-
POINT-BASED IONIZING RADIATION DOSIMETRY USING RADIOCHROMIC
MATERIALS AND A FIBREOPTIC READOUT SYSTEM
by
Alexandra Rink
A thesis submitted in conformity with the requirements for the
degree of Doctor of Philosophy
Graduate Department of Medical Biophysics University of
Toronto
© Copyright by Alexandra Rink (2008)
-
ii
Abstract
Point-Based Ionizing Radiation Dosimetry Using Radiochromic
Materials And Fibreoptic
Readout System
Doctor of Philosophy, 2008
Alexandra Rink
Department of Medical Biophysics
University of Toronto
Real-time feedback of absorbed dose at a point within a patient
can help with radiological
quality assurance and innovation. Two radiochromic materials
from GafChromic MD-55 and
EBT films have been investigated for applicability in real-time
in vivo dosimetry of ionizing
radiation. Both films were able to produce a real-time
measurement of optical density from a
small volume, allowing positioning onto a tip of an optical
fibre in the future. The increase in
optical density was linear with absorbed dose for MD-55, and
non-linear for EBT. The non-
linearity of EBT is associated with its increased sensitivity to
ionizing radiation compared to
MD-55, thus reaching optical saturation at a much lower dose.
The radiochromic material in
EBT film was also shown to polymerize and stabilize faster,
decreasing dose rate dependence in
real-time measurements in comparison to MD-55. The response of
the two media was tested
over 75 kVp – 18 MV range of x-ray beams. The optical density
measured for EBT was constant
within 3% throughout the entire range, while MD-55 exhibited a
nearly 40% decrease at low
energies. Both materials were also shown to be temperature
sensitive, with the change in optical
density generally decreasing when the temperature increased from
~22°C to ~37°C. This was
accompanied by a shift in the peak absorbance wavelength. It was
illustrated that some of this
decrease can be corrected for by tracking the peak position and
then multiplying the optical
density by a correction factor based on the predicted
temperature. Overall, the radiochromic
-
material in GafChromic EBT film was found to be a better
candidate for in vivo real-time
dosimetry than the material in GafChromic MD-55.
A novel mathematical model was proposed linking absorbance to
physical parameters
and processes of the radiochromic materials. The absorbance at
every wavelength in the
spectrum was represented as a sum of absorbances from multiple
absorbers, where absorbance is
characterized by its absorption coefficient, initiation
constant, and polymerization constant.
Preliminary fits of this model to experimental data assuming two
absorbers suggested that there
is a trade-off between EBT’s greater sensitivity and its dose
linearity characteristics. This was
confirmed by experimental results.
iii
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iv
Dedicated to my dear parents.
-
Acknowledgments The assistance and wisdom of many people went
into this work. I would gratefully like to
acknowledge the contributions, in whatever form they were, of
the following:
• my co-supervisors, Dr. David Jaffray and Dr. Alex Vitkin, for
all the paper edits, research
guidance and advice
• committee members, Dr. Christine Allen and Dr. Mike Rauth for
all the support
• Yuen Wong, Brian Taylor, Jason Ellis, and Matt Filletti for
machining all the phantoms
and doing the various small “rush” jobs
• Robert Rothwell and Robert Rusnov for all the assistance with
electrical and optical work
• Dr. Robert Heaton, Hamideh Alasti, Duncan Galbraith, Dr.
Mohammad Islam, and Dr.
Jean-Pierre Bissonnette for their experience
• Bern Norrlinger for his experience and help with any and every
accelerator that ever
broke
• Tony Manfredi for all the assistance with the Elekta
accelerators
• Dr. Robert Weersink and David Giewercer for assistance and
wisdom with fibre optics
• Joanne Kniaz of Advanced Optical Microscopy Facility for the
microscopy work
• Dr. David Lewis and Dr. Sangya Varma of International
Specialty Products for their
contributions to this work, experience and guidance
• Dr. Douglas Moseley for all the help with Matlab, the carpool
rides, and outrageous
conversations on the GO train
• Steve Ansell and Graham Wilson for all the computer support,
psychotherapy lunches
and Chinese noodles
• Jinzi Zheng and Jeremy Hoisak for all the coffee breaks which
kept me sane
• my parents, Gala and Youri Rink, for never looking back or
regretting any choices in life
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Table of Contents CHAPTER 1:
INTRODUCTION..................................................................................................
1
I. Ionizing Radiation in Cancer Treatment
...............................................................................
2
II. Radiation Dose
......................................................................................................................
3
III. Radiation Dosimetry
............................................................................................................
5
A. Basic
Interactions..............................................................................................................
5
B. Standards and Protocols for
Dosimetry............................................................................
6
C. Estimation of Dose Delivered in
Therapy.........................................................................
7
IV. The Challenges of Dose Measurement in the Clinical Setting
............................................ 7
A. Clinical Applications and Ideal Dosimeter
.......................................................................
7
B. Current in vivo
Dosimeters..............................................................................................
10
C. Optical Methods
..............................................................................................................
11
V. Outline of
Thesis.................................................................................................................
13
CHAPTER 2: REAL-TIME RESPONSE OF GAFCHROMIC® MD-55 FILM TO
IONIZING
RADIATION
................................................................................................................................
21
I. Introduction
.........................................................................................................................
22
Review of GafChromic® MD-55
..........................................................................................
22
General
Experience...............................................................................................................
22
Solid-state Polymerization of Diacetylenes
..........................................................................
25
II. Methods and Materials
........................................................................................................
29
A. ΔOD of GafChromic® MD-55 at Various
Doses............................................................
38
B. Sensitivity as a Function of Layer
Thickness..................................................................
39
C. ΔOD of GafChromic® MD-55 at Various Dose
Rates.................................................... 39
D. ΔOD Dependency on Temperature
.................................................................................
40
E. Continuous Versus Pulsed Irradiation
.............................................................................
40
III.
Results................................................................................................................................
41
A. ΔOD of GafChromic® MD-55 at Various
Doses............................................................
41
B. Sensitivity as a Function of Layer
Thickness..................................................................
44
C. ΔOD of GafChromic® MD-55 at Various Dose
Rates.................................................... 45
D. ΔOD Dependency on Temperature
.................................................................................
47
E. Continuous Versus Pulsed Irradiation
.............................................................................
49
IV.
Discussion..........................................................................................................................
49
vi
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A. OD of GafChromic® MD-55 at Various Doses
..............................................................
50
B. Sensitivity as a Function of Layer
Thickness..................................................................
51
C. ΔOD of GafChromic® MD-55 at Various Dose
Rates.................................................... 52
D. ΔOD Dependency on Temperature
.................................................................................
53
E.
Applications.....................................................................................................................
54
V. Conclusion
..........................................................................................................................
55
ACKNOWLEDGEMENTS..................................................................................................
56
CHAPTER 3: REAL-TIME RESPONSE OF GAFCHROMIC® EBT
....................................... 61
I. Introduction
.........................................................................................................................
62
II. Method and
Materials..........................................................................................................
62
A. ΔOD of EBT Film Versus Time
.....................................................................................
66
B. Sensitivity and Stability Comparison Between EBT and MD-55
Films......................... 66
C. Dependence of Real-Time OD Measurements on Dose Rate for the
EBT Film ............ 67
D. Structure of Active Crystals in MD-55 and EBT
Films.................................................. 67
III. Results and Discussion
......................................................................................................
67
A. OD of EBT Film Versus
Time........................................................................................
67
B. Sensitivity and Stability Comparison Between EBT and MD-55
Films......................... 70
C. Dependence of Real-Time ΔOD Measurements on Dose Rate for the
EBT Film.......... 73
D. Structure of Active Crystals in MD-55 and EBT
Films.................................................. 75
IV. Conclusion
.........................................................................................................................
77
ACKNOWLEDGEMENTS..................................................................................................
78
CHAPTER 4: EFFECTS OF VARYING DOSE RATE ON REAL-TIME
MEASUREMENTS
OF OPTICAL DENSITY OF GAFCHROMIC® EBT
.................................................................
81
I. Introduction
.........................................................................................................................
82
II. Methods and Materials
........................................................................................................
82
III. Results and Discussion
......................................................................................................
85
IV. Conclusion
.........................................................................................................................
88
ACKNOWLEDGEMENTS..................................................................................................
89
CHAPTER 5: CHARACTERIZATION OF GAFCHROMIC® EBT: TEMPERATURE
AND
HUMIDITY
EFFECTS.................................................................................................................
91
I. Introduction
.........................................................................................................................
92
Chemical Background and General Experience
...................................................................
92
II. Methods and Materials
........................................................................................................
94 vii
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A. Temperature Dependence
................................................................................................
96
B. Absorbance and Sensitivity Dependence on Water
Content............................................ 97
III. Results and Discussion
......................................................................................................
99
A. Temperature Dependence
................................................................................................
99
B. Absorbance and Sensitivity Dependence on Water
Content.......................................... 104
IV. Conclusion
.......................................................................................................................
109
ACKNOWLEDGEMENTS................................................................................................
109
CHAPTER 6: ENERGY DEPENDENCE OF GAFCHROMIC®
............................................. 112
MD-55 AND
EBT.......................................................................................................................
112
I. Introduction
.......................................................................................................................
113
II. Methods and Materials
......................................................................................................
114
Solid Water™ Phantom
......................................................................................................
114
Ionizing Radiation Exposures
.............................................................................................
115
Optical Measurements
........................................................................................................
117
III. Results and Discussion
....................................................................................................
118
IV. Conclusion
.......................................................................................................................
123
ACKNOWLEDGEMENTS................................................................................................
124
CHAPTER 7: MATHEMATICAL MODEL OF RADIOCHROMIC MEDIUM RESPONSE
TO
IONIZING RADIATION
...........................................................................................................
127
I. Introduction
.......................................................................................................................
128
II. Methods and Materials
......................................................................................................
129
III. Results and Discussion
....................................................................................................
132
V. Conclusion
........................................................................................................................
138
ACKNOWLEDGEMENTS................................................................................................
138
CHAPTER 8: SUMMARY AND FUTURE
DIRECTIONS.....................................................
142
I.
Summary.............................................................................................................................
143
II. Future
Directions...............................................................................................................
146
A. Optical
Probe.................................................................................................................
146
B. Organization of Monomers and Polymers
....................................................................
148
C. Importance of Chemical Composition and
Structure....................................................
148
D. New Radiochromic Materials
.....................................................................................
149
E. Polymerization Kinetics as a Function of Dose Per
Pulse.......................................... 149
F.
............................................................................
150 Model-Fitting Algorithm and Code
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List of Tables Table 1. List of criteria for in vivo point-based
real-time dosimeter. ............................................
9
Table 2. Evaluation criteria for in vivo point-based real-time
dosimeter. ................................... 23
Table 3. Comparison of inferred dose and percent error using
calibration plot and pre-exposure
calibration as methods of
calculation............................................................................................
44
Table 4. Coefficients of equations of best fit characterizing
ΔOD/DGy as a function of dose rate.
.......................................................................................................................................................
87
Table 5. Average percent standard deviation for each dose,
uncertainty, and the difference
between the two for each dose delivered.
.....................................................................................
88
Table 6. Correction factors for the temperature correction
scheme, calculated for doses of 50 –
400 cGy shown for a selection of predicted temperature values..
.............................................. 103
Table 7. The x-ray and photon beams employed in the
investigations...................................... 116
Table 8. Comparison of response of EBT film, normalized to
response at 6 MV, as measured
approximately 24 hours after exposure to that measured
immediately at the end of exposure .. 122
Table 9. Model parameters using two absorbers for MD-55 and EBT
and a fit with 1 second
pulse averaging.
..........................................................................................................................
136
List of Figures Figure 1. Schematic of a typical relationship
between tumour control probability (TCP) and
normal tissue complication probability (NTCP) versus dose.
........................................................ 4
Figure 2. Structures of: (a) diacetylene monomers, upon exposure
to ionizing radiation,
polymerizes into (b) butatriene structure polymer; as the
polymer chain grows, it rearranges via
(c) an intermediate between butatriene structure and acetylene
structure, into (d) acetylene
structure polymer.
.........................................................................................................................
26
Figure 3. A model of optical density of GafChromic® MD-55 versus
time before, during and
after
exposure................................................................................................................................
28
Figure 4. Schematic of experimental
setup..................................................................................
30
Figure 5. Emission spectrum of the LED as detected by the
spectrophotometer. ....................... 31
Figure 6(a-c). Solid Water™ phantom (a) assembled, (b)
disassembled, (c) schematic. ............ 32
Figure 7. Schematic of cross-section of film holder in Solid
Water™ phantom.. ....................... 33
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Figure 8. Change in absorbance of GafChromic® MD-55 film at
various wavelengths plotted
before exposure, immediately after end of exposure, and 15 and
60 minutes after the end of
exposure.
.......................................................................................................................................
34
Figure 9. Change in optical density and rate of change in
optical density for GafChromic® MD-
55 film as a function of time before, during and after exposure
to 381 cGy with 6 MV X-rays.. 35
Figure 10. Termination of exposure is taken as the intercept of
the two fitted lines: first line
corresponding to data obtained during exposure and second line
corresponding to data obtained
after end of
exposure.....................................................................................................................
36
Figure 11. Change in optical density can be calculated for any
exposure by subtracting initial
OD from final
OD.........................................................................................................................
37
Figure 12. Schematic of setup for temperature dependency
experiments. .................................. 40
Figure 13. Change in optical density for GafChromic® MD-55
exposed to 381 cGy with 6 MV
X-rays as a function of
time..........................................................................................................
41
Figure 14. Change in OD for five pieces of film, each exposed to
381 cGy with 6 MV X-rays (at
the doserate of 285
cGy/min)........................................................................................................
42
Figure 15. Inferred dose using ΔOD measurements and calibration
plot as a function of applied
dose.
..............................................................................................................................................
42
Figure 16. Change in optical density for a piece of GafChromic®
MD-55 film during several
exposures applied approximately 5 minutes apart.
.......................................................................
43
Figure 17. Optical density as a function of dose for a system
utilizing one, two and four pieces
of stacked
film...............................................................................................................................
45
Figure 18. Change in optical density as a function of dose for
doses delivered at 95 cGy/min,
286 cGy/min and 671
cGy/min.....................................................................................................
46
Figure 19. Rate of change in optical density as given by the
linear fit of data obtained during
exposure as a function of applied dose, for doses delivered at
95 cGy/min, 286 cGy/min and 571
cGy/min.........................................................................................................................................
47
Figure 20. Position of wavelength of maximum absorbance for
GafChromic® MD-55 as a
function of irradiation/measurement
temperature.........................................................................
48
Figure 21. Change in OD for a given dose as a function of
applied/measured temperature using
both a constant spectral averaging window and a shifting
spectral averaging window. .............. 48
Figure 22. Schematic of experimental
setup................................................................................
63
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Figure 23. Emission of the light emitting diode used in
experimental setup, as measured by
spectrometer..................................................................................................................................
63
Figure 24. Schematic of layers in EBT film.
...............................................................................
64
Figure 25. Change in absorbance of EBT film over a range of
wavelengths before, immediately
after, and at two time points post-exposure.
.................................................................................
65
Figure 26. Optical density versus time for a single piece of EBT
film; optical density versus time
for five pieces of EBT film shown on a reduced time scale
(inset). ............................................. 68
Figure 27. Wavelength of maximum absorbance for EBT film versus
time during and after
exposure to 9.52 Gy at 2.86 Gy/min with 6 MV
X-rays...............................................................
69
Figure 28. Optical denisty of EBT film versus time for various
spectral averaging windows.... 70
Figure 29. Optical density for EBT and MD-55 films during and
after exposure....................... 71
Figure 30. Percent increase in OD for EBT and MD-55 films after
exposure, calculated with
respect to OD at the end of exposure.
...........................................................................................
72
Figure 31. Percent increase in OD for EBT and MD-55 films within
one hour after exposure. . 73
Figure 32. Optical density for EBT film exposed to 9.52 Gy,
delivered with 6 MV at 0.95
Gy/min and 5.71 Gy/min.
.............................................................................................................
74
Figure 33. Microscope images of monomer crystals within the
sensitive media of MD-55 and
EBT
films......................................................................................................................................
76
Figure 34. Optical density versus time for a 50 cGy irradiation
at 16 cGy/min.......................... 84
Figure 35. The average sensitivity as a function of dose rate,
for various doses......................... 85
Figure 36. Chemical formula of pentacoasa-10,12-dyinoic acid
(PCDA), and lithium salt of
PCDA (LiPCDA)..
........................................................................................................................
93
Figure 37. Change in absorbance spectra for EBT film exposed to
1 Gy with 6 MV and 75 kVp
beams..
..........................................................................................................................................
95
Figure 38. Schematic of the modified phantom, with plastic water
hoses on either side of the
film and optical fibers.
..................................................................................................................
96
Figure 39. Wavelength of maximum change in absorbance of
commercial EBT films irradiated
to 1 Gy as a function of measured temperature.
.........................................................................
100
Figure 40. Values of wavelength of maximum absorbance for
various doses delivered to
commercial EBT films as a function of measured
temperature..................................................
100
Figure 41. Change in optical density for 1 Gy dose calculated
for optical range of 630-640 nm,
and an optical range of 10 nm centered about wavelength of
maximum absrobance, versus
measured temperature..
...............................................................................................................
101
xi
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Figure 42. Temperature calculated using the position of
wavelength of maximum absorbance
versus measured temperature, shown with a line of best fit..
..................................................... 102
Figure 43. Change in optical density for films irradiated to 1
Gy using a fixed optical integration
range of 630 to 640 nm, moving optical range of 10 nm about the
peak of maximum absorbance,
and as calculated using the peak of maximum absorbance and
temperature-dependent correction
factor..
.........................................................................................................................................
102
Figure 44. Percent decrease in net OD for a 3 Gy dose, following
different times in a desiccator
at 50
ºC........................................................................................................................................
105
Figure 45. Spectral comparisons of absorbance of desiccated and
normal unlaminated EBT film.
.....................................................................................................................................................
106
Figure 46. Absorbance of unlaminated EBT film after time in
desiccator at 50 ºC. ................. 107
Figure 47. Spectral comparisons of absorbance of desiccated,
rehydrated, and normal
unlaminated EBT film irradiated to 3 Gy.
..................................................................................
107
Figure 48. Absorbance spectra of exposed unlaminated films using
“plate-like” form of
polymer, and the rehydrated form of “hair-like” polymer.
......................................................... 108
Figure 49. 30 cm × 30 cm × 4 cm phantom with the film insert
............................................... 114
Figure 50. Sample of time-dependent OD with time for a 1 Gy
irradiation with a 75 kVp
Therapax DXT 300 beam at 8 cGy/min for MD-55, HS, and EBT film.
................................... 119
Figure 51. Un-normalized change in OD for 1 Gy total dose for
MD-55, HS and EBT films for
irradiations delivered at various equivalent x-ray energies
........................................................ 119
Figure 52. Change in OD per Gy for MD-55, HS and EBT, as a
function of equivalent x-ray
energy..........................................................................................................................................
120
Figure 53. Increased sensitivity of HS and EBT films with
respect to MD-55, for a dose of 1 Gy
.....................................................................................................................................................
123
Figure 54. Change in absorbance of a single absorber versus time
for different A parameters,
keeping k and p parameters constant.
.........................................................................................
132
Figure 55. Change in absorbance of a single absorber versus time
for different k parameters,
keeping A and p parameters
constant..........................................................................................
133
Figure 56. Change in absorbance of a single absorber versus time
for different p parameters,
keeping A and k parameters constant.
.........................................................................................
134
Figure 57. Experimental absorbance of MD-55 film at the main
absorbance peak, and the model
fit..
...............................................................................................................................................
135
xii
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Figure 58. Experimental absorbance of EBT film at the main
absorbance peak, and the model
fit..
...............................................................................................................................................
135
Figure 59. Schematics of single and dual fibre optical dosimeter
prototypes. .......................... 147
xiii
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xiv
List of Abbreviations and Symbols ΔA change in absorbance
ΔOD change in optical density
ΔODv change in visual density
ΔV small volume
ε(λ) extinction coefficient at wavelength λ
λ wavelength
λmax wavelength of maximum absorbance
ρ density 60Co Cobalt-60
A absorbance
A(λ) absorbance at wavelength λ
AAPM American Association of Physicists in Medicine
bi polymer initiation constant per dose
c concentration
cGy centiGray
D dose
DGy dose in Gy
EBT radiochromic film intended for External Beam Therapy
E energy
eV electron-volt
FWHM full width half maximum
Gy gray (J/kg)
HS radiochromic film of High Sensitivity
HVL half-value layer
I intensity
ID background intensity
IR reference intensity
I0s initial intensity
Is sample intensity
ICRU International Commission of Radiation Units
IMRT intensity modulated radiation therapy
-
IGRT image guided radiation therapy
ISP International Specialty Products
ki polymer initiation constant
keV kilo electron-volt
kVp peak kilovoltage
l length
LED light emitting diode
LINAC linear accelerator
LiPCDA Lithium pentacosa-10,12-diynoate (lithium salt of
PCDA)
MD-55 radiochromic film intended for Medium Dose, size 5×5
MeV mega electron-volt
MOSFET metal oxide semiconductor field-effect transistor
MSDS Material Safety Data Sheet
MV megavolt
N0 initial number of monomer chains
Nm remaining number of monomer chains
Nip number of initiated polymer chains
Nfp number of fully-formed polymer chains
NTCP normal tissue complications probability
OD optical density
ODv visual density (weighted by known response of human eye)
OSL optically stimulated luminescence
pi polymerization kinetics constant
PCDA pentacosa-12,12-diynoic acid
PDD percent depth dose
PMMA poly-methyl methacralate
QTH quartz-tungsten-halogen
SAD source-to-axis distance
SSD source-to-surface distance
t time
TCP tumour control probability
TG Task Group
TLD thermoluminescent dosimeter
xv
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TPR tissue-phantom ratio
UV ultraviolet
Z atomic number
xvi
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1
CHAPTER 1: INTRODUCTION
-
2The work within this thesis describes a novel method for
performing real-time dosimetry using
fibre-optic read-out of radiochromic materials. The radiochromic
materials are investigated for
their applicability in clinical dosimetry measurements in vivo
and in vitro. Their performance as
a function of dose and time is modeled, with parameters linked
to physical properties of the
materials and the processes that occur during exposure to
radiation. A system is thus established
for evaluating radiochromic dosimeters for clinical dosimetry,
whereby their performance can be
at least in part be predicted by their physical properties.
In this chapter, clinical rationale for the proposed real-time
dosimeter is established by
outlining the need for in vivo dosimetry and the inability of
the dosimeters presently available on
the market to meet that need.
I. Ionizing Radiation in Cancer Treatment
Ionizing radiation is encountered under many circumstances in
medicine, and specifically in
oncology. It is used to identify and locate the cancer, to
target it, and to treat it, with
approximately 50% of cancer patients receiving radiation therapy
for management of their
disease.* High energy photons (referred to as x-rays and gamma
rays) are known to damage
tissue. Although the exact details of tissue damage are still
not fully understood, it is believed
high energy photons induce ionization of important molecules
within the cells, such as
deoxyribonucleic acid. Ionization refers to removal of an
electron from a molecule, making it
unstable. These unstable molecules may react in a way that would
prevent them from
functioning properly, eventually leading to cell death.
The source of radiation can be external or internal (known as
brachytherapy), varying
greatly in energy and intensity. Energy can vary from 21 – 660
keV(1) gamma rays from
decaying radionuclides in brachytherapy seeds, to 18 MV x-ray or
20 MeV electron beams from
a linear accelerator (LINAC). The dose rate can be as low as
0.4-2 Gy/h(1) (where Gy=1J/kg) for
low dose rate brachytherapy, to as high as 6 Gy/min for LINAC
treatments. The majority of the
external treatments are divided into dose fractions delivered
daily, five days a week, over several
weeks, with only a small percentage of treatments delivered in a
single large dose (known as
stereotactic radiosurgery) from a 60Co unit called GammaKnife or
from a LINAC using a 6 MV
x-ray beam. In recent years, treatments have become more
conformal to the tumour due to
implementation of Intensity Modulated Radiation Therapy (IMRT)
and Image-Guided Radiation
Therapy (IGRT). With the development of these new technologies,
a trend has been evolving *
http://www.cancer.gov/cancertopics/factsheet/Therapy/radiation
-
3towards higher target absorbed dose values, fewer fractions,
smaller treatment volumes, and
steeper dose gradients. These developments need to be validated
in terms of actual dose
delivered.
II. Radiation Dose
Cell damage from ionizing radiation may result in several
different outcomes, including repair of
damage by the cell, cell death, and survival with mutation.(2)
Depending on the type of damage
and the tissue irradiated, the biological effect can take
anywhere between a few hours (acute) to
many years (late) to manifest. During radiation therapy, the
dose and its distribution are
important for the outcome of the treatment and prevention of
further complications. A high
enough dose has to be delivered to the tumour and affected
organs to obtain high probability of
tumour control, and a minimal dose should be delivered to
healthy surrounding organs to limit
probability of acute or late effects.(2) To maintain high
probability of tumour control, the
International Commission of Radiation Units (ICRU) recommends
uniformity of tumour dose
within +7/-5% of the total prescribed dose.(3) The upper limit
exists because the dose prescribed
is often limited by the dose delivered to the surrounding
healthy organs during irradiation, which
is dependent on the type of treatment delivery. Generally,
conformal treatment allows for higher
dose to be delivered to the tumour and for lower dose be
delivered to the surrounding tissues,
though the total volume of tissue irradiated may increase. On
the other hand, the probability of
cancer recurrence due to geometric miss may increase.
The probability of biological effect taking place (whether it be
tumour cell kill or normal
tissue complications) versus dose is called a dose response
curve.(2) The curves for tumour
control probability (TCP) and normal tissue complication
probability (NTCP) are often plotted as
sigmoid relationships (Figure 1). That is, there is nearly no
effect at first, then the probability
rises sharply, and levels off to a plateau. Thus delivering a
smaller dose to the tumour than that
required for cure or control would sharply increase the
probability of relapse. On the other hand,
if the patient receives a dose to the tumour that is much higher
than that prescribed, then it is also
likely that the patient receives a higher dose to the
surrounding normal tissue. Given the
sigmoidal relationship between dose and effect, the risk of
acute or late effects increases
dramatically.
Because of the conformality of modern treatments, describing the
dose distribution by a
single dose to the tumour and using the +7/-5% recommendation
for guidance is an
oversimplification. As the treatments become tailored to each
patient’s needs, the dose
-
41.0
0.5
Prob
abili
ty
Dose (Gy)
TCP NTCP
0.9
+5%-5%
30 40 50
Figure 1. Schematic of a typical relationship between tumour
control probability (TCP) and
normal tissue complication probability (NTCP) versus dose. The
NTCP curve is based on two
values (marked by X): doses at which 5% and 50% of patients
develop complications when 2/3
of their liver is irradiated.(4) Dashed line represents a dose
of 42.5 Gy, yielding 90% probability
of tumour control, and 37.5% probability of normal tissue
complications (liver failure).
Increasing the tumour dose by 5% (dotted line) of the prescribed
dose increases TCP by only
2.5%, but increases NTCP to 50%. On the other hand, delivering
the same distribution with 5%
lower dose (dotted line), decreases NTCP to 25%, but also
decreases TCP to 82.5%, which may
compromise treatment outcome.
distributions become more diverse. Systematic errors larger than
5% in dose delivery (measured
as entrance, exit dose, or combination of the two during
treatment) to a small percent of patients
(~ 1%) have been published.(5-7) These can be due to
inadequacies in dose calculation
algorithms,(8) setup errors, or a human error on behalf of the
many individuals involved in the
process of patient treatment. Although doses to the patient can
be calculated or inferred from a
-
5relative measurement, the American Association of Physicists in
Medicine Task Group 40
recommended that clinics have access to an in vivo dosimetry
system.(9) While radiation
transport algorithms are constantly being improved in order to
perform dose calculations, and
phantoms become more complex to better represent human anatomy,
conditions where dosimetry
and simulation of humans remain a challenge still exist.
Accurate assessment of the dose
distribution in brachytherapy treatment and in regions near in
homogeneities for external beam
treatments is vital to rapid innovation and development of new
radiation therapy technologies
and techniques. Such an assessment can be done by performing in
vivo dose measurements.
However, performing such measurements under clinical conditions
is challenging.
III. Radiation Dosimetry
A. Basic Interactions
The interaction of ionizing radiation with matter results in a
dose deposited within that
matter, where dose is defined as the absorbed energy per mass
(J/kg, or Gy).(10) In radiotherapy,
the dose quoted is often dose to water, as most tissues within
the body have similar radiological
properties as water (common exceptions are lung tissue, bone and
teeth). The ionizing radiation
can be directly ionizing (charged particles) or indirectly
ionizing (photons).(10)
The photons, as they pass through the medium, are attenuated by
the medium and scatter
from their original path. The processes of attenuation are due
to coherent scattering,
photoelectric effect, Compton effect, pair/triplet production,
or photonuclear interactions. In
radiation therapy, the middle three are the interactions
important for dose deposition, and the
probability of any of these events happening when a photon beam
passes through the medium
depends on the energy of the photon, density, and the atomic
number (Z) of the medium.
Photoelectric effect is the predominant interaction for
low-energy photons (below 100 keV). The
probability of photon interacting in this manner in a medium of
a given density increases with Z3
of the medium. Here all of the photon’s energy is transferred to
one of the inner shell electrons
of an atom. This electron then continues through the medium with
a kinetic energy equal to the
energy of the initial photon less the binding energy of the
electron. In a Compton interaction, the
photon interacts with a valence shell electron, transferring
part of photon’s energy to an electron
and the two then continue at a given angle from each other from
the point of interaction, such
that the momentum is conserved. In this interaction, the photon
does not transfer all of its energy
to the electron. The probability of this interaction occurring
in a medium of given density is
-
6approximately independent of Z of the medium, and is
predominant for photon energies around 1
mega-electron-volt (MeV). For high energy photons (over 1.022
MeV) pair production can
occur. In these interactions, as the photon interacts with the
Coulomb field near the nucleus, the
photon is absorbed giving rise to an electron and a positron. If
the photon interacts with the field
of the atomic electron, the atomic electron also acquires energy
and escapes from the atom, thus
yielding triplet production. The process of triplet production
requires the energy of the photon to
be greater than 2.044 MeV. The probability of pair production
for a medium of given density is
roughly proportional to Z, while triplet production is
independent of Z of the medium.(10)
The electrons that result from these interactions of photons
with the medium in turn travel
through the medium themselves. The electron interacts with
almost every atom in its path whose
electric field is detectable. Most of these interactions
transfer small fractions of the electron’s
energy, and thus the electron is often thought of as losing the
energy gradually in a frictionlike
process. Some of these energy losses result in a photon
(Bremsstrahlung) being emitted when
the electron changes direction due to an electric field from a
nearby nucleus. The energy lost in
this way does not contribute to the locally deposited dose.
Electron interactions that do
contribute to local dose will either excite the shell electrons
of a nearby atom to a higher energy
level, or ionize it. The rate of energy loss per distance
decreases with increasing Z of the
medium and increasing kinetic energy of the electron.(10)
B. Standards and Protocols for Dosimetry
Ionizing radiation dose can be measured well in standard
conditions following set
protocols(11-14). In most cases, using dosimetry equipment
calibrated at a national standard
laboratory (such as National Research Council of Canada) or
traceable to such a calibration, and
performing measurements under controlled conditions allows for
accurate dosimetry in air and in
water or plastic phantoms, with uncertainties below 1%.(12,15)
However, in some cases, such as
intravascular brachytherapy, absorbed dose standards may vary by
as much as 10% between
measurements and different Monte Carlo calculations.(16) When
using the dosimetric gold
standard, the ion chamber, some of the controlled conditions
include a known temperature and
pressure, type and energy of the beam, distance from the source
and depth (if phantom is
used).(12) Unfortunately, these parameters may not always be
known to a high level of precision
and accuracy in clinical conditions.
-
7C. Estimation of Dose Delivered in Therapy
Doses under uncontrolled conditions, delivered during imaging
and therapy, can be
obtained in several different ways. They can be computed using
various algorithms as is done in
actual treatment planning,(17) with the algorithms constantly
improving to include dose
calculations for brachytherapy and imaging procedures, as well
as external beam irradiations.(18-
21) The dose can also be inferred from a relative dose
measurement performed during the
procedure (such as skin dose measurement), or measured directly
at a point of interest. Because
the points of interest on the patient may be inside the patient,
such as at the tumour site,
performing a direct measurement is often trickier than the other
two approaches.
IV. The Challenges of Dose Measurement in the Clinical
Setting
While real-time dosimetry may be useful for in vitro
measurements at several points of time
varying radiation fields, such as those in high dose rate
brachytherapy or IMRT, the discussion
of clinical applications here is kept to in vivo measurements.
Predicting the three-dimensional
cumulative dose distribution within a patient over the course of
their treatment can be complex,
given the variations arising from minor patient positioning
errors, treatment beam fluctuations,
motion during treatment, changes in anatomy as the patient loses
weight or the tumour shrinks,
and possibly other sources of error. Thus measurements of dose
at or within a patient are often
desired as part of a quality assurance, for investigative
purposes of a new procedure, or for
implementation of new technology protocol. Performing dose
measurements inside patients is
more complicated than skin dose measurements, and is not nearly
as straightforward as phantom
dosimetry which is often utilized in the clinic.
A. Clinical Applications and Ideal Dosimeter
A dosimeter that can accurately measure ionizing radiation dose
in vivo under various
clinical conditions may simplify and improve the current state
of dosimetry. It can be used for
quality assurance of both external beam and brachytherapy
treatments. If an error in positioning,
machine output, transcription or some other error occurs that
results in a discrepancy of planned
dose above a set threshold, treatment can be interrupted, and
the discrepancy investigated. The
dosimeter may also be used to track dose in an organ that moves
in and out of the radiation field
during respiration. In a brachytherapy procedure, the real-time
dose rate measurement may be
used as feedback to verify proper positioning of seeds. If the
dose rate is higher or lower than
-
8anticipated, the insertion of the next set of seeds may be
adjusted to get the proper dose rate and
dose at the point of measurement.
For a dosimeter to be an appropriate option for in vivo
measurements in most clinical
scenarios, the overall construction and the dosimetric medium
must satisfy several requirements,
listed in Table 1. The requirements can be used as a set of
guidelines for evaluation of a new
dosimetric medium. The presence of the dosimeter must not
perturb the tissue or the dose
distribution. It must also be sufficiently small (1) to be able
to resolve a sharp dose gradient in a
radiation field. However, the size of the sensitive medium must
be sufficiently large to yield
good signal statistics for high precision measurements. In part,
the signal statistics can be
controlled if the dosimeter uses passive read-out method, as is
discussed later in this Chapter.
The dosimeter should have near water-equivalent composition (2),
such that its response
with change in energy is similar as that of water.(22) This
allows for a single dosimeter to be used
across all energies encountered both in external beam and
brachytherapy treatments without
performing a separate calibration. The dosimeter for quality
assurance purposes should respond
in real time (3), providing dose or dose rate estimate within a
few seconds from beginning of
irradiation so that treatment can be interrupted if the dose
rate is outside of the value expected.
The dosimeter also has to show a dose response that is
independent of the dose rate used to
deliver that dose (6). The dose estimate should have high dose
resolution (5) in order to detect
small variations (~1 cGy) in the dose delivered (daily fractions
are often ~200 cGy, and total
doses are 24-70 Gy, depending on the treatment and fractionation
pattern), and the response
should be ideally linear with dose (4) for simple computation.
Some of the other issues to be
taken into consideration are environmental conditions (7), such
as the temperature dependence of
the dosimeter. The dose estimate should be independent of the
temperature of the dosimeter,
which can vary from near room temperature on skin surface to as
high as ~38 °C within the
patient. Finally, the dosimeter must be non-toxic (8) and
biocompatible, and would preferably
be inexpensive enough to be disposable after each patient.
A dosimeter, as described above, which can be used across a wide
range of energies
could be implemented in both external beam radiation therapy and
brachytherapy, simplifying
the dosimetric procedures to a single device. Accurate
assessment of the dose given to the
patient using a reliable dosimeter with a water-equivalent
response would save time and money
over using multiple dosimeters with a significant over- or
under-response to low energy X-rays
and inferring the dose via correction factors and
calculations.
-
9Table 1. List of criteria for in vivo point-based real-time
dosimeter.
Criterion
#
Criterion Comments
1 small size(22)
(
-
10B. Current in vivo Dosimeters
Several dosimeters currently available on the market are used
for some in vivo
dosimetry measurements. These are in vivo ion chambers, diodes
and MOSFETs (metal oxide
semiconductor field effect transistors). An ion chamber is
classified as an absolute dosimeter: it
can be used to measure the absorbed dose to its own sensitive
volume without any calibration.(10)
However, it often needs to be calibrated as knowing the exact
measurement volume, and mass of
air contained, is required for absolute dosimetry. The ion
chamber measures the total ionization
produced by electron interactions in air, the charge is
collected by an electrode set at a high
voltage, and this value can be related to dose. The mass of air
contained must yield reasonable
signal statistics, limiting in vivo ion chambers to dosimetry in
bladder and rectum, too large for
use in tissue.
A silicon semiconductor diode is what is generally used as an in
vivo radiation detector.
When the diode is exposed to ionizing radiation, electron-hole
pairs are created throughout the
diode, and as they move through the diode, a measurable current
is created. The amount of
silicon required for measurement (known as the die) is 0.01-0.1
mm3, and the current related to
deposited dose can be measured in real-time via the coaxial
cable by the electrometer.(23) For in
vivo dosimetry, the die is covered with material for protection
and for proper buildup. The
buildup is necessary for skin dose measurements to give the
photons enough medium to interact
with in order to create the electrons that will in turn interact
with the silicon.(23) This buildup
and the protective cover make the diodes rather bulky (up to 3
cm in length and ~7 mm in
diameter), making it difficult or impossible to position into
all tissues of the patient because of
their size. Some diode configurations also suffer from angle
dependence of their response (due
to inhomogeneity of the buildup material and coaxial cable
attached), and they have been shown
to perturb the dose distribution directly behind the diode by as
much as 30%, with the effect
more pronounced at lower beam energies.(24) Read-out was also
shown to vary with
temperature,(24,25) complicating dosimetry further by the fact
that the temperature of the diode
may not always be known during its use.
A MOSFET is a small silicon transistor.(26) A p-type silicon
semiconductor sits on an
insulating oxide layer, which separates it from a conducting
metal band.(27) The p-type silicon
has positive charges accumulated within, proportional to the
negative voltage bias applied at the
conducting metal band. The measurement of dose is related back
to the threshold voltage
(voltage required to allow current to flow through the
semiconductor).(26,27) As the ionizing
radiation travels through the MOSFET, charges generated within
are trapped, causing the
-
11threshold voltage to shift proportionally to deposited
dose.(26,27) MOSFETs can be used as real-
time dosimeters(27) and are much smaller than diodes (some are
as small as 1 mm in diameter,
known as micro-MOSFETs), decreasing beam attenuation and dose
perturbation effects that are
observed for diodes.(26) Their small size also allows for
dosimetry in small beams, down to a few
mm (4.4 mm) in beam diameter.(28) Having high Z components and
not being water-equivalent,
MOSFETs have large differences in calibration factors,(29) and
require separate calibrations to be
performed at different beam energies.(26) On the other hand,
they show good agreement with the
ion chamber for a given energy down to a depth of 34 cm.(30)
They have also been shown to
exhibit directional anisotropies in response because of the
silicon substrate beneath the sensitive
volume,(28,31) and, like diodes, are known to exhibit
temperature dependence.(26)
C. Optical Methods
Energy independence of a dosimeter can in large part be met by
staying clear of metallic
components within the dosimeter. As such, there has been a
considerable amount of effort over
the last few decades to find a dosimeter based on optical
characteristics of a radiation sensitive
medium and fibre-optic readout. Among such radiation sensitive
media are doped optical
fibres,(32-34) plastic scintillators,(35-39) thermoluminescent
dosimeters (TLDs),(34,40) optically
stimulated luminescent (OSL) dosimeters,(34,41,42) and a
fluorescing ruby.(43) The media can be
subdivided into two categories: light emitters and light
modifiers. Light emitting dosimeters
(such as scintillators, TLDs and OSL media) produce signal that
is proportional to the absorbed
dose. Thus the number of photons and the signal statistics are
dependent on dose, and is out of
user’s control. On the other hand, light modifying dosimeters
alter some aspect of the
interrogating light, the properties and the intensity of which
is controlled by the user. This
allows for higher precision measurements, because the number of
photons can be increased if the
noise is too high. The other major difference between the two
types of optical dosimeters is that
the light emitting media are reusable, whereas light modifying
media have to be disposed off
after a certain dose. Reusable dosimeters are often less
expensive per use, but “age” and one
must be careful to not assume the signal per dose remains
constant as the total dose delivered is
increased. Dosimeters that integrate dose to give a single
signal at the end, such as light
modifying media, have the ability to always keep the reading,
and can be measured multiple
times as the read-out is non-destructive. As they are also
disposable, the need for disinfecting
between patients is eliminated, simplifying their use, as well
as reducing the risk of spreading
infection.
-
12Fluorescing rubies and scintillating fibres automatically emit
light when exposed to
ionizing radiation, whereas TLDs and OSL dosimeters must be
stimulated by either heat or light,
respectively, to obtain a light signal. These materials work by
trapping electrons in higher
energy states when they are exposed to ionizing radiation. When
the electrons move down
(either automatically or due to stimulation) to their ground
state, photons corresponding to the
energy difference between the two states are emitted. TLDs
cannot be read out in real-time, as
they require annealing after irradiation and a lengthy read-out
processes for accurate dose
estimate.(5) When one considers the high temperatures that TLDs
must be heated to (at least 100
°C, depending on the type of TLD),(28,40) it is hard to imagine
how this would be done safely
within a patient. Some fibre-based read-out schemes have been
suggested,(40) but have not been
implemented clinically. OSL and plastic scintillator dosimeters
are promising, and some have
been made to be nearly energy independent.(38) However, they
continue to suffer from
interferences such as fibre scintillation and Cerenkov
radiation, where removal of the latter often
requires accurate knowledge of pulse sequences and careful
timing.(42,44,45) The alternative is to
use scintillators that have high emission wavelength, such that
the Cerenkov radiation (which
drops off with 1/λ3) from the fibre doesn’t interfere much with
the dose-related signal from the
sensor.(37) However, the signal per given dose from such
scintillators is generally decreased
compare to the signal from scintillators with low emission
wavelength, and thus measurements
of dose are noisy.(37) While rubies fluoresce at high enough
wavelength and long enough after
the pulse such that the Cerenkov radiation is irrelevant to the
measurement, they have a high Z
and are not water equivalent.(43)
Light modifying dosimeters, such as doped optical fibres and
Fricke xylenol-orange
solutions or gels create light-absorbing colour centres when
exposed to ionizing radiation. This
is done either via electron trapping,(46) or via formation of a
complex with a dye,(47) respectively.
Doped optical fibres are generally not water equivalent due to
high Z (often Pb) components
used as doping material.(33,34,46) A method for reducing Z by
incorporating dopants such as Na,
Mg, and Li has been proposed.(48) However, these optical fibres
have not been implemented,
likely because of reduced sensitivity compared to higher-Z
counterparts. Finally, while certain
gels can be used as optical dosimeters, these are typically
utilized in 3D dosimetry by making 3D
phantoms out of the gel,(49-52) and no effort to incorporate
them in fibre-optic dosimeter has been
made; rather, they are used in post-exposure volumetric readout
(e.g. MR).
-
13
V. Outline of Thesis
Another type of optical dosimeter makes use of what is known as
a radiochromic medium. This
type of material changes colour, or gets darker, upon exposure
to ionizing radiation, and is in the
category of light modifiers. Some radiochromic films are
manufactured under the name of
GafChromic® (International Specialty Products, or ISP). These
films contain one or two gelatin
layers with organic monomers arranged in a small crystal or
micelle-like structure suspended
within them.(53-55) The monomers undergo polymerization when
exposed to radiation. The
absorbance spectrum of the resulting polymer systems is then
related back to the absorbed
dose.(55-57) Historically, these films are used for
two-dimensional dose distribution
measurements,(58,59) and the measurements are performed 3-24
hours (depending on the
film)(54,55) after the end of irradiation to ensure stable
readout. This is because the
polymerization reaction is not instantaneous, and proceeds even
after the source of ionizing
radiation is removed. This, in turn, causes the absorbance to
change with time, producing errors
in dose estimate. (59-61)
Despite the recommendation that these media be read out 3-24
hours after irradiation,
radiochromic media are being investigated in this work for
applicability in real-time patient
dosimetry. They have some advantages, including a near
water-equivalent organic
composition,(54,55) and the ability to produce signal from a sub
cubic millimetre volume.(55) They
also absorb predominantly in the red region of the visible
spectrum, where Cerenkov radiation
does not interfere. Because the radiochromic material is a light
modifier, the signal statistics can
in part be controlled by the user, by increasing or decreasing
the interrogation light. More
importantly, if the performance of these systems during and
after irradiation can be characterized
and accounted for, they may provide real-time dose estimates
with an acceptable error despite
the above-mentioned issues. If these systems are understood,
reverse engineering may be
possible to create a radiochormic material that polymerizes
faster and has appropriate sensitivity
for a given application.
In the present work, response of two films (GafChromic MD-55 and
EBT) were assessed as
a function of dose, time, dose rate, temperature, and energy and
results are described in Chapters
2 to 6. Chapter 2 investigates in detail the possibility of
using the radiochromic material,
GafChromic MD-55, as a point-based dose measurement material in
real-time. Although
throughout the experiments described in this thesis the
measurements were made immediately
after the end of irradiation, the endpoint was chosen only
because this is when the dose is known.
It is easy to imagine how, once the relationship between optical
density and dose is established,
-
14optical density measurements can be made any time during
irradiation. Thus, the dose can be
estimated during irradiation as well, making it a true real-time
dosimeter.
The film was investigated for signal linearity, reproducibility,
dose rate and temperature
dependence. Chapter 3 compares the performance of GafChromic
MD-55 with a medium from
another film, GafChromic EBT. This chapter focuses on
differences in sensitivity and linearity
of MD-55 and EBT, and discusses the fundamental chemical and
structural difference between
the two monomer systems. Chapter 4 describes the investigation
and quantification of the dose
rate dependence of GafChromic EBT. Chapter 5 describes
temperature and humidity
investigations of GafChromic EBT (performed in collaboration
with Dr. D.F. Lewis and Dr. S.
Varma, researchers of ISP). Chapter 6 compares energy dependence
between two sensitive
media present in three films (MD-55, EBT and HS, where MD-55 and
HS use the same
formulation). A novel mathematical model of the response to dose
with time both during and for
short periods after the end of irradiation is also developed,
with the preliminary results described
in Chapter 7. The parameters of the model are based on physical
properties and processes
occurring during exposure to ionizing radiation and
interrogation with read-out light. Ideally,
this would allow for future engineering or selection of
radiochromic media that meet the in vivo
requirements, by working backwards from the desired response to
radiation as predicted by the
model to physical and chemical properties. The thesis concludes
with a summary of current
investigations and ideas for future work.
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21
CHAPTER 2: REAL-TIME RESPONSE OF GAFCHROMIC® MD-55 FILM TO
IONIZING RADIATION
Portions of the following have been published as “Suitability of
radiochromic medium for real-
time optical measurements of ionizing radiation dose” by
Alexandra Rink, I. Alex Vitkin, and
David A. Jaffray in Medical Physics 32(4), p. 1140-1155
(2005)
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22
I. Introduction
The goal of these investigations is to develop a dosimeter that
is economically and logistically
acceptable (low-cost, disposable, reusable, and sterilizable).
To meet these requirements, a water
equivalent dosimeter which undergoes an immediate change in
optical properties upon exposure
to ionizing radiation is proposed. The difference in a
particular quantitative optical property is to
be measured via optical fibers, and ionizing radiation dose is
to be inferred through a calibration
model. In the initial embodiment of the device, the radiation
sensitive material present in
GafChromic® MD-55 radiochromic film was investigated for
suitability in the application of
external beam patient dosimetry. A list of requirements in
choosing an in vivo dosimeter against
which GafChromic MD-55 film is investigated is given in Table
2.
Review of GafChromic® MD-55
To better understand the results presented in this paper, the
reader is provided with a
review of literature and explanation of solid-state
polymerization. An understanding of the
process that forms the basis for radiochromic dosimetry is
required if the real-time dosimetry
system is to be quantified and optimized. The time course of the
energy transfer and subsequent
processes that lead to changes in optical density are also
important for rational design.
General Experience
Radiochromic films have been used for nearly 30 years in the
field of dosimetry.(1)
Commercially available radiochromic dosimeters are manufactured
by International Specialty
Products (ISP), and some are sold under the product name of
GafChromic® MD-55. A broad
assessment of its characteristics suggest that it is a good
candidate for the proposed point-based
dosimeter: the sensitive medium from GafChromic® MD-55 film can
be packaged as a small
volume placed at the tip of an optical fiber (closed system to
minimize any interference from the
tissue, such as humidity); it has response characteristics
within 5% of water and striated muscle
for photons of energy in the range of 0.1-10 MeV, and electrons
in range of 0.01-30 MeV.(2)
Upon exposure to heat, ultraviolet (UV) light, and high-energy
photons and electrons, the
monomers polymerize to provide an absorbance spectrum with two
peaks (675 and 615 nm),
creating a polymer with a blue tint.(2-4) The signal linearity
requirement appears to have also
been met, since the change in absorbance is a linear function of
the absorbed dose,(5) although the
dynamic range of this function depends on the wavelength at
which the measurements are
-
23Table 2. Evaluation criteria for in vivo point-based real-time
dosimeter.
Criterion
#
Criterion Comments
1 small size(6)
(
-
24obtained.(7-11)
The film has been reported to resolve dose to 1.5 Gy with a
precision of 5% or better,
using the 671 nm absorption peak,∗ and this resolution can be
further increased by increasing the
thickness of sensitive layer.(12) The requirement of real-time
readout appears to be a significant
impediment to use of GafChromic® MD-55 film. Time frames of 24 –
48 hours after exposure
are recommended. Additional investigations are required to
resolve this issue.
Less than 5% difference in net change in absorbance of
GafChromic® MD-55 film
exposed to 10 Gy at dose rates of 0.034-3.422 Gy/min is
expected.∗ However, validity of the
measurements done with this film has been questioned for low
dose-rate brachytherapy. Ali and
colleagues reported in 2003 the kinetics of film darkening as
function of post-exposure time
depends on the total dose, with the development being faster at
the lower doses.(13) These
findings are a concern for real-time dosimetry and require
further investigation. While the focus
of this study is to apply the dosimeter in the context of
external beam radiotherapy, where dose-
rates are typically greater than those in brachytherapy, a range
of doses and dose-rates, over
which post-exposure development from the first few fractions of
the treatment does not introduce
error in the absorbance reading and final dose estimate, should
be clearly defined.
McLaughlin et al. [1996] reported that propagation of the
polymerization is complete
within 2 ms of a single 20 Gy 50 ns pulse.(4) It is unclear,
however, if the polymerization
occurred mostly due to ionizing radiation or heat. There
literature describes a continuous
increase in absorbance even after irradiation is
complete,(14,15) with the absorbance being a
function of a logarithm of elapsed time.(16) Hence, it has
generally been recommended to
perform the measurements 24 h (2) to 48 h later(16) by both
researchers and manufacturers.*
Measurements are further complicated by the shift in wavelength
of maximum absorbance (λmax)
to lower wavelengths as dose increases.(2,7,14,15)
GafChromic® MD-55 film is stable during storage or short
exposures to ambient light,(17)
satisfying part of seventh requirement of in vivo dosimeter.
However, the temperature
dependence of absorbance of GafChromic® MD-55 is complicated,
and humidity and pressure
dependence poorly documented. Increase in temperature reported
to correspond to a decrease in
absorbance and a peak shift to lower λ (λmax = 677.5 nm at
18.6°C, 673 nm at 28.0 °C for 6.9
Gy),(2,16) with the latter effect being reversible if
temperature fluctuations occur during
∗ International Specialty Products (ISP) product
information.
-
25measurement, not but irreversible if the temperature was
varied during irradiation.(2) Others
report an increase in absorbance with an increase in
temperature.(14,18) This discrepancy is likely
due to a choice of wavelength for absorbance measurements, as
the λmax depends on temperature,
and also due to a range of temperatures sampled. It has been
shown that a He-Ne laser operating
as low as 0.1 mW will cause an increase in absorbance of
GafChromic® MD-55 in five minutes,
with this effect being stronger for films exposed to smaller
doses.(19) For this reason, the
absorbance measurements should be performed using low optical
powers to prevent
polymerization due to the heat produced by the light. Above
60°C, the colour of the film
changes from blue to red, as the