP) the difference between the dose delivered to the PTV and the OAR should be
sufficiently high (Brady, Heilmann, and Molls, 2006).
In external beam therapy a sequential set of protocols, often referred to as the
chain of radiotherapy, has been defined and adopted as the complete routine fol-
lowed before and after the dose delivery. It has evolved into a more involved routine
in the past years as the delivery and dosimetric techniques improved. Although, the
fundamental links of the chain still comprises of the same broad steps which are
briefly explained as follows.

1. The patient is immobilized and a high quality three dimensional medical im-
age is acquired to anatomically locate the disease. These images can be any
high quality imaging modality like X-ray CT (Computed Tomography), PET
(Positron Emission Tomography), MRI (Magnetic Resonance Imaging) images
or any combination thereof.

2. Then the target volumes, such as the PTV and the OAR are identified and con-
toured. Once the desired contours of the dose delivery have been identified,
2.3. Modern Linear Accelerators 31

sophisticated simulation models or algorithms are used to create treatment

plans. This complete process is referred to as Treatment Planning. Its goal is to
create optimized dose delivery plans which result in dose distributions with
maximal conformity. This in principle should include the complete delivery
plan for the linac and its components, dose-volume histograms (DVHs), iso-
dose plots of 2D and 3D dose distributions and the prediction of the biological
outcome. A DVH is the graphical representation summarizing the computed
dose distribution within a volume of interest, such as PTV and OAR, of a pa-
tient which would result from a proposed radiation treatment plan (Bidmead
and Rosenwald, 2007). In Elekta Synergy R
, treatment plans are developed
using a treatment planning system called Monaco (Elekta 2018) as can be seen
in Fig. 2.21.

F IGURE 2.21: Graphical User Interface of Monaco displaying pros-

trate treatment plans. The plots on the top right are dose volume
histograms (DVHs). The different colors are associated to the dose
delivered to different target volumes. The other three plots represent
the dose distribution for different treatment plans for the same pa-
tient. The dose level in different anatomical regions is represented
by different colors. Red represents the region with the highest dose
delivery. The DVH can represent up to three plans by using solid,
dashed and dotted lines (Monaco 2018).

3. The validation of such a treatment plan undergoes Quality Assurance (QA).

QA in radiotherapy is a set of all protocols that ensure consistent and safe
fulfillment of a radiotherapy treatment. It is an essential part of radiotherapy
and is involved with every part of the process including treatment planning.
The dose distributions delivered by a treatment plan are verified extensively
using either computational models or by measuring dose distributions in a
phantom. The validation of treatment plans for the Elekta Synergy R
linac
employed in this study is currently done by delivering the plan on a phantom
and analyzing the dose distribution (Rosenwald, 2007).
4. Then the patient is positioned on the table and the position is verified accu-
rately using EPID and cone beam CT (Computed tomography).
5. Once the position has been verified, the dose is delivered according to the de-
signed and validated treatment plan. This also involves in-vivo dosimetry pro-
cedures which are still an investigatory work.
32 Chapter 2. Scientific Background

6. To asses the response of the treatment, medical images are acquired again after
a certain amount of time has passed and then analyzed.

This study is involved with the step 2 and 3 of this clinical workflow.

2.4 Monte Carlo Simulation

Monte Carlo (MC) simulation offers an alternative to analytical techniques for un-
derstanding a statistic’s sampling distribution and evaluating its behavior in ran-
dom samples (Mooney, 1997). It is essentially a numerical solution to an event
involving object interactions evolving in time, while following a set of predefined
probabilities. These are performed by carrying out simulated experiments. In each
experiment, the values of the input random variables are sampled based on their
probabilistic distributions and the output variables are calculated. A number of ex-
periments are carried out in the same manner and the results are used to determine
the statistical behavior of the output variables.
In the simulation models concerning radiotherapy, the object interaction is usu-
ally the interaction between atomic particles in the simulated world (Seco and Ver-
haegen, 2016; Cruse, 1997). These interactions are governed by probabilistic laws
which are determined by experimentally studying such interactions in the real world.
Examples of such probabilities are the cross-sections involved in the interaction of
X-ray photons with matter as explained in section 2.2.2.

2.4.1 The Monte Carlo Linac Model

Monte Carlo simulations are superior to analytical solutions for modeling and an-
alyzing radiation transport for X-ray beam therapy. There are two approaches to
model a linac. The first approach is to model the entire linac and use it to store parti-
cles in a Phase Space. A Phase Space is a virtual plane in the track of a particle beam
which records the information of the particles passing through it. It usually stores
the information out in a binary file which then can be used as a source, instead of
simulating the entire linac again. The Phase Space in principle can be positioned
at any step of the beam path, however the most common position chosen is right
above the moving collimator assembly, as the rest of the linac in the beam upstream
is static relative to each other (as can be seen in Fig. 2.22). This is called the phase
space approach (Seco and Verhaegen, 2016). In the second approach, distinct and
correlated histograms of the physical quantities of the particles like the energy, mo-
mentum and location are determined. They are then used as a virtual linac to create
pseudo particles with these quantities alloted to them according to the individual
histograms (Nath et al., 1994).
Fig 2.22 shows a typical schematic model of a linac Monte Carlo simulation
model. Different manufactures may have a different order of the components shown
in the schematic, but these are essentially the ones required in a Monte Carlo model.
All the components of this model, except the mirror and the backscatter plate, have
been explained in section 2.3.2. The backscatter-plate absorbs the backscattered par-
ticles from the secondary collimator assembly (MLC and diaphragm) and the mirror
is used to verify the leaf positions, as shown and described in Fig. 2.23 (Loverock,
2007).
The Phase Space involved in this study stores 9 physical quantities of every par-
ticle passing through it. Table 2.2 enumerates the complete information of the Phase
Space File.
2.4. Monte Carlo Simulation 33

F IGURE 2.22: A schematic representation of the major linac compo-

nents modeled in MC. Adapted from Seco and Verhaegen, 2016.

TABLE 2.2: Information stored in the PhSp

Physical Quantity Data Type Number of Bytes

Particle Type (Photon or electron) int 4
Statistical weight float64 8
Momentum in X float64 8
Momentum in Y float64 8
Momentum in Z float64 8
Energy float64 8
Position in X float64 8
Position in X float64 8
Position in X float64 8

2.4.2 Geant4
Geant4 (Geometry And Tracking) is an open source simulation toolkit, written in
C++, which can be customized vigorously for accurately simulating passage of par-
ticles through matter. It was developed by The European Organization for Nuclear
Research (CERN) and is based on an object-oriented framework to enhance the ease
of use (CERN, 2018).
The simulation model can be configured by defining almost every intricate de-
tail of the setup. This includes the geometry, the spatial position and relative move-
ment, the density and the material composition. The physics can also be governed
by defining the physical processes to be included, the number and the type of par-
ticles involved and their statistical weight among others. The detector position can
be defined precisely including the resolution and spatial position and dimension.
Multiple detectors can be used at the same time and the response format can also be
customized. Furthermore, the complete information of events and tracks during the
simulation can be stored. The toolkit at the fundamental level includes abundant
34 Chapter 2. Scientific Background

F IGURE 2.23: The mirror is part of an optical system used for reflect-
ing the information received from the reflectors on the leaves as a
verification measure. Mylar is a highly reflective material (Loverock,
2007).

physical models to mimic the interaction of particles with matter.

The simulated model can also be visualized via graphic tools, such as OpenGL
(Open Graphics Library) to verify spatial position and dimension as shown in Fig.
2.24. OpenGL is an application programming interface for rendering 2D and 3D
vector graphics.

F IGURE 2.24: Visualizing the setup model using OpenGl. The inter-
face comes with a dialog box which can be used to edit the model and
run the simulations in real-time.

All simulations done in this study have been performed using Geant4 10.01.p02.
 35

Chapter 3

Optimization of Phase Space File

A Phase Space (PhSp) File is a record of all or a part of the information of the particles
passing through an imaginary plane in the path of a particle beam. It is a powerful
tool used in decreasing redundancy in MC simulations by employing it as the beam
source instead of modeling the entire linac. Optimizing a commissioned PhSp, vali-
dated for a specific linac model, to a different linac model requires a set procedure to
determine the progress of the optimization. This procedure involves comparing the
simulation and the measured dose profiles in every optimization cycle. The infor-
mation in the PhSp file, used as the beam source in the model, is then manipulated
according to the quantified discrepancies between measured and simulated profiles.
Such discrepancies from hereon will be referred to as cost values. This process is
repeated until a minimum cost value is reached. Furthermore, dosimetric commis-
sioning of an IMRT planning system requires a systematic sequence to be followed,
for example, the guidelines mentioned in The American Association of Physicists in
Medicine (AAPM) report (Ezzell et al., 2003). Keeping in line with these guidelines,
the simulated lateral and percentage depth dose (PDD) profiles were compared to
the corresponding measurements as a reference for the optimization. The PDD pro-
file is the dose distribution at different depths in the absorption medium and lateral
profile is the dose distribution in a plane perpendicular to the beam central axis and
at a certain depth in the absorption medium (Ezzell et al., 2003). The dimension and
spatial position of the detectors for the two profiles are mentioned in section 3.1.
In this study, a commissioned PhSp for the MC model of an Elekta Precise for a
6 MeV photon beam was used, available at the International Atomic Energy Agency
(IAEA) website (Capote, 2011) and optimized it for a 6 Mev photon beam of an
Elekta Synergy. The information optimized is the energy and the momentum of the
particles.

3.1 Measurements and Modeling

All measurements were performed using a 6 MeV Elekta Synergy R
linac coupled
to Elekta Agility TM collimator (Elekta, Stockholm, Sweden) and a Blue Phantom
(IBA Dosimetry, Schwarzenbruck, Germany), installed at Klinikum der Universität
München - Campus Großhadern, Munich, Germany. Measured PDD and lateral pro-
files for field sizes of 2x2, 5x5, 10x10 and 20x10 cm2 were used in this study as a ref-
erence for the calculation of the cost. Both PDD and lateral profiles were measured
using a microDiamond P60019 Synthetic Diamond Detector (PTW, Freiburg, Ger-
many) which offers sub-mm resolution for field sizes up to 40x40 cm2 (PTW, 2018a).
Measurements for the lateral profiles were taken at a source to surface distance of
900 mm and a depth of 15 mm in water, with 1-mm step size in the penumbra region
36 Chapter 3. Optimization of Phase Space File

(A) (B)

F IGURE 3.1: (A) Visual construction of the MC Model used for PDD
profiles. (B) Visual construction of the MC Model used for lateral
profiles. The labeled components in both the models: (a) Detector; (b)
Water Phantom; (c) Inline Diaphragm; (d) Crossline MLC; (e) Photon
Beam Direction. The model is not drawn to scale.

and 4-mm elsewhere. The PDD profiles were measured from the surface of the wa-
ter phantom to a depth of 300 mm, with 1-mm step size in the build-up region. The
step size then increased to 2-mm up to the 50th dose measuring point and further
increased to 4 mm for the rest of the measurement.
A virtual water phantom was defined in the existing MC model of the equip-
ment. A command-based scoring method, with 1 mm step size, was used for dose
recording in the phantom for both PDD and profile simulations. The visual schematic
of the MC model, including the collimator assembly, is presented in Fig. 3.1.
The commissioned IAEA Phase Space (Capote, 2011) was recorded at a distance
of 27.21 cm from the X-ray source. A new PhSp positioned 2.79 cm below the origi-
nal IAEA PhSp was generated, from hereon referred to as the LMU PhSp, recording
only the relevant information for the simulations performed for the present investi-
gation. This LMU PhSp has been optimized in this study.
The linac was modeled following the "phase-space" approach introduced in chap-
ter 2. The LMU PhSp was used as a substitute for the static part of the linac head.
The dynamic part of the model, namely the AgilityTM collimator, labeled as (c) and
(d) in Fig. 3.1 was modeled and commissioned in Martins et al., 2017.

3.2 Cropping the PhSp

In complex systems governed by more than 5 dimensions, MC Techniques have been
proven to be more advantageous in computing accurate results when compared to
analytical or deterministic algorithms. In radiotherapy, the number of dimensions in
the system is even higher (Seco and Verhaegen, 2016). This includes the momentum
(in x, y and z direction), the position (in x, y and z direction) along with the energy
and the type of the particle to account for in the least. Thus, the simulation time
increases appreciably.
To reduce the simulation time and effectively increase its efficiency a technique
referred here as cropping has been introduced in this study. In this technique a new
3.2. Cropping the PhSp 37

PhSp is generated, cropping the original PhSp into a smaller radius as represented in
Fig.3.2. This radius has been referred to as the cropping radius or the cut-off radius.
The location of the particles, the dimension and spatial position of the detector and
the field size of the photon beam in the MC Model determine the smallest appropri-
ate cropping radius. An example of cropping is presented in Fig. 3.2, in which the
cropped PhSp only has the information of the particles within 0 to 20 mm.

F IGURE 3.2: An example of cropping the original PhSp (on the left)
to generate a cropped PhSp (on the right). The cropping radius is 20
mm which reduces the simulation time by a factor of 20.
38 Chapter 3. Optimization of Phase Space File

3.3 Optimization Of Energy

Multiple techniques have been developed to determine the total dose imparted to
the patient in high energy X-ray photon therapy which has been explained in details
in Rosenwald, Rosenberg, and Shentall, 2007. One of the techniques is the pencil
beam algorithm as explained in comprehensive studies done by Ahnesjö, Andreo,
and Brahme, 1987; Ahnesjö, Saxner, and Trepp, 1992. In this technique it is assumed
that the entire photon beam is composed of a collection of numerous smaller and
narrow photon beams. These narrow beams are referred to as pencil beams which
deposit the dose largely along their central axis. This dose distribution arising from
a pencil beam inside a medium is referred to as the pencil beam dose kernel.
The total energy released per unit mass at a distance r from the source, by a
mono energetic pencil beam of energy E is referred to as the terma, TE , differential
µ
in energy E. It is determined by Eq. (3.1) where ρ is the mass attenuation coefficient
and φE (r )is the primary photon fluence differential in energy at a distance r from
the source. The pencil beam kernel is a function of the distance from the source r
and the energy of the pencil beam, E. Furthermore, it is dependent on the density of
the medium ρ. Given a pencil beam kernel,hρ , and the terma differential in energy
E, TE , the absorbed dose can be calculated using (3.2) as mentioned in the paper by
Ahnesjö, Andreo, and Brahme, 1987.

µ
TE (r ) = EφE (r ) (3.1)
ρ
Z Z Z Z
D (r ) = TE (s)hρ ( E, r − s)dEd3 s (3.2)

This shows that the PDD profile of a poly-energetic photon beam depends sig-
nificantly on its energy. Thus, PDD profiles can be taken as a measure to optimize
the energy spectrum of the PhSp.
Furthermore, the mathematical manipulation to the energy was chosen as a sim-
ple addition or subtraction to keep it uncomplicated. This meant that an addition of
0.2 MeV to the PhSp would be performed by adding 0.2 MeV to the energy of every
photon in the PhSp as presented in Fig. 3.3. This manipulation shifts the mean and
the median of the energy spectrum by the same amount. The only constraint iden-
tified in this manipulation was the annihilation peak at approximately 0.511 MeV
which was independent of the energy distribution and thus was not affected by the
manipulation. The annihilation peak comes from an abundance of photons with en-
ergy very close or equal to 0.511 MeV. This is indirectly related to the production
of positrons during pair-production. These positrons usually travel a small distance
and then annihilate with an interacting electron producing two photons of approxi-
mately 0.511 MeV energy.

3.3.1 The Cost Function

In the optimization process, it was crucial to quantify the discrepancies between
the measurement and the simulated profiles. For this purpose, a cost function was
chosen. This cost function was used to quantitatively determine these discrepancies,
referred to as cost values. Furthermore, it was also required for the automation of
the process where a qualitative or a visual evaluation would have been inadequate.
3.3. Optimization Of Energy 39

F IGURE 3.3: The blue histogram represents the energy spectrum of

the original PhSp. The green histogram represents the energy spec-
trum of the manipulated PhSp for which the energy of all the particles
has been increased by 0.2 MeV. The annihilation peak at ∼0.511 MeV
remains undisturbed.
40 Chapter 3. Optimization of Phase Space File

F IGURE 3.4: The measured depth dose profiles for all field sizes. All
measurements were performed using a 6 MeV Elekta Synergy R
linac
coupled to Elekta AgilityTM collimator (Elekta, Stoockholm, Sweden)
in a Blue Phantom (IBA Dosimetry, Schwarzenbruck, Germany), in-
stalled at Klinikum der Universität München - Campus Großhadern,
Munich, Germany

The χ2 function given by Eq. (3.3) is the chosen cost function for PDD (Aljarrah
et al., 2006). It was selected because of its simplicity and accurate reflection of the
disagreement between the simulation and the measurement profiles. Furthermore,
it is reasonably insensitive to statistical uncertainty as shown in the extensive study
presented in the paper Aljarrah et al., 2006. In Eq. (3.3), χ2 is the cost, Dim is the
normalized dose at a dose deposition point i for the measured profiles and Dis is the
normalized dose, normalized to the mean of the dose deposited at points near or at
the point of maximum dose, at a dose deposition point i for the simulated profiles.
n is the total number of points used in the calculation of the cost.

1 n
∑
(m) (s)
χ2 = ( Di − Di ) 2 (3.3)
n i =1

The measured and the simulated depth dose profiles consists of approximately
300 dose values normalized to the maximum as can be seen in Fig. 3.4 and 3.5 (left).
The measured dose values are positioned at a step size of 1 mm in the buildup re-
gion. The step size then increases to 2 mm up till the 50th dose deposition point and
then further increases to 4 mm elsewhere. The corresponding step size in the simu-
lated profiles is consistent throughout the depth at 1 mm. Due to this difference in
the total number of measured and simulated dose deposition points, the direct use
of (3.3) was not possible. To overcome this problem, both measured and simulated
scatter plots were fitted to a continuous function.
This fitting function used to plot continuous curves using the measured and sim-
ulated profiles is given by (3.4). This fitting formula used is an improvement over
the proposed formula in Wierzbicki, Sixel, and Podgorsak, 1993, given by Eq. (3.5)
which did not have a linear coefficient (cd).
3.3. Optimization Of Energy 41

F IGURE 3.5: Well fitted curve using the formula given by Eq. 3.4 (left).
The same plot was erroneously fitted +on using the formula given by
Eq. 3.5 (right).

f (d) = a1 exp(−b1 d) − a2 exp(−b2 d) + cd (3.4)

f (d) = a1 exp(−b1 d) − a2 exp(−b2 d) (3.5)

Here d is the depth, f (d) is the dose at depth d and a1 , a2 , b1 , b2 and c are the
fitting coefficients.
The formula described by Eq. (3.5) was unable to determine acceptable fitting
parameters for numerous simulated and measured profiles as shown in Fig. 3.5.
The "curve_fit" function in the "optimize" class of Python 2.7 library Scipy was used
for all curve fittings.
The initial cost values for field sizes 2x2, 5x5, 10x10 and 20x20 cm2 are presented
in the results section (Fig. 3.9).

3.3.2 Acceptable Cropping for PDD

To reduce the simulation time, a cropped PhSp was used instead of the original PhSp
for estimating the optimal fix for the energy. To determine an acceptable cropping
radius for PDD, large energy perturbations of 3 MeV were added to radially sym-
metric regions of the PhSp. The corresponding PDD profiles were then simulated
using the perturbed PhSp files and a field size of 10x10 cm2 . The effect of the pertur-
bations associated to different regions were then analyzed.
It was observed that beyond a radius of 20 mm, the influence of the particles
contained in the PhSp dropped significantly. In the six plots presented in Fig. 3.6,
the energies of the particles within different radial regions, specifically from 0 to 5
mm, 5 to 10 mm, 10 to 15 mm, 15 to 20 mm, 20 to 40 mm and 40 to 60 mm, were
perturbed by the addition of 3 MeV and the PDD profiles were simulated. The sim-
ulation results (the curves drawn in purple) were then compared to the simulated
PDD profile of the unperturbed original PhSp (the curves drawn in orange). The
disagreement in the two curves were quantified using the previously explained cost
function. It can be seen that the cost values are negligible for the regions beyond 20
mm. This indicated that a cropping radius of 20 mm was acceptable for the purpose
of determining the optimal fix for the energy. Further validations were performed
by comparing the simulated PDD profiles generated using a cropped PhSp and the
original PhSp. The comparison of the two PDD profiles using a field size of 10x10
42 Chapter 3. Optimization of Phase Space File

cm2 is presented in Fig. 3.7 where the cost was calculated to be a relatively small
value of 0.82%.
3.3. Optimization Of Energy 43

(A) (B)

(C) (D)

(E) (F)

F IGURE 3.6: The effect of large energy perturbation to the energy of

the particles within distinct radially symmetric regions of the PhSp
is presented. The PDD profile simulated using a perturbed PhSp is
represented by the purple curve. The PDD profile simulated using
the original full PhSp is represented by the orange curve. Different
plots signify the different radially symmetric regions within which
the energy of the particles was increased by 3 MeV. These regions are:
(A) 0 to 5 mm, (B) 5 to 10 mm, (C) 10 to 15 mm, (D) 15 to 20 mm,
(E) 20 to 40 mm and for (F) 40 to 60 mm. The corresponding cost (%)
consistently decreased from ∼466% in (A) to ∼0.73% in (F).
44 Chapter 3. Optimization of Phase Space File

F IGURE 3.7: Comparison of the PDD profile generated using a

cropped PhSp (drawn in purple) to the PDD profile generated using
the full PhSp (drawn in orange). The cropping radius was 20 mm and
the field size used was 10x10 cm 2 . The final cost (%) is determined to
be 0.82%.

3.3.3 Small Energy Perturbations

The energy was increased instead of decreasing as the simulated dose profile curve
was lower than the measured dose profile curve as presented in Fig. 3.9 (plots on
the left). Moreover, Eq. (3.2) gives a positive correlation of the dose with the energy.
Thus, it was suspected that a higher energy was needed for the optimization. The
cropped PhSp generated using the original PhSp and a cropping radius of 20 mm
was used in determining the optimal fix for energy. The energy of all the particles in
four such identical cropped PhSps was increased by 0.1 MeV, 0.2 MeV, 0.3 MeV and
0.4 MeV respectively. The corresponding PDD profiles were simulated for a field
size of 10x10 cm2 and compared with the measured PDD profile. This comparison
is presented in Fig. 3.8. It can be inferred from the cost values that a local minimum
between 0.3 MeV and 0.4 MeV existed. Moreover, by comparing the measured PDD
curves to the ones simulated using the original PhSp (Fig. 3.9), it can be inferred
that the energy of the particles inside the original PhSp needed to be increased. This
is indicated by the disagreement in the relative dose values at increasing depths in
water.
Four identical PhSps were generated using the cropped PhSp, with energy per-
turbation of 0.3 MeV. The energy of the particles in these four PhSps were then in-
creased in steps of 0.02 MeV resulting in a total energy perturbation of 0.32, 0.34,
0.36 and 0.38 MeV. The corresponding PDD profiles were generated using field sizes
2x2, 5x5, 10x10 and 20x20 cm2 and analyzed. It was observed that the PDD profile
generated using the PhSp with 0.32 MeV perturbation provides the lowest cost val-
ues in regard to all the field sizes. Thus the optimal energy fix was determined to be
0.32 MeV. The final validation was performed using the full PhSp. The results are
presented in section 3.3.5.
3.3. Optimization Of Energy 45

( A ) Adding 0.1 MeV to the energy of all the ( B ) Adding 0.2 MeV to the energy of all the
particles particles

( C ) Adding 0.3 MeV to the energy of all the ( D ) Adding 0.4 MeV to the energy of all the
particles particles

F IGURE 3.8: The PDD profiles generated using cropped PhSps with
different energy perturbations. The corresponding cost values (%)
between the measured PDD profile (green curve) and the simulated
PDD profile (red curve) is presented.

3.3.4 Methodology
Finally, a methodology containing sequential steps to optimize the energy of the
PhSp was developed as part of the complete optimization. This methodology has
been validated for the entire PhSp. The steps are presented below.

1. Add large energy perturbations to all the particles in radially symmetric re-
gions of the original PhSp and generate the corresponding PDD profiles. Gen-
erate a cropped PhSp using an acceptable cropping radius as explained in sec-
tion 3.3.2.

2. Add/subtract energies in steps of 0.1 MeV to all the particles in the cropped
PhSp. Simulate the corresponding PDD profiles as presented in section 3.3.3.

3. Identify the energy perturbation which produces the lowest cost locally by
analyzing the simulation results of all field sizes. The simulations should be
performed for all field sizes to avoid over-fitting for a specific field size. An
over-fitted fix in the context of this study implies that it is producing low cost
values for a specific field size while producing relatively high cost values for
other field sizes. This concept has been explained comprehensively in Babyak,
2004 within the paradigm of regression models.
46 Chapter 3. Optimization of Phase Space File

4. Add/subtract energies in even smaller steps of 0.02 MeV to all the particles in
the cropped PhSp. Simulate the corresponding PDD profiles as presented in
section 3.3.3.

5. Identify the energy perturbation which produces the lowest cost locally by
analyzing the simulation results of all field sizes

6. Steps 4 and 5 can be repeated multiple times, using even smaller perturbations
to identify an optimal energy fix of desired accuracy.

7. Add/subtract the identified optimal fix to the entire PhSp and validate for all
field sizes using the full PhSp.

3.3.5 Final Results

As explained in section 3.3.3, the manipulation of the energy was done in steps of
0.1 MeV starting from 0.1 up to 0.4 MeV and then in steps of 0.02 MeV.
The optimal energy fix was determined to be 0.32 MeV. The results are presented
in Fig. 3.9 for field size of 2x2, 5x5, 10x10 and 20x20 cm2 . Full PhSps were used
in this validation. The corresponding cost values of the comparison between the
measured PDD profile (green curves) and the simulated PDD profile (red curves)
are presented as well. Table 3.1 summarizes the initial and final reduced cost values
for the four field sizes used in this study.

TABLE 3.1: The initial and final cost values for the optimization of
energy. The simulated PDD profiles were generated using the full
PhSp.

Field Size(cm2 ) Initial Cost(%) Final Cost(%)

2x2 2.89 1.10
5x5 6.37 1.39
10x10 11.17 1.05
20x20 9.14 1.31

Furthermore, it was observed that the optimization of the energy also improved
the inline lateral profiles. Inline profiles were simulated for the original PhSp and the
optimized PhSp, with optimized energy information for field sizes 2x2, 5x5, 10x10
and 20x20 cm2 . The results are presented in Table 3.2. A different cost calculation
technique was used in case of lateral profiles which is explained in section 3.4.2.

TABLE 3.2: The initial and final cost values for the inline lateral profile
after the optimization of energy for field size of 2x2, 5x5, 10x10 and
20x20 cm2 .

Field Size(cm2 ) Initial Cost(%) Final Cost(%)

2x2 -14.43 -1.81
5x5 -5.91 -1.09
10x10 -4.26 -1.30
20x20 -7.97 -1.57
3.3. Optimization Of Energy 47

A similar comparison for the crossline profiles showed that the optimization of
energy did not improve the cost values considerably. Moreover, the cost values in-
creased instead of decreasing in case of 5x5 and 20x20 cm2 field size. The results are
presented in Table 3.3.

TABLE 3.3: The initial and final cost values for the crossline lateral
profile before and after the optimization of energy for field size of
2x2, 5x5, 10x10 and 20x20 cm2 .

Field Size(cm2 ) Initial Cost(%) Final Cost(%)

2x2 -22.75 -22.37
5x5 -20.36 -24.71
10x10 -16.06 -15.23
20x20 -10.77 -12.69
48 Chapter 3. Optimization of Phase Space File

F IGURE 3.9: Comparison of the measured PDD profiles to simulated

PDD profiles using the original unperturbed PhSp (left) and the op-
timized PhSp (right), for field sizes of 2x2, 5x5, 10x10 and 20x20cm2 .
The corresponding cost values (%) are presented together with the
curves. All profiles have been generated using the full PhSp for vali-
dation.
3.4. Optimization of Momentum 49

3.4 Optimization of Momentum

The optimization of energy (section 3.3) involved manipulating only its magnitude,
as energy is a scalar quantity. Momentum is a vector, unlike energy, and thus pos-
sesses a direction and a magnitude. The magnitude depends only on the photon’s
energy as a photon is intrinsically massless (Nagashima, 2010 p.14). Furthermore,
the energy of the photons was previously optimized. This effectively meant that
only the direction of the momentum had to be optimized.

3.4.1 The Momentum Direction and the Geometric Penumbra

The photon beam has a position dependent divergence for every particle in the PhSp.
The divergence of a random particle located at A, as shown in Fig. 3.10, has been
presented. The beam is traveling in the -Y direction. The momentum of this particle
−→ −→
is in the direction AB making an angle α with the beam direction, AC. The diver-
gence div, for this particle is defined as (3.6), where Px , Py and Pz are the momentum
in the x, y and z direction.

s
Px2 + Pz2
div = tan α = (3.6)
Py2

F IGURE 3.10: 3D visualization of the photon beam. The blue plane

represents the PhSp in the XZ plane. A random particle is located at
A on the PhSp with the total momentum in the direction AB making
an angle α with the beam direction. The beam is traveling in the -Y
direction.
50 Chapter 3. Optimization of Phase Space File

F IGURE 3.11: Measured inline lateral profiles for field size 10x10 cm2 .
The fitting function used is a sigmoid which will be explained in sec-
tion 3.4.2.

The dose in lateral profile within the water phantom has a distinct steep climb as
can be seen in Fig. 3.11. This is called the penumbra of the lateral dose profile which
is typically taken as the dose profile between 20% and 80% of the maximum dose. It
is the dose profile at the geometric penumbra of the radiation region. The geometric
penumbra, p geom , is defined as the width of the radiated region where the source is
partly shielded by the collimator, as shown in Fig. 3.12.

F IGURE 3.12: A schematic visualization of the geometric penumbra,

AB and CD. These regions receive partial shielding from the collima-
tor assembly. SCD is the distance of the collimator from the source.
The geometrical edge is the ideal edge of the radiation limit for a point
source at the source position along the central axis. f is the distance of
the profile plane from the source. The geometric penumbra decreases
with increasing SCD, increasing f and/or decreasing source size.

The dose profile in this region depends largely, but not exclusively, on the photon
source size, the distance from the source and the source to collimator distance (SCD).
This photon source size in X-ray beam therapy strongly depends on the electron spot
3.4. Optimization of Momentum 51

size which the electron beam makes on the target. Experimental studies on the de-
pendence of the dose profile in the penumbra region and the electron spot size have
been presented in Sterpin et al., 2011; Wang and Leszczynski, 2007. Furthermore,
any change in the divergence of the particles in the PhSp reflects as a change in the
virtual photon source size when traced back along the beam upstream as can be seen
in Fig. 3.13. This also effectively changes the virtual electron spot size. Lastly, as the
divergence is essentially a function of the momentum of the particle, the penumbra
region in the lateral profiles were taken as a measure to optimize the momentum of
the particles inside the PhSp.

F IGURE 3.13: A schematic visualization of changing focal spot of the

electron beam size with the change in divergence of the photon beam.
Here the focal spot is in reference to the electron spot.

3.4.2 The Cost Function

With emphasis placed on the accuracy of the penumbra region of the lateral profiles,
a cost function, which is a good indicator of the disagreement between the simula-
tion and the measurement, was defined. A sigmoid was chosen as the corresponding
fitting function. The rationale of choosing sigmoid are presented later in this section.
A sigmoid function has a characteristic "S" shaped curve and is defined by Eq.
(3.7),

1
y= (3.7)
1 + exp(−k ( x − x0 ))

Here k is the slope and x0 is the position of the center of the sigmoid. The cost
functions are defined by (3.8) and (3.9),

k − k̂
cost f or k = × 100 (3.8)
k
x0 − x̂0
cost f or x0 = × 100 (3.9)
x0

Here k and x0 are the fitting parameters for measurements, and k̂ and x̂0 are the
fitting parameters for the simulations.
The difference in the fitting parameters were chosen as the cost function instead
of a simple χ2 function (Eq. (3.3) in section 3.3.1) as the latter only provides an
absolute quantified value of disagreement. However, the difference in the fitting
52 Chapter 3. Optimization of Phase Space File

parameters are more informative. They indicate distinctly the quantified positive or
negative disagreement in the slope and the position of the center of the sigmoid.
The "curve_fit" function in the "optimize" class of Python 2.7 library Scipy was
used for all sigmoid fittings. It takes the set of Cartesian coordinates of the curve as
input and returns fitting parameters (k and x0 ) of a sigmoid function optimized to
follow this curve as shown in Fig. 3.14.

Rationale for using Sigmoid

The sigmoid has been found to be stable against different fitting periods. A fitting
period from 0.0 to 1.0, for normalized dose values normalized to the mean of the
dose deposited near and at the center, implies that all dose values from 0.0 to 1.0,
along with their corresponding positions were selected as the input for finding out
the optimized fitting parameters for a sigmoid function.
Two cases of fitting using sigmoid with different fitting periods has been consid-
ered as can be seen in Fig. 3.14. The corresponding cost values were then calculated
which are presented in Table 3.4. The cost values for k for the two cases have a dif-
ference of less than 0.2%, being 25.12% and 25.15% . The corresponding x0 values
have no difference.
On conducting a similar analysis with a linear fitting for the penumbra region, it
was found that the difference in the cost values for k and x0 between two different
fitting periods were more than 36% and 39% respectively, as can be seen from Table
3.5. The cost functions used in the case of linear fitting were the same as Eq. (3.8)
and (3.9) where k is the slope and x0 is the y-intercept of the linear function.
Thus, it can be concluded that the sigmoid fitting is a much more stable fitting
function and is hence a preferable choice for comparisons of lateral profiles. A sim-
ilar conclusion has been pointed out in Aljarrah et al., 2006 discouraging the use of
linear fitting.

TABLE 3.4: The Sigmoid Fitting Parameters

Fitting Period cost(k) cost(x0 )

0.0 - 1.0 25.12% 1.27%
0.0 - 1.1 25.15% 1.27%

TABLE 3.5: The Linear Fitting Parameters

Fitting Period cost(k) cost(x0 )

0.2 - 0.8 15.58% 16.4%
0.2 - 0.9 9.85% 10.49%
3.4. Optimization of Momentum 53

F IGURE 3.14: Two cases of sigmoid fitting with different fitting peri-
ods. The corresponding cost values for k and x0 are shown.

3.4.3 Correlation between the Divergence and Penumbra

Every particle in the PhSp has a divergence (as given by Eq. (3.6) in section 3.4.1)
which is linearly dependent on its radial position, as can be seen from the green line
in Fig. 3.15. This linear relationship from hereon will be referred to as the beam
divergence line. The individual divergences of the particles define the divergence
of the photon beam macroscopically. Hence, by changing the divergence of every
particle in a controlled manner, the macroscopic divergence of the entire beam can
be steered. However, this change or perturbation must be consistent with the beam
divergence line. This implies that the perturbed divergence must have a linear rela-
tionship with the radius as well. Thus, the only perturbation possible is the change
in the slope of the beam divergence line.
54 Chapter 3. Optimization of Phase Space File

F IGURE 3.15: The slope of the beam divergence line, shown in green,
is perturbed by a factor of µ, transforming it to the beam divergence
line shown in red. The Y-intercept value is maintained at c.

The Slope perturbation factor : µ and its identities

To manipulate the slope of the beam divergence line, the divergence of all the par-
ticles must be manipulated. These transformed divergences of the particles in the
PhSp should also be linearly dependent on the radial position to be consistent with
the transformed beam divergence line (the red straight line in Fig. 3.15). The slope
of the original beam divergence line, shown as the green line in Fig. 3.15, is defined
as m. The slope of the transformed beam divergence line is defined as m̂, which is
related to m by Eq. (3.10).

m̂ = µm (3.10)

Here µ is the perturbation factor for the slope of the beam divergence line. The
individual transformation identities for the momentum of the particles to carry out
a perturbation factor µ are presented in this section.
The original quantities are div(r ), m, c, Px , Py and Pz , where div(r ) is the diver-
gence of a particle at a radial distance r, m and c is the slope and the y-intercept
of the linear relationship between the divergence and the radial distance (as can be
seen in Fig. 3.15). Px , Py and Pz are the momentum of the particle, whose divergence
is being transformed in the x, y and z direction. div ˆ (r ), k̂, ĉ, P̂x , P̂y and P̂z are the re-
spective transformed quantities. The beam direction is in -Y and the PhSp is placed
at the XZ plane as presented in Fig. 3.10
3.4. Optimization of Momentum 55

The equations and constraints to be considered for divergence manipulation are

listed as following:

div(r ) = mr + c (3.11)
ˆ (r ) = m̂r + ĉ
div (3.12)
m̂ = µm (3.13)
ĉ = c (3.14)
P̂x Px
= (3.15)
P̂z Pz
2 2 2 2
Px + Py + Pz = P̂x + P̂y2 + P̂z2 = 1 (3.16)

Eq. (3.11) and (3.12) are the straight line function for the original and the trans-
formed divergence with varying radius, r. Eq. (3.13) is the transformation of the
slope of the beam line divergence from m to m̂. Eq. (3.14) maintains the divergence
of the particles in the central region of the PhSp. Eq. (3.15) is the constraint identified
which assures that the momentum of the particles do not twist around the central
axis by maintaining the ratio between Px and Pz . Eq. (3.16) is the normalization
condition of the momentum which needs to be maintained.
The goal is to find the transformation identities to be applied to P̂x , P̂y and P̂z ,
given a momentum perturbation factor µ. Starting with Eq. (3.11) and (3.12)

div(r ) − c
m= (3.17)
r
ˆ
div(r ) − c
m̂ = (3.18)
r
Replacing (3.17) and (3.18) in (3.13)

ˆ = µ(div − c) + c
div (3.19)

Using (3.19) and the original definition for the divergence (3.6)
s
P̂x2 + P̂z2 Px2 + Pz2
= ( µ ( 2
− c ) + c )2 (3.20)
2
P̂y Py

Using (3.16) and (3.20)

s
1 Px2 + Pz2
= (µ( − c ) + c )2 + 1 (3.21)
P̂y2 Py2
56 Chapter 3. Optimization of Phase Space File

Let the definition of γ be,

s
Px2 + Pz2
γ = (µ( − c ) + c )2 + 1 (3.22)
Py2

Using (3.21) and (3.22), the equation describing the transformed Py is obtained as

1
P̂y2 = (3.23)
γ

Let the definition of ω be,

Px
ω= (3.24)
Pz
Using (3.20) and (3.23)

s
Px2 + Pz2
γ( P̂x2 + P̂z2 ) = (µ( − c ) + c )2 (3.25)
Py2

Substituting (3.24) in (3.25) the equation describing the transformed Pz is ob-

tained
s
Px2 + Pz2
γ(ω 2 P̂z2 + P̂z2 ) = (µ( − c ) + c )2
Py2
1 1
P̂z2 = 2
(1 − ) (3.26)
1+ω γ

Finally, using (3.24) and (3.26) the equation describing the transformed Px is ob-
tained as

ω2 1
P̂x2 = (1 − ) (3.27)
1 + ω2 γ

The final transformation identities for Px , Py and Pz (as referred from (3.23), (3.26)
and (3.27)) for a transformation m → µm are summarized below

2 ω2 1
P̂x = 2
(1 − ) (3.28)
ω +1 γ
2 1
P̂y = (3.29)
γ
2 1 1
P̂z = 2 (1 − ) (3.30)
ω +1 γ

where
Px
ω=
Pz
3.4. Optimization of Momentum 57

and
s
Px2 + Pz2
γ = (µ( − c ) + c )2 + 1
Py2

Sigmoid Fitting Parameters for Varying µ

The identities given by Eq. (3.28), (3.29) and (3.30) were used to find a correlation
between the slope perturbation factor, µ, and the fitting parameters, k and x0 , of the
sigmoid. An investigatory study was carried out to determine whether a distinct
relationship exists between the slope perturbation factors and the sigmoid fitting
parameters. For this purpose, multiple simulations were performed, the details of
which are explained in this section.
To reduce the simulation time to a minimum, a cropped PhSp of 5 mm cropping
radius and a field size of 2x2 cm2 was chosen. The inline profiles were simulated
and the corresponding fitting parameters of the sigmoid were computed. The PhSp
was then perturbed by a factor of 0.001% (µ = 1.00001) and the inline profiles were
simulated again to find the new fitting parameters. This process was repeated 800
times perturbing the original PhSp each time by a factor of 0.001% higher (∆µ =
1.00001) than the previous simulation. This arithmetic progression is presented in
Table 3.6 for further clarification. The final perturbation factor in the last simulation
was 0.8% (µ = 1.008).

TABLE 3.6: The arithmetic progression of the perturbation factor with

respect to the sequence of simulation.

Sequence µ
0 1.00000
1 1.00001
2 1.00002
3 1.00003
.... ....
800 1.008

The results are presented in Fig. 3.16 and 3.17. The correlation was identified by
fitting a straight line through the scatter plot using linear regression as represented
by the red line in the aforementioned figures. It can be inferred from the two plots
that the fitting parameters k and x0 have a negative linear correlation with µ. This
implies that as the slope of the beam line divergence is increased, the corresponding
fitting parameters decrease in value. This was a crucial detection in this study. The
fitting parameters could now be steered using different perturbation factors.
58 Chapter 3. Optimization of Phase Space File

F IGURE 3.16: The sigmoid fitting parameter, k, for different slope per-
turbation factors (blue dots). The red line represents the linear fit to
the data.

F IGURE 3.17: The sigmoid fitting parameter, x0 , for different slope

perturbation factors (blue dots). The red line represents the linear fit
to the data.

3.4.4 Statistical Uncertainties among Simulations

It was observed that the sigmoid fitting parameters for multiple simulations using
the same configuration was different. These differences were as high as 15% in few
cases as can be seen in Fig. 3.18.
In order to establish the minimum number of simulations required to find a sta-
ble median, 50 identical simulations were performed and the median was calculated
using sets with different number of simulations, ranging from 1 to 50. The results,
presented in Fig. 3.19, indicate that the median becomes fairly stable when 20 or
more instances of simulation are considered. In this study 24 instances of simula-
tions is taken for every configuration as a cautionary measure.
3.4. Optimization of Momentum 59

F IGURE 3.18: Fitting Parameter k determined by multiple instances

of the same simulation for different field sizes.

F IGURE 3.19: Median of the varying fitting parameter k plotted

against sets with different number of instances of the same simula-
tion.

and it was obsere

3.4.5 Acceptable Cropping for Lateral Profiles

Similar to the technique adopted in the optimization of energy, cropped PhSp were
used in place of original ones for estimating the optimal slope perturbation factor (µ)
for the optimization of momentum. This reduced the simulation time substantially.
The cropping radius however was much larger because of the spatial dimension and
position of the detectors.
The IAEA PhSp was generated on a plane placed 272.10 mm below the X-ray
source as shown in the schematic presented in Fig. 3.20. The LMU PhSp was gen-
erated on a plane placed 27.9 mm below the IAEA PhSp, and thus positioned 300
mm away from the X-ray source. For a field size of 20x20 cm2 at the isocenter, the
distance OD must be 100 mm. Thus, the corresponding distance BC (30 mm) hereon
referred to as the relevant radius is computed by Eq. (3.31). BC represents the aper-
ture of the collimator that generates the field OD, beyond which the radiation is
60 Chapter 3. Optimization of Phase Space File

blocked. This marks the radius of the LMU PhSp within which the particles are of
relevance. The relevance of the particles beyond this radius drops substantially. The
minimum cropping radius should be much greater than this relevant radius as a cau-
tionary measure. The relevant radius gives a close approximation of the minimum
cropping radius, however multiple simulations using the cropped PhSp should be
performed and validated against the profiles generated using full PhSp.

300mm( AB) 1000mm( AO)

tanθ = = (3.31)
BC 100mm(OD )

The sigmoid fitting parameters of crossline and inline profiles generated using
the full PhSp are presented in Table 3.7 and 3.8 for field sizes 2x2 and 5x5 cm2 re-
spectively. These values have been compared with the corresponding fitting param-
eters generated using a cropped PhSp of cropping radius 20 mm. The percentage
differences (Diff%), as can be seen in the same table, in all of the cases is acceptable.
This proves that the cropping radius of 20 mm for the field size 2x2 and 5x5 cm2 is
acceptable.

TABLE 3.7: Comparing the inline fitting parameters determined us-

ing a cropped PhSp and the full PhSp.

Field Size (cm2 ) (k, x0 )Full PhSp (k, x0 )Cropped PhSp (k, x0 )Diff%
2x2 0.9782,9.418 0.9712, 9.379 0.71%, 0.41%
5x5 0.8724,23.196 0.8742,23.184 0.20%, 0.04%

TABLE 3.8: Comparing the crossline fitting parameters determined

using a cropped PhSp and the full PhSp.

Field Size (cm2 ) (k, x0 )Full PhSp (k, x0 )Cropped PhSp (k, x0 )Diff%
2x2 0.7892, 9.5179 0.7696, 9.5010 2.48%, 0.17%
5x5 0.7392, 23.335 0.7432, 23.3261 0.54%, 0.03%
3.4. Optimization of Momentum 61

F IGURE 3.20: The spatial configuration of the setup for simulating

the lateral profiles. The isocenter is at a distance of 1000 mm from
the surface. The medium is a Blue (Water) Phantom (IBA Dosime-
try, Schwarzenbruck, Germany). The source to surface distance is
900 mm. The LMU PhSp is placed at a distance of 300 mm from the
source. The detector for the lateral profiles is placed at a depth of 15
mm from the surface. (Not drawn to scale).

3.4.6 Finding the Optimal Slope Perturbation Factor for Crossline (µcr ) or
Inline (µin )
In this section, the sequential steps followed to find the optimal slope perturbation
factor for particles in the crossline ,µcr or inline direction, µin are presented. The two
perturbation factors µcr and µin are determined using the same technique. For the
purpose of this demonstration, µcr has been determined and the final cost values are
presented. The field size is 10x10 cm2 and a cropped PhSp, with a cropping radius
of 50 mm, has been used.
The technique follows 10 steps which are presented below.

1. The PhSp was cropped to an acceptable cropping radius as explained in section

3.4.5.
2. A second cropped PhSp was generated and perturbed by a relatively large
factor of 0.8% using the transformation identities 3.28, 3.29 and 3.30.
3. Crossline profiles were generated using the two PhSps. 24 instances of simu-
lation for each PhSp were performed.
4. The fitting parameters, k and x0 , were determined for all 48 profiles and their
respective medians were calculated as can be seen in Fig. 3.21.
62 Chapter 3. Optimization of Phase Space File

5. A straight line passing through the two medians was then plotted (the diago-
nal red line in Fig. 3.21). This signifies the statistical correlation between the
fitting parameters and the perturbation factor. It is analogous to the linear cor-
relation presented in Fig. 3.16 and 3.17. The µcr , for the field size 10x10 cm2 , is
the intersection between the red line and the green line, where the latter rep-
resents the k value for the measured curve. The intersection is highlighted by
the green dot in Fig. 3.21.

6. The steps (1-5) were repeated for the field size 2x2, 5x5 and 20x20 cm2 and the
respective µcr specific to every field size was determined.

7. The final µcr , which in this example was determined to be 1.00605, was taken
as the average of the four µcr values, specific to each field size, as mentioned
in step 6.

8. A third full PhSp was then perturbed by the determined µcr . 24 instances of
simulations were performed to generate crossline profiles.

9. The median of the respective fitting parameters was determined, represented

by the boxplot in the middle in Fig. 3.21, and the final cost values were calcu-
lated. The final k and x0 (median of the respective k and x0 fitting parameter)
and the final cost values are presented in the mentioned figure.

This process is repeated to determine µin by generating inline profiles instead of

crossline profiles.
It was observed that the optimal perturbation factors for k and x0 were very
different from each other. However, the gradient descent of x0 with respect to in-
creasing µ was exceedingly slower than the corresponding decreasing rate of k. A
perturbation factor of 0.8% decreased the k by ∼ 20% and x0 by merely ∼ 0.75%.
Moreover, the absolute difference in error in case of x0 was evaluated to be less than
0.3 mm as can be seen in Fig. 3.21(B). Hence, the perturbation factor for k was given
precedence over the perturbation factor for x0 , which will not be considered in the
remaining sections of this study. It was made certain the final cost values for x0 were
within reasonable limits for all field sizes.
3.4. Optimization of Momentum 63

F IGURE 3.21: The linear correlation of the slope perturbation factor

and the sigmoid fitting parameters are represented by the diagonal
red lines. The green horizontal lines represent the fitting parameters
of the measured crossline profile. The green dot represents the inter-
section of both lines, which gives the optimal perturbation factor in
the crossline direction for the field size 10x10 cm2 . The optimized fit-
ting parameters are represented by the boxplots in the middle. The
final cost values are mentioned in the bottom left of the plots.

3.4.7 Merging µcr and µin : Approaches and Results

It was found that the optimal perturbation factors for crossline and inline, µcr and
µin , were very different from each other being 1.00605 and 1.00051 respectively. This
essentially means that the divergence of the beam in the crossline direction is differ-
ent from the divergence in the inline direction. Merging the two optimal perturba-
tion factors has been a challenge as there is a considerable cross correlation between
the factors and their profiles. This has been better explained in the coming sections.
The final cost values for the crossline profiles achieved by following the methodol-
ogy, explained in the previous section 3.4.6, are presented in Table. 3.9. The initial
64 Chapter 3. Optimization of Phase Space File

costs (after the optimization of energy) for inline profiles were already low, as pre-
sented in Table 3.10, thus the focus was kept on optimizing the crossline profiles
while maintaining the low cost values for inline. ∆Cost is given by Eq. (3.32). ∆Cost
written in green represents a drop in cost and in red represents a gain in cost.

∆Cost = || Initial Cost| − | Final Cost|| (3.32)

TABLE 3.9: Results of the crossline profile (corresponding to fitting

parameter k) following the methodology, explained in the previous
section 3.4.6. ∆Cost written in green represents a drop in cost and in
red represents a gain in cost

Field Size (cm2 ) Initial Cost Final Cost ∆Cost

2x2 -22.37% -1.82% 20.55%
5x5 -24.71% -1.62% 23.09%
10x10 -15.23% -2.67% 12.56%
20x20 -12.69% -1.49% 11.20%

Furthermore, the methodology explained in section 3.4.6 optimizes the PhSp sep-
arately for crossline and inline. This meant that in the end, there were two PhSps,
one was optimized for crossline profiles and the other for inline profiles. Multiple
approaches were formed and tested to merge the two factors. Among them, the
three best performing approaches have been presented in the coming sections.
Initial cost values for all the field sizes are given in Table 3.10 as reference for the
results presented in the coming sections.

TABLE 3.10: Initial cost values for inline and crossline profiles as ref-
erence.

Field Size (cm2 ) Initial Cost for Crossline Initial Cost for Inline
2x2 -22.37% -1.81%
5x5 -24.71% -1.09%
10x10 -15.23% -1.30%
20x20 -12.69% -1.57%

The φ2 approach
This approach uses Eq. 3.33 to find the optimal perturbation factor, µop for every par-
ticle as a function of its radial position in the PhSp plane. It was initially assumed
that the crossline dose profiles are largely dependent on the divergence of the parti-
cles near the crossline. Here φ is the angular position of the particle with respect to
the crossline direction as can be seen in Fig. 3.22 (A). The PhSp is in the XZ plane,
represented by the blue circle.

µop = cos(φ)2 µcr + sin(φ)2 µin (3.33)

3.4. Optimization of Momentum 65

The technique to find the corresponding µin and µcr remains the same as in sec-
tion 3.4.6. However, in step 8 (3.4.6) when a third full PhSp is simulated, the per-
turbation is carried out using Eq. (3.33) instead of a flat perturbation, as presented
in Fig. 3.22 (B) (the red and the green horizontal line). The final perturbation µop is
represented by the thick blue line in the same figure.
The result is presented in Table 3.12. It can be seen that the cost values for
crossline and inline profiles are much higher than the cost values achieved in sec-
tion 3.4.6. The inline cost increases even when the divergence of the particles within
a local angular distance from the inline direction is not considerably perturbed. This
can be seen by the behavior of the thick blue line in Fig. 3.22 (B) which represents
the different perturbation factors with varying angular position from crossline to
the inline direction. Furthermore, the crossline profiles failed in maintaining their
low cost values even when the slope of the beam line divergence was considerably
perturbed locally. Thus, it is perceived from the results that the dose profile in the
inline does not strictly depend only on the divergence of the local particles. It also
depends on the divergence of the particles located far away. This dependence how-
ever decreases on going further away from the inline direction. The same could be
inferred for the crossline. This proves that the initial assumption was wrong. A
more intuitive explanation is presented in Fig. 3.22 (A). The PhSp is represented as
the blue circle in the XZ plane. The relevance of the divergence of the particles for
the crossline profile is represented as different shades of pink. The more intense the
color the higher the relevance.

TABLE 3.11: Results of the crossline profile for φ2 approach. ∆Cost

written in green represents a drop in cost and in red represents a gain
in cost.

Field Size (cm2 ) Cost for Crossline(∆Cost) Cost for Inline(∆Cost)

2x2 -12.20% (10.17% ) 4.82% (-3.01% )
5x5 -12.96% (11.75% ) 4.50% (-3.41% )
10x10 -4.29% (10.94% ) 5.88% (-4.58% )
20x20 -9.49% (3.2% ) 1.44% ( 0.13% )
66 Chapter 3. Optimization of Phase Space File

(A)

(B)

F IGURE 3.22: (A) A schematic representation of the PhSp plane (the

blue circle). The angular position of a particle on the PhSp is denoted
by φ. The pink shaded region is a visual representation of the degree
of relevance of the particles for the crossline dose profile, as explained
in the text (not shaded to scale). (B) The variation of µop with increas-
ing angular distance, φ as presented in this section, represented by
the thick blue line. The green and the red horizontal lines are the
individual flat perturbation factors, µcr and µin respectively.
3.4. Optimization of Momentum 67

The compensated φ2 approach

The compensated φ2 approach is derived from the φ2 approach presented in the
previous section. In this technique, the µcr was revamped to a higher value to com-
pensate for the eventual fall off with increasing angular position as presented in Fig.
3.23. The µin was also lowered to compensate for an increase in divergence with
decreasing φ. The optimal perturbation factor was calculated using Eq. (3.34) where
0 are compensated crossline and inline perturbation factors given by Eq.
µ0cr and µin
(3.35) and (3.36).

µop = cos(φ)2 µ0cr + sin(φ)2 µin

0
(3.34)
µ0cr = ζ · µcr , ζ ≥ 1 (3.35)
0
µin = η · µin , η ≤ 1 (3.36)

F IGURE 3.23: The variation of µop with increasing angular distance,

φ as presented in this section, represented by the thick blue line.

The optimization was performed in iterations of different compensated values of

the two perturbation factors. The amount of compensation was estimated using the
final cost values of the previous iteration. These cost values can either be negative
or positive. A positive cost value indicates the need of convergence, which implies
decreasing the perturbation factor and a negative cost value indicates the need of
divergence, which implies increasing the perturbation factor.
Four iterations of different perturbation factors and their corresponding cost val-
ues are presented for the field size 2x2 and 5x5 cm2 . The results presented in Table
3.12, also plotted in Fig. 3.24, show a very clear trade-off between the cost values
for crossline (drawn in purple) and inline (drawn in orange). The cost values for
the crossline steadily increase (mostly) while the cost values for the inline steadily
decrease with different combinations of µ0cr and µin0 .
68 Chapter 3. Optimization of Phase Space File

TABLE 3.12: Cost values for different combinations of µ0cr and µin 0 .
∆Cost written in green represents a drop in cost and in red represents
a gain in cost.

Field Size (cm2 ) µ0cr 0

µin Cost for Crossline(∆ Cost) Cost for Inline(∆ Cost)
2x2 1.01045 0.999 -6.07%(16.30%) 9.28%(-7.47%)
5x5 1.01045 0.999 -2.47%(22.24%) 8.45%(-7.36%)

2x2 1.01063 0.998 -8.12%(14.25%) 10.28%(-8.47%)

5x5 1.01063 0.998 -3.23%(21.48%) 8.17%(-7.08%%)

2x2 1.01053 0.997 -8.24%(14.13%) 8.10%(-6.29%)

5x5 1.01053 0.997 -4.07%(20.64%) 6.40%(-5.31%)

2x2 1.01053 0.996 -12.57%(9.80%) 6.79%(-4.98%)

5x5 1.01053 0.996 -6.95%(17.76%) 5.83%(-4.74%)

F IGURE 3.24: The variation of absolute cost with different combina-

tions of µ0cr and µin
0 . Iteration sequence are just integers denoted to
every such combination. A trade-off between the crossline and the
inline cost values is evident. Iteration sequence 3 represents the last
combination enumerated in Table 3.12.
3.4. Optimization of Momentum 69

The compensated φ6 approach

This approach is a derivation of compensated φ2 approach. It has been established
that there is a cross-correlation between µcr and the inline profile, and between µin
and the crossline profile as explained in the previous approach. Furthermore, it has
also been established that there is a trade-off between cost values for crossline and
inline profiles for different combinations of µ0cr and µin . Thus, this approach is based
on a faster fall off as can be seen in Fig. 3.25 to control this cross-relation and the
subsequent trade-off. The thick pink line is the total optimal perturbation factor
based on the compensated φ2 approach. The thick blue line is the total optimal
perturbation factor for this approach. It has a faster fall with increasing angular
position φ when compared to compensated φ2 approach. It is calculated using Eq.
(3.37).

µop = cos(φ)6 (µ0cr − 1) + sin(φ)6 (µin

0
− 1) + 1 (3.37)

F IGURE 3.25: The variation of µop with increasing angular distance,

φ as presented in this section, represented by the thick blue line. The
thick pink line is the variation of µop with increasing angular distance,
φ, as presented in section 3.4.7.

Crossline profiles were generated corresponding to a higher value of µ0cr , 1.0120,

0 was kept at 1. The cost values
as compared to the values considered in 3.4.7. The µin
2
for the field size 2x2 and 5x5 cm showed a slight improvement over the cost values
achieved in the previous section. The crossline and inline profiles were then gener-
ated for the field size 2x2, 5x5, 10x10 and 20x20 cm2 with full PhSp for validation.
The final cost values are presented in Table 3.13.
70 Chapter 3. Optimization of Phase Space File

TABLE 3.13: Final cost values of the best performing approach, com-
pensated φ6 , for field sizes 2x2, 5x5, 10x10 and 20x20 cm2 using the
full PhSp. ∆Cost written in green represents a drop in cost and in red
represents a gain in cost.

Field Size (cm2 ) µ0cr 0

µin Cost for Crossline(∆ Cost) Cost for Inline (∆ Cost)
2x2 1.01200 1.000 -10.87%(9.89%) 5.49%(-3.68%)
5x5 1.01200 1.000 -7.42%(17.29%) 5.74%(-4.65%)
10x10 1.01200 1.000 -1.97%(13.26%) 4.58%(-3.28%)
20x20 1.01200 1.000 -7.87%(4.82%) 1.71%(0.14%)
3.4. Optimization of Momentum 71

3.4.8 Final Results

The final cost values achieved using the best performing approach, compensated
φ6 (3.4.7), as compared to the initial cost values for lateral profiles, prior to energy
optimization, are presented in Tables 3.14 and 3.15. The difference in the cost values
are presented in the column ∆Cost. The drop in cost is written in green and a gain in
cost is written in red. The optimal perturbation factors for crossline,µ0cr , and inline,
0 , is determined to be 1.01200 and 1.000 respectively. The profiles were generated
µin
for field sizes 2x2, 5x5, 10x10 and 20x20 cm2 . The full PhSp, optimized for energy
and momentum, was used. Overall, there has been a reduction in the cost by an
average of 7.10% when compared to the initial cost values determined before the
optimization of energy and momentum. This refers to the average ∆Cost value.

TABLE 3.14: Final cost values of the crossline profiles for the best per-
forming approach, compensated φ6 , generated for field sizes 2x2, 5x5,
10x10 and 20x20 cm2 using the full PhSp as compared to the initial
cost values before the optimization of energy and momentum. The
initial cost values before the optimization of energy can be obtained
from Table 3.3. ∆Cost written in green represents a drop in cost and
in red represents a gain in cost.

Field Size (cm2 ) Initial Cost Final Cost ∆Cost

2x2 -22.75% -10.87% 11.88%
5x5 -20.36% -7.42% 12.94%
10x10 -16.06% -1.97% 14.09%
20x20 -10.77% -7.87% 2.9%

TABLE 3.15: Final cost values of the inline profiles for the best per-
forming approach, compensated φ6 , generated for field sizes 2x2, 5x5,
10x10 and 20x20 cm2 using the full PhSp as compared to the initial
cost values before the optimization of energy and momentum. The
initial cost values before the optimization of energy can be obtained
from Table 3.2. ∆Cost written in green represents a drop in cost and
in red represents a gain in cost.

Field Size (cm2 ) Initial Cost Final Cost ∆Cost

2x2 -14.43% 5.49% 8.94%
5x5 -5.91% 5.74% 0.17%
10x10 -4.26% 4.58% 0.32%
20x20 -7.97% 1.71% 6.26%
72 Chapter 3. Optimization of Phase Space File

3.5 Discussion
A PhSp is essentially an enormous matrix of interconnected numerical values. These
values define the physical properties of the particles it stores. The PhSp is character-
istic to the linac MC model which generates it. In this study an attempt was made to
manipulate a PhSp of one linac model to optimize it for another linac model.
The complete optimization of the PhSp involved optimizing 4 physical quan-
tities, the energy and the momentum in the three directions. A technique named
cropping was introduced in which the phase space file was cropped into smaller ra-
dially symmetric circles. It was observed that this technique was powerful to fasten
the estimation of the optimal perturbation factors for both energy and momentum.
The optimization of energy was straightforward and less challenging than the opti-
mization of momentum. For the energy optimization, a simple addition/subtraction
operation is necessary. In this study, it was found that an optimal addition of 0.32
MeV should be applied to all photons inside the original PhSp (correspondent to the
IAEA Elekta Precise PhSp), in order to adapt this for modeling the Elekta Synergy
linac. This optimal perturbation decreases the PDD cost values to a maximum of
1.39% for all field sizes. Moreover, the agreement between measured and simulated
lateral profiles in the inline directions increased after the energy of the particles was
optimized. Fig. 3.26 shows lateral profiles for the 2x2 cm2 field in the inline direc-
tion, as simulated with the original PhSp (left) and with the energy-optimized PhSp
(right), in comparison to the measured lateral profile. The absolute cost values for k
and x0 decreased from 7.86% to 1.09% and from 1.41% to 0.93%, respectively.

(A) (B)

F IGURE 3.26: (A) Inline dose profile for a field size 2x2 cm2 before the
optimization of energy. (B) Inline dose profile for a field size 2x2 cm2
after the optimization of energy and momentum. The profile after the
optimization of energy has a lower cost value.

It was also observed that the percentage depth dose profiles retained their low
cost values after the momentum was optimized as can be seen in Fig. 3.27.
The optimization of the momentum, however, was very demanding. A distinct
mathematical relationship between the sigmoid fitting parameters of the lateral pro-
files and the slope of the beam line divergence was detected. This provided a di-
rection on how to manipulate the divergence of the particles. Due to statistical un-
certainties, a minimum number of simulation instances for the same configuration
was estimated, and in the present work 24 instances were used. The median of
the fitting parameters was then taken as the final result of that simulation. Accept-
able cropping radii were determined for all field sizes to improve the efficiency of
3.5. Discussion 73

(A) (B)

F IGURE 3.27: (A) Percentage Depth Dose profile for a field size 10x10
cm2 before the optimization of momentum. (B) Percentage Depth
Dose profile for a field size 10x10 cm2 after the optimization of mo-
mentum.

simulations. A methodology was developed to determine the optimal perturbation

factors for the particles in the inline and crossline directions. Multiple approaches
were implemented and analyzed for the optimization of momentum to merge the
two determined perturbation factors. It was observed that crossline and inline dose
profiles do not strictly depend on the divergence of the particles positioned locally.
An attempt at optimizing the crossline profiles affected the inline profiles consider-
ably. The change in the slope of the beam line divergence from the crossline direction
to the inline direction requires in depth research. Three approaches were presented
with results. The best approach was determined to be compensated φ6 approach,
explained in section 3.4.7. The optimal perturbation factors were determined using
this approach and the corresponding crossline and inline profiles were generated
using the final perturbed full PhSp, after applying the optimal perturbation for both
energy and momentum. The final cost values were determined and compared with
the initial cost values determined before the optimization of energy. Collectively, the
cost has decreased substantially and with an average ∆Cost of 7.10%.
To find out if the cropping radius influences in determining the perturbation val-
ues for the lateral profiles, a study was performed comparing two cropped PhSp
with two different cropping radii, 30 mm and 50 mm, using the technique explained
in section 3.4.6. Field sizes 2x2, 5x5 and 10x10 cm2 were used to determine the opti-
mal perturbation factors in case of cropped PhSp with cropping radius 30 mm while
all field sizes were used for the PhSp with the cropping radius 50 mm. The results
are presented in Table 3.16.

TABLE 3.16: Optimal perturbation factors determined using PhSp

cropped with different cropping radii.

Cropping radius µcr µin Simulation time

30mm 1.00601 1.00042 ∼1 day
50mm 1.00605 1.00051 ∼2 days

It can be inferred from the results that a smaller cropping radius of 30 mm and
lateral profiles for 3 field sizes were sufficient to determine the optimal perturbation
74 Chapter 3. Optimization of Phase Space File

factor with acceptable precision. The time taken for estimating the perturbation fac-
tors was reduced by half when a cropping radius of 30 mm was taken. Furthermore,
it was observed that a cropping radius of 20 mm was acceptable for determining
the cost values of the profiles for field size 2x2 and 5x5 cm2 but was not sufficient
in finding out the optimal perturbation factors. A cropping radius of 5 mm is not
acceptable in calculating absolute cost values for 2x2 cm2 . It was however, useful in
testing theories quickly, similar to the study presented in section 3.4.4. To conclude
the discussion, it is crucial to mention that measurements of the dose profiles in mul-
tiple angular directions between the crossline and the inline on the lateral plane are
required for further investigation. These measurements taken from the linac will
assist in determining the slope of the beam line divergence as it transitions from the
crossline direction to the inline.
 75

Chapter 4

EPID-based QA Tool

In 1982 Anders Brahme, then an Assistant Professor at Stockholm University, Swe-

den, published his revolutionary work, “Solution of an integral equation encoun-
tered in rotation therapy”. In essence he had solved the inverse planning problem in
conformal radiotherapy. Convery and Rosenbloom, 1992, in their paper, presented
a novel method to perform efficient IMRT delivery with an MLC which is still used.
Bortfeld et al., 1990 proved that a conformal dose delivery is possible with less than
10 fields from different angles. After a decade more of research and development,
IMRT was routinely being used in radiotherapy by the beginning of this century.
Thus, the advent of the IMRT created the need of rigorous Quality Assurance (QA)
procedures. The development of imaging devices like EPID opened up new possi-
bilities for the QA of patient specific parameters. Although conventionally used as a
verification device for the patient position, its potential in the field of dosimetry was
soon identified (Nijsten et al., 2007; Podesta et al., 2014).
In the clinical work-flow of conformal radiotherapy (described in section 2.3.4),
once the treatment plan has been designed it needs to be validated. The research
project by Alhazmi et al., 2018, of which this work is a part of, aims at developing an
EPID-based approach to reconstruct a 3D dose distribution as imparted to a virtual
cylindrical water phantom. This approach is intended to be used as a measure for
validating the treatment plans before they are used in the dose delivery. For this pur-
pose a Novel EPID-based Audit Tool (NEAT) has been developed. It is a compact
Graphical User Interface (GUI) which can be used to reconstruct the aforementioned
3D dose distribution from start to end without the need of dealing with the low level
code directly. NEAT is then used to audit the reconstruction algorithm by recon-
structing dose distributions corresponding to 22 VMAT treatment plans. VMAT is
an advanced technique of IMRT and has been explained in the chapter "Scientific
Background" (Chapter 2). The published paper, describing the reconstruction algo-
rithm and the peripheral methodologies, Alhazmi et al., 2018 from hereon will be
referred to as the parent paper.

4.1 Materials and Methods

MATLAB (Matrix Laboratory) is a licensed computing environment offered by Math-
Works, Inc., Natick, Massachusetts, US. It is specifically designed for matrix calcula-
tions (MATLAB 2018). The GUI has been developed using the built in functionality
offered by MATLAB, MATLAB GUI. The complete back-end code for the GUI, writ-
ten in MATLAB, has been provided by the research team of the parent paper. The
details of this paper will be briefly explained later in this chapter. Three separate
MATLAB toolboxes were purchased and installed, Curve Fitting, image Processing
and Statistics and Machine Learning as required by the reconstruction algorithm.
76 Chapter 4. EPID-based QA Tool

Microsoft Visual Studio was used for all C++ developmental needs. It is an inte-
grated development environment from Microsoft Corporation, Redmond, Washing-
ton, US (Microsoft, 2018).
Two applications written in C++ were developed by the research team of the par-
ent paper as part of the complete project, the automatic FrameGrabber and the iCOM
logger. Once initialized, the FrameGrabber continuously acquires frames from the
EPID regardless of whether the EPID is being radiated or not. Each frame is tagged
with a timestamp in nanosecond resolution. The iCOM logger once initialized, gen-
erates a separate time log file containing many details including the gantry angle,
the dose rate value, the position of the collimator assembly and the time in nanosec-
onds as soon as the beam is turned on. The information in this log file is used to
associate the gantry position to the corresponding EPID frame acquired using the
time-stamp as the stitching link.
All measurements were performed on Elekta Synergy R
linac coupled to Elekta
AgilityTM collimator (Elekta, Stockholm, Sweden) installed at Klinikum der Uni-
versität München - Campus Großhadern, Munich, Germany, using 6 MeV photon
beam. A PerkinElmer XRD 1640 AL5 P aSi EPID (Elekta iViewGT) mounted at
source to surface distance (SSD) of 160 cm was used for all frame acquisitions. A
self-contained computer system, from hereon referred to as the EPID computer, was
used for the EPID frame acquisitions.
A total of 22 VMAT treatment plans were audited using NEAT. These included
treatment plans for tumors located in different anatomical regions of the body such
as head and neck, prostate, esophagus, lymph nodes, cervix, scalp, vagina and
bronchi. The complete process of each audit consisted of three sequential steps
broadly, which are explained in this section.

4.1.1 Frame Acquisition

The center of the EPID is accurately positioned manually along the beam central axis
before the treatment plan is performed, as presented in Fig. 4.1. The frame acquisi-
tion cable is redirected to the EPID computer from the Elekta iViewGT computer as
shown in Fig. 4.2. NEAT is initialized using MATLAB. The field Frames Acquisition
Directory is browsed to the desired path where the frames are to be stored, as can be
seen in Fig. 4.3. The new path will be stored as the default and will be preloaded
in the Frames Acquisition Directory field the next time NEAT is initiated. A threshold
value is chosen which controls the cut-off range of acceptable radiation value. For
example, a threshold of 1.2 will acquire the EPID frames but will not store them un-
less the EPID is being radiated. A threshold value of 0.9 will acquire the EPID frames
and store them regardless of the radiation received by the EPID. Once the threshold
value is changed in NEAT, it will be stored as the default value.
The FrameGrabber and iCOM Logger are initialized by clicking on Start. After
few frames have been acquired without any radiation, the beam is turned on and the
treatment plan is performed. Once the plan is complete, both the processes are ter-
minated by clicking on Stop. The frames are then available in the Frames Acquisition
Directory.

3D Dose Reconstruction
Once the frames of the treatment plan are acquired, the 3D dose reconstruction is
performed using NEAT as the interface, and the reconstruction algorithm provided
by the research team of the parent paper, as the back-end code base. The first step
4.1. Materials and Methods 77

F IGURE 4.1: The accurate positioning of the EPID before the treat-
ment plan is performed as required. The center of the EPID is posi-
tioned along the isocenter axis at a depth of 160 cm from the X-ray
source. The green field is the laser guide which assists in estimating
the photon beam field position. The isocenter axis passes through the
intersecting point of the faint red cross.

in the reconstruction algorithm is to convert the pixel values in the frames to dose
values as imparted to a water equivalent medium, using predetermined conversion
factors and a set of correction procedures. The dose values thus obtained are back-
projected upstream at different depths. A series of mathematical operations are then
applied to this conglomeration of 2D planar distributions to obtain a 3D dose distri-
bution. The complete reconstruction technique has been explained comprehensively
in Alhazmi et al., 2018.
The interface of NEAT removes the need of dealing with the low level code. The
offset is loaded by clicking on Choose offset. This is usually the first frame in the treat-
ment plan, acquired without any radiation. It is used to filter out noise from the rest
of the frames. On clicking Choose offset a browse window of the file explorer pops
up. The offset frame is now chosen. Once the offset is successfully loaded the OFF-
SET in the STATUS wire-frame turns from EMPTY to LOADED. On clicking the Start
Reconstruction another browse window of the file explorer pops up. All the frames
required for reconstruction of the treatment plan are now selected by the user. These
include all the frames acquired while frames acquisition of a single treatment plan.
Once the frames are successfully loaded, the reconstruction starts. After the recon-
struction is complete, a Digital Imaging and Communications in Medicine (DICOM)
file is ready to be viewed or saved. DICOM is an international standard to transmit,
store, retrieve, print, process, and display medical imaging information (Sage et al.,
2007; DICOM Standard 2018). The DICOM in the STATUS wireframe turns from AB-
SENT to READY. It can be viewed through Show Reconstruction, as shown in Fig. 4.4.
Alternatively, the file can can be stored using Save DICOM. On clicking Save DICOM
a text field appears to type in the desired name of the new DICOM file, as shown in
Fig. 4.5. The interface also suggests a name, created using the current date and time.
The DICOM file is then saved at the same path as the Frames Acquisition Directory.
78 Chapter 4. EPID-based QA Tool

(A) (B)

F IGURE 4.2: (A) The Elekta iViewGT computer, enclosed in the blue
rectangle, receives the frames during the treatment. (B) The frame ac-
quisition cable is redirected to the EPID computer, shown in the pic-
ture, from the Elekta iViewGT computer, thus effectively redirecting
the acquired frames to the self-contained EPID computer.

F IGURE 4.3: The start interface of NEAT.

4.1. Materials and Methods 79

F IGURE 4.4: Once the reconstruction is complete the DICOM file can
be viewed by clicking on Show Reconstruction.

F IGURE 4.5: Once the reconstruction is complete the DICOM file can
be saved by clicking on Save DICOM.
80 Chapter 4. EPID-based QA Tool

Gamma Evaluation
In the final step a 3D gamma index evaluation, with the dose distribution calculated
by the Treatment Planning System (TPS), was performed for all the reconstructed 3D
dose distributions. The gamma index method was proposed and evaluated by Low
et al., 1998 in details, though it is summarized in this section for clarity. The gamma
index is used in determining the degree of agreement between a calculated and a
reference dose distribution and is given by Eq. (4.1).

r
r2 (~rc ,~rr ) δ2 (~rc ,~rr )
Γ(~rc , ~rr ) = + , γ(~rr ) = min{Γ(~rc , ~rr )} ∀ {~rc } (4.1)
∆d2 ∆D2
r (~rc ,~rr ) = |~rc −~rr | (4.2)
δ(~rc ,~rr ) = D (~rr ) − D (~rr ) (4.3)

Here, ~rc and ~rr are the radial vectors of all the points in the volume for the cor-
responding calculated 3D dose distribution and the reference 3D dose distribution.
r (~rc ,~rr ) is given by Eq. (4.2) and δ(~rc ,~rr ) is given by Eq. (4.3), where D (~r ) is the dose
deposited at the point ~r. For a certain distance to agreement (DTA) criteria, ∆d, and
a certain dose difference criteria, ∆D, the pass-fail decision is given by:

γ(rr ) ≤ 1 , calculation passes

γ(rr ) > 1 , calculation f ails

Here, γ(~rr ) is calculated using (4.1). These values are determined for every point
in the dose volume for the calculated dose distribution against the reference dose
distribution. In this study the result is given as a passing rate of the gamma criteria
(3 mm, 3 %), where 3 mm is the DTA and 3% is the dose difference criteria. This
represents the cumulative passing rate of all the points in the dose volume.
Gamma evaluation is not supported by NEAT and was computed on a sepa-
rate system using VeriSoft R
Patient Plan Verification Software, PTW, Freiburg, Ger-
many. This software offers multiple tools for dose comparison ranging from basic
visual comparison to detailed quantitative evaluation (PTW, 2018b). The results are
presented in section 4.2.
4.2. Final Results 81

4.2 Final Results

Every reconstruction was saved as a separate DICOM file corresponding to one of
the 22 treatment plans. These files were then compared to the reconstructed dose
distributions of the Treatment Planning System (TPS), as explained in chapter 2 sec-
tion 2.3.4. Gamma evaluation, as explained in the previous section, was performed
by VeriSoft R
. An example of this comparison using the software has been presented
in Fig. 4.6.

F IGURE 4.6: Comparison of the TPS calculated and a NEAT recon-

structed dose distribution of an exemplary treatment plan. The top
left and bottom left plots are the coronal plane of the TPS calculated
and NEAT reconstructed dose distributions, respectively. The differ-
ently colored contours stand for different dose percentages. The top
right plot is the 1D lateral profile of the corresponding vertical cen-
tral line in the top left plot. The bottom right plot is the visual plot of
gamma passing rates for the coronal plane. The red colored regions
stand for failing points with dose values higher than the reference
dose values. Here reference dose value is the TPS calculated dose dis-
tribution. The blue colored regions (not present in the plot) stand for
failing points with dose values lower than the reference dose values.

In this study 22 VMAT treatment plans were performed and evaluated. Before
the frame acquisition, the EPID is positioned manually such that its center point
intersects with the beam central line as shown in Fig. 4.1. This manual interven-
tion introduces errors in the alignment of the reconstructed dose positions as shown
in Fig. 4.7 (A). This shift is in the inline direction, also known as the target-gantry
(TG) direction. To determine a correction factor for this error, the first set of frame
acquisitions is performed for a square shaped beam with a field size of 10x10 cm2
without any linac rotation. These frames are reconstructed and compared with the
corresponding TPS calculations. If the 1D dose profile, for this reconstruction, in the
coronal plane is misaligned, then the reconstructed dose distribution is shifted by
a factor which aligns both the profiles. This factor is the aforementioned correction
factor in TG direction, hereby referred to as the TG factor. The coronal plane is the
82 Chapter 4. EPID-based QA Tool

plane normal to the beam central line. In this study, this TG factor is determined to
be 3.6 mm in the -Z direction as shown in Fig. 4.1. As a part of this audit process, it
was essential that such a correction factor is taken into consideration as an accurate
positioning of the EPID was a pre-requisite for the reconstruction algorithm. Fur-
thermore, the reconstructed dose distribution for the 10x10 cm2 field was also used
to determine a recalibration or normalization factor (NF). If in a certain case, the ab-
solute dose values of the reconstructed dose distribution are considerably higher or
lower than the corresponding TPS calculations, then the reconstructed dose values
are normalized using an appropriate NF. This factor, when applied to the recon-
structed dose distribution shifts the dose values, while retaining its complex shape
as shown in Fig. 4.7 (B) and (C). The NF determined using the 10x10 cm2 field size
reconstruction was 3%.

(A)

(B) (C)

F IGURE 4.7: (A) A comparison of the 1D dose profile of the TPS cal-
culation (drawn in orange) and the reconstruction (drawn in blue) in
the coronal plane for an exemplary treatment plan. (B) A misalign-
ment in the TG direction is corrected and the blue plot shifts to the
right by 3.6 mm. This represents the TG factor. (C) The misalignment
in the absolute dose values is corrected and the blue plot is raised by
3%. This represents the NF.
4.2. Final Results 83

The values for gamma criteria (3%, 3 mm) are presented in Table 4.1. "NF" stands
for the normalization factor used in the evaluation and "TG corrected" implies that
it has been fixed for the error in alignment. In this audit, a passing rate higher than
a threshold of 95% will be considered satisfactory, which is highlighted in green.
The color yellow implies a passing rate between 80% and 95% and the color red
implies a passing rate lower than 80%. It can be seen from the results that without
normalization the reconstruction has very low passing rates with only a third of the
total number of treatment plans achieving more than 95%. On employing the 3% NF,
the passing rates improve considerably, with 13 out of 22 treatment plans passing the
threshold. It was observed that for few reconstructions a higher normalization factor
produces much better passing rate.

TABLE 4.1: (3%, 3 mm) gamma index evaluation for the NEAT recon-
structed dose distribution for 22 treatment plans. NF stands for nor-
malization factor. TG corrected implies that the reconstruction has
been shifted by 3.6 mm in the -Z direction to correct for the EPID
positioning discrepancy. Passing rates highlighted in green represent
values greater than 95%. Yellow represents passing rates between
80% and 95%. Red represents passing rates below 80%. TP stands
for Treatment Plan. The reconstructions which had achieved a pass-
ing rate higher than the threshold was not corrected further using NF
8%, as a higher NF produced a worse passing rate.

TP # Tumor location/type TG corrected TG corrected TG corrected

No NF NF: 3% NF: 8%
TP1 Esophagus 95.6% 99.4% -
TP2 Prostate 69.9% 88.8% 99.5%
TP3 Sarcoma 87.0% 99.0% -
TP4 Head and Neck 95.0% 99.8% -
TP5 Mediastinum 98.9% 98.2% -
TP6 Bronchi 85.2% 96.8% -
TP7 Scalp 98.0% 96.7% -
TP8 Bronchi 76.6% 95.6% -
TP9 Head And Neck 85.7% 95.7% -
TP10 Vagina 59.1% 82.9% 99.7%
TP11 Pelvis 72.8% 90.9% 99.5%
TP12 Lung 98.4% 100% -
TP13 Scalp 52.0% 71.4% 99.5%
TP14 Head And Neck 49.3% 73.0% 97.8%
TP15 Head And Neck 56.0% 80.8% 99.1%
TP16 Bronchi 96.8% 99.8% -
TP17 Head And Neck 69.1% 87.7% 99.0%
TP18 Head And Neck 61.0% 83.9% 99.1%
TP19 Head And Neck 87.8% 98.7% -
TP20 Esophagus 79.0% 93.7% 99.6%
TP21 Lymphoma 98.4% 98.4% -
TP22 Cervix 87.8% 99.5% -
84 Chapter 4. EPID-based QA Tool

4.3 Discussion
For this audit, a GUI, named Novel EPID-based Audit Tool (NEAT) has been de-
veloped. It was created as a clinical tool for reconstructing dose distributions as
imparted to a water phantom, using in air-frames acquired by EPID. Furthermore,
NEAT was used to reconstruct the 3D dose distributions of 22 VMAT treatment
plans. The reconstructed dose distributions were then compared with the TPS cal-
culated dose distributions using a gamma index evaluation with a criteria of (3%, 3
mm). The result has been presented in Table 4.1.
Along with the frame acquisitions of the treatment plans, 10x10 cm2 field size
frames were also acquired in air. The reconstructed dose distribution for this ra-
diation was compared to the corresponding TPS calculated dose distribution. Two
corrections factors were identified using this comparison. First was the TG factor, to
compensate for the EPID positioning error, introduced during the manual position-
ing of the EPID before the acquisition of the frames, as can be seen in Fig. 4.1. The
second was the normalization factor (NF). It can be expected that the dose response
of the EPID changes over time. This factor should compensate for any drop in the
response. It should be noted that the reconstruction algorithm, as presented in the
parent paper, Alhazmi et al., 2018, has its own extensive calibration matrix, deter-
mined by taking a myriad of readings from the linac, which are then processed to
determine the values in the calibration matrix. Although, this complete procedure
takes few hours and cannot be practically performed each day a dose distribution is
reconstructed. Thus, it is recommended in the audit to perform the 10x10 cm2 field
size radiation and reconstruct the dose distribution with the frames acquired. The
two factors should then be determined and employed during the gamma evaluation.
This acquisition and reconstruction takes only few minutes but the reconstruction
improves considerably.
The TG factor remains the same for all dose distributions, however the ideal
NF does not remain the same. This should be investigated further to improve the
consistency of the algorithm.
Furthermore, the 5 best performing reconstructions were tested against different
gamma criterias, (2%, 2 mm) and (1%, 1 mm). The results are presented in Table 4.2.
4 out of the 5 reconstructions were able to pass the strict criteria of (2%, 2 mm), how-
ever all were unable to reach the threshold in case of a stricter (1%, 1 mm) criteria.

TABLE 4.2: (2%, 2 mm) and (1%, 1 mm) gamma index evaluation for
the NEAT reconstructed dose distribution for the the 5 best perform-
ing reconstructions. Passing rates highlighted in green represent val-
ues greater than 95%. Yellow represents passing rates between 80%
and 95%. Red represents passing rates below 80%.

TP # Tumor location/type (2%, 2 mm) (1%, 1 mm)

TP1 Esophagus 95.1% 64.5%
TP4 Head And Neck 95.4% 64.9%
TP12 Pelvis 98.6% 72.3%
TP16 Bronchi 96.6% 68.2%
TP22 Cervix 94.7% 66.3%

It can be concluded that, with the appropriate normalization factor, the recon-
struction algorithm was able to produce exceedingly high passing rates for all cases.
4.3. Discussion 85

However, this normalization factor must be determined using a more reliable tech-
nique which requires further investigation.
 87

Chapter 5

Conclusion and Outlook

5.1 Conclusion
Optimization of PhSp
In radiation dosimetry, Monte Carlo techniques offer a powerful tool for modeling
radiation transport. If accurately implemented, a MC model is exceedingly precise
in the determination of the absorbed dose. However, accurate modeling of medical
linear accelerators is often a daunting task. The internal components must be known
in details for an accurate MC modeling. If these details are not known, it becomes
almost impossible to model the linac.
In this study an alternative approach to this problem was researched. Commis-
sioned PhSp files of a validated linac model were optimized for another linac with-
out the need of detailed knowledge of the internal components. A technique referred
to as cropping was introduced. It turned out to be a powerful technique without
which fast experimental validations of theories would not have been possible. It
was discerned that the optimization works well with energy. An optimal fix of 0.32
MeV was found. This fix was then applied to the full PhSp and PDD profiles were
generated for all field sizes considered for validation. The cost values for PDD, using
the PhSp with optimized energy were all under 1.39%. The optimization of energy
also improved the cost values of inline lateral profiles. No significant improvement
was observed for crossline profiles.
The optimization of momentum proved to be relatively more challenging. A dis-
tinct relationship between the sigmoid fitting parameters of the lateral profiles and
the slope of the beam line divergence was detected and studied. This provided a
good guidance on how to manipulate the particle’s momentum. It was observed that
multiple simulation instances of the same configuration produced varying results.
An investigatory study was performed to estimate the least number of simulations
needed to determine a fairly stable fitting parameter. Utilizing the results from these
sub-studies, slope perturbation factors for crossline and inline were determined in-
dividually. Furthermore, a general methodology was developed to determine slope
perturbation factors. Individually the optimization of momentum for the crossline
and inline produced low cost values. Implementing the two fixes in the same PhSp
has proven to be difficult. Multiple approaches were formulated, implemented and
then analyzed. Three approaches were presented along with their results. The best
performing approach was then used to determine the optimal perturbation factors
which produced the lowest cost values. The full PhSp was perturbed using these
factors and lateral profiles were generated for all the considered field sizes and the
corresponding cost values were determined. The average drop in the cost values,
as compared to the initial cost values before the optimization of momentum and af-
ter the optimization of energy, was determined to be around 3.58% for all profiles.
88 Chapter 5. Conclusion and Outlook

The cost values were compared to the initial cost values, determined before the opti-
mization of energy. The average drop in the cost values was evaluated to be around
7.10%.

EPID-based QA Tool
EPID is conventionally used in patient positioning, owing to its sub-mm resolution
and fast frame acquisition capability. However, numerous works have been pub-
lished on utilizing the EPID in the pre-treatment dosimetric verification of treatment
plans. One such work has been published by Alhazmi et al., 2018 which presents
a robust algorithm to reconstruct 3D dose distributions. The EPID frames are ac-
quired in air, into a self-contained computer, while the treatment plan is being per-
formed using the linac without the patient or a phantom. These frames are then
used to reconstruct 3D dose distributions as imparted to a water equivalent cylin-
drical medium using the reconstruction algorithm, described comprehensively in
the paper.
In this study, a GUI named Novel EPID-based Audit Tool (NEAT) was devel-
oped as a clinical tool to reconstruct the 3D dose distributions using these algo-
rithms. It facilitates the implementation of the algorithm in clinical routine, as it
enables the user to easily perform the full process from acquisition to reconstruction
without dealing with the low level code. 22 VMAT treatment plans were acquired
and the corresponding 3D dose distributions were reconstructed using NEAT. These
dose distribution were then compared with the corresponding TPS calculated dose
distribution using a gamma evaluation of criteria (3%, 3 mm). Two correction fac-
tors, Target Gantry (TG factor) and normalization factor (NF), were determined us-
ing a reconstruction corresponding to a square shaped beam with a field size of
10x10 cm2 without any linac rotation. These factors were employed while perform-
ing the gamma evaluation. Out of 22 reconstructions, 13 passed the threshold with
the gamma criteria of (3%, 3 mm). It was observed that a higher NF improved the
pass percentages of the failing reconstructions. Further investigation is required to
form a reliable technique which determines the ideal NF for every reconstruction.

5.2 Outlook
In the past decades, MC Techniques have presented powerful numerical solutions,
superior to analytical ones in the field of X-ray photon therapy. Yet, to exploit these
techniques, an accurate MC model is required. The PhSp optimization techniques
introduced and analyzed in this study offers an alternative approach to model the
linac when detailed information of its internal components are not known.

Additional measurements, extensive validations and further approaches

Further studies can involve measuring lateral dose profiles in multiple directions be-
tween crossline and inline. This would assist in studying the behavior of the slope of
beam line divergence, as it transitions from the crossline to the inline directions. The
validation of the PhSp should also be performed for lateral dose profiles at different
depths. Furthermore, these techniques must be attempted with multiple PhSps for
extensive validation. An approach using the momentum component in x direction,
Px , and the momentum component in z direction, Pz , in place of the location x and z,
can be formed implemented and analyzed. This should broaden the understanding
of the divergence in different angular directions.
5.2. Outlook 89

Automated engine
An automated engine can be implemented for unsupervised optimization. It is con-
ceivable that all the individual steps followed in the optimization of the PhSp can
be stitched together and automated. Such an engine should be able to run indepen-
dently using correlations detected in this study. Currently, many of the steps are
initialized manually as the framework is still in its rudimentary form.

GitHub repository : phaselab

GitHub Inc. is a web-based hosting service for version control (GitHub, 2018). It
offers cloud repositories where individual programmers can commit their computer
code for smooth collaboration among them. A public repository, named phaselab,
developed in Python can be maintained at GitHub containing regularly used func-
tions, such as cropping, perturbing the energy, perturbing the slope of the beam
line divergence, plotting histograms, plotting dose profiles and calculating cost val-
ues. These functions can be elegantly classified into specific classes which can then
be imported and utilized in Python programs. The purpose of such a repository
is to ascertain that all the functions utilized in optimizing a PhSp is under a single
Python library. This is expected to bring collaboration from other programmers and
data scientists while at the same time the development of a well-structured object
oriented code base will be achieved. The initial version of this repository is under
development and will be made available by January 2019.

Virtual Source Models

Once the PhSp has been fully optimized it can be used to create virtual source models
(VSM) as presented in Nwankwo et al., 2017. A VSM is created using the distinct
probability distribution functions (PDFs) of the individual information, such as the
energy, the momentum in the x direction, the y location of the particle etc., contained
in the PhSp. The PDFs also have an interdependence among them, as an example, a
high energy particle would probably be located near the center. These distinct PDFs
and the interdependence relations are then used to allocate a full set of information
to newly generated particles. Thus, these source models should be able to yield any
number of particles and improve statistical certainty.

Machine Learning Kernels

Machine Learning is the field of study committed to building complex analytical
models which has the capability of learning and improving from a set of training
data without being explicitly programmed. It is exciting to think about an integra-
tion of Machine Learning (ML) techniques with MC simulations.
Once the PhSp is optimized, it can be used to generate a training set. This set
should contain different 3D dose distributions generated by unique MLC/diaphragm
plans. These plans are responsible for generating complex field shapes from dif-
ferent directions. During a simulation, the PhSp is static, the only variable is the
complete plan of the changing field shape, with varying angular direction, which
generates a distinct dose distribution. A functional is identifiable in this setup, in
which the PhSp represents the functional, the input is the MLC/diaphragm posi-
tions and the output is the 3D dose distribution. In such a functional the mathemat-
ical operation is simulation. In principle, such a functional can also be defined with
the mathematical operation as convolution. A convolutional neural network can be
90 Chapter 5. Conclusion and Outlook

trained using the aforementioned training data set. Such a trained model should
be capable of identifying numerous parameters which are too subtle to be noticed
otherwise. This model should take the MLC/diaphragm plan as the input, in the ap-
propriate format, and should produce a 3D matrix containing the dose distribution.
This is an ambitious yet exciting field of research which might have the potential to
challenge the efficiency of MC simulations.

NEAT 2.0
The current version of NEAT is rudimentary and has a considerable scope of im-
provement. A gamma evaluation section can be added to the interface which com-
pares the reconstructed DICOM file to a reference file. The Frames Acquisition Direc-
tory text box can be changed into a drop down box displaying the last 5 selected file
paths. An optional auto stop button can be installed which automatically identifies
when the the linac beam is no longer on and stops the acquisition, at the same time
popping a notification. This would make the interface more independent. An op-
tional auto-start reconstruction button can be installed which starts the reconstruc-
tion automatically after the frames have been acquired. A log file generator for the
interface can be implemented which creates a log file, containing every information
of all the interface activities. This should also be helpful in archiving the treatment
informations which is a critical issue in clinical routines. Thus an improved version
of NEAT, NEAT 2.0 is a potential project for any future work.

The complete research presented in the first part of this thesis was an attempt at
contributing to the understanding of the gross and subtle correlations between the
properties of photons in the Phase Space and the resulting dose profiles. The second
part of the thesis was an attempt at improving the efficiency of the QA procedure in
a clinical routine of radiotherapy by developing a GUI. While this thesis concludes
here, the research on the understanding of the aforementioned correlations and on
the improvement of EPID dosimetry has much to offer.
 91

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 97

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