Embed Size (px)
Citation preview
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity
This article has been downloaded from IOPscience Please scroll down to see the full text article
2008 Phys Med Biol 53 N53
(httpiopscienceioporg0031-9155534N04)
Download details
IP Address 1311046210
The article was downloaded on 23052012 at 1655
Please note that terms and conditions apply
View the table of contents for this issue or go to the journal homepage for more
Home Search Collections Journals About Contact us My IOPscience
IOP PUBLISHING PHYSICS IN MEDICINE AND BIOLOGY
Phys Med Biol 53 (2008) N53ndashN58 doi1010880031-9155534N04
NOTE
Formaldehyde increases MAGIC gel dosimetermelting point and sensitivity
Juliana Polezze Fernandes Bruno Fraccini Pastorello Draulio Barros deAraujo and Oswaldo Baffa1
Departamento de Fisica e Matematica FFCLRP Universidade de Sao Paulo Av Bandeirantes3900 14040-901-Ribeirao Preto SP Brazil
E-mail baffaffclrpuspbr
Received 19 March 2007 in final form 10 January 2008Published 1 February 2008Online at stacksioporgPMB53N53
AbstractPolymeric gel dosimeters are being used to verify three-dimensional (3D) dosedistributions of different types of radiotherapy treatments especially the mostcomplexes ones An important factor that can limit the wider use of this kindof dosimeter is temperature as gel melting can destroy 3D information Thiswork shows that adding formaldehyde to the gel preparation increases themelting point allowing its use in warmer environments including up to bodytemperature An addition of 3 in mass of the formaldehyde solution to aMAGIC type gel dosimeter increased its melting point from 25 to 69 C Alsoimportant were a 125 increase in gel sensitivity and an expressive decreasein relaxation rate R2 uncertainty
1 Introduction
Advances in treatment techniques with ionizing radiation are generating complex dosedistributions that ideally need to be verified before a patientrsquos treatment Some dosimetershave already been considered for such an application (Jordan 2006) Among them polymericgels show the best results and perspectives (Baldock 2006) They allow three-dimensionaldose visualization (De Deene et al 1998 Gustavsson et al 2003) they are tissue equivalent(Kron et al 1993 Pantelis et al 2004) do not present angular dependence with the incidentradiation and have a spatial resolution in the order of millimeters (Khan 1984)
There are many types of gel dosimeters and recently the polymeric normoxic onesare have gained special attention since they are easy to manufacture (Fong et al 2001De Deene et al 2006 Venning et al 2005) The first normoxic gel available was the MAGIC(methacrylic and ascorbic acid in gelatin initiated by copper) (Fong et al 2001) Its response
1 Address for correspondence DFM FFCLRP Universidade de Sao Paulo Av Bandeirantes 3900 14040ndash901-Ribeirao Preto SP Brazil
0031-915508040053+06$3000 copy 2008 Institute of Physics and Engineering in Medicine Printed in the UK N53
N54 J Polezze Fernandes et al
Table 1 Gel composition for a 50 ml volume with varying amounts of formaldehyde to assess itseffect on gelrsquos melting point In all samples 41 g of gelatin bovine skin 250 Bloom 176 mg ofascorbic acid 295 g of methacrylic acid and 1 mg of copper sulfate were used The formaldehydesolution used contains a minimum of 37 and was stabilized in 10 methanol
Ultra pure Formaldehyde Formaldehyde MeltingSample deionized water (ml) solution (ml) solution ( mass) point (C)
1 4200 mdash mdash 2502 4150 050 1 2453 4125 075 15 2654 4100 100 2 2705 4075 125 25 2906 4050 150 3 690
to irradiation occurs by the polymerization of methacrylic acid and protection against oxygensuppression by the acid ascorbicndashcopper complex (De Deene et al 2002) The polymerizationis proportional to the absorbed dose and can be quantified by transverse relaxation rateR2 (= 1T2) measurements in magnetic resonance imaging (MRI) As the absorbed doseis increased the polymerization and the number of macromolecules in the gel are increasedand thus the mobility of the protons decreases causing a T2 decrease leading to an increasein R2
The main advantage of gel-based dosimeters is its practicability to measure 3D dosedistributions in clinical setting with equipment already available for imaging However thereare several factors that may disturb their ability to precisely measure dose distributions oneof them is temperature (De Deene et al 2006) since at relatively low temperatures around25 C the gel in its current formulation can melt and 3D dose information is lost Madsenet al (1982) used formaldehyde to increase the melting point of certain gels used in ultrasoundphantom simulations with good results Studies to increase the gelatin melting temperatureaiming the use of gelatin as drug capsules for oral intake were also performed by other authors(Lefebvre et al 2006 Gold et al 1997 Ofner et al 2001 Tengroth et al 2005) These studiesshow that the presence of formaldehyde increases cross-linking leading to an increase ofmelting temperature Thus motivated by these previous studies we herein study the influenceof formaldehyde in MAGIC gels as an alternative to increase its melting point and the influenceof formaldehyde addition in the gel dosimetric response
2 Materials and methods
21 Gel manufacturing
Gelatin (bovine skin 250 Bloom Gelita Rcopy) was added to water at room temperature and thenheated to 45 C where the mixture was kept until the gelatin had completely melted afterapproximately 30 min The heater was then turned off and the mixture was cooled to 35 Cwhen ascorbic acid (Vetec Rcopy) copper sulfate (Vetec Rcopy) and the formaldehyde (Merck Rcopy) as awater solution with 37 minimum stabilized with 10 methanol were added All reagentswere used without additional purification After approximately 5 min the methacrylic acid(Acros Rcopy) was finally added The solution was stirred continuously during the entire mixingprocedure The ideal concentration of formaldehyde required to increase the melting pointwas studied Table 1 shows the gel compositions analyzed
To study the melting point each sample was poured into a 50 ml beaker All gels werestored in a refrigerator at a temperature of 10 C for one day before use The samples
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N55
were heated and their temperatures were monitored with a digital thermometer until completemelting of the gel we considered the melting point as the temperature at which the gel lost itsgel appearance and became a viscous solution
To compare the sensitivity of MAGIC gels two sets of gels were prepared at the sametime and with the same conditions except for the addition of formaldehyde to one of thesamples (the same composition as sample 6 table 1) and the other was left without it (the samecomposition as sample 1 table 1) For this study the gels were poured into a 5 ml cylindricalblood collection tube with low vacuum and sealed for further irradiation and imaging
22 Irradiation
The gel phantoms were irradiated with a cobalt 60 (Gammatron Siemens) unit from theUniversity Hospital and Clinics of the Medical School of Ribeirao Preto This equipment isroutinely checked for its dose rate according to the 398 IAEA protocol yielding an uncertaintysmaller than 3 We used a single beam with its central axis parallel to the diameter of thecylindrical tubes inserted in a plastic slab that assured the build-up region at the front surfaceof the gel Doses of 1 2 3 4 5 and 10 Gy were delivered and one tube was not irradiated asa reference
23 Magnetic resonance image acquisition and processing
MR images were acquired after the thermal equilibrium of the gel tubes with the MR scannerroom temperature 1 day after the irradiation to allow enough time for reaction completionand uniform thermal equilibrium
MRI images to evaluate R2 were acquired using a 15 T scanner (Siemens MagnetonVision) with a head coil and single spin echo sequences with echo times of 22 60 and 120 msa repetition time of 3000 ms and a matrix size of 128 times 256 pixels The slice thickness was 5mm and the FOV was 240 mm The transverse relaxation rate R2 (=1T2) was calculated byfitting the image signal intensities to the following mono exponential equation
SSE(T E) = SSE(0) eminusR2T E + SLO (1)
where SLO is the signal level offset and SSE(0) is the signal intensity at TE = 0 msImage processing was performed using a specific program developed by our group
(Carneiro et al 2006 2005) in MatLab Rcopy 65 (Mathworks Inc) The transverse relaxationrate R2 was evaluated on a pixel-wise basis of a selected region of interest (ROI) and ahistogram was used to assess its distribution The ROI was selected on the entire gel area anda Gaussian distribution was assumed with its peak value representing the mean R2 value itsstandard deviation was also calculated
3 Results and discussions
The presence of formaldehyde in the gel preparation increased the gel melting point asindicated in table 1 For gel preparation with 3 in volume concentration of the formaldehydesolution (sample 6) the melting point was 69 C which is high enough to allow convenientgel manipulation in all clinical environments without the need of a thermal protection duringits transportation from the laboratory where it is prepared to the radiotherapy department orto the magnetic resonance scanner to prevent the loss of the dose distribution in the volumeirradiated
The addition of formaldehyde to the gel increased its melting point but it is important toascertain the effect of this compound on the gel response to the irradiation The dosendashresponse
N56 J Polezze Fernandes et al
0 2 4 6 8 10
0
2
4
6
8
10
12
14
R2
(s-1)
Dose (Gy)
MAGIC MAGIC with formaldehyde y = 095x + 130
(R=098516 p=32810-4) y = 105x - 007
(R=099644 plt00001)
Figure 1 Dosendashresponse curves for the two MAGIC gels with (sample 6) and withoutformaldehyde (sample 1) The lines connecting the experimental points represent a linear fit ofthe data with correlation coefficients of 0985 and 0996 for gels without and with formaldehyderespectively
0 2 4 6 8 100
1
2
3
4
5
6
7
8
9
10
11
R2
(s-1)
Dose (Gy)
300 Bloom 250 Bloom
y = 075x - 010 (R=0989 p=1610-4) y = 10x + 031 (R=0998 plt00001)
Figure 2 Influence of the gelatin Bloom on the sensitivity of the MAGIC gel dosimeters Thelines connecting the experimental points represent a linear fit of the data It can be seen that thehigher the Bloom the smaller the sensitivity to radiation
curves of MAGIC gel with and without formaldehyde are shown in figure 1 the error bars arethe standard deviation of the mean values in the selected ROI It is interesting to note that theerror for low and high dose points decreased for the gels containing formaldehyde this seemsto indicate that the presence of this compound yields a more uniform gel
As an alternative to increase the melting point of gels McJury et al (2000) have shownthat using gelatin with a higher strength or Bloom would increase the melting point of the gelHence such influence was studied in MAGIC gels with formaldehyde Although the increaseof the Bloom of the gelatin increases the gelsrsquo melting point a decrease in its sensitivity wasalso observed (figure 2) making this route not appropriate for our goals
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
IOP PUBLISHING PHYSICS IN MEDICINE AND BIOLOGY
Phys Med Biol 53 (2008) N53ndashN58 doi1010880031-9155534N04
NOTE
Formaldehyde increases MAGIC gel dosimetermelting point and sensitivity
Juliana Polezze Fernandes Bruno Fraccini Pastorello Draulio Barros deAraujo and Oswaldo Baffa1
Departamento de Fisica e Matematica FFCLRP Universidade de Sao Paulo Av Bandeirantes3900 14040-901-Ribeirao Preto SP Brazil
E-mail baffaffclrpuspbr
Received 19 March 2007 in final form 10 January 2008Published 1 February 2008Online at stacksioporgPMB53N53
AbstractPolymeric gel dosimeters are being used to verify three-dimensional (3D) dosedistributions of different types of radiotherapy treatments especially the mostcomplexes ones An important factor that can limit the wider use of this kindof dosimeter is temperature as gel melting can destroy 3D information Thiswork shows that adding formaldehyde to the gel preparation increases themelting point allowing its use in warmer environments including up to bodytemperature An addition of 3 in mass of the formaldehyde solution to aMAGIC type gel dosimeter increased its melting point from 25 to 69 C Alsoimportant were a 125 increase in gel sensitivity and an expressive decreasein relaxation rate R2 uncertainty
1 Introduction
Advances in treatment techniques with ionizing radiation are generating complex dosedistributions that ideally need to be verified before a patientrsquos treatment Some dosimetershave already been considered for such an application (Jordan 2006) Among them polymericgels show the best results and perspectives (Baldock 2006) They allow three-dimensionaldose visualization (De Deene et al 1998 Gustavsson et al 2003) they are tissue equivalent(Kron et al 1993 Pantelis et al 2004) do not present angular dependence with the incidentradiation and have a spatial resolution in the order of millimeters (Khan 1984)
There are many types of gel dosimeters and recently the polymeric normoxic onesare have gained special attention since they are easy to manufacture (Fong et al 2001De Deene et al 2006 Venning et al 2005) The first normoxic gel available was the MAGIC(methacrylic and ascorbic acid in gelatin initiated by copper) (Fong et al 2001) Its response
1 Address for correspondence DFM FFCLRP Universidade de Sao Paulo Av Bandeirantes 3900 14040ndash901-Ribeirao Preto SP Brazil
0031-915508040053+06$3000 copy 2008 Institute of Physics and Engineering in Medicine Printed in the UK N53
N54 J Polezze Fernandes et al
Table 1 Gel composition for a 50 ml volume with varying amounts of formaldehyde to assess itseffect on gelrsquos melting point In all samples 41 g of gelatin bovine skin 250 Bloom 176 mg ofascorbic acid 295 g of methacrylic acid and 1 mg of copper sulfate were used The formaldehydesolution used contains a minimum of 37 and was stabilized in 10 methanol
Ultra pure Formaldehyde Formaldehyde MeltingSample deionized water (ml) solution (ml) solution ( mass) point (C)
1 4200 mdash mdash 2502 4150 050 1 2453 4125 075 15 2654 4100 100 2 2705 4075 125 25 2906 4050 150 3 690
to irradiation occurs by the polymerization of methacrylic acid and protection against oxygensuppression by the acid ascorbicndashcopper complex (De Deene et al 2002) The polymerizationis proportional to the absorbed dose and can be quantified by transverse relaxation rateR2 (= 1T2) measurements in magnetic resonance imaging (MRI) As the absorbed doseis increased the polymerization and the number of macromolecules in the gel are increasedand thus the mobility of the protons decreases causing a T2 decrease leading to an increasein R2
The main advantage of gel-based dosimeters is its practicability to measure 3D dosedistributions in clinical setting with equipment already available for imaging However thereare several factors that may disturb their ability to precisely measure dose distributions oneof them is temperature (De Deene et al 2006) since at relatively low temperatures around25 C the gel in its current formulation can melt and 3D dose information is lost Madsenet al (1982) used formaldehyde to increase the melting point of certain gels used in ultrasoundphantom simulations with good results Studies to increase the gelatin melting temperatureaiming the use of gelatin as drug capsules for oral intake were also performed by other authors(Lefebvre et al 2006 Gold et al 1997 Ofner et al 2001 Tengroth et al 2005) These studiesshow that the presence of formaldehyde increases cross-linking leading to an increase ofmelting temperature Thus motivated by these previous studies we herein study the influenceof formaldehyde in MAGIC gels as an alternative to increase its melting point and the influenceof formaldehyde addition in the gel dosimetric response
2 Materials and methods
21 Gel manufacturing
Gelatin (bovine skin 250 Bloom Gelita Rcopy) was added to water at room temperature and thenheated to 45 C where the mixture was kept until the gelatin had completely melted afterapproximately 30 min The heater was then turned off and the mixture was cooled to 35 Cwhen ascorbic acid (Vetec Rcopy) copper sulfate (Vetec Rcopy) and the formaldehyde (Merck Rcopy) as awater solution with 37 minimum stabilized with 10 methanol were added All reagentswere used without additional purification After approximately 5 min the methacrylic acid(Acros Rcopy) was finally added The solution was stirred continuously during the entire mixingprocedure The ideal concentration of formaldehyde required to increase the melting pointwas studied Table 1 shows the gel compositions analyzed
To study the melting point each sample was poured into a 50 ml beaker All gels werestored in a refrigerator at a temperature of 10 C for one day before use The samples
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N55
were heated and their temperatures were monitored with a digital thermometer until completemelting of the gel we considered the melting point as the temperature at which the gel lost itsgel appearance and became a viscous solution
To compare the sensitivity of MAGIC gels two sets of gels were prepared at the sametime and with the same conditions except for the addition of formaldehyde to one of thesamples (the same composition as sample 6 table 1) and the other was left without it (the samecomposition as sample 1 table 1) For this study the gels were poured into a 5 ml cylindricalblood collection tube with low vacuum and sealed for further irradiation and imaging
22 Irradiation
The gel phantoms were irradiated with a cobalt 60 (Gammatron Siemens) unit from theUniversity Hospital and Clinics of the Medical School of Ribeirao Preto This equipment isroutinely checked for its dose rate according to the 398 IAEA protocol yielding an uncertaintysmaller than 3 We used a single beam with its central axis parallel to the diameter of thecylindrical tubes inserted in a plastic slab that assured the build-up region at the front surfaceof the gel Doses of 1 2 3 4 5 and 10 Gy were delivered and one tube was not irradiated asa reference
23 Magnetic resonance image acquisition and processing
MR images were acquired after the thermal equilibrium of the gel tubes with the MR scannerroom temperature 1 day after the irradiation to allow enough time for reaction completionand uniform thermal equilibrium
MRI images to evaluate R2 were acquired using a 15 T scanner (Siemens MagnetonVision) with a head coil and single spin echo sequences with echo times of 22 60 and 120 msa repetition time of 3000 ms and a matrix size of 128 times 256 pixels The slice thickness was 5mm and the FOV was 240 mm The transverse relaxation rate R2 (=1T2) was calculated byfitting the image signal intensities to the following mono exponential equation
SSE(T E) = SSE(0) eminusR2T E + SLO (1)
where SLO is the signal level offset and SSE(0) is the signal intensity at TE = 0 msImage processing was performed using a specific program developed by our group
(Carneiro et al 2006 2005) in MatLab Rcopy 65 (Mathworks Inc) The transverse relaxationrate R2 was evaluated on a pixel-wise basis of a selected region of interest (ROI) and ahistogram was used to assess its distribution The ROI was selected on the entire gel area anda Gaussian distribution was assumed with its peak value representing the mean R2 value itsstandard deviation was also calculated
3 Results and discussions
The presence of formaldehyde in the gel preparation increased the gel melting point asindicated in table 1 For gel preparation with 3 in volume concentration of the formaldehydesolution (sample 6) the melting point was 69 C which is high enough to allow convenientgel manipulation in all clinical environments without the need of a thermal protection duringits transportation from the laboratory where it is prepared to the radiotherapy department orto the magnetic resonance scanner to prevent the loss of the dose distribution in the volumeirradiated
The addition of formaldehyde to the gel increased its melting point but it is important toascertain the effect of this compound on the gel response to the irradiation The dosendashresponse
N56 J Polezze Fernandes et al
0 2 4 6 8 10
0
2
4
6
8
10
12
14
R2
(s-1)
Dose (Gy)
MAGIC MAGIC with formaldehyde y = 095x + 130
(R=098516 p=32810-4) y = 105x - 007
(R=099644 plt00001)
Figure 1 Dosendashresponse curves for the two MAGIC gels with (sample 6) and withoutformaldehyde (sample 1) The lines connecting the experimental points represent a linear fit ofthe data with correlation coefficients of 0985 and 0996 for gels without and with formaldehyderespectively
0 2 4 6 8 100
1
2
3
4
5
6
7
8
9
10
11
R2
(s-1)
Dose (Gy)
300 Bloom 250 Bloom
y = 075x - 010 (R=0989 p=1610-4) y = 10x + 031 (R=0998 plt00001)
Figure 2 Influence of the gelatin Bloom on the sensitivity of the MAGIC gel dosimeters Thelines connecting the experimental points represent a linear fit of the data It can be seen that thehigher the Bloom the smaller the sensitivity to radiation
curves of MAGIC gel with and without formaldehyde are shown in figure 1 the error bars arethe standard deviation of the mean values in the selected ROI It is interesting to note that theerror for low and high dose points decreased for the gels containing formaldehyde this seemsto indicate that the presence of this compound yields a more uniform gel
As an alternative to increase the melting point of gels McJury et al (2000) have shownthat using gelatin with a higher strength or Bloom would increase the melting point of the gelHence such influence was studied in MAGIC gels with formaldehyde Although the increaseof the Bloom of the gelatin increases the gelsrsquo melting point a decrease in its sensitivity wasalso observed (figure 2) making this route not appropriate for our goals
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
N54 J Polezze Fernandes et al
Table 1 Gel composition for a 50 ml volume with varying amounts of formaldehyde to assess itseffect on gelrsquos melting point In all samples 41 g of gelatin bovine skin 250 Bloom 176 mg ofascorbic acid 295 g of methacrylic acid and 1 mg of copper sulfate were used The formaldehydesolution used contains a minimum of 37 and was stabilized in 10 methanol
Ultra pure Formaldehyde Formaldehyde MeltingSample deionized water (ml) solution (ml) solution ( mass) point (C)
1 4200 mdash mdash 2502 4150 050 1 2453 4125 075 15 2654 4100 100 2 2705 4075 125 25 2906 4050 150 3 690
to irradiation occurs by the polymerization of methacrylic acid and protection against oxygensuppression by the acid ascorbicndashcopper complex (De Deene et al 2002) The polymerizationis proportional to the absorbed dose and can be quantified by transverse relaxation rateR2 (= 1T2) measurements in magnetic resonance imaging (MRI) As the absorbed doseis increased the polymerization and the number of macromolecules in the gel are increasedand thus the mobility of the protons decreases causing a T2 decrease leading to an increasein R2
The main advantage of gel-based dosimeters is its practicability to measure 3D dosedistributions in clinical setting with equipment already available for imaging However thereare several factors that may disturb their ability to precisely measure dose distributions oneof them is temperature (De Deene et al 2006) since at relatively low temperatures around25 C the gel in its current formulation can melt and 3D dose information is lost Madsenet al (1982) used formaldehyde to increase the melting point of certain gels used in ultrasoundphantom simulations with good results Studies to increase the gelatin melting temperatureaiming the use of gelatin as drug capsules for oral intake were also performed by other authors(Lefebvre et al 2006 Gold et al 1997 Ofner et al 2001 Tengroth et al 2005) These studiesshow that the presence of formaldehyde increases cross-linking leading to an increase ofmelting temperature Thus motivated by these previous studies we herein study the influenceof formaldehyde in MAGIC gels as an alternative to increase its melting point and the influenceof formaldehyde addition in the gel dosimetric response
2 Materials and methods
21 Gel manufacturing
Gelatin (bovine skin 250 Bloom Gelita Rcopy) was added to water at room temperature and thenheated to 45 C where the mixture was kept until the gelatin had completely melted afterapproximately 30 min The heater was then turned off and the mixture was cooled to 35 Cwhen ascorbic acid (Vetec Rcopy) copper sulfate (Vetec Rcopy) and the formaldehyde (Merck Rcopy) as awater solution with 37 minimum stabilized with 10 methanol were added All reagentswere used without additional purification After approximately 5 min the methacrylic acid(Acros Rcopy) was finally added The solution was stirred continuously during the entire mixingprocedure The ideal concentration of formaldehyde required to increase the melting pointwas studied Table 1 shows the gel compositions analyzed
To study the melting point each sample was poured into a 50 ml beaker All gels werestored in a refrigerator at a temperature of 10 C for one day before use The samples
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N55
were heated and their temperatures were monitored with a digital thermometer until completemelting of the gel we considered the melting point as the temperature at which the gel lost itsgel appearance and became a viscous solution
To compare the sensitivity of MAGIC gels two sets of gels were prepared at the sametime and with the same conditions except for the addition of formaldehyde to one of thesamples (the same composition as sample 6 table 1) and the other was left without it (the samecomposition as sample 1 table 1) For this study the gels were poured into a 5 ml cylindricalblood collection tube with low vacuum and sealed for further irradiation and imaging
22 Irradiation
The gel phantoms were irradiated with a cobalt 60 (Gammatron Siemens) unit from theUniversity Hospital and Clinics of the Medical School of Ribeirao Preto This equipment isroutinely checked for its dose rate according to the 398 IAEA protocol yielding an uncertaintysmaller than 3 We used a single beam with its central axis parallel to the diameter of thecylindrical tubes inserted in a plastic slab that assured the build-up region at the front surfaceof the gel Doses of 1 2 3 4 5 and 10 Gy were delivered and one tube was not irradiated asa reference
23 Magnetic resonance image acquisition and processing
MR images were acquired after the thermal equilibrium of the gel tubes with the MR scannerroom temperature 1 day after the irradiation to allow enough time for reaction completionand uniform thermal equilibrium
MRI images to evaluate R2 were acquired using a 15 T scanner (Siemens MagnetonVision) with a head coil and single spin echo sequences with echo times of 22 60 and 120 msa repetition time of 3000 ms and a matrix size of 128 times 256 pixels The slice thickness was 5mm and the FOV was 240 mm The transverse relaxation rate R2 (=1T2) was calculated byfitting the image signal intensities to the following mono exponential equation
SSE(T E) = SSE(0) eminusR2T E + SLO (1)
where SLO is the signal level offset and SSE(0) is the signal intensity at TE = 0 msImage processing was performed using a specific program developed by our group
(Carneiro et al 2006 2005) in MatLab Rcopy 65 (Mathworks Inc) The transverse relaxationrate R2 was evaluated on a pixel-wise basis of a selected region of interest (ROI) and ahistogram was used to assess its distribution The ROI was selected on the entire gel area anda Gaussian distribution was assumed with its peak value representing the mean R2 value itsstandard deviation was also calculated
3 Results and discussions
The presence of formaldehyde in the gel preparation increased the gel melting point asindicated in table 1 For gel preparation with 3 in volume concentration of the formaldehydesolution (sample 6) the melting point was 69 C which is high enough to allow convenientgel manipulation in all clinical environments without the need of a thermal protection duringits transportation from the laboratory where it is prepared to the radiotherapy department orto the magnetic resonance scanner to prevent the loss of the dose distribution in the volumeirradiated
The addition of formaldehyde to the gel increased its melting point but it is important toascertain the effect of this compound on the gel response to the irradiation The dosendashresponse
N56 J Polezze Fernandes et al
0 2 4 6 8 10
0
2
4
6
8
10
12
14
R2
(s-1)
Dose (Gy)
MAGIC MAGIC with formaldehyde y = 095x + 130
(R=098516 p=32810-4) y = 105x - 007
(R=099644 plt00001)
Figure 1 Dosendashresponse curves for the two MAGIC gels with (sample 6) and withoutformaldehyde (sample 1) The lines connecting the experimental points represent a linear fit ofthe data with correlation coefficients of 0985 and 0996 for gels without and with formaldehyderespectively
0 2 4 6 8 100
1
2
3
4
5
6
7
8
9
10
11
R2
(s-1)
Dose (Gy)
300 Bloom 250 Bloom
y = 075x - 010 (R=0989 p=1610-4) y = 10x + 031 (R=0998 plt00001)
Figure 2 Influence of the gelatin Bloom on the sensitivity of the MAGIC gel dosimeters Thelines connecting the experimental points represent a linear fit of the data It can be seen that thehigher the Bloom the smaller the sensitivity to radiation
curves of MAGIC gel with and without formaldehyde are shown in figure 1 the error bars arethe standard deviation of the mean values in the selected ROI It is interesting to note that theerror for low and high dose points decreased for the gels containing formaldehyde this seemsto indicate that the presence of this compound yields a more uniform gel
As an alternative to increase the melting point of gels McJury et al (2000) have shownthat using gelatin with a higher strength or Bloom would increase the melting point of the gelHence such influence was studied in MAGIC gels with formaldehyde Although the increaseof the Bloom of the gelatin increases the gelsrsquo melting point a decrease in its sensitivity wasalso observed (figure 2) making this route not appropriate for our goals
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N55
were heated and their temperatures were monitored with a digital thermometer until completemelting of the gel we considered the melting point as the temperature at which the gel lost itsgel appearance and became a viscous solution
To compare the sensitivity of MAGIC gels two sets of gels were prepared at the sametime and with the same conditions except for the addition of formaldehyde to one of thesamples (the same composition as sample 6 table 1) and the other was left without it (the samecomposition as sample 1 table 1) For this study the gels were poured into a 5 ml cylindricalblood collection tube with low vacuum and sealed for further irradiation and imaging
22 Irradiation
The gel phantoms were irradiated with a cobalt 60 (Gammatron Siemens) unit from theUniversity Hospital and Clinics of the Medical School of Ribeirao Preto This equipment isroutinely checked for its dose rate according to the 398 IAEA protocol yielding an uncertaintysmaller than 3 We used a single beam with its central axis parallel to the diameter of thecylindrical tubes inserted in a plastic slab that assured the build-up region at the front surfaceof the gel Doses of 1 2 3 4 5 and 10 Gy were delivered and one tube was not irradiated asa reference
23 Magnetic resonance image acquisition and processing
MR images were acquired after the thermal equilibrium of the gel tubes with the MR scannerroom temperature 1 day after the irradiation to allow enough time for reaction completionand uniform thermal equilibrium
MRI images to evaluate R2 were acquired using a 15 T scanner (Siemens MagnetonVision) with a head coil and single spin echo sequences with echo times of 22 60 and 120 msa repetition time of 3000 ms and a matrix size of 128 times 256 pixels The slice thickness was 5mm and the FOV was 240 mm The transverse relaxation rate R2 (=1T2) was calculated byfitting the image signal intensities to the following mono exponential equation
SSE(T E) = SSE(0) eminusR2T E + SLO (1)
where SLO is the signal level offset and SSE(0) is the signal intensity at TE = 0 msImage processing was performed using a specific program developed by our group
(Carneiro et al 2006 2005) in MatLab Rcopy 65 (Mathworks Inc) The transverse relaxationrate R2 was evaluated on a pixel-wise basis of a selected region of interest (ROI) and ahistogram was used to assess its distribution The ROI was selected on the entire gel area anda Gaussian distribution was assumed with its peak value representing the mean R2 value itsstandard deviation was also calculated
3 Results and discussions
The presence of formaldehyde in the gel preparation increased the gel melting point asindicated in table 1 For gel preparation with 3 in volume concentration of the formaldehydesolution (sample 6) the melting point was 69 C which is high enough to allow convenientgel manipulation in all clinical environments without the need of a thermal protection duringits transportation from the laboratory where it is prepared to the radiotherapy department orto the magnetic resonance scanner to prevent the loss of the dose distribution in the volumeirradiated
The addition of formaldehyde to the gel increased its melting point but it is important toascertain the effect of this compound on the gel response to the irradiation The dosendashresponse
N56 J Polezze Fernandes et al
0 2 4 6 8 10
0
2
4
6
8
10
12
14
R2
(s-1)
Dose (Gy)
MAGIC MAGIC with formaldehyde y = 095x + 130
(R=098516 p=32810-4) y = 105x - 007
(R=099644 plt00001)
Figure 1 Dosendashresponse curves for the two MAGIC gels with (sample 6) and withoutformaldehyde (sample 1) The lines connecting the experimental points represent a linear fit ofthe data with correlation coefficients of 0985 and 0996 for gels without and with formaldehyderespectively
0 2 4 6 8 100
1
2
3
4
5
6
7
8
9
10
11
R2
(s-1)
Dose (Gy)
300 Bloom 250 Bloom
y = 075x - 010 (R=0989 p=1610-4) y = 10x + 031 (R=0998 plt00001)
Figure 2 Influence of the gelatin Bloom on the sensitivity of the MAGIC gel dosimeters Thelines connecting the experimental points represent a linear fit of the data It can be seen that thehigher the Bloom the smaller the sensitivity to radiation
curves of MAGIC gel with and without formaldehyde are shown in figure 1 the error bars arethe standard deviation of the mean values in the selected ROI It is interesting to note that theerror for low and high dose points decreased for the gels containing formaldehyde this seemsto indicate that the presence of this compound yields a more uniform gel
As an alternative to increase the melting point of gels McJury et al (2000) have shownthat using gelatin with a higher strength or Bloom would increase the melting point of the gelHence such influence was studied in MAGIC gels with formaldehyde Although the increaseof the Bloom of the gelatin increases the gelsrsquo melting point a decrease in its sensitivity wasalso observed (figure 2) making this route not appropriate for our goals
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
N56 J Polezze Fernandes et al
0 2 4 6 8 10
0
2
4
6
8
10
12
14
R2
(s-1)
Dose (Gy)
MAGIC MAGIC with formaldehyde y = 095x + 130
(R=098516 p=32810-4) y = 105x - 007
(R=099644 plt00001)
Figure 1 Dosendashresponse curves for the two MAGIC gels with (sample 6) and withoutformaldehyde (sample 1) The lines connecting the experimental points represent a linear fit ofthe data with correlation coefficients of 0985 and 0996 for gels without and with formaldehyderespectively
0 2 4 6 8 100
1
2
3
4
5
6
7
8
9
10
11
R2
(s-1)
Dose (Gy)
300 Bloom 250 Bloom
y = 075x - 010 (R=0989 p=1610-4) y = 10x + 031 (R=0998 plt00001)
Figure 2 Influence of the gelatin Bloom on the sensitivity of the MAGIC gel dosimeters Thelines connecting the experimental points represent a linear fit of the data It can be seen that thehigher the Bloom the smaller the sensitivity to radiation
curves of MAGIC gel with and without formaldehyde are shown in figure 1 the error bars arethe standard deviation of the mean values in the selected ROI It is interesting to note that theerror for low and high dose points decreased for the gels containing formaldehyde this seemsto indicate that the presence of this compound yields a more uniform gel
As an alternative to increase the melting point of gels McJury et al (2000) have shownthat using gelatin with a higher strength or Bloom would increase the melting point of the gelHence such influence was studied in MAGIC gels with formaldehyde Although the increaseof the Bloom of the gelatin increases the gelsrsquo melting point a decrease in its sensitivity wasalso observed (figure 2) making this route not appropriate for our goals
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
Formaldehyde increases MAGIC gel dosimeter melting point and sensitivity N57
The importance of increasing the melting point of gel dosimeters is recognized by manyinvestigators as a way to assure the preservation of the spatial information otherwise morecomplex phantoms should be made (Silva et al 2003) In this study it was demonstrated thatthe melting point of the MAGIC-type gel dosimeter was increased using formaldehyde andthis also provided an improvement in the sensitivity of the dosendashresponse by about 105 anda reduction in the uncertainty in R2 (figure 1) The alternative method of increasing the gelrsquosmelting point by increasing the gelatinrsquos Bloom is not adequate because it is followed by adecrease in sensitivity that could compromise the performance of the gel dosimetry system(figure 2)
The addition formaldehyde to the MAGIC gel dosimeter does not influence its tissueequivalence since formaldehydersquos mass concentration in the dosimeter is only 3
Formaldehyde increases gel melting point by increasing the cross-linking reactions ingelatin molecules (Hall et al 1997 Rice et al 1998) possibly requiring a higher thermal energyto break down the chemical bonds Finally the slopes for MAGIC gels with formaldehydeand 250 Bloom gelatin in figures 1 and 2 respectively are slightly different a 5 differencewas observed in these two batches A possible explanation is due to the fact that the batcheswere different and the environmental conditions were not the same however the difference iswithin the accepted uncertainty for this kind of measurement
In conclusion the addition of formaldehyde to MAGIC-type gel dosimeters increasesthe melting point up to 69 C and dosimeter sensitivity by about 105 when compared tostandard MAGIC gels It also decreased the uncertainty in R2 As a result the new formulationfor this gel is more reliable for 3D dose distribution measurements and is easier to handle
Acknowledgments
This work was partially supported by CAPES and FAPESP The technical support fromC Brunello L Rocha and JL Aziani is also appreciated
References
Baldock C 2006 Historical overview of the development of gel dosimetry a personal perspective Proc 4th Int ConfRadiother Gel Dosimetry J Phys Conf Ser 56 14ndash22
Carneiro A A O Fernandes J P de Araujo D B Elias J Jr Martinelli A L C Covas D T Zago M A Angulo I LSt Pierre T G and Baffa O 2005 Liver iron concentration evaluated by two magnetic methods magneticresonance imaging and magnetic susceptometry Magn Reson Med 54 122ndash8
Carneiro A A O Vilela G R de Araujo D B and Baffa O 2006 MRI relaxometry methods and applications Br JPhys 36 9ndash15
De Deene Y De Wagter C Van Duyse B Derycke S De Neve W and Achten E 1998 Three-dimensional dosimetryusing polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy inhead-and-neck cancer Radiother Oncol 48 283ndash91
De Deene Y Hurley C Venning Vergote K Mather M Healy B J and Baldock C 2002 A basic study of somenormoxic polymer gel dosimeters Phys Med Biol 47 3441ndash63
De Deene Y Vergote K Claeys C and DeWagter C 2006 The fundamental radiation properties of normoxic polymergel dosimeters a comparison between a methacrylic acid based gel and acrylamide based gels Phys MedBiol 51 653ndash73
Fong P M Keil D C Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dosedistributions at normal room atmosphere Phys Med Biol 46 3105ndash13
Gold T B Buice R G Lodder R A and Digenis G A 1997 Determination of extent of formaldehyde-inducedcrosslinking in hard gelatin capsules by near-infrared spectrophotometry Pharma Res 14 1046ndash50
Gustavsson H Karlsson A Back S A J Olsson L E Haraldsson P Engstrom P and Nystrom H 2003 MAGIC-type polymer gel for three-dimensional dosimetry intensity-modulated radiation therapy verification MedPhys 30 1264ndash71
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
N58 J Polezze Fernandes et al
Hall T J Bilgen M Insana M F and Krouskop T A 1997 Phantom materials for elastography IEEE Trans UltrasonFerroelectr Freq Control 44 1355ndash65
Jordan K 2006 Review of recent advances in non gel dosimeters Proc 4th Int Conf Radiotherapy Gel Dosimetrypp 268ndash78
Khan F M 1984 The Physics of Radiation Therapy (Ed) (Philadelphia PA Lippincott Williams amp Wilkins)Kron T Metcalfe P and Pope J M 1993 Investigation of the tissue equivalence of gels used for NMR dosimetry Phys
Med Biol 38 139ndash50Lefebvre D R Han J Lipari J M Long M A McSwain R L and Wells H C 2006 Dielectric analysis for in-situ
monitoring of gelatin renaturation and crosslinking J Appl Polym Sci 101 2765ndash75Madsen E L Zagzebski J A and Frank G R 1982 Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking
materials Ultrasound Med Biol 8 277ndash87McJury M Oldham M Cosgrove V P Murphy P S Doran S Leach M O and Webb S 2000 Radiation dosimetry
using polymer gels methods and applications Brazilian J Radiol 73 919ndash29Ofner C M III Zhang Y Jobeck V C and Bowman B J 2001 Crosslinking studies in gelatin capsules treated with
formaldehyde and in capsules exposed to elevated temperature and humidity J Pharma Sci 90 79ndash88Pantelis E Karlis A K Kozicki M Papagaiannis P Sakelliou L and Rosiak B M 2004 Polymer gel water equivalence
and relative energy response with emphasis on low photon energy dosimetry in brachytherapy Phys MedBiol 49 3495ndash514
Rice J R Milbrandt R H Madsen E L Frank G R Boote E J and Blechinger J C 1998 Anthropomorphic 1H MRShead phantom Med Phys 25 1145ndash56
Silva N A Nicolucci P and Baffa O 2003 Spatial resolution of magnetic resonance imaging Friche-gel dosimetry isimproved with a honeycomb phantom Med Phys 30 17ndash20
Tengroth C Gasslander U Andersson F O and Jacobsson S P 2005 Cross-linking of gelatin capsules with formaldehydeand other aldehydes an FTIR spectroscopy study Pharma Dev Technol 10 405ndash12
Venning A J Hill B Brindha S Healy B J and Baldock C 2005 Investigation of the PAGAT polymer gel dosimeterusing magnetic resonance imaging Phys Med Biol 50 3875ndash88
