Physics:Gel dosimetry

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Gel dosimeters, also called Fricke gel dosimeters, are manufactured from radiation sensitive chemicals that, upon irradiation with ionising radiation, undergo a fundamental change in their properties as a function of the absorbed radiation dose. Over many years individuals have endeavoured to measure absorbed radiation dose distributions using gels. As long ago as 1950, the radiation-induced colour change in dyes was used to investigate radiation doses in gels.[1] Further, in 1957 depth doses of photons and electrons in agar gels were investigated using spectrophotometry.[2] Gel dosimetry today however, is founded mainly on the work of Gore et al who in 1984[3] demonstrated that changes due to ionising radiation in Fricke dosimetry solutions,[4] developed in the 1920s, could be measured using nuclear magnetic resonance (NMR).

Gel dosimeters generally consist of two types; Fricke and polymer gel dosimeters and are usually evaluated or 'read-out' using magnetic resonance imaging (MRI), optical computer tomography (CT), x-ray CT or ultrasound.

Since 1999 the DosGel and IC3DDose Conference Series on gel dosimetry has been held at various international venues.

Fricke gel dosimeters

Gore et al investigated[5] the nuclear magnetic resonance (NMR) relaxation properties of irradiated Fricke or ferrous sulphate dosimetry solutions[6] showing that radiation-induced changes, in which ferrous (Fe2+) ions are converted to ferric (Fe3+) ions, could be quantified using NMR relaxation measurements. In 1986 Appleby et al[7] reported that Fricke dosimetry solutions dispersed throughout a gel matrix could be used to obtain three-dimensional (3D) spatial dose information using magnetic resonance imaging (MRI). It was subsequently shown that irradiated Fricke-type gel dosimeters did not retain a spatially stable dose distribution due to ion diffusion within the irradiated dosimeters.[8] Fricke solutions with various gelling agents such as gelatine, agarose, sephadex and polyvinyl alcohol (PVA) were investigated along with chelating agents such as xylenol orange (XO) to reduce diffusion. Numerous authors subsequently published results of their work to inhibit the ion diffusion with limited success and which was summarised by Baldock et al in 2001.[9] By the early 1990s the diffusion problem was considered to be a significant one in the advancement of gel dosimetry.

Polymer gel dosimeters

Polymer systems for the use of radiation dosimetry were first proposed as early as 1954, where Alexander et al[10] discussed the effects of ionising radiation on polymethylmethacrylate. Following this, Hoecker et al[11] in 1958 investigated the dosimetry of radiation-induced polymerisation in liquids, and in 1961 Boni[12] used polyacrylamide as a gamma dosimeter. Much later in 1991, Audet et al[13] reported changes in NMR transverse relaxation measurements of irradiated polyethylene oxide. In 1992, Kennan et al[14] reported on NMR longitudinal relaxation studies performed on an irradiated aqueous solution of N,N’-methylene-bis-acrylamide and agarose, which showed that the relaxation rates increased with absorbed dose.

In 1992 a new gel dosimetry formulation was proposed by Maryanski et al,[15] which was based on the polymerisation of acrylamide and N,N’-methylene-bis-acrylamide (bis) monomers infused in an aqueous agarose matrix. This system was given the acronym BANANA due to the use of the chemical components (bis, acrylamide, nitrous oxide and agarose).[16] This type of gel dosimeter did not have the associated diffusion problem of Fricke gels and was shown to have a relatively stable post-irradiation dose distribution. The polymerisation reaction occurred by cross-linking of the monomers induced by the free radical products of water radiolysis. In 1994 the BANANA formulation was refined[17] by replacing agarose with gelatine and given the acronym BANG (bis, acrylamide, nitrogen and aqueous gelatine), the first of a series of new polymer gel formulations. In 1994 this formulation was patented[18] and became commercially available through MGS Research Inc. as BANG®. Subsequently, due to the naming of the commercial product, PAG[19] became the polymer gel dosimeter acronym of choice for most authors. Numerous authors subsequently published results of work investigating different compositions and formulations of polymer gel dosimeters which were summarised by Lepage et al.[20]

Although polymer-type dosimeters did not have the diffusion limitations of Fricke-type gel dosimeters, there was another significant limitation in their use. Due to the nature of their free radical chemistry, polymer gel dosimeters were susceptible to atmospheric oxygen inhibition of the polymerisation processes. As a result, these gel dosimeters had to be manufactured in an oxygen-free environment,[21][22] such as in a glove box pumped with nitrogen gas. Along with the use of potentially toxic chemicals,[23] this was a significant limitation in the introduction of gel dosimetry into the clinic.

During this period a number of studies were undertaken to investigate the clinical applications of radiological tissue-equivalent[24][25][26] PAG-type polymer gel dosimeters using MRI.[27][28][29][30][31] De Deene et al[32] undertook an investigation into the overall accuracy of an anthropomorphic polymer gel dosimetry phantom for the verification of conformal radiotherapy treatments. It was established that significant issues relating to the accuracy of this dosimetry technique were a result of oxygen inhibition in the polymer gel and MRI imaging artefacts.

Authors continued to investigate clinical aspects of polymer gel dosimetry using MRI including conformal therapy, IMRT and IMAT,[33][34][35][36][37][38][39] stereotactic radiosurgery,[40][41][42][43][44][45][46][47] brachytherapy,[48][49] low energy X-rays,[50] high-LET and proton therapy,[51][52][53][54] boron capture neutron therapy[55][56] and tissue inhomogeneities.[57][58]

Normoxic polymer gel dosimeters

A significant development in the field of gel dosimetry occurred when results of using an alternative polymer gel dosimeter formulation were published by Fong et al in 2001.[59] This new type of polymer gel dosimeter, known as MAGIC gel, bound atmospheric oxygen in a metallo-organic complex thus removing the problem of oxygen inhibition and enabling polymer gels to be manufactured on the bench-top in the laboratory. This created what was to be known as a normoxic gel dosimeter, compared with the previous PAG formulation which subsequently became known as a hypoxic gel dosimeter. The MAGIC polymer gel formulation consisted of methacrylic acid, ascorbic acid, gelatine and copper. The principal behind the MAGIC gel is in the ascorbic acid oxygen scavenger. Ascorbic acid binds free oxygen contained within the aqueous gelatine matrix into metallo-organic complexes and this process is initiated by copper sulphate. It was subsequently shown by De Deene et al in 2002 that other antioxidants could be used in the manufacture of normoxic gels[60] including tetrakis (hydroxymethyl) phosphonium chloride, having first been suggested to Baldock by Billingham in 1996.[61] Numerous authors subsequently published results of work investigating different compositions and formulations of normoxic polymer gel dosimeters and were summarised by Senden.[62] Other work has also included the development of less toxic polymer gels.[63]

The fundamental science underpinning polymer gel dosimetry was reviewed along with the various 'read-out' and evaluation techniques and clinical dosimetry applications in the 2010 Topical Review publication by Baldock et al.[64]

DosGel and IC3DDose conference series

In June 1995 whilst attending the American Association of Physicists in Medicine (AAPM) annual meeting in Boston, US, Clive Baldock and L. John Schreiner discussed the appropriateness of organising some form of specialist meeting or workshop on gel dosimetry. In September 1996 Clive Baldock and Lars Olsson, whilst attending the European Society for Radiotherapy & Oncology (ESTRO) annual meeting in Vienna, Austria initiated the organising of the international conference series on gel dosimetry which began as DosGel 99, the 1st International Workshop on Radiation Therapy Gel Dosimetry held in Lexington, Kentucky in 1999 and hosted by Geoff Ibbott. Since 1999, subsequent DosGel conferences were held in Brisbane, Australia (2001), Ghent, Belgium (2004), Sherbrooke, Canada (2006) and Crete, Greece (2008). In 2010 the conference was held in Hilton Head, South Carolina, USA and underwent a name-change to IC3DDose. Subsequent IC3DDose conferences were held in Sydney, Australia (2012), Ystad, Sweden (2014), Galveston, Texas, USA (2016), Kushan, China (2018) and virtually (2021).

The aim of the first workshop was to bring together individuals, both researchers and users, with an interest in the application of 3-dimensional radiation dosimetry techniques in the treatment of cancer, with a mix of presentations from basic science to clinical applications. This has remained an objective for all of the conferences. One rationale of DosGel 99 was stated as supporting the increasing clinical implementation of gel dosimetry, as the technique appeared, at that time, to be leaving the laboratories of gel dosimetry enthusiasts and entering clinical practice. Clearly by labelling the first workshop as the 1st, there was a vision of a continuing series, which has been fulfilled. On the other hand, the expectation of widespread clinical use of gel dosimetry has perhaps not been what was hoped for and anticipated. Nevertheless, the rapidly increasing demand for advanced high-precision 3D radiotherapy technology and techniques has continued apace. The need for practical and accurate 3D dosimetry methods for development and quality assurance has only increased. By the 6th meeting, held in South Carolina in 2010, the Conference Scientific Committee recognised the wider developments in 3D systems and methods and decided to widen the scope, whilst keeping the same span from basic science to applications. This was signalled by a change of name from DosGel to IC3DDose, a name that has continued to the latest conference, the 11th IC3DDose conference, held virtually in May 2021.

See also

  • Hugo Fricke

References

  1. ↑ Day M J and Stein G 1950 Chemical effects of ionizing radiation in some gels Nature 166 146– 7
  2. ↑ Andrews H L, Murphy R E and LeBrun E J 1957 Gel dosimeter for depth dose measurements Rev Sci Instrum 28 329–32
  3. ↑ Gore J C, Kang Y S and Schulz R J 1984 Measurement of radiation dose distributions by nuclear magnetic resonance (NMR) imaging Phys Med Biol 29 1189–97
  4. ↑ Fricke H and Morse S 1927 The chemical action of roentgen rays on dilute ferrous sulphate solutions as a measure of radiation dose Am J Roentgenol Radium Therapy Nucl Med 18 430–2
  5. ↑ Gore J C, Kang Y S and Schulz R J 1984 Measurement of radiation dose distributions by nuclear magnetic resonance (NMR) imaging Phys Med Biol 29 1189–97
  6. ↑ Fricke H and Morse S 1927 The chemical action of roentgen rays on dilute ferrous sulphate solutions as a measure of radiation dose Am J Roentgenol Radium Therapy Nucl Med 18 430–2
  7. ↑ Appleby A, Christman E A and Leghrouz A 1986 Imaging of spatial radiation dose distribution in agarose gels using magnetic resonance Med Phys. 14 382-4
  8. ↑ Schulz R J, de Guzman A F, Nguyen D B and Gore J C 1990 Dose-response curves for Fricke- infused agarose gels as obtained by nuclear magnetic resonance Phys Med Biol 35 1611-22
  9. ↑ Baldock C, Harris P J, Piercy A R, Healy B 2001 Experimental determination of the diffusion coefficient in two-dimensions in ferrous sulphate gels using the finite element method Australas Phys Eng Sci Med 24 19-30
  10. ↑ Alexander P, Charlesby A and Ross M 1954 The degradation of solid polymethylmethacrylate by ionizing radiations Proceedings of the Royal Society A223 392
  11. ↑ Hoecker F E and Watkins I W 1958 Radiation polymerization dosimetry Int J Appl Rad Isotop 3 31-35
  12. ↑ Boni A L 1961 A polyacrylamide gamma dosimeter Radiation Research 14 374-80
  13. ↑ Audet C and Schreiner L J 1991 Radiation dosimetry by NMR relaxation time measurements of irradiated polymer solutions Proc Intl Soc Mag Reson Med (New York)
  14. ↑ Kennan R P, Maryanski M J, Zhong J and Gore J C 1992. Hydrodynamic effects and cross relaxation in cross linked polymer gels Proc Intl Soc Mag Reson Med (New York)
  15. ↑ Maryanski M J, Gore J C and Schulz R J 1992 3-D radiation dosimetry by MRI: solvent proton relaxation enhancement by radiation-controlled polymerisation and cross-linking in gels Proc Intl Soc Mag Reson Med (New York)
  16. ↑ Maryanski M J, Gore J C, Kennan R P and Schulz R J 1993 NMR relaxation enhancement in gels polymerized and cross-linked by ionizing radiation: a new approach to 3D dosimetry by MRI Magn Reson Imaging 11 253-58
  17. ↑ Maryanski M J, Schulz R J, Ibbott G S, Gatenby J C, Xie J, Horton D and Gore J C 1994 Magnetic resonance imaging of radiation dose distributions using a polymer-gel dosimeter Phys Med Biol 39 1437-55
  18. ↑ Maryanski M J, Gore J C and Schulz R 1994 Three-dimensional detection, dosimetry and imaging of an energy field by formation of a polymer in a gel US Patent 5321357
  19. ↑ Baldock C, Burford R P, Billingham N, Wagner G S, Patval S, Badawi R D and Keevil S F 1998 Experimental procedure for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry Phys Med Biol 43 695-702
  20. ↑ Lepage M, Jayasekera M, Bäck S Å J, Baldock C 2001 Dose resolution optimization of polymer gel dosimeters using different monomers Phys Med Biol 46 2665-80
  21. ↑ Baldock C, Burford R P, Billingham N, Wagner G S, Patval S, Badawi R D and Keevil S F 1998 Experimental procedure for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry Phys Med Biol 43 695-702
  22. ↑ De Deene Y, De Wagter C, Van Duyse B, Derycke S, De Neve W and Achten E 1998 Three- dimensional dosimetry using polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy in head-and-neck cancer Radiotherapy and Oncology 48 283–291
  23. ↑ Baldock C and Watson S 1999 Risk assessment for the manufacture of radiation dosimetry polymer gels in DOSGEL 1999 Proceedings of the 1st International Workshop on Radiation Therapy Gel Dosimetry (Lexington, USA) Eds L J Schreiner and C Audet
  24. ↑ Keall P, Baldock C, 1999. A theoretical study of the radiological properties and water equivalence of three types of gels used for radiation dosimetry Australas Phys Eng Sci Med 22 85-91
  25. ↑ Venning AJ, Nitschke KN, Keall PJ, Baldock C, 2005. Radiological properties of normoxic polymer gel dosimeters Med Phys 32 1047-1053
  26. ↑ Brown S, Venning A, De Deene Y, Vial P, Oliver L, Adamovics J and Baldock C 2008 Radiological properties of the PRESAGE and PAGAT polymer dosimeters Applied Radiation and Isotopes 66 (12) 1970-1974
  27. ↑ Maryanski M J, Gore J C, Kennan R P and Schulz R J 1993 NMR relaxation enhancement in gels polymerized and cross-linked by ionizing radiation: a new approach to 3D dosimetry by MRI Magn Reson Imaging 11 253-58
  28. ↑ Maryanski M J, Schulz R J, Ibbott G S, Gatenby J C, Xie J, Horton D and Gore J C 1994 Magnetic resonance imaging of radiation dose distributions using a polymer-gel dosimeter Phys Med Biol 39 1437-55
  29. ↑ Ibbott G S, Maryanski M J, Eastman P, Holcomb S D, Zhang Y, Avison R G, Sanders M and Gore J C 1997 Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of BANG polymer gel dosimeters Int J Radiat Oncol Biol Phys 38 1097-103
  30. ↑ Oldham M, Baustert I, Lord C, Smith T A D, McJury M, Warrington A P, Leach M O and Webb S 1998a An investigation into the dosimetry of a nine-field tomotherapy irradiation using BANG-gel dosimetry Phys Med Biol 43 1113–32
  31. ↑ Low D A, Harms W B, Mutic S and Purdy J A 1998 A technique for the quantitative evaluation of dose distributions Med Phys 25 656-61
  32. ↑ De Deene Y, De Wagter C, Van Duyse B, Derycke S, Mersseman B, De Gersem W, Voet T, Achten E and De Neve W 2000 Validation of MR-based polymer gel dosimetry as a preclinical three-dimensional verification tool in conformal radiotherapy Magn Reson Med 43 116–25
  33. ↑ Cosgrove V P, Murphy P S, McJury M, Adams E J, Warrington A P, Leach M O and Webb S 2000 The reproducibility of polyacrylamide gel dosimetry applied to stereotactic conformal radiotherapy Phys Med Biol 45 1195-210
  34. ↑ Vergote K, De Deene Y, Claus F, De Gersem W, Van Duyse B, Paelinck L, Achten E, De Neve W, De Wagter C 2003 Application of monomer/polymer gel dosimetry to study the effects of tissue inhomogeneities on intensity-modulated radiation therapy (IMRT) dose distributions Radiotherapy and Oncology 67 119-28
  35. ↑ Duthoy W, De Gersem W, Vergote K, Coghe M, Boterberg T, De Deene Y, De Wagter C, Van Belle S and De Neve W 2003 Whole abdominopelvic radiotherapy (WAPRT) using intensity- modulated arc therapy (IMAT): First clinical experience Int J Radiation Oncology Biol Phys 57 1019-32
  36. ↑ Love P A, Evans P M, Leach M O and Webb S 2003 Polymer gel measurement of dose homogeneity in the breast: comparing MLC intensity modulation with standard wedged delivery Phys Med Biol 48 1065-74
  37. ↑ Vergote K, De Deene Y, Duthoy W, De Gersem W, De Neve W, Achten E 2004 Validation and application of polymer gel dosimetry for the dose verification of an intensity-modulated arc therapy (IMAT) treatment Phys Med Biol 49 287-305
  38. ↑ Duthoy W, De Gersem W, Vergote K, Boterberg T, Derie C, Smeets P, De Wagter C and De Neve W 2004 Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer Int J Radiation Oncology Biol Phys 60 794-806
  39. ↑ Sandilos P, Angelopoulos A, Baras P, Dardoufas K, Karaiskos P, Kipouros P, Kozicki M, Rosiak J M, Sakelliou L, Seimenis I and Vlahos L 2004 Dose verification in clinical IMRT prostate incidents Int J Radiation Oncology Biol Phys 59 1540-7
  40. ↑ Ertl A, Berg A, Zehetmayer M and Frigo P 2000 High-resolution dose profile studies based on MR imaging with polymer BANG gels in stereotactic radiation techniques Magn Reson Imaging 18 343-349
  41. ↑ Grebe G, Pfaender M, Roll M and Luedemann L 2001 Dynamic arc radiosurgery and radiotherapy: Commissioning and verification of dose distributions Int J Radiat Oncol Biol Phys 49 1451-60
  42. ↑ Pappas E, Seimenis I, Angelopoulos A, Georgolopoulou P, Kamariotaki Paparigopoulou M, Maris T, Sakelliou L, Sandilos P and Vlachos L 2001 Narrow stereotactic beam profile measurements using N-vinylpyrrolidone based polymer gels and magnetic resonance imaging Phys Med Biol 46 783-97
  43. ↑ Audet C, Hilts M, Jirasek A and Duzenli C 2002 CT gel dosimetry technique: Comparison of a planned and measured 3D stereotactic dose volume J Appl Clin Med Phys 3 110-8
  44. ↑ Novotny J Jr, Dvorak P, Spevacek V, Tintera J, Novotny J, Cechak T and Liscak R 2002 Quality control of the stereotactic radiosurgery procedure with the polymer-gel dosimetry Radiother Oncol 63 223-30
  45. ↑ Scheib S G and Gianolini S 2002 Three-dimensional dose verification using BANG gel: a clinical example J Neurosurg 97 582-7
  46. ↑ Watanabe Y, Perera G M and Mooij R B 2002 Image distortion in MRI-based polymer gel dosimetry of Gamma Knife stereotactic radiosurgery systems Med Phys 29 797-802
  47. ↑ Karaiskos P, Petrokokkinos L, Tatsis E, Angeloupolos A, Baras P, Kozicki M, Papagiannis P, Rosiak J M, Sakelliou L, Sandilos P and Vlachos L 2005 Dose verification of single shot gamma knife applications using VIPAR polymer gel and MRI Phys Med Biol 50 1235-50
  48. ↑ Farajollahi A R, Bonnett D E, Ratcliffe A J, Aukett R J and Mills J A 1999 An investigation into the use of polymer gel dosimetry in low dose rate brachytherapy Br J Radiol 72 1085–92
  49. ↑ Wuu C-S, Schiff P, Maryanski MJ, Liu T, Borzillary S, and Weinberger J 2003 Dosimetry study of Re-188 liquid balloon for intravascular brachytherapy using polymer gel dosimeters and laser- beam optical CT scanner Med Phys 30 132-7
  50. ↑ Boudou C, Briston M C, Corde S, Adam J F, Ferrero C, Esteve F and Elleaume H 2004 Synchrotron stereotactic radiotherapy: dosimetry by Fricke gel and Monte Carlo simulations Phys Med Biol 49 5135-44
  51. ↑ Ramm U, Weber U, Bock M, Kramer M, Bankamp A, Damrau M, Thilmann C, Bottcher H D, Schad L R, and Kraft G 2000 Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy Phys Med Biol 45 N95-N102
  52. ↑ Jirasek A I and Duzenli C 2002 Relative effectiveness of polyacrylamide gel dosimeters applied to proton beams: Fourier transform Raman observations and track structure calculations Med Phys 29 569-77
  53. ↑ Heufelder J, Stiefel S, Pfaender M, Ludemann L, Grebe G and Heese J 2003 Use of BANG polymer gel for dose measurements in a 68 MeV proton beam Med Phys 30 1235-40
  54. ↑ Gustavsson H, Back S A J, Medin J, Grusell E and Olsson L E 2004 Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements Phys Med Biol 49 3847-55
  55. ↑ Farajollahi A R, Bonnett D E, Tattam D and Green S 2000 The potential use of polymer gel dosimetry in boron neutron capture therapy Phys Med Biol 45 N9–N14
  56. ↑ Gambarini G, Colli V, Gay S, Petrovich C, Pirola L and Rosi G 2004 In-phantom imaging of all dose components in boron neutron capture therapy by means of gel dosimeters Applied Radiation and Isotopes 61 759–763
  57. ↑ Vergote K, De Deene Y, Claus F, De Gersem W, Van Duyse B, Paelinck L, Achten E, De Neve W, De Wagter C 2003 Application of monomer/polymer gel dosimetry to study the effects of tissue inhomogeneities on intensity-modulated radiation therapy (IMRT) dose distributions Radiotherapy and Oncology 67 119-28
  58. ↑ Love P A, Evans P M, Leach M O and Webb S 2003 Polymer gel measurement of dose homogeneity in the breast: comparing MLC intensity modulation with standard wedged delivery Phys Med Biol 48 1065-74
  59. ↑ Fong P M, Keil D C, Does M D and Gore J C 2001 Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere Phys Med Biol 46 3105–13
  60. ↑ De Deene Y, Hurley C, Venning A, Mather M, Healy B, Whittaker A, Baldock C 2002 A basic study of some normoxic polymer gel dosimeters Phys Med Biol 47 3441–63
  61. ↑ Baldock C 2009 Historical overview of the development of gel dosimetry: another personal perspective Journal of Physics: Conference Series 164 (1) 012002
  62. ↑ Senden R J, De Jean P, McAuley K B and Schreiner L J 2006 Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose–response using different monomers Phys Med Biol 51 3301–14
  63. ↑ Senden R J, De Jean P, McAuley K B and Schreiner L J 2006 Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose–response using different monomers Phys Med Biol 51 3301–14
  64. ↑ Baldock C, De Deene Y, Doran S, Ibbott G, Jirasek A, Lepage M, McAuley KB, Oldham M, Schreiner LJ 2010. Polymer gel dosimetry. Physics in Medicine and Biology 55 (5) R1



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