Download Three-dimensional Dose Verification Using Normoxic Polymer Gel

Three-dimensional Dose Verification Using Normoxic Polymer Gel Dosimeters for
Tomotherapy
Tung-Hsin1, Chien-Yi Hsiao2, Wu Mu-Bai Chang2, Geoffrey Zhang3, Ji-An Liang2,
Tzung-Chi Huang2,*
1
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming
University, Taipei, Taiwan
2
Department of Biomedical Imaging and Radiological Science, China Medical
University, Taiwan
3
Department of Radiation Oncology, Moffitt Cancer Center, Florida, USA
*Corresponding author:
Tzung-Chi Huang, Ph.D.
155 Li-Nong St., Sec. 2, Taipei, Taiwan 112
Tel: 886-4-22053366
Fax: N/A
E-mail: [email protected]
Abstract
The aim of this study is to evaluate the feasibility of using MAGAT as a near
real-time 3-dimensional dose measurement device for tomotherapy. MAGAT is a new
type of normoxic polymer gel dosimeter, which responses well to absorbed dose and
can be easily made in the presence of normal oxygen surroundings. Its dose response
was measured by irradiating MAGAT-gel-filled testing vials with tomotherapy and its
linear relationship with dose was present from 0 to 6.5 Gy. One group of gel samples
were measured in near real-time, in which the gel phantom was read right after the
irradiation. The other group was measured 12 hours after irradiation so the gel
phantom can be exposed to oxygen. Several post-imaging processing filters including
Nagao, Guess, median, mean, min and max, were applied on megavoltage computed
tomography (MVCT) images for better discrimination on dose responses. Our results
show that dose responses for MVCT with real-time and 12-hour delayed measurement
were 4.76 and 4.69 ΔSI．cGy-1, respectively, and show no significant difference
(p-value = 0.72). For study of the filtering effects, Gauss, median and mean filters
offer better linear correction coefficients of dose response. In conclusion, the MAGAT
polymer gel dosimeter read from MVCT imaging is a promising method for dose
verification in clinical tomotherapy.
Key Words: Dose Verification, Polymer Gel Dosimeters, Tomotherapy, Radiation
dosimetry
Introduction
Tomotherapy delivers radiation using a rotating intensity-modulated fan beam
geometry, and the modulation varies with gantry angle. Because the resultant
dose-distributions comprise modulated contributions from many angles, the system
has the potential to deliver highly conformal treatments. It was designed to be a
purpose-built image guided radiotherapy (IGRT) machine. The capability for
continuous rotation, coupled with translation of the patient through the gantry, allows
helical treatment arcs in a way similar to helical or spiral diagnostic CT scanners. The
helical tomotherapy accelerator is mounted on a slip ring gantry. This allowed a CT
detector array (Xenon filled linear array) to be mounted opposite the source. The
primary purpose of this detector is for megavoltage computed tomography (MVCT),
delivery verification, and dose reconstruction [1,2]. This on-board linear array of ion
chambers also has demonstrated its advantage for quality assurance and beam
alignment commissioning [3]. Additionally, it has also proved useful for quantifying
required dose planning parameters.
The mostly used radiation dose measurement detectors in the clinics, including
ion chamber, film and thermal-luminiscence detector (TLD), are often applied in 1- or
2-dimensional (1D or 2D) dose measurements. The gel dosimeter can measure
3-dimensional (3D) dose distribution directly. There are two categories of gel
dosimeters, Fricke gel and polymer gel. Fricke gel was proposed and studied first for
3D dose measurement [4]. Due to its low dose sensitivity and small dose
measurement range, Fricke gel has not been clinically used in radiotherapy dose
measurement. Monomer molecules in a polymer gel dosimeter solution change to
polymer molecules via polymerization after ionizing radiation irradiated. This
polymerization process changes the solution to gum. The amount of such
mononer-polymer conversion is proportional to the radiation dose within a certain
dose range. Dose measurement is thus achieved by the assessment of the
polymerization in the dosimeter. Normoxic polymer is an improved polymer gel,
which can be made in room temperature [5]. MAGAT normoxic polymer has the
characteristics of tissue equivalence and higher dose sensitivity [6].
Magnetic resonance imaging (MRI) has been the most widely used signal read
out device in 3D gel dosimetry research [7]. Other related research applied
kilo-voltage computed tomography (kVCT) [8-11] and kilo-voltage cone beam
computed tomography (kVCBCT) systems [11] as signal readers for gel dose
measurement. The aim of this study is to evaluate the feasibility of using MVCT as a
near real-time measurement device in dose estimation for tomotherapy with normoxic
polymer gel dosimetry. In order to eliminate higher noise level induced by MVCT
high energy photons as compared to that of kVCT, various post-imaging processing
filters including Nagao, Guess, median, mean, min and max , were also applied on
MVCT images for better discrimination on dose responses.
Materials and methods
The clinical helical tomotherapy unit (TomoTherapy Inc., Madison, Wisconsin,
USA) consists of a 6-MV linear accelerator with a binary multi-leaf collimator and a
xenon CT detector system. The MVCT mode of the linear accelerator reduces the
nominal energy to about 3.5 MV, and transverse 4-mm MVCT images were obtained.
This results in the acquisition of volumetric images at acceptable doses, typically
between 0.5 cGy and 3 cGy [12], which are comparable with doses required from
planar images on contemporary MV electronic portal imaging devices (EPIDs).
The MAGAT normoxic polymer gel was prepared under normal oxygen
conditions using gelatin (porcine skin, type A, 300 Bloom, Sigma Aldrich),
methacrylic acid (monomer purity > 98%, Sigma Aldrich), tetrakis hydroxyl methyl
phosphonium choloride (THPC) solution (80% solution in water, Sigma Aldrich), as
an oxygen scavenger, and distilled water (high performance liquid chromatography
grade) (Table 1). The gelatin was given to distilled water and heated to 50°C in a
water bath. A clear solution was achieved and cooled down to 35°C. The methacryliac
acid and THPC solution were then added to the gelatin solution. A homogeneous
liquid mixture was achieved by continuous stirring. All gels were prepared and poured
into 60 ml plastic vials of 25 mm in diameter and 115 mm in height and filled to the
top to minimize oxygen presence in the vials. A study has indicated that gels need to
be exposed to oxygen for at least 12 hr after irradiation to terminate their intrinsic
polymerization reactions and then kVCT can be used as a reading device [13].
This study examined effects on the timing of dose reading, including right after
irradiation and 12 hours delay. Gel-filled vials were irradiated with uniform doses of
0–650 cGy with a step of 50cGy, using tomotherapy accelerator. MVCT was used to
scan the samples to see signal changes in gel dosimeters. In the MVCT images of the
gel samples after irradiation, higher grey levels correspond to higher radiation dose
received. A region of interest (ROI) was delineated for each dose region and then was
used to calculate individual signal intensity. The dose response was generated by the
mean and standard deviation within each ROI of the MVCT image and mapped to
known doses. R-square error from fitted linear function on dose response was
analyzed for irradiated dose consistency. Dose response curves with different reading
timing were measured and compared. The optimal timing of dose reading was
determined by the analysis of the dose readings with different time delays. In terms of
MVCT imaging, density changes resulted from high photon energy in gel were
examined. Various filters including Nagao, Guess, median, mean, min and max filters
were applied to the 3D MVCT images for diminution of imaging noise and better
discrimination on dose responses.
Results and Discussion
Figure 1 shows dose response curves obtained with no time delay (real time) and
12-hour delay after irradiation, respectively, without use of filter. The difference in
signal intensity linearly increased with the radiation dose. Linear fitting was applied
to both sets of data with slope of 4.76 ΔSI．cGy-1 (real time) and 4.69ΔSI．cGy-1
(12-hour delay), respectively. No significant difference (p=0.72) was revealed with
different reading timing, exhibiting the accuracy of dose response for real-time
measurement.
Figure 2 and Figure 3 demonstrate the difference between the calibration curves
with different filters applied to the data set of real-time and 12-hour delay readings,
respectively. In Figure 2, almost all similar dose response curves were obtained with a
range of slope from 4.33 ΔSI．cGy-1 to 4.76 ΔSI．cGy-1. Data with Nagao, Gauss,
median, mean, min and without filter showed no statistically difference (p=0.99),
while that with max filter would induce substantially dose sensitivity reduction
(p=0.01). Thus, interpreting data with max filter might be not suitable for MVCT gel
dosimetry. Figure 3 shows dose response curves for 12-hour delay reading from 0 cGy
to 650 cGy in testing various imaging filters. Likewise, the slopes of dose response
curves were 4.69, 3.62, 4.51, 4.40, 4.44, 3.85 and 3.30 for without filter, with Nagao,
Gauss, median, mean, max and min filter respectively, and no statistically difference
was revealed (p=0.99). It is worth mentioning that dose response with max filter was
similar to those with other filters. For both real-time and 12-hour delayed readings,
Gauss, median and mean filters were found to be optimized for the calibration curve
generation.
MAGAT gel dosimeter has the advantages of 3D dose measurement, tissue
equivalence, high dose sensitivity, easy preparation, low cost, capability of
accumulative dose measurement and its signal is not spreading with time. However,
one needs to be cautious in temperature and composition control in preparation to
avoid hydrolysis and polymerization. Incomplete prepared gel dosimeter also affects
the dose response. The dose delivered by the MVCT to the dosimeter is about 1% of a
fractional dose in radiotherapy treatment. The additional dose from the MVCT scan is
thus within the tolerance. The higher the dose absorbed by the dosimeter, the higher
the attenuation to the MVCT photons by the gel. The response is linear to the
absorbed dose within the dose range in radiotherapy.
The tomotherapy unit is the dose delivering system and its MVCT is the dose
reading system when MAGAT polymer dosimeter is used, which not only provides a
robust treatment quality assurance system, but also warrants the measurement
consistency.
Conclusions
In this work, we have investigated the dose response curves for MAGAT
polymer gel dosimeter using tomotherapy as the dose delivering machine and its
MVCT as the 3D dose reader. This study is the first attempt to explore the potential
role of using MVCT as a reading device for gel dosimeters. The dose responses,
measured at different MVCT imaging times, showed no significantly difference. For
effects of different filters, Gauss, median and mean filters offer better linear correction
coefficients of dose response. In conclusion, normoxic polymer gel dosimeter
combined with MVCT as a dose reading device provides a useful method for
tomotherapy in three-dimensional real-time dose measurement and verification.
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Table 1. Composition of 100ml MAGAT gel
Chemical
Concentration
Gelatine
6%, 6 g
Methacryic acid (MAA)
9%, 9 g
THPC
10 mM
Distilled water
85%, 85 ml
4000
3500
5000
3000
5000
4500
2500
Real-time
ΔSI = 4.76．Dose + 0.13
R-square: 0.950
4500
4000
2000
4000
3500
12-hour delay
ΔSI = 4.69 ．Dose - 0.005
R-square: 0.954
1500
3500
3000
1000
3000
2500
ΔSI
500
2000
0
0
1500
200
2000
1000
1500
500
1000
0
0
100
2500
300
400
500
600
700
800
500
100
200
300
400
0
0
500
100
600
200
700
300
800
400
500
600
700
800
Dose (cGy)
Figure 1. Dose response curves of real-time reading (●) and 12 hours delay
reading (○). The horizontal axis is the absorbed dose in cGy, and the vertical
axis is the MVCT signal intensity difference, ΔSI.
5000
Real time
4500
4000
3500
ΔSI
3000
2500
2000
1500
1000
500
0
0
100
200
300
400
500
600
700
800
Dose (cGy)
Figure 2. Dose response curves for real-time reading with no filter(○) and with
Nagao (□), Gauss (×), median (●), mean (+), max (＊) and min (◊) filters. The
horizontal axis is the absorbed dose in cGy, and the vertical axis is the MVCT
signal intensity difference, ΔSI.
5000
4500
4000
3500
ΔSI
3000
2500
2000
1500
1000
500
0
0
100
200
300
400
500
600
700
800
Dose (cGy)
Figure 3. Dose response curves for 12 hours delayed reading with no filter(○)
and with Nagao (□), Gauss (×), median (●), mean (+), max (＊) and min (◊)
filters. The horizontal axis is the absorbed dose in cGy, and the vertical axis is
the MVCT signal intensity difference, ΔSI.