GMBR Ibd

Measurement of absorbed dose to the
skin and its relation with microcircular

changes in breast cancer radiotherapy
Master of Science thesis in Medical Radiation Physics
Stockholm University
Linköping University
(May 27, 2016)
Supervisor:
Author: Erik Tesselaar - PhD, Medical
Chahed Yacoub Radiation Physics, Department of
Medical and Health Sciences,
Linköping University
Co-supervisors:
Bo Nilsson
Emelie Adolfsson
Medical Radiation Physics
Chahed Yacoub Stockholm University 1(44)
Abstract
Radiation therapy has been shown to increase local and regional control as well as overall
survival with breast cancer, but the vast majority of patients develop acute skin reactions,
which are in part related to microvascular changes. These reactions vary between different
skin sites. The aim of this work is to determine the absorbed dose to the skin by measure-
ments and investigate if there is a correlation between the absorbed dose at different areas of
the breast and the local changes in microcirculation in the skin after breast cancer radiother-
apy. The study includes characterisation of the Gafchromic EBT3 film and Epson Perfection
V600 Photo scanner which are used for absorbed dose determination. The measurements
were done both on an anthropomorphic female phantom and on a patient undergoing breast
cancer radiotherapy. Twenty-one pieces of film (2×1 cm2 ) were placed on the surface of
the breast (both for the phantom and patient) and irradiated with a prescribed dose to the
target of 2.66 Gy with two opposed fields using 6 MV beam.
It was observed that mainly 45-64 % of the prescribed dose was deposited at the surface,
both for the phantom and patient. Using laser speckle contrast imaging and polarised light
spectroscopy, the regional changes in mean blood perfusion and in mean red blood cell
concentration (RBCC) at the end of the treatment with a total prescribed dose of 42.6
Gy, compared to baseline, were measured in both the treated and untreated breast of the
same patient. Although marked increases in perfusion were seen in different areas of the
treated breast, there was no significant correlation between the changes in perfusion and
the absorbed dose at these areas. However, a statistical correlation was found between the
changes in RBCC and the absorbed skin dose at the same areas. To further elucidate the
relation between the changes in skin microcirculation and the absorbed radiation dose during
breast cancer radiotherapy, future studies using a larger number of patients are needed.
Contents
1 Introduction 4
2 Background 4
2.1 Skin reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2 Dose distribution in the build-up region . . . . . . . . . . . . . . . . . . . . . . . 6
2.2.1 Obliquity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.2.2 Exit dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.3 Detectors for surface dose determination . . . . . . . . . . . . . . . . . . . . . . . 7
3 Materials and Methods 8

3.1 Gafchromic EBT Film . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.1.1 Energy dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.1.2 Variability with film sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.2 Scanner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.2.1 Temporal variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.2.2 Variability with ROI size . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.2.3 Spatial variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.3 Calibration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.4 Film handling for phantom- and patient study . . . . . . . . . . . . . . . . . . . 13
3.5 Anthropomorphic phantom study . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.5.1 Treatment planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.5.2 Phantom irradiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.5.3 Entrance and exit dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.6 Patient study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.6.1 Treatment of patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.6.2 Laser Speckle Contrast Imaging . . . . . . . . . . . . . . . . . . . . . . . . 16
3.6.3 Polarised Light Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.6.4 Skin microcirculation measurements . . . . . . . . . . . . . . . . . . . . . 18
4 Results 19
4.1.1 Energy dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.1.2 Variability with film sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.2 Scanner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.2.1 Temporal variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.2.2 Variability with ROI size . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
4.2.3 Spatial variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
4.3 Calibration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
4.5 Patient study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4.5.1 Pearson’s correlation test . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
5 Discussion 34
5.2 Scanner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
5.3 Calibration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

5.5 Patient study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
6 Conclusions 39
7 Acknowledgement 40
8 Bibliography 40
9 Appendix 44
List of acronyms
CPE Charge Particle Equilibrium
CT Computed Tomography
ICRP International Commission on
Radiological Protection
ICRU International Commission on Radiation
Units and Measurements
LRA Lateral Response Artefacts
LSCI Lateral Speckle Contrast Imaging
MPV Mean Pixel Value
MU Monitor Unit
MV Megavoltage
OBI On-Board Imaging
PDD Percentage Depth Dose
PLSI Polarised Light Spectroscopy Imaging
PTV Planning Target Volume
PU Perfusion Units
RBCC Red Blood Cell Concentration
ROI Region of Interest
RTOG/EORTC The Radiation Therapy Oncology Group
European Organisation for Research and
Treatment of Cancer
SD Standard Deviation
SSD Source-Surface Distance
TB Tangential Beam
VMAT Volumetric Modulated Arc Therapy
1 Introduction
The aim of radiotherapy is to eradicate the tumour while sparing the normal tissue as much as
possible. Unfortunately, the number of new cancer cases increases from year to year [1] and the
importance to fulfil the aim of the radiotherapy becomes more important since the radiation
not only affects the mitosis and causes cell death to the tumour cells, but also the normal
cells are affected as an inevitable consequence. According to some studies, 90-95 % of breast
cancer patients treated with external radiotherapy will to some extent develop some kind of skin
reaction of different grades due to the radiosensitivity of the skin [2],[3]. Porock et al. suggest
that only 4-8 % of the women completed the treatment without any reactions [3]. To study the
effect of the dose to the skin, there is a need of appropriate techniques that have the ability to
measure the energy deposition of the ionisation radiation at shallow depth and techniques that
have the ability to verify the changes in the microcirculation quantitatively either by looking
at the blood flow or the concentration of red blood cells.
Previous studies have concentrated on estimating the absorbed dose at superficial depth of the
skin [4], [5], [6] and the skin reactions due to the radiation have been investigated by subjective
methods. Nowadays the possibility to objectively examine the changes in microcirculation of
the skin has arisen [7], [8]. It is therefore of interest to determine the absorbed dose at depths
which also include the upper dermis, where the skin microcirculation is predominately located.
The aim is to determine the absorbed dose to the skin for an anthropomorphic female phantom
and a female breast cancer patient and to investigate if there is a correlation between the
absorbed dose and the changes in microcirculation in the skin of the breast in breast cancer
radiotherapy.
2 Background
2.1 Skin reactions
The skin consist of two main layers; the epidermis which is the superficial layer and the dermis
which is the deep layer. According to ICRP [9] and ICRU [10], the recommended depth for
skin dose assessments is 70 µm. The dermis begin at a depth of approximately 100 µm [11] and
can be up to a few millimetres thick. This is however an estimate since the depth may vary
considerably between individuals and location on the body [12]. New cells are created in the
basal layer of the epidermis and peregrinate to the more superficial layer of the skin, which leads
to that the most superficial cells fall off (see Figure 1). The blood vessels, hair follicles, glands
and nerves are located in the dermis and support the renewing of the lost cells in the epidermis.
As the skin is exposed to radiation, the self-renewing property of epidermis is disrupted since
the ionising radiation damages the ability of the clonogenic stem cells to undergo mitosis.
Figure 1: The main skin structures of epidermis and dermis. (Adapted from M. Well et al. [13])
Archambeau et al. suggested that the critical prescribed dose to the skin threshold (beginning of
the loss of basal cells) is 20-25 Gy and the prescribed dose at which the basal cells are completely
damaged is 50 Gy [14]. Considering these values, the skin problems thus start approximately
after 10 days of the treatment assuming 2.66 Gy per fraction and increases with each fraction.
Observation from clinical practice shows that the maximum acute skin reactions are observed
one week after the end of the treatment. However, no studies have been found that prove this
statement for energies and doses that are of interest in this thesis.
The acute effects of radiation in the skin are observed visually by increased redness of the skin
during the treatment which is due to increased blood flow in the sub-papillary vascular plexus
and often referred to as erythema. The late toxicity is due to the fact that the microcirculation
and connective tissue are disturbed by the ionising radiation. The effect appears months or
years later and may in some cases be permanent [15].
Some areas on the body are more likely to develop skin reactions. Skin folds under the breast and
the head and neck have been found to be particularly sensitive [16], [17], [18], [19]. Those areas
which contain skin folds are in general more moist. Except the other factors, e.g. irradiation
time, that affect the skin reaction severity, also the age, health and ethnicity play a role [3],
[20].
Several treatment techniques have been developed during the last years to ensure a better
sparing of the normal tissue, including the skin and to get a more conformal dose to the target.
However, some techniques involved in the treatment still increase the dose to the skin. These
include the use of a bolus to cover a scar when the dose is built up and the use of tangential
fields in the treatment of breast cancer. A particular problem with radiation therapy for breast
cancer is the sloping form of the breast which makes the probability higher for some thin areas
to receive a higher dose [13].
Although a few grading systems have been proposed for skin reactions, the most commonly used
in both clinics and research is introduced by The Radiation Therapy Oncology Group/European
Organisation for Research and Treatment of Cancer (RTOG/EORTC), see Table 1. There are
two limitations with this scoring system. Firstly, it does not distinguish between dry desqua-
mation and faint erythema but instead they are scored the same. According to the patients,
these reactions do not have the same severity grade. Secondly, only the subjective opinion of
the observers are considered and the results are often underrated in severity if compared to
the opinion of the patients [13]. Despite this, this grading score does distinguish for example
between faint erythema and tender/bright erythema which makes it useful.
Table 1: RTOG/EORTC acute scoring criteria - skin [21]

0 1 2 3 4
No change Follicular, faint or Tender or bright Confluent, moist Ulceration,
of baseline dull erythema; erythema, patchy desquamation haemorrhage,
epilation; dry moist desquamation; other than skinfolds, necrosis
desquamation; moderate oedema pitting oedema
decreased
sweating
2.2 Dose distribution in the build-up region
When the megavoltage (MV) photon beam hits the patient or phantom, secondary charged par-
ticles are released and deposit their kinetic energy in the media through Coulomb interactions.
The range of these secondary particles corresponds to the dose build-up region and refers to
the region between the surface (z=0) and the depth dose maximum z=zmax . In this region,
there is lack of electronic equilibrium, i.e. charge particle equilibrium (CPE) and the dose gra-
dient is steep. According to Metcalfe et al., the relative dose in the first millimetres using a 6
MV photon beam and a field size of 10×10 cm2 increases from 14 % to 43 % [22]. However,
this example refers to one measurement and varying results may exist. Nevertheless, the steep
dose gradient at shallow depth makes the determination of the surface dose a challenge since a
small variation in the depth may result in large dose alteration. This issue becomes even more
emphasised for curved structures such as the breast.
The factors that contribute to the surface dose are the photons scattered from the collimator,
flattening filter and air, the backscattered photons from the patient/phantom and the electrons
with high energies produced in the air or shielding in the vicinity of the patient/phantom by
photon interactions. However, the largest contribution to the surface dose is due to the scattered
electrons and not due to the scattered photons. For higher energy photon beams, there is less
contribution to the surface dose. For normal incident beams, approximately 15 % of the dose is
deposited at the surface for 6 MV beam while for the 18 MV beam 10 % is deposited for a field
size of 10×10 cm2 [23]. The surface dose is also dependent on the field size [24] and according
to Kry et al., the surface dose given as percentage of dose maximum (entrance dose) increases
linearly with field size [11].
2.2.1 Obliquity
Photon beams with oblique incident angles affect the surface dose as the skin sparing is reduced
compared to normally incident beams. The increase in surface dose is explained by the fact that
the secondary electrons will be ejected closer to the surface and the probability is higher that
these electrons will be scattered back to the surface when using an oblique photon beam.
The depth dose maximum zmax is also decreased with increasing incident angles [25], [26].
According to Gerbi et al., the decrease in zmax may additionally be due to the fact that the
ionisation chamber was placed in the central axis of the beam. Thus, due to the inverse square
law and geometry of the beam, a large part of the beam will hit the surface of the phantom far
from the central axis, leading to that the ionisation chamber will not be able to detect all the
electrons ejected in the phantom [26]. It was concluded that the largest increase in absorbed
dose to the surface is observed at the first 3 mm of tissue for 6 MV x-ray beams.
Gerbi et al. also studied the variation of surface dose and oblique angles of incident (0◦ -84◦ )
depending on the beam quality (6-, 10-, 18- and 24 MV) using a plane parallel ionisation
chamber in a polystyrene phantom. He observed that for angles above 45◦ , the absorbed doses
compared to absorbed dose for normally incident beam, increase markedly for 10-, 18- and 24
MV beams compared to 6 MV beam. It was explained by the fact that photons of higher energy
will travel further into the body before depositing their energy while low energy photons will
have a much shorter penetration depth in the body and deposit most of their energy closer to
the surface [26]. However, it is of importance to notice that Gerbi used a flat phantom for these
measurements and the results will vary if one consider a curved surface instead.
For smaller angles (< 40◦ ) the effect on the surface dose is small. At ∼55◦ , the dose increases
with 50 % compared to normal incident beam [27]. For 6 MV with a field size of 10×10 cm2 ,
the relative surface dose is 58-65 % (of Dmax ) at a beam angulation of 90◦ [28] [29].
2.2.2 Exit dose
Exit dose refers to the dose given to the phantom/patient at beam exit area. The dose curve
is somewhat more bended downwards towards the exit point than what is expected from the
extrapolation curve. The reason for this observation is loss of scattering contribution beyond
the dose exit point but still this effect of a more bended dose curve than expected by the
extrapolated curve is considered to be negligible [23]. The exit dose is a contributing factor to
the skin dose and must be considered for megavoltage treatment. Measurements have shown
that the contribution to the skin dose from the exit dose is less than predicted by the percentage
depth dose (PDD). The main reason is the lack of material in the vicinity of the patient that
backscatter the charged particles. For a 6 MV beam, the relative difference is approximately
15 % [29], [30], [31].
2.3 Detectors for surface dose determination
An appropriate detector for surface dose determination in this project would be a detector that
has a high sensitivity in the expected dose range (0.1-3 Gy), which is made of a near tissue
equivalent material and that measures the ionisation at a depth closely corresponding to the
depth of the upper dermis. It should also be possible to place the detector at different locations
on the curved surface of the breast in order to make regional comparisons of the absorbed
dose.
Several detectors have been used in studies for estimation of the surface dose. The most com-
mon detectors that have been investigated for this purpose are TLDs, MOSFET/MOSkin,
radiochromic films and extrapolation ionisation chambers [5], [32], [33]. The extrapolation
chamber has been recommended as the detector of choice for measurements in the build-up
region under such conditions where charge particle equilibrium is non-existing due to its high
accuracy[34], [35]. However, the plane parallel chambers have shown to exhibit a great over-
response in dose when used in the build-up region with oblique angles of beam incident and
when used at a surface of a phantom. Thus, making this type of chamber unsuitable for this
study [36]. Furthermore, for measurements on anthropomorphic phantom/patients with curved
surface, plane-parallel chamber would not be the detector to choose. Other detectors with ap-
propriate properties are the MOSFET/MOSkin detectors that have a linear response and are
reproducible in the dose range 0.05 Gy to 3 Gy [5].
Another detector type that has been used in skin dose estimations is thin TLDs with a thickness
of approximately 130 µm and it overestimates the surface dose by less than 10 % over a beam
quality range that includes 60 Co, 6 MV and 21 MV [12]. Lastly, the use of radiochromic film for
surface dose measurements has many advantages, due to its minimal energy dependence, tissue
equivalent properties and allows for high spatial resolution at shallow depths [GafchromicT M
EBT3, Scan handling guide, P/N 828533 12/14, Rev. 1], [37], [38], [39]. The recommended
dose range for these films is 0.01-10 Gy and measures at a depth between 100-128 µm. All
the other mentioned detectors measure at a certain point while the Gafchromic films measures
over an area. In this study, it is thus more convenient to obtain the dose over an area than a
certain point. Also, the method for measuring would require longer time if the detector has to
be moved around to measure regional changes of the dose and it would thus not be possible
to perform patient measurements. It is therefore concluded that the Gafchromic EBT3 film is
the ultimate choice for this study. An overview of the characteristics of detectors suitable for
measurements of surface dose and in the build-up region is done by Shea et al. [35].
3 Materials and Methods
3.1 Gafchromic EBT Film
In this study, the dosimetry device of choice is the Gafchromicr EBT3 film (Ashland Specialty
Ingredients, Bridgewater). The photon energy dependence of a Gafchromic EBT film dosimeter
has been investigated and showed to be minimal by several studies [40], [41]. Rink et al.
concluded that the mean change in optical density is 3 % compared to that in 60 Co beam over
an energy range of 75 kVp-18 MV [41].
A study by Nakano et. al confirmed the suitability and accurateness of the Gafchromic film for
surface dosimetry as well as the suggestion of using this detector for in vivo measurements [42].
These conclusions are based on the fact that the film material has similar interaction properties
as the skin and allows for high spatial resolution for dose measurements at submillimetre depth
[43].
The film batch used in this study has lot number 11031501. Each film sheet is composed of a 100
µm matte polyester (1.35×10−2 g/cm2 ), an active layer of ∼28 µm (∼3.36×10−3 g/cm2 ) and a
second layer of 100 µm matte polyester, see Figure 2 [GafchromicT M EBT3, Scan handling guide,
P/N 828533 12/14, Rev. 1], [44]. This symmetric structure of the EBT3 film gives advantages
for the placing of the film on the scanner. The film is thus independent on which side that is
facing the light source as it is scanned. The active layer is composed of crystalline diacylene
monomer and a yellow marker dye. When the film is exposed to radiation, the monomer will
develop different tint of blue colour depending on the dose due to polymerisation inside the
active layer. The yellow dye makes the UV/light sensitivity of the film decreased and enables
multi-channel dosimetry (discussed later in this section). The higher the light transmission and
increasing time-after exposure, the darker colour of the film. By scanning the film and using
a calibration curve it is possible to obtain the dose since the light transmission of the film is
proportional to the dose. According to the manufacturer, the EBT3 films have a recommended
dose range of 0.01-10 Gy.
Figure 2: Configuration of GafchromicT M EBT3 Dosimetry Film.
The procedures describing how to handle the film are recommended by the AAPM Report No.
63 [45] and followed in a large extent in this study to ensure high accuracy of the readout.
The scan response of the EBT3 film have been observed to be sensitive to how the user place
the film on the scanner. The film is not dependent on the obliquity of the beam which is an
advantages when it is used as a dose verification tool during tangential beam (TB) irradiations
and for modalities such as VMAT [43].
By using the multi-channel method it is possible to obtain a dose-independent part and a dose-
dependent part of the signal. The dose-dependent part contains relevant information regarding
dosimetry while the dose-independent part includes information related to scanner artefacts e.g.
noise and differences in the response of the film coating [46]. Placing the film on a RGB scanner
will result in response for each colour channel (red, green and blue). The signals contain different
amount of dose-dependent and dose-independent information. Since the red channel response
is strongly dose-dependent, it is chosen to be as the only channel studied in this project.
An important consideration regarding the possible artefacts related to the scanning of the films
is the lateral response artefact (LRA). The LRA appears as a consequence of how the film is
positioned on the scanner and the dose [47]. The lateral position on the scanner refers to the
location along the course which is perpendicular to the scan direction. By placing the film in
portrait orientation the response will be overestimated in comparison to the response obtained
when the film is positioned in landscape orientation (the short side of the film is parallel to the
scan direction). The measured optical density increases markedly towards the lateral edges of
the scan area but the increases are however negligible in the centre. As mentioned, the dose
is another contribution to the LRA. The observations show an increased difference in response
for a certain lateral position as the dose is increased (> 1 Gy) [46], [47]. This effect is more
pronounced for the red colour channel due to its high dose-dependent property but nowadays
considered less severe when using multi-channel scanner. The Gafchromic EBT3 manufacturer
recommends the user to scan in landscape orientation and to position the film at the centre of
the scanner to minimize the LRA. Although this artefact have been clearly observed in several
studies, the extent of this artefact using the Epson scanner will be investigated to ensure the
same conclusion as the manufacturer.
3.1.1 Energy dependence
According to the manufacturer of the EBT3 film, these films should be energy independent.
This was checked for the two beam qualities that are common in breast cancer therapy: 6 MV
and 15 MV. The procedure was done by using one sheet of film that was cut into two smaller
pieces with an area of 5×6 cm2 each and marked to keep track of their orientation relative to
the original film and assure that the film pieces are scanned in the same orientation. The films
were consequentially placed in a PMMA slab at 3 cm depth with a backscatter material of 10
cm using a SSD of 100 cm. The films were irradiated with approximately 1 Gy for both beam
qualities. The same procedure was done for both energies.
3.1.2 Variability with film sheet
As stated by the manufacturer and confirmed by Åstrand [48], the different film sheets from
the same batch should be identical and thus it should be sufficient to do the calibration for
only one film sheet per batch of films. This was verified in this study by irradiation of three
pieces of films (5×6 cm2 ) from three different film sheets. Each piece of film was irradiated
separately. The film set-up used is the same as in section 3.1.1 and all films were irradiated
with approximately 1 Gy using 6 MV beam.
3.2 Scanner
To scan a film, the flatbed Epson Perfection V600 Photo scanner (model: J252A, serial no.:
*LU5W000052*) is used. This type of scanner uses the triplet-channel method and can collect
images at a depth of 16 bits per colour channel. The spatial resolution of such scanner is
6400×9600 dpi (optical density).
The program EPSON Scan (Ver. 3.9.2.0SV) was used for digitalising of the films. The settings
could not be chosen exactly as proposed by the EBT3 manufacturer due to an older version of
the program. Thus, the films were scanned in professional mode and reflective document type
with 48-bit colour and a spatial resolution of 75 dpi. As recommended, all image adjustment
features were turned off.
To enable the calculation of the mean pixel value (MPV) by choosing a ROI, a program named
ImageJ [49] was used. The digitised images were opened with ImageJ and a ROI was chosen.
The program measured the area of a ROI (number of pixels), the MPV and the standard
deviation for every MPV.
To minimize the source of error, the variation of the MPV over time, with the ROI size and the
position of the film on the scanner was investigated. For all films, the scanning was done in the
landscape orientation and the orientation was marked on the films with a pen.
3.2.1 Temporal variability
An unexposed film sheet was placed in the centre of the scanner and scanned 15 times in 49
minutes. The film was not taken out or moved after each scan to not add any other dependency.
Using the program ImageJ, a ROI consisting of 36051 pixels corresponding to an area of 44 cm2
was chosen for all 15 images.
3.2.2 Variability with ROI size
An unexposed film sheet was placed in the centre of the scanner and scanned 30 times without
removing it from the scanner. Using the program ImageJ, three different sizes of ROIs were
chosen to see if there is an effect which needs to be considered. The small ROI has an area of
0.31 cm2 and consists of 256 pixels. The medium ROI covers 9600 pixels and has an area of
11.73 cm2 . The largest ROI consists of 81 472 pixels and has an area of 99.54 cm2 .
The results show a pronounced difference in MPVs between the medium ROI and large ROI.
Therefore, one of the images obtained from 30 scans was alternated in terms of contrast (bright-
ness) by changing the window settings in ImageJ to see more clearly the variation of optical
density. Furthermore, paper sheets were scanned to see if the variation in optical density is due
to the scanner background or the LED-lamp in the scanner. Lastly, a film sheet was irradiated
to 200 MUs using a 6 MV beam was scanned after 24 hours and the contrast was altered to
conclude whether the variation of the optical density over the scan area will affect the irradiated
films further on in the project.
3.2.3 Spatial variability
An unexposed film was cut into a piece of 5×5 cm2 . The film piece was marked with a small
arrow to keep track of the orientation relative to the original sheet and thus allow for correct
placement on the scanner, see Figure 3. The varied variables in this experiment are x and y,
where x is the distance between the right edge of the scan area and the centre of the film area.
The variable y defines the distance between the nether end of the scan area and the centre of
the film area. By varying x and y according to Table 2, a result of different MPVs is obtained.
The ROI was chosen in the centre of the film and included 5621 pixels.
Table 2: The six different placements of the film on the scanner area.
Scan number Distance x cm Distance y cm
1 11 7
2 11 15
3 11 25
4 7 3
5 19 26
6 3 15
Figure 3: a) Scan area (22×30 cm2 ), b) Film area, c) ROI. The film is handled as recommended
by AAPM [45].
3.3 Calibration
All irradiations in this thesis are done using a Clinac IX (Varian Medical Systems, installed
in 2011 at Linköping university hospital, Sweden). The electrometer UNIDOSwebline (PTW,
Germany) was turned on one hour before the irradiation to warm up and exclude possible errors
connected with the electrometer readout. An electric voltage of -400 V was applied before the
electrometer was connected to the Farmer ionisation chamber type 2571 (serial number 1921).
This ionisation chamber has a sensitive volume of 0.69 cm3 and thin walls consisting of high
purity graphite. The useful energy range is between 50 keV and 35 MeV [50]. According to the
specification of this chamber it is recommended to expose the chamber to 2 Gy prior the start
of measurements. Furthermore, it is of importance to correct for influence factors (for example
pressure and temperature) for each measurement. The chamber is cross calibrated to an identical
chamber which has been calibrated at the Swedish secondary standard dosimetry laboratory at
Swedish Radiation Safety Authority once every other year using 60 Co-source.
By calibration, it is possible to relate the darkening of the EBT film to absorbed dose. Thus, the
chamber was irradiated to six different dose levels using: 10, 20, 35, 50, 75 and 100 monitor units
(MUs) and the readout (charge) was given by the electrometer in the unit nC. The electrometer
showed non leakage current for all irradiations. During the phantom breast experiment, it was
found that an extension of the calibration curve was needed. The same set up was used and
five irradiations were added: 100, 125, 150, 175 and 200 MUs.
Figure 4: Illustration of the set-ups using an ionisation chamber in one case and a film in the
other case. Phantom material is PMMA and a SSD of 100 cm is used.
Twelve pieces of film with an area of 5×6 cm2 each were placed separately in a PMMA phantom
at 3 cm depth with a backscatter material of 10 cm using a SSD of 100 cm, as illustrated in
Figure 4. A field size of 10×10 cm2 was used and the film was placed in the centre of the field.
All 12 films originate from the same sheet of film and were marked with number of MU together
with the direction relative to the original film sheet. One of the films was kept unirradiated (0
MU) while the other remaining films were irradiated to 10, 20, 35, 50, 75, 100, 125, 150, 175
and 200 MU. The scanning of the films was done twice: 24 hours and 48 hours after irradiation
to see if there are significant differences in the readout depending on the time after exposure.
According to AAPM, it is recommended to read the films at least 24 hours after exposure, but
to wait 48 hours is preferred [45].
Two films were irradiated by an assistant to ”unknown” doses to further verify the uncertainties
in the calibration curve. The readouts of the ionisation chamber (type 2571) were noted by the
assistant and the determined absorbed doses were to be compared with the doses obtained
from the calibration fitted curve. All absorbed dose determinations in this study are done
by following the IAEA TRS-398 [51] and using the appropriate correction factors. The beam
correction factors used are valid for 6 MV photon beam considering reference condition in a
water phantom (SSD of 100 cm, 10 cm depth and 10×10 cm2 field). The films were scanned 24
hours and 48 hours after exposure.
3.4 Film handling for phantom- and patient study
Prior to the treatment, a sheet of film was cut into 63 pieces with an area of 2×1 cm2 . To
guarantee that it is possible to use such small pieces of film and later draw small sized ROIs
without influencing the MPVs, a test was made on the films used for calibration in section 3.3.
For all twelve films, a line profile was drawn in x- and y-direction respectively in ImageJ. The
MPVs for each line profile were imported to Matlab, divided by the mean value and the absolute
relative difference from the mean was calculated. A threshold for the relative difference was
chosen to 1.5 % and the number of pixels exceeding this threshold were calculated for the four
edges of the film. The number of pixels were converted into centimetres by knowing that 1 pixel
is 0.035 cm. This procedure was done for all twelve films and the mean distance from each
edge of the films was calculated including the result from each film. The results shows that not
more then 0.2-0.3 cm as an edge margin is needed to get stabilized MPVs within a ROI. Thus
making it possible to conclude that the use of small pieces of film during the treatment will not
add uncertainties.
3.5 Anthropomorphic phantom study
3.5.1 Treatment planning
An anthropomorphic adult female phantom (Model number 702-004, CIRS, Virginia, USA)
was used in this project and was scanned in a CT scanner (Siemens SOMATOM) to enable
treatment planning. The phantom was placed in supine position with the arms removed and in
the isocentre by utilising the lasers in the treatment room. To keep track of orientation of the
phantom relative to the lasers and to place the phantom in the same manner during treatment,
three crosses were painted on the phantom where the lasers crossed. Two crosses are located
on each side of the phantom and one cross on the thorax. Small lead bullets were taped in each
cross to ensure that the phantom is placed in the isocentre, that all three bullet are in the same
CT slice and to define a user origin in the treatment plan. The CT-examination was done using
the standard protocol for breast cancer patients at Linköping university hospital. The protocol
contains information such as the slice thickness 2.0 mm and the applied voltage 120 kV.
The CT images were transferred to the Eclipse TPS (Varian Medical Systems, CA) to enable
the creation of a treatment plan. The plan included a treatment schedule of 2.66 Gy in 16
fractions using only 6 MV beam for the left breast. In case of patients with larger breast sizes
than this phantom, a combination of 6 MV and 15 MV is used to allow for larger penetration
depth of the photons in the tissue. The PTV is contoured at 5 mm margin from the skin
surface. According to the recommendations, at least 98 % of the PTV must be given 93 % of
the prescribed dose and the dose maximum in PTV must not exceed 108 % of the prescribed
dose. The treatment plan includes two opposed fields. The first field is 9.3×12.0 cm2 at a
gantry angle of 124◦ . The second field is 9.6×11.6 cm2 at a gantry angle of 305◦ . Both fields
were slightly blocked by the multileaf collimators (MLCs). In order to get a more homogeneous
dose distribution, three compensation fields were added. Two fields were added at 124◦ and
one field at 305◦ . The maximum ratio of the PTV that can achieve 93 % of the prescribed
dose using this plan was 96.26 %. The restrictions could not be completely fulfilled but are
still considered approved by the doctors and are not critical for this study. The treatment plan
showing the dose distribution in colour wash and the dose volume histogram are presented in
Figure 5.
Figure 5: The treatment plan for the left breast, showing the dose distribution in colour wash
and the dose volume histogram in Eclipse
3.5.2 Phantom irradiation
The phantom was placed in the isocentre by using the lasers in the room and at an SSD of
100 cm. Before placing the films on the phantom, On-Board Imager (OBI) system was used
to take kV-images. These images were matched to the CT-images taken previously and the
system calculated if further adjustments of the couch were needed to match the positioning of
the phantom. Thereafter, 21 pieces of film were placed on the left breast of the female phantom,
as shown in Figure 6. The phantom was irradiated according to the treatment plan.
Figure 6: The illustration shows a 3D image of the phantom and the film placement on the left
breast. The right picture of the real phantom shows the phantom after irradiation of the full
treatment with 21 films taped over the left breast.
3.5.3 Entrance and exit dose
To estimate how much the entrance dose and exit dose contribute to the absorbed dose re-
spectively, a set of 21 new films were placed at exactly the same positions as presented in
Figure 6. The phantom was irradiated with only one of the fields in the treatment plan and
its corresponding compensation field. The same procedure was done for the second field with
its corresponding compensation fields using 21 new films. It was decided visually by using the
field-light on the phantom for a certain field (124◦ and 305◦ ) which films that should represent
the entrance dose and which films that should represent the exit dose. For the 124◦ field, the
following films represent the entrance dose: 7 and 15-17, while the films at placement 9 and 10
represent the exit dose. For the 305◦ field, the entrance dose will be represented by the films
placed at 9 and 10. The exit dose will be represented by the films placed at 6, 7, 15 and 16.
All films were scanned 24 h after exposure.
3.6 Patient study
3.6.1 Treatment of patient
The patient study protocol was approved by the Regional Ethics Board in Linköping, Sweden
(DNr 2014/299-31) and a female patient with breast cancer agreed to be a part of this study. The
patient has undergone surgery for the removal of the tumour prior to the start of radiotherapy.
The tumour was located in the right breast and the prescribed dose for this patient is the same
as chosen for the phantom, namely 2.66 Gy in 16 fractions using 6 MV beam. The treatment
plan included two opposed fields: one field at 57◦ with two compensations fields and the second
field at 234◦ with one compensation field. The patient was told to not use any kind on lotion
on that area the same day as the treatment to not affect the films in any manner.
During the treatment, the patient laid in supine position using an overhead arms positioner
that supports the arms and a Prostep that supports the legs. These are fixation techniques
that are usually used during breast cancer radiotherapy treatments. The placement of the films
was done before the images were taken with OBI in order to not affect the positioning of the
patient. Twenty-one pieces of film (2×1 cm2 ) were taped on the breast as shown in Figure 18.
The placement of the films is similar to that described in section 3.5.2 but instead it is mirrored
on the right breast.
3.6.2 Laser Speckle Contrast Imaging
To assess the changes in skin blood flow in the breasts during treatment, a laser speckle con-
trast imaging (LSCI) camera was used (PeriCam PSI, Perimed AB, Järfälla, Sweden). LSCI is
a high resolution and fast technique that uses coherent light for visualization of the microcir-
culation.
When coherent light from the LSCI camera hits the surface of the tissue, photons start to travel
through the media. The pattern of how the photons migrate through the tissue can be explained
as random and is correlated to the optical properties of the tissue. When an interaction with
a moving object occurs, such as the red blood cells (RBCs), the frequency of the scattered
light will be shifted depending on the wavelength, the scattering angle and the velocity of the
object. The light waves will interfere and cause a speckle pattern. The random speckle pattern
appear as granular dark and bright areas. It can vary depending on the motion of the RBCs
and is detected by the CCD camera which is a part of a PeriCam PSI system. If there is no
motion, the speckle pattern is stationary, while the speckle pattern will change over time if the
illuminated volume contains moving objects. It is affected in such way that the local speckle
pattern becomes blurred out and a lower contrast observed at higher blood flows since the
moving RBCs are those that scatter the light. Contrary, high contrast regions represent areas
where the blood flow is low. Thus, an adequate correlation between the speckle contrast and
blood perfusion is possible. The speckle contrast C is usually defined as [52]:
σ
C≡ ¯ (1)
I
where σ is the standard deviation of the intensity I and I¯ is the mean intensity of the speckle
pattern. When the blood flow increases in the illuminated tissue volume, the standard deviation
will decrease due to blurring and result in a low speckle contrast. The mean intensity does not
change.
It was chosen that the camera should take 21 frames per second. For each of the the frames, the
speckle contrast is determined for every 3×3 pixel matrix over the whole frame. By overlapping
all 21 frames and taking the mean contrast over every 3×3 pixel matrix from all the 21 frames,
a resultant image is reconstructed. Thus, the noise in the image can be reduced. In total,
five images (15×15 cm2 each) are obtained with one second time difference in between. The
spatial resolution of the system is 20 pixels per millimetre. The PeriCam PSI version that is
used in this study uses normal resolution (100 µm/pixel at 10 cm camera-surface-distance) with
variable measurement area [53].
3.6.3 Polarised Light Spectroscopy
Polarised Light Spectroscopy is a noninvasive technique that is based on a digital camera and has
the ability to measure the concentration of the RBCs in the upper dermis using polarised light.
This technique has been shown to be insensitive to motion artefacts, has the ability to measure
on relatively large skin areas and produce images with high spatial resolution. In vitro study
showed that this technique is independent of the oxygen concentration in the blood[7].
A polarised light spectroscopy imaging (PLSI) system (TiVi600, Wheelsbridge AB, Linköping,
Sweden) was used in this study for the purpose of measuring the changes in RBC concentration
(RBCC). This camera system is equipped with 96 white light LED-sources and two polarisation
filters, one in front of the flash and one in front of the detector lens. The light source produces
randomly polarised (RP) light that becomes linearly polarised as it passes through the polari-
sation filter. As the light hits the skin, a portion becomes randomly polarised while a portion
of the light remain linearly polarised, see Figure 7. The linearly polarised light is directly re-
flected from the epidermis, while the randomized light changes characteristics as it is randomly
scattered in the tissue. The polarisation filter that is located in front of the lens filters away the
directly reflected light so that only the randomly polarised light can reach the detection array.
The higher the RBCC is in the blood, the higher is the total detected intensity/signal.
The RBCs have a tendency to absorb light in certain wavelength range in a larger extent than
other wavelengths. The absorption of light in red wavelength region (∼600-700 nm) is much
lesser than that of light in green wavelength region (∼500-600 nm). This behaviour is not
observed for other tissue components of the dermis than the RBCs, where less light is absorbed
and the extent of the wavelength-dependency is less. The images are divided into red, green
and blue (RGB) images. The RGB values are then used to calculate the RBCC by an algorithm
that utilises the differences in absorption in the different wavelengths ranges. The algorithm
subtracts each pixel value in the green colour image from the corresponding pixel value in the red
colour image. The difference is then divided by the detected signal and the TiVi-indices (Tissue
Viability indices) are obtained. The TiVi-indices are linearly correlated to the concentration of
the RBCs in the volume of tissue. (A more detailed description of the technology is done by
O’doherty et. al [7]). Due to the fact that the PLSI technology measures at relatively large
areas, it has the ability to include variability in the response between different sites of the skin
due to inhomogeneities in the microcirculation. These heterogeneities are due to difference in
innervation, physiological response and vessel density.
Figure 7: A schematic overview of how the polarised light spectroscopy works. The randomly
polarised (RP) white light from 96 LED-sources gets linearly polarised by a first filter before
hitting the skin surface. A part of the light will be backscattered from the surface while another
part will be randomly polarised by the tissue. Only the randomly polarised light will be able
to pass through the second filter, becomes linearly polarised before it reaches the detection
array and a 8-bit RGB-images can be produced by digitised image processing. (Adapted from
O’Doherty et. al [7])
3.6.4 Skin microcirculation measurements
Before the treatment start, baseline images were taken with LSCI and PLS to measure the
skin microcirculation. After the 16th fraction of a total delivered dose of 42.6 Gy, images were
taken with both techniques to compare to the baseline images and thus obtain the changes in
skin microcirculation due to radiotherapy. Twenty-one ROIs that represent the film placement
during irradiation, were drawn on the images obtained from both LSCI and PLS using the
PSIWin software and ImageJ, respectively. A subtraction between the mean perfusion values
obtained with LSCI before the start of the treatment and after the 16th treatment was done
to get the change in blood flow. The same calculations were done for the TiVi-indices, where
the values obtained before the baseline images were subtracted from the TiVi-indices values
obtained after the 16th fraction.
4 Results
4.1.1 Energy dependence
The results of the comparison between 6 MV and 15 MV are presented in Table 3. The
MPVs for both beam qualities (as the films are scanned 24 h and 48 h after exposure) are
normalised to approximately 1 Gy. The MPVs are normalised to the absorbed dose to get a
relative difference that is independent of the ionisation chamber signal and thus considering one
parameter less. The relative differences are obtained by comparing the normalised MPVs (24 h)
for both energies. The same calculation was done for the normalised MPVs (48 h). According
to Table 3, the largest relative difference for the MPVs is 0.59 %.
Table 3: The MPVs obtained 24 h and 48 h after exposure normalised to 1 Gy, given for the
two energies: 6 MV and 15 MV. The relative differences between the two energies for both
time-after-exposure are represented as well.
Energy [MV] MPV (24 h)/absorbed dose MPV (48 h)/absorbed dose
[Gy−1 ] [Gy−1 ]
6 28652.2 28487.9
15 28483.7 28344.2
Difference [%] 0.59 0.51
4.1.2 Variability with film sheet
The results of the variability with film sheet are shown in Table 4. Film 1 is chosen to be the
reference film since the irradiated pieces of film in previous sections originate from the same
sheet. Thus, the MPVs and absorbed doses for Film 2 and Film 3 are compared to Film 1
and the absolute relative differences are calculated. The results indicate not more than 2.2 %
deviation for both time-after-exposure.
Table 4: The variation in MPV and absorbed dose for 3 different film sheets from the same
lot. The films were irradiated to ∼1 Gy. Film 2 and 3 are compared to Film 1 and the relative
differences are represented in this table.
MPV (24 h) Absorbed dose MPV (48 h) Absorbed dose
(24 h) [Gy] (48 h) [Gy]
Film 1 28853.9 0.92 28758.0 0.91
Film 2 28799.6 0.92 28673.7 0.92
Film 3 28952.6 0.90 28812.9 0.91
Diff. (Film 2/Film 1) [%] 0.19 % 0.00 % 0.29 % 1.10 %
Diff. (Film 3/Film 1) [%] 0.34 % 2.17 % 0.19 % 0.00 %
4.2 Scanner
4.2.1 Temporal variability
The variation in MPVs over a time period of 49 minutes is shown in Figure 8 with a linear
fitting. The error bars indicates the variation in pixel values within the chosen ROI. The mean
of the MPVs (± 1 standard deviation (SD)) is calculated to be 43121 ± 18.
Figure 8: Mean pixel value variation over a time of 49 minutes for 15 scans using the same film
sheet. The error bars are calculated by ImageJ and represent the variation of the pixel values
in the chosen ROI within 1 SD.
4.2.2 Variability with ROI size
The variations in MPVs for the small, medium and large sized ROIs are shown in Figure 9.
A linear fitting was done for all three ROIs. The mean of the MPVs over a ROI (± 1 SD) is
calculated to be 43166 ± 13, 43032 ± 13 and 43028 ± 16 for small ROI, medium ROI and large
ROI, respectively.
Figure 10 shows the MPVs for all three ROIs over the scan number. The relative difference
between the large ROI and the medium ROI is calculated for every scan number. The mean
relative difference thus refers to the mean of all the relative differences calculated between two
ROI sizes. The mean relative difference between the MPVs for the large ROI and medium ROI
is calculated to be 0.3 %. The mean relative difference between the MPVs for the medium ROI
and small ROI is calculated to be 0.01 %.
Figure 9: MPVs for 30 consequently scans using small ROI size (256 pixels), medium ROI size
(9600 pixels) and a large ROI size (81 472 pixels). The error bars are calculated by ImageJ and
represent the variation of the pixel values in the chosen ROI within ± 1 SD. The linear fitting
is done for all three ROIs.
Figure 10: Mean pixel value for the three different ROIs: small (256 pixels), medium (9600
pixels) and large (81 472 pixels).
The effect of higher MPVs for the large ROI compared to the medium and small ROI (see
Figure 10) was further investigated by altering the contrast for scan number 15 as shown in
Figure 11. The contrast was altered for other scan numbers and for other films than the one
used in this section. The same trend with inhomogeneities of MPVs was observed. A ROI with
an area of 4.7 cm2 was placed on the green-region (image 1) and the yellow-region (image 2)
using the image of scan number 15. Their MPVs shown in Table 5 were compared and gives an
absolute relative difference of 36.7 %.
Figure 11: The image of scan number 15 with changed contrast (brightness). The contrast was
changed by changing the window settings in ImageJ. The MPVs from the ROIs in image 1 and
image 2 are compared.
Table 5: The obtained MPVs for the ROIs in image 1 and image 2 using scan number 15.
MPV Image 1 MPV Image 2 Difference [%]
32118.6 50669.3 36.61
To conclude whether it is the scanner or the films that causes the inhomogeneities seen in Figure
11, a sheet of paper was scanned and the contrast (brightness) was modified by changing the
window settings in ImageJ, see Figure 12 image number 1. Furthermore, to check if this is
due to the LED-lamp distributing the light non-uniformly or the scanner background being
inhomogeneous, two paper sheets were placed on the scanner surface and were scanned. The
contrast of the image was modified and the image is shown in Figure 12 image 2. The same
procedure was done with 10 paper sheets to see if it is possible to exclude that the heterogeneities
are due to LED-lamp. The image of the 10 paper sheets is represented as image 3 in Figure
12.
Figure 12: Image 1: One paper sheet scanned. Image 2: Two paper sheets scanned. Image 3:
Ten paper sheets scanned. The contrast (brightness) was alternated by changing the window
settings in ImageJ for all three images.
The contrast of the image of the exposed film was altered and is shown in Figure 13. Two ROIs
with an area of 6.3 cm2 each where drawn on the darkest and brightest part of the image, see
image 1 and 2 respectively in Figure 13. The MPVs were obtained and the absorbed doses were
calculated from the exponential fitted curve (24 h) in Figure 15. The MPVs and absorbed doses
for both ROIs were compared and are represented in Table 6.
Figure 13: The image of a film sheet irradiated to 200 MUs with 6 MV beam and with modified
contrast in ImageJ. The MPVs from ROIs in image 1 and image 2 are compared.
Table 6: The obtained MPVs for the ROIs in image 1 and image 2 using a film sheet irradiated
to 200 MUs with 6 MV beam. The two ROIs are compared in terms of MPV and absorbed
dose (obtained from the calibration curve (24 h)) and the difference is represented as relative
difference.
MPV Absorbed dose [Gy]
Image 1 21879.8 2.09
Image 2 22264.7 2.00
Difference [%] 1.76 4.50
4.2.3 Spatial variability
The MPVs for different placements of the films on the scanner surface are shown in Figure 14.
The positioning of the films was varied according to Table 2. A ROI was chosen in the centre
of the each film and included 5621 pixels.
The recommend placement of the film is in the centre, as in scan number 2 (x=11 cm, y=15 cm).
Hence all the obtained MPVs are compared to scan number 2. The two placements that result
in the largest discrepancy are scan number 1 and 5 with an absolute percentage deviation of 0.56
% and 0.48 %, respectively. Nevertheless, the absolute mean percentage deviation compared to
scan number 2 is calculated to be only 0.23 %.
Figure 14: The MPVs for different placements of the film on the scanner area.
4.3 Calibration
The results of the calibration are shown in Figure 15 for 24 h and 48 h after exposure. For
both plots, a second degree exponential fitting was done in Matlab. In the same plots, the films
irradiated with ”unknown” doses are shown as well. The error bars for each film are obtained
from ImageJ and shown in the plots. For comparison reason, the two plots in Figure 15 are
plotted together and shown in Figure 16. The absolute mean relative difference between the
MPVs for scanning after 24 h and 48 h was calculated to be 0.33 %. The absolute mean relative
difference between the doses for 24 h and 48 h was calculated to be 0.34 %.
Figure 15: The calibration curves are obtained using the MPVs and by calculation of the
absorbed dose using the ionisation chamber readout. Exponential fitting of second degree is
used to obtain the calibration curve. The scanning of the films is done 24 hours and 48 hours
after exposure. Two films were irradiated to unknown doses, scanned after 24 h and 48 h and
plotted in the figures as well.
Figure 16: The variation in MPVs with dose. Exponential fitting of second degree is used and
the two curves represent the films scanned 24 hours and 48 hours after exposure.
Using the fitted curves from Figure 15 for respective time-after-exposure, the absorbed doses
for the films irradiated to ”unknown” doses were obtained and are presented in Table 7. The
absorbed doses that are calculated using the ionisation chamber signal, are shown in the same
table. The film dose values are compared to the ionisation chamber dose values and the absolute
relative difference is shown in the table as well. According to the results, the relative difference
can reach up to approximately 2 %.
Table 7: The film doses are obtained from the fitted calibration curves. The ionisation cham-
ber absorbed doses are calculated from chamber signal. The film doses are compared to the
ionisation chamber absorbed doses and represented as absolute relative differences.
Film dose Film dose Ionisation chamber
(24 h) [Gy] (48 h) [Gy] absorbed dose [Gy]
Film 1 0.1415 0.1387 0.1389
Film 2 0.8216 0.8220 0.8125
Film 1 Diff. [%] 1.87 0.14
Film 2 Diff. [%] 1.12 1.17
The doses at the different film placements were calculated using the calibration curve from
time-after-exposure of 24 h. In Table 8, the doses for the full treatment are presented and
compared to the prescribed dose of 2.66 Gy. The comparisons of the calculated surface doses
and the prescribed dose are presented as relative doses given in percent. The absorbed doses
are schematically shown in Figure 17 on a 3D Matlab illustration based on the phantom’s
CT-data.
Table 8: The absorbed dose at different film placement using the female phantom. The relative
dose gives percentage of the absorbed dose relative to the prescribed dose of 2.66 Gy.
Film placement Absorbed dose [Gy] Relative dose [%]
1 1.60 60.2
2 1.57 59.0
3 1.62 61.0
4 1.36 51.1
5 1.68 63.2
6 1.47 55.3
7 1.39 52.3
8 1.55 58.3
9 1.30 48.9
10 1.24 46.6
11 1.51 56.8
12 1.68 63.2
13 0.10 3.8
14 0.51 19.2
15 1.37 51.5
16 1.18 44.4
17 1.30 48.9
18 0.11 4.1
19 0.86 32.3
20 1.07 40.2
21 0.14 5.3
Figure 17: A 3D Matlab-illustration of the female phantom with 21 films placed on the surface
of the left breast. The colour bar gives the absorbed dose in Gy for each film. The doses are
obtained from one fraction with a prescribed dose of 2.66 Gy.
The absorbed doses using the field at 124◦ and two compensation fields with the same incident
angle for irradiation of the phantom are shown in Table 9. The doses are compared to the
prescribed dose and presented in the table as relative doses given in percent. In Table 10, the
doses are represented for the field at 305◦ with one compensation field.
Table 9: The absorbed dose at different film placement with treatment at 124◦ gantry angle
using the female phantom. The relative dose gives percentage of the absorbed dose relative to
the prescribed dose of 2.66 Gy.
Film placement Dose field 124◦ [Gy] Relative dose [%]
1 0.92 34.6
2 0.65 24.4
3 0.94 35.3
4 0.92 34.6
5 0.94 35.3
6 0.69 26.0
7 0.57 21.4
8 0.92 34.6
9 0.92 34.6
10 0.81 30.2
11 0.83 31.2
12 0.96 36.1
13 0.04 1.5
14 0.10 3.8
15 0.68 25.6
16 0.50 18.8
17 0.56 21.1
18 0.05 1.9
19 0.55 20.7
20 0.54 20.3
21 0.03 1.1
Table 10: The absorbed dose at different film placement with treatment at 305◦ gantry angle
using the female phantom. The relative dose gives percentage of the absorbed dose relative to
the prescribed dose of 2.66 Gy.
Film placement Dose field 305◦ [Gy] Relative dose [%]
1 0.63 23.7
2 0.86 32.3
3 0.59 22.2
4 0.38 14.3
5 0.70 26.3
6 0.70 26.3
7 0.71 26.7
8 0.58 21.8
9 0.37 13.9
10 0.36 13.5
11 0.64 24.1
12 0.64 24.1
13 0.07 2.6
14 0.38 14.3
15 0.60 22.6
16 0.64 24.1
17 0.70 26.3
18 0.04 1.5
19 0.09 3.4
20 0.28 10.5
21 0.05 1.9
4.5 Patient study
The local skin doses at different areas of the breast were calculated using the calibration curve
(24 h) and presented in Table 11 (see the film placements in Figure 18). The absorbed doses
are compared to the prescribed dose of 2.66 Gy and presented as relative doses given in percent
in the same table. A 3D illustration of the films placed on the patient’s breast representing the
absorbed doses, was done in Matlab using the patient’s CT-data (see Figure 19).
Figure 18: The film placement on the right breast of a female patient before irradiation. The
right image shows the breast is taken in anterior direction. The left image shows the breast
from right in the lateral direction.
Table 11: The absorbed dose at different film placement during a patient treatment. The
relative dose gives percentage of the absorbed dose relative to the prescribed dose.
Film placement Dose treatment [Gy] Relative dose [%]
1 1.56 58.6
2 1.63 61.3
3 1.53 57.5
4 1.40 52.6
5 1.63 61.3
6 1.49 56.0
7 1.56 58.6
8 1.55 58.3
9 1.29 48.5
10 1.28 48.1
11 1.62 60.9
12 1.69 63.5
13 0.19 7.1
14 1.53 57.5
15 1.34 50.4
16 1.33 50.0
17 1.36 51.1
18 0.37 13.9
19 1.23 46.2
20 1.17 44.0
21 1.13 42.5
Figure 19: A 3D Matlab illustration of the female patient with 21 films placed on the skin of
the right breast. The colour bar gives the absorbed doses in Gy for each film. The doses are
obtained from one fraction with a prescribed dose of 2.66 Gy.
Figure 20 shows how the change in perfusion (blood flow) and TiViindex (RBCC) due to the 16
irradiations of the patients breast vary with the skin doses obtained at the same regions. The
absorbed doses are calculated from the doses obtained from Table 11 and multiplied by a factor
16 to get the total accumulated dose at the end of the treatment.
Figure 20: The left plot shows the variation of the change in mean perfusion of the patient with
the absorbed skin dose. The right plot shows the variation of the change in TiViindex of the
patient with the absorbed skin dose. The absorbed dose represent the total skin dose after 16
fractions with a prescribed dose of 2.66 Gy/fraction.
Table 12: For all film placements: the total absorbed skin dose after 16 fractions (2.66
Gy/fraction), the change in mean perfusion and in TiViindex (RBCC) before the start of the
treatment and after the 16th fraction.
Film Absorbed Change in mean Change in TiViindex
placement dose [Gy] perfusion [PU] [A.U.]
1 25.00 190.37 184.35
2 26.08 154.93 244.91
3 24.48 107.31 211.14
4 22.40 66.69 129.37
5 26.08 30.75 67.27
6 23.84 7.86 130.33
7 25.00 74.71 105.86
8 24.80 17.06 141.33
9 20.64 21.29 74.32
10 20.48 28.42 49.09
11 25.92 22.25 77.33
12 27.04 16.94 136.00
13 3.04 27.79 23.53
14 24.48 16.60 65.00
15 21.44 2.11 -35.03
16 21.28 6.05 -3.95
17 21.76 7.64 -33.21
18 5.92 1.21 13.97
19 19.68 17.81 65.46
20 18.72 24.06 65.76
21 18.08 33.54 67.58
4.5.1 Pearson’s correlation test
Pearson’s correlation test measures the correlation between two variables to see if a linear
correlation exist. The correlation is referred to as Pearson’s r and indicates a perfect correlation
if r = +1/-1. If there is no correlation between two variables, the correlation coefficient r equals
0. However, some assumptions must be accounted for when performing this type of correlation
test. These assumptions include that the two variables must be from the same sample group,
measured independently and be sampled from a Gaussian distributed sample. The covariance
is assumed to be linear [54].
This statistical test was applied to the data in Table 12 using GraphPad Prism [Version 6.07]
[55]. Although visually, no linear correlation seems to exist in Figure 20. The results from the
Pearson’s correlation test are presented in Table 13 where the correlation was tested between
the change in mean perfusion and the absorbed dose, as well as between the change in TiViindex
and the absorbed dose. The test was chosen to be two-tailed test with a significance level
α=0.05
Table 13: Pearson’s correlation coefficient r calculated to test the correlation between the
change in mean perfusion and absorbed dose as well as between the change in TiViindex and
the absorbed dose. A two-tail test with a significance level of 0.05 was done.
X/Y Change in mean PU/ Change in TiViindex /
Absorbed dose Absorbed dose
Pearson’s r 0.30 0.48
P-value (two-tailed) 0.18 0.03
Significance (α = 0.05) No Yes
5 Discussion
The discussion will include analysis of the measurement devices used, the methods and the
results. In the analysis of the data obtained in this study, it is worth considering all effects that
may influence the results. Some of these effects affects the measurements and results more than
others which are considered to be of less importance.
The LRA will be more pronounced in the red channel due to its high dose dependency for doses
above 1 Gy. However, no literature has discussed the reason for why the dose affects the LRA
but only the fact that a lower relative response is observed towards the edges of the scan area
and this effect increases with increased dose. Since the doses in the this study do not exceed 2
Gy and all the films were placed in the centre of the scan area, it is concluded that the variation
in response due to LRA will not affect the results.
The low variation in MPVs (maximum of 0.59 %) with beam quality (6 MV and 15 MV) confirm
the statement by the manufacturer as the films being minimally energy independent and agree
with the conclusions from other studies [40], [41]. However, since both the phantom and patient
had relatively small breast, they were irradiated with only 6 MV. Thus, the variation in MPVs
due to the beam quality will not have an impact of the results in this project but may be useful
for future studies. In future studies when including a larger population of patients, it would
further be of interest to investigate the energy dependence of the films in an energy range down
to a few kV. This is to see how the film response will vary due to the OBI which will have
an impact of the film response during patient irradiation. Other studies have confirmed the
variations in the film response due to energy dependence in kV-range [56], [57].
The relative difference for the variation of MPVs and absorbed doses with film sheet are con-
sidered small with a maximum variation of 0.34 % for the MPVs and 2.17 % for the absorbed
doses. The conclusion drawn from these results is that all sheets of film in this lot should
approximately give the same correlation between the darkening of the film and the absorbed
dose.
The films may have been affected by skin oils and sweat to a small extent since all the films
were picked up from the edges by hand. The extent of which this affects the results is unknown
but it is expected to have a negligible impact. Furthermore, the tape that were used to position
the film pieces on the phantom and patient will probably also have a small impact. To exclude
possible dependence due to these factors, the chosen ROIs in ImageJ were selected in the middle
of the film pieces with a small margin to the edges.
When considering the active depth of the films, it is important to have in mind that the pixel
values are a result of the integrated ionisation over the active volume/layer. The active layer of
the film is ∼ 28 µm (∼3.36×10−3 g/cm2 ) and the obtained absorbed doses are thus considered
to be at a depth between 100-128 µm (1.35×10−2 - 1.69×10−2 g/cm2 ).
5.2 Scanner
The results show a small increase in MPV over time, see Figure 8. The small increase was
unpredicted since scanning the same film a few times and assuming that the LED-lamp in the
scanner may affects the film, the result would be a reduction in MPV with time instead. This is
since the LED-lamp may darken the film and give lower MPVs. A study done by Åstrand shows
that the MPV decreases with time [48], although she used another scanner (Epson Perfection
V700 Photo). A conclusion that can be made from these results is that the LED-lamp affecting
the films is not the reason for the observed increase but it is expected however to be another
unknown property of the scanner that gives these results.
Comparing the sizes of the error bars calculated by ImageJ in Figure 8 with the standard
deviations of the mean MPVs, it is observed that the error bars covers a larger range of the
MPVs (a variation in pixel value of approximately ±230) than the calculated SDs (a variation
of ±18). These results indicates that the variation of the pixel values within a chosen ROI is
larger than the variation of the MPVs over time. Considering this, it is concluded that no warm
up time is needed for the scanner.
The same trend between the error bars in Figure 9 and the calculated SDs in section 4.2.2 is
observed, where the SDs are small in comparison to the error bars. Thus, the slightly increase
of the MPVs within a chosen ROI size after scanning the same film sheet 30 times, will not have
an impact on the absorbed dose determinations in the study. Figure 10 shows that the MPVs
decrease markedly between the large ROI and medium ROI, while the difference between the
medium and small ROI is less pronounced. However, the results clearly shows that mean of
the MPVs for the small and medium ROI are comparable (0.01 % mean difference), while the
difference is more pronounced when comparing the mean of the MPVs from medium and large
ROI (0.3 % mean difference). The optical density increases towards the lateral edges of the
scan area which can be a probable cause for the higher MPV for the large ROI. When analysing
the images in Figure 11 with alternated contrast, the results show that certain areas of the film
appear as more green-coloured and have reduced MPVs. It is expected that the LED-lamp in
the scanner contributes to an uneven distribution of the optical density over the scan area and
lead to variations in MPVs that can vary up to 37 %.
The large relative difference in MPVs between the two ROIs shown in Figure 11 may have
influenced the results in Figure 10. The large ROI size probably include regions with both high
MPVs (yellow) and low MPVs (green), while the smallest ROI is likely to mostly include the
green regions. Nevertheless, the results in Figure 11 do not conclude whether these effects are
influenced by inhomogeneities in the scanner or the films. From Figure 12 image number 1, it can
be assumed that the inhomogeneities are apparently a scanner property and not a film property.
Furthermore, it is observed in image 2 and 3 in the same figure that the scanner background
does indeed contribute to the inhomogeneity, but also when using ten paper sheets to not let
the light be reflected from the scanner background, the inhomogeneities are visible. Thus, a
conclusion can be made that it is both the the LED-lamp in the scanner and the background
contribute to an uneven distribution of the optical density over the scan area.
The heterogeneities appearing due to the scanning of the films are less pronounced when the
film has been exposed to radiation and the MPVs vary with only 1.76 % (see Figure 13 and
Table 6). The variation in the absorbed dose can vary up to 4.5 %. The large difference in the
relative differences between the MPVs and the absorbed dose is not surprising, since according
to the calibration curve the relationship between the MPVs and absorbed dose is not linear.
If a linear relationship would be obtained instead, the relative differences would be the same.
However, it must be noted that the variations in optical density found in this study may be
specific for this scanner and the same trend will not necessarily be found in another scanner
of the same type. Note as well that the most extreme regions in term of colour darkening are
compared here and the selection of the regions was done only subjectively. Despite the fact that
the films used in the phantom and patient studies were placed centrally on the scan area, the
variation in MPVs of 4.5 % is considered to be large and may have affected the absorbed dose
determinations in this study to some extent.
The spatial variability of the MPVs depending on the film placement on the scanner area
was shown to be minimal (< 1 %). Nevertheless, this effect will not affect the absorbed dose
determination in any manner since all the films were placed centrally on the scanner surface as
recommended by the manufacturer of the Grafchromic EBT3 film.
5.3 Calibration
The same trend is observed for both plots in Figure 15, where the MPVs decrease with in-
creased dose. A similar exponential trend of the calibration curve is observed by Åstrand [48].
However, the absolute MPVs are not identical to those represented in this study due to different
factors including the calibration method and the scanner used. The results give a mean relative
difference of 0.33 % and 0.34 % between the scanning after 24 h and 48 h for the MPVs and
dose, respectively. The small relative differences are considered to be negligible in the absorbed
dose determinations in the study. It was therefore concluded to scan the films after 24 h after
exposure and not necessary 48 h after exposure, due to the time limitation in this study. Further
uncertainties appear when comparing the calculated doses for the films that were irradiated to
”unknown” doses with the absorbed doses that were calculated using the ionisation chamber
signal. The maximum relative difference of approximately 2 % is somehow an estimation of
uncertainties in the calibration curve.
An important consideration regarding the calibration is the irradiation setup used in this study.
The setup do not completely match the reference geometry setup recommended by the IAEA
TRS-398, since the correction factors are calculated for a water phantom and 10 cm depth in
water. Here, a PMMA phantom is used and a depth of 3 cm. Seuntjens et al. concluded
that a small error in the perturbation factors is introduced due to the fact that a non-reference
geometry is used and the dose ratio water to PMMA is accurate within 0.4 %[58].
The results show that for the full treatment, the absorbed doses lay in a range between 0.10-1.68
Gy. The trend of the doses shows clearly that the midline regions of the breast are exposed to
the highest doses and the trend is most pronouncedly in the central regions. The lowest dose
is observed at film placement 13 while the highest doses are obtained for placement 5 and 12
(relative dose of 63.2 %). The lateral side of the breast seems to receive higher doses than the
other half of the breast, as illustrated in Figure 17.
The fact that the highest surface doses are observed at the midline of the breast is not surprising
since those films are irradiated with both of the tangential radiation fields. The films that were
completely out of the irradiation field are film placement 13, 18 and 21. The results from Table
8 show that these films represent the lowest doses. However, the low doses observed for these
films are due to scattered radiation. The fact that mainly within 45-64 % of the prescribed dose
is deposited in the skin is in good agreement with the founding by Almberg [59] and Rudat
[60]. Almberg et al. concluded that around 45-65 % of the target dose results in surface dose
while Rudat et al. concluded that 40-60 % of the target dose is deposited at the surface. Both
studies used TB-IMRT and Gafchromic film dosimetry.
A surprising result is obtained if the doses from Table 9 and Table 10 are added up together
and compared to the doses in Table 8. A mean relative difference of 8.3 % is observed. The
expectation was to see that the added doses from the fields at 124◦ and 305◦ would result in
the same doses as the full treatment. It is less likely to be caused by the film placement, even
though the films were not moved during the full treatment but replaced during the separate field
irradiation. This is since the tape pieces from the full treatment were left on the phantom in
order to place the new films at the exact same position when irradiating with separate fields. The
mean relative difference may in this case not be representative of the differences since the overall
relative differences seems to be around 4-5 % while the largest relative differences are observed
for film placement 18-21 where the relative difference vary between 17-42 %. These films receive
relatively low doses and have probably been affected by the amount of scattered radiation. A
contribution to this large difference may be the fact that the full treatment irradiation and the
separated fields irradiation were done on different days. Thus, the set-up of the phantom is not
identical and also the accelerator output is expected to vary slightly.
When the films were taped on the phantom surface, it was complicated to keep the films totally
attached to the surface. Instead, the edges of the film tended to lift up from the phantom
surface. Although, the ROIs were chosen with a small margin to the edges to exclude those
areas where the films were lifted up, this film behaviour may has affected the absorbed doses.
Considering the lack of backscatter contribution from the phantom at these regions on the film
pieces, the absorbed doses may be underestimated.
For the gantry angle 124◦ , the maximum dose is observed at film placement 12 with a dose
of 0.96 Gy which corresponds to 36.1 % of the prescribed dose of 2.66 Gy. For the gantry
angle 305◦ the maximum dose is observed at film placement 2 with a dose of 0.86 Gy which
corresponds to 32.3 % of the prescribed dose. The reason for the higher doses at 124◦ than at
305◦ is due to the extra compensation field. However, the same trend as for the full treatment
is observed here, where the highest doses appear centrally and in the midline direction of the
breast.
For the 124◦ , the films that represent the entrance dose are 7 and 15-17 as mentioned previously
(see Figure 6). According to absorbed doses from Table 9, the average dose is 0.58 Gy which
is 21.8 % of the prescribed dose of 2.66 Gy. The exit dose is represented by the films placed at
9 and 10. Thus, the average exit dose is 0.87 Gy which is 33.7 % of the prescribed dose. For
the 305◦ field, the entrance dose is represented by the films placed at 9 and 10. The average
entrance dose for these two films is 0.37 Gy and corresponds to 14 % of the prescribed dose.
The films that represent the exit dose for this field are 6, 7, 15 and 17 and give and average
dose of 0.66 Gy which is 24.9 % of the prescribed dose. Considering these results, the exit dose
contributes more to the surface dose than the entrance dose for both fields.
For some of the films, the beam was incident with a large obliquity. Due to the fact that the
effective depth of the electrons resulting from photon interaction is larger for obliquity incident
beams than for perpendicular incident beams, the result will be a higher dose for those films.
For the 124◦ field, the beam was incident on the films placed on the midline of the breast (1,
3, 5, 8, 11 and 12) with an angle of approximately 90◦ . This explains the higher dose at those
regions. The beam incident angle at those six films with the 305◦ field is estimated to be 70◦ .
Comparing the results in Table 9 and Table 10 at those regions, it is observed that a higher
absorbed skin dose is obtained for the 124◦ field. This is a result due to the larger anglulation of
incident beam which gives a larger effective depth of the electrons. Note that it is of importance
to take into account the extra compensation field that was added at the 124◦ compared to the
305◦ field and the beam angle are only subjective estimations. It is furthermore important to
consider the rough estimations of the angulation due to the difficulty to determine the angle
between the beam and the skin at a particular point.
5.5 Patient study
The results show that the absorbed doses are in a range between 0.19-1.69 Gy. The three highest
doses appear to be at film placement 2, 5 and 12 , which is in agreement with the findings from
the phantom study. These doses correspond to 61.3 %, 61.3 % and 63.5 % of the prescribed
dose, respectively. The lowest absorbed doses are observed at film placement 13 with a dose of
0.19 Gy and film placement 18 with a dose of 0.37 Gy. These low doses are probably due to
the fact the films were positioned outside the radiation field. Furthermore, the same trend is
observed for the patient as for the phantom, where the higher doses seems to be situated on
the midline of the breast.
In patient study, it is worth considering that the films were attached directly to the skin and may
therefore have been affected by skin oils and sweat in a larger extent than in the phantom study.
Furthermore, the films in the patient study were irradiated during the OBI in comparison to the
films in the phantom study which were placed on the phantom after the OBI. However, these
differences between the phantom and patient study does not seem to affect the absorbed doses if
comparing the dose ranges from both studies. The dose range (0.10-1.68 Gy, see Table 8) from
the phantom study is in good agreement with the dose range obtained from the patient study
(0.19-1.69 Gy, see Table 11). Similarity between both studies were also found in the overall
absorbed skin dose distribution over the breast. The fact that the size of the patient’s breast
happened to be of comparable size to the phantom breast, may explain the results. However,
it is important to consider the impact of the diaphragmatic motion in the patient study that
adds further uncertainties but is absent in the phantom study.
An increase in mean perfusion is observed at all 21 regions in Table 12. But the largest increases
are centrally on the breast (film placements 1, 2 and 3). The same trend is observed for the
change in mean RBCC but for film placements 15, 16 and 17, the RBCC decreases after the
radiotherapy treatment. The reason for why the largest changes appear centrally may be due to
the vascular reactivity or the capillary density. Furthermore, studies have shown that large skin
reactions appear in regions with skin folds which would mean that an increase in perfusion and
RBCC at film placement 14 was expected. But the change in microcirculation do not indicate
that this region is more sensitive for this patient. Nevertheless, the expectation was to see that
the regions that gets the highest absorbed dose, will also result in highest increase in perfusion
and RBCC.
Note that there are uncertainties related to the absorbed doses in Table 12, since these doses
are obtained by multiplying the doses in Table 11 by a factor 16 to get the total accumulated
skin dose after the end of the treatment. Thus, it is assumed in this study that the patient
will receive the same skin doses in every fraction in the treatment, which is an estimation. The
skin dose may vary between the fractions, not only due to the small variation in the accelerator
output but also due to the diaphragmatic motion of the patient.
Since the patient had undergone surgery for tumour-removal before the breast cancer radiother-
apy was scheduled, it was expected that marked difference in the change in microcirculation
would be observed in the scar region. The surgery scar was located below the film placements
3, 8 and 12. The scar does not seems to affect the mean perfusion since the change in blood
flow does not seems to be markedly affect by the scar in comparison to other regions on the
breast. However, the change in RBCC is clear at film placements 3, 8 and 12 (see Table 12).
The redness around the scar was also observed visually. The increase RBCC in the scar can
be explained by an increase in capillary density and diameter and by vasodilation due to tissue
repair mechanisms.
The results of the Pearson’s r in Table 13 show that for both tests, the two variables tend to
increase or decrease together due to the positive sign. However, the correlation is better between
the change in TiViindex with the absorbed dose, than it is for the change in mean perfusion.
Furthermore, the p-value is lower for TiViindex which indicates that there is a low probability
that the correlation is by chance. The conclusion from these statistical tests is that there is no
statistical correlation between the change in mean blood perfusion and the absorbed dose for
this patient. Whereas, a significant statistical correlation exist between the change in RBCC
(TiViindex ) and the absorbed dose (α = 0.05).
When discussing the microcirculation change, it is of importance to account for the biological
factors influencing the results, such as the thickness of the epidermis. A conclusion drawn
in a study by Sandby-Moller et. al is the positive correlation between the thickness of the
cellular epidermis and the blood content, i.e. a thicker layer of the cellular epidermis indicate
a greater blood supply. This result was mainly observed in males [61]. Observations of the
increase in blood perfusion with radiation skin dose was found by Nyström. Nyström et al.
investigated the possibilities to correlate the skin reaction with radiation dose, using inter alia
laser Doppler technique which measures the blood perfusion. A general result was observed,
that in 79 % of the cases a significant increase in perfusion is observed with increased radiation
dose, i.e. the blood flow in the treated area increases with increased skin dose [62]. However,
a conclusion could not be drawn regarding how much a specific radiation dose will increase the
blood perfusion. This is since the radiosensitivity of the individuals varies and thus also the
increase in the perfusion.
6 Conclusions
The absorbed doses from the phantom study and the patient study were in good agreement
and within similar dose ranges. It was also observed that the midline region of the breast is
exposed the highest absorbed doses using two tangential fields. The blood perfusion in the skin
does indeed increase as the treated areas are exposed to radiation. Although, no significant
correlation was observed between the increase in blood perfusion and the absorbed skin dose
for this patient. The overall changes in RBCC concentration (TiViindex ) could be significantly
correlated to the absorbed skin dose. However, from the results in this study, it is not reliable to
conclude whether a general correlation exist or not between the changes in skin microcirculation
and the absorbed dose due the small population sample. In order to get more reliable results,
a larger sample must be included in future work. It was also found to be difficult to perform
a concrete error-analysis which sums up all the error-sources in the study. Furthermore, there
is biological properties that are difficult to take into account for, such as the thickness of the
epidermis and general health condition. Therefore, the skin doses found in this study can not
simply be generalized to other patients. In order to make this possible in the future, a new
study should test the correlation over a larger sample with different breast geometries. It would
also be of interest to include patients that have undergone mastectomy that often experience
more pronounced skin reactions due to the use of bolus during radiotherapy.
The uncertainties related to subjective scoring criteria of the skin reactions have been stated.
Future studies should continue with quantification of the skin reactions that appear as a con-
sequence of the radiation therapy and include biological related properties (skin thickness, age,
sex etcetera) in the prediction of the absorbed skin dose based on the microcirculation proper-
ties. In this way, it may be possible to predict the radiosenstivity of the patient and the risk of
skin damage in the beginning of the radiotherapy treatment.
Even though the results from this study can not contribute to the development of the treatment
technique in radiotherapy or be directly implemented in the clinic, this study shows that the
method is reliable and a correlation may exist between the changes in microcirculation and the
absorbed skin dose in breast cancer radiotherapy.
7 Acknowledgement
I would like to thank my supervisors E. Tesselaar, E. Adolfsson and B.Nilsson for your help and
guidance throughout the project. I would also like to thank all the staff at department of Medical
and Health Sciences at Linköping University Hospital for making me feel welcome. Another
thank goes to my family and soon-to-be husband Dr. Milad Gabro for all the motivation and
support you have giving me during the project.
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9 Appendix
Figure 21: Positioning of the 21 films on the anthropomorphic female phantom’s breast before
irradiation at Linköping University hospital [Mars 23, 2016].

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Measurement of absorbed dose to the

skin and its relation with microcircular

(May 27, 2016)

3 Materials and Methods 8

5.4.1 Entrance and exit dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

2.1 Skin reactions

Table 1: RTOG/EORTC acute scoring criteria - skin [21]

2.2 Dose distribution in the build-up region

2.2.2 Exit dose

2.3 Detectors for surface dose determination

3 Materials and Methods

3.1 Gafchromic EBT Film

Figure 2: Configuration of GafchromicT M EBT3 Dosimetry Film.

3.1.1 Energy dependence

3.1.2 Variability with film sheet

3.2.1 Temporal variability

3.2.2 Variability with ROI size

3.2.3 Spatial variability

3.4 Film handling for phantom- and patient study

3.5 Anthropomorphic phantom study

3.5.1 Treatment planning

3.5.2 Phantom irradiation

3.5.3 Entrance and exit dose

3.6 Patient study

3.6.1 Treatment of patient

3.6.2 Laser Speckle Contrast Imaging

3.6.3 Polarised Light Spectroscopy

3.6.4 Skin microcirculation measurements

4.1 Gafchromic EBT Film

4.1.1 Energy dependence

4.1.2 Variability with film sheet

4.2.1 Temporal variability

of the MPVs (± 1 standard deviation (SD)) is calculated to be 43121 ± 18.

4.2.2 Variability with ROI size

4.2.3 Spatial variability

4.4 Anthropomorphic phantom study

4.4.1 Entrance and exit dose

4.5 Patient study

4.5.1 Pearson’s correlation test

5.1 Gafchromic EBT Film

5.4 Anthropomorphic phantom study

5.4.1 Entrance and exit dose

5.5 Patient study

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