1992, The British Journal of Radiology, 65, 167-169
Technical note Magnetic resonance imaging of Fricke-doped agarose gels for the visualization of radiotherapy dose distributions in a lung phantom By S. J . Thomas, MA, MSc, I. D. Wilkinson, MSc, *A. K. Dixon, M D , MRCP, FRCR and P. P. Dendy, PhD Medical Physics Department, Addenbrooke's Hospital, Cambridge CB2 2QQ and * Department of Radiology, University of Cambridge, Hills Road, Cambridge, UK (Received 22 February 1991 and in revised form 6 June 1991, accepted 2 July 1991)
Keywords: Magnetic resonance, Ferrous sulphate dosimetry, Radiotherapy, Treatment planning
When calculating a treatment plan for a radiation beam that passes through an inhomogeneity such as lung, the dose at each point needs to be modified to correct for the effect of the inhomogeneities. Many algorithms exist for making such corrections. Algorithms must be verified by measurements in phantoms. Measurements with an ionization chamber in a solid phantom can only be performed at a limited number of points, giving poor spatial resolution. Film dosimetry gives better spatial resolution, but the introduction of non-tissue equivalent photographic film represents a considerable perturbation of a tissue equivalent phantom. Shultz et al (1990) and Olsson et al (1990) have recently described techniques for the measurement of absorbed dose using magnetic resonance imaging (MRI) of agarose gels doped with Fricke (iron (II) sulphate) solution. After Fe 2+ has been oxidized by irradiation to Fe 3+ , the gel fixes the position of the ions, so that the distribution of Fe 3+ in the gel corresponds to the dose distribution. The gel is then imaged to produce a map of the longitudinal proton relaxation time (T,). As a result of the paramagnetic properties of Fe 3 + , Tx is inversely proportional to Fe 3+ concentration and hence to absorbed dose of radiation. Thus, the technique provides a method of determining a continuous distribution of radiation dose within a phantom. This paper describes preliminary work using the technique on a phantom containing a volume of low density material designed to simulate lung. The measured distribution is compared with that calculated using a treatment planning program. Methods and materials Phantom design A box was made of Perspex (PMMA) with internal dimensions 15 cm x 15 cm x 18 cm. An insert of expanded polystyrene 7.5 cm x 15 cm x 10 cm was fixed in the box at one side, extending from 3 cm to 13 cm below the surface. The box was filled with dosimetric gel to within 1 cm of the surface. The polystyrene was wrapped in clingfilm to prevent seepage of gel. The total volume of gel used was 2.7 1. Vol. 65, No. 770
Production of Fricke gel The final concentrations of reagents within each litre of gel were 1 mM ammonium iron (II) sulphate, 1 mM sodium chloride and 25 mM sulphuric acid; all these were AnalaR grade from BDH Chemicals. The concentration of agarose (type 1-A from Sigma Chemical Company) was 1 % by weight. To make 2.75 1 of gel, the reagents for the Fricke solution were dissolved in 1.0 J of de-ionized water and oxygenated by passing oxygen through a sintered glass bulb. The agarose was added to 1.0 1 of de-ionized water, stirred for half an hour and heated to 120°C in a pressure cooker. It was cooled to 100°C and diluted to 1.751 with boiling de-ionized water. This solution was then oxygenated using a sintered glass bulb whilst cooling to 60°C before the Fricke solution was added. The mixture was stirred thoroughly and bubbles removed by suction before the gel was poured into the Perspex mould. The gel was placed in a refrigerator to solidify and left for several hours at room temperature before irradiation. Irradiation Cobalt-60 radiation from a TEM MS-80 cobalt unit was used. The field size was 10 cm x 10 cm with a source-surface distance of 80 cm. The dose given corresponded to 45 Gy at a depth of 0.5 cm below the surface of the gel. Magnetic resonance imaging A Picker 2055 HP magnetic resonance imager operating at 1.5 Tesla was used to acquire two sets of images immediately after irradiation. An inversion-recovery sequence (repetition time (TR) 2000 ms, inversion time (TI) 600 ms) gave a r,-weighted image, and a spin-echo sequence (TR 2000 ms, echo time (TE) 30 ms) gave a proton-density weighted image. The parameters for both sequences were: a 25 cm field of view; an acquisition matrix of 256 x 256; a slice thickness of 10 mm and two signal averages. From these two data sets a map of Tx values was calculated using software provided by the 167
Technical note
electron densities relative to water of the gel and the expanded polystyrene, as determined from the CT attenuation values, were 1.007 and 0.06, respectively. The expanded polystyrene is of lower density than lung. This was chosen to give a sharper contrast between the two sides of the phantom and to provide a more severe test of a treatment planning algorithm than would be provided by a region of higher density. A dose distribution was calculated using a modified Batho power-law algorithm (Thomas, 1991) incorporated into a treatment planning program written in C. This algorithm has been tested, using ionization dosimetry, for a wide range of energies and field sizes. Results and discussion Figure 1. Isodose distribution for 10 cm x 10 cm cobalt beam at 80 cm corrected for inhomogeneity. The isodoses are superimposed on a CT image of the phantom.
manufacturer. Previous work (Wilkinson, 1989) has demonstrated the linear response of this MR system to r, by using calibrated gadolinium-doped agarose gels. Radiotherapy treatment planning A computed tomography (CT) image was obtained using a Siemens Somatom Plus system and subsequently transferred to an IBM AT compatible computer. The
The isodoses superimposed on the CT image are shown in Figure 1. Figures 2 (a & b) show the computed Tx map, with two different window settings. The reciprocal of Tx varies linearly with dose, so the darker the image the higher the dose. Visually, there is a close resemblance between this image and the isodose distribution. Figure 3 shows the MR values of 1/71, plotted against calculated dose at various points in the phantom. The triangles show points measured on a line 2.5 cm from the central axis of the beam (away from the inhomogeneity), the circles show points in the region below the inhomogeneity. These lie slightly to the right of the
Figure 2. Computed T, MR images of the phantom in the same plane as for Figure 1. (a) Shown with a window width of 490 ms, centred on 284 ms and (b) with a window width of 114 ms, centred on 253 ms.
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The British Journal of Radiology, February 1992
(1990), migration of ions is one of several practical aspects of the technique that remain to be evaluated. Conclusions
Absorbed dose in Gy Figure 3. (1/T,) MR values plotted against calculated dose at a number of positions in the phantom. The circles are for points beneath the inhomogeneity and the triangles are for points away from the inhomogeneity.
curve through the triangles, suggesting that the treatment planning algorithm may be overestimating the dose behind the inhomogeneity by a few percent. This overestimate could result from the fact that the 1dimensional power-law algorithm treats all inhomogeneities as semi-infinite slabs and makes no correction for loss of scatter in more complex situations. Further work will be required to determine whether this shift is real or within experimental error. The curve through the triangles is linear to approximately 30 Gy and shows signs of saturation at higher doses. This is in agreement with the results of Shultz et al (1990). Ordinary purity de-ionized water and AnalaR reagents have given satisfactory results. It does not seem to be necessary to use the triple distilled water and ultrahigh purity reagents required for conventional Fricke dosimetry. Acquiring the MR imaging of the phantom as soon as possible after irradiation minimized migration of the Fe3+ ions within the gel. As recently discussed by Day
Vol. 65, No. 770
Fricke gels show great promise for the visualization of three-dimensional dose distributions in phantoms. In this paper the feasibility of the method has been demonstrated using a treatment plan with a simple irradiation geometry. The technique readily lends itself to determination of dose distribution in more complex situations, where it is harder for treatment planning programs to make accurate predictions. Examples of such situations include conformational therapy, stereotactic radiosurgery and the calculation of dose near inhomogeneities in electron therapy. The doses required are of the order of tens of Gy. Although these are higher than those needed for ionization chambers, film or thermoluminescent dosemeter, they should not in general, lead to unacceptably long irradiation times. Doses of the order of tens of Gy are common prescriptions in radiosurgery. Verification of standard treatment plans, or conformational therapy with multi-leaf collimators, will involve gel irradiation times of less than half an hour, since dose-rates at the isocentre of linear accelerators are typically a few Gy per minute. Acknowledgments This work was made possible by the generous assistance of the Addenbrooke's Hospital Cancer Scanning Appeal Fund, the East Anglian Regional Health Authority and the Department of Health. References DAY, M. J., 1990. Radiation dosimetry using nuclear magnetic resonance: an introductory review. Physics in Medicine and Biology, 35, 1605-1609. OLSSON, L. E., FRANSSON, A.,
ERICSON, A. & MATTSON,
S.,
1990. MR imaging of absorbed dose distributions for radiotherapy using ferrous sulphate gels. Physics in Medicine and Biology, 35, 1623-1631. SCHULTZ, R. J., DE GUZMAN, A. F., NGUYEN, D. B. & GORE,
J. C , 1990. Dose-response curves for Fricke-infused agarose gels as obtained by nuclear magnetic resonance. Physics in Medicine and Biology, 35, 1611-1622. THOMAS, S. J., 1991. A modified power-law formula for inhomogeneity corrections in beams of high energy X-rays. Medical Physics, 18(4), 719-723. WILKINSON, I. D., 1989. Evaluation of the Picker Vista MR 2055 HP system. Report to the Medical Devices Directorate of the Department of Health (Department of Health, London).
169
Technical note Magnetic resonance imaging of Fricke-doped agarose gels for the visualization of radiotherapy dose distributions in a lung phantom By S. J . Thomas, MA, MSc, I. D. Wilkinson, MSc, *A. K. Dixon, M D , MRCP, FRCR and P. P. Dendy, PhD Medical Physics Department, Addenbrooke's Hospital, Cambridge CB2 2QQ and * Department of Radiology, University of Cambridge, Hills Road, Cambridge, UK (Received 22 February 1991 and in revised form 6 June 1991, accepted 2 July 1991)
Keywords: Magnetic resonance, Ferrous sulphate dosimetry, Radiotherapy, Treatment planning
When calculating a treatment plan for a radiation beam that passes through an inhomogeneity such as lung, the dose at each point needs to be modified to correct for the effect of the inhomogeneities. Many algorithms exist for making such corrections. Algorithms must be verified by measurements in phantoms. Measurements with an ionization chamber in a solid phantom can only be performed at a limited number of points, giving poor spatial resolution. Film dosimetry gives better spatial resolution, but the introduction of non-tissue equivalent photographic film represents a considerable perturbation of a tissue equivalent phantom. Shultz et al (1990) and Olsson et al (1990) have recently described techniques for the measurement of absorbed dose using magnetic resonance imaging (MRI) of agarose gels doped with Fricke (iron (II) sulphate) solution. After Fe 2+ has been oxidized by irradiation to Fe 3+ , the gel fixes the position of the ions, so that the distribution of Fe 3+ in the gel corresponds to the dose distribution. The gel is then imaged to produce a map of the longitudinal proton relaxation time (T,). As a result of the paramagnetic properties of Fe 3 + , Tx is inversely proportional to Fe 3+ concentration and hence to absorbed dose of radiation. Thus, the technique provides a method of determining a continuous distribution of radiation dose within a phantom. This paper describes preliminary work using the technique on a phantom containing a volume of low density material designed to simulate lung. The measured distribution is compared with that calculated using a treatment planning program. Methods and materials Phantom design A box was made of Perspex (PMMA) with internal dimensions 15 cm x 15 cm x 18 cm. An insert of expanded polystyrene 7.5 cm x 15 cm x 10 cm was fixed in the box at one side, extending from 3 cm to 13 cm below the surface. The box was filled with dosimetric gel to within 1 cm of the surface. The polystyrene was wrapped in clingfilm to prevent seepage of gel. The total volume of gel used was 2.7 1. Vol. 65, No. 770
Production of Fricke gel The final concentrations of reagents within each litre of gel were 1 mM ammonium iron (II) sulphate, 1 mM sodium chloride and 25 mM sulphuric acid; all these were AnalaR grade from BDH Chemicals. The concentration of agarose (type 1-A from Sigma Chemical Company) was 1 % by weight. To make 2.75 1 of gel, the reagents for the Fricke solution were dissolved in 1.0 J of de-ionized water and oxygenated by passing oxygen through a sintered glass bulb. The agarose was added to 1.0 1 of de-ionized water, stirred for half an hour and heated to 120°C in a pressure cooker. It was cooled to 100°C and diluted to 1.751 with boiling de-ionized water. This solution was then oxygenated using a sintered glass bulb whilst cooling to 60°C before the Fricke solution was added. The mixture was stirred thoroughly and bubbles removed by suction before the gel was poured into the Perspex mould. The gel was placed in a refrigerator to solidify and left for several hours at room temperature before irradiation. Irradiation Cobalt-60 radiation from a TEM MS-80 cobalt unit was used. The field size was 10 cm x 10 cm with a source-surface distance of 80 cm. The dose given corresponded to 45 Gy at a depth of 0.5 cm below the surface of the gel. Magnetic resonance imaging A Picker 2055 HP magnetic resonance imager operating at 1.5 Tesla was used to acquire two sets of images immediately after irradiation. An inversion-recovery sequence (repetition time (TR) 2000 ms, inversion time (TI) 600 ms) gave a r,-weighted image, and a spin-echo sequence (TR 2000 ms, echo time (TE) 30 ms) gave a proton-density weighted image. The parameters for both sequences were: a 25 cm field of view; an acquisition matrix of 256 x 256; a slice thickness of 10 mm and two signal averages. From these two data sets a map of Tx values was calculated using software provided by the 167
Technical note
electron densities relative to water of the gel and the expanded polystyrene, as determined from the CT attenuation values, were 1.007 and 0.06, respectively. The expanded polystyrene is of lower density than lung. This was chosen to give a sharper contrast between the two sides of the phantom and to provide a more severe test of a treatment planning algorithm than would be provided by a region of higher density. A dose distribution was calculated using a modified Batho power-law algorithm (Thomas, 1991) incorporated into a treatment planning program written in C. This algorithm has been tested, using ionization dosimetry, for a wide range of energies and field sizes. Results and discussion Figure 1. Isodose distribution for 10 cm x 10 cm cobalt beam at 80 cm corrected for inhomogeneity. The isodoses are superimposed on a CT image of the phantom.
manufacturer. Previous work (Wilkinson, 1989) has demonstrated the linear response of this MR system to r, by using calibrated gadolinium-doped agarose gels. Radiotherapy treatment planning A computed tomography (CT) image was obtained using a Siemens Somatom Plus system and subsequently transferred to an IBM AT compatible computer. The
The isodoses superimposed on the CT image are shown in Figure 1. Figures 2 (a & b) show the computed Tx map, with two different window settings. The reciprocal of Tx varies linearly with dose, so the darker the image the higher the dose. Visually, there is a close resemblance between this image and the isodose distribution. Figure 3 shows the MR values of 1/71, plotted against calculated dose at various points in the phantom. The triangles show points measured on a line 2.5 cm from the central axis of the beam (away from the inhomogeneity), the circles show points in the region below the inhomogeneity. These lie slightly to the right of the
Figure 2. Computed T, MR images of the phantom in the same plane as for Figure 1. (a) Shown with a window width of 490 ms, centred on 284 ms and (b) with a window width of 114 ms, centred on 253 ms.
168
The British Journal of Radiology, February 1992
(1990), migration of ions is one of several practical aspects of the technique that remain to be evaluated. Conclusions
Absorbed dose in Gy Figure 3. (1/T,) MR values plotted against calculated dose at a number of positions in the phantom. The circles are for points beneath the inhomogeneity and the triangles are for points away from the inhomogeneity.
curve through the triangles, suggesting that the treatment planning algorithm may be overestimating the dose behind the inhomogeneity by a few percent. This overestimate could result from the fact that the 1dimensional power-law algorithm treats all inhomogeneities as semi-infinite slabs and makes no correction for loss of scatter in more complex situations. Further work will be required to determine whether this shift is real or within experimental error. The curve through the triangles is linear to approximately 30 Gy and shows signs of saturation at higher doses. This is in agreement with the results of Shultz et al (1990). Ordinary purity de-ionized water and AnalaR reagents have given satisfactory results. It does not seem to be necessary to use the triple distilled water and ultrahigh purity reagents required for conventional Fricke dosimetry. Acquiring the MR imaging of the phantom as soon as possible after irradiation minimized migration of the Fe3+ ions within the gel. As recently discussed by Day
Vol. 65, No. 770
Fricke gels show great promise for the visualization of three-dimensional dose distributions in phantoms. In this paper the feasibility of the method has been demonstrated using a treatment plan with a simple irradiation geometry. The technique readily lends itself to determination of dose distribution in more complex situations, where it is harder for treatment planning programs to make accurate predictions. Examples of such situations include conformational therapy, stereotactic radiosurgery and the calculation of dose near inhomogeneities in electron therapy. The doses required are of the order of tens of Gy. Although these are higher than those needed for ionization chambers, film or thermoluminescent dosemeter, they should not in general, lead to unacceptably long irradiation times. Doses of the order of tens of Gy are common prescriptions in radiosurgery. Verification of standard treatment plans, or conformational therapy with multi-leaf collimators, will involve gel irradiation times of less than half an hour, since dose-rates at the isocentre of linear accelerators are typically a few Gy per minute. Acknowledgments This work was made possible by the generous assistance of the Addenbrooke's Hospital Cancer Scanning Appeal Fund, the East Anglian Regional Health Authority and the Department of Health. References DAY, M. J., 1990. Radiation dosimetry using nuclear magnetic resonance: an introductory review. Physics in Medicine and Biology, 35, 1605-1609. OLSSON, L. E., FRANSSON, A.,
ERICSON, A. & MATTSON,
S.,
1990. MR imaging of absorbed dose distributions for radiotherapy using ferrous sulphate gels. Physics in Medicine and Biology, 35, 1623-1631. SCHULTZ, R. J., DE GUZMAN, A. F., NGUYEN, D. B. & GORE,
J. C , 1990. Dose-response curves for Fricke-infused agarose gels as obtained by nuclear magnetic resonance. Physics in Medicine and Biology, 35, 1611-1622. THOMAS, S. J., 1991. A modified power-law formula for inhomogeneity corrections in beams of high energy X-rays. Medical Physics, 18(4), 719-723. WILKINSON, I. D., 1989. Evaluation of the Picker Vista MR 2055 HP system. Report to the Medical Devices Directorate of the Department of Health (Department of Health, London).
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