Dosimetry of High Intensity Electron Beams Produced by Dedicated ...

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Dosimetry of High Intensity Electron Beams Produced by Dedicated Accelerators in Intra-Operative Radiation Therapy (IORT) Ernesto Lamanna, Member, IEEE, Antonino Secondo Fiorillo, Member, IEEE, Carlo Bruno, Anna Santaniello, Yvette Flore Tchuente Siaka, Andrea Berdondini, Matteo Bettuzzi, Rosa Brancaccio, Franco Casali, Maria Pia Morigi, Giuliana Barca, and Francesca Castrovillari

Abstract—The technique of High Dose Intra-Operative Radiation Therapy (HDR-IORT) consists in the delivery of irradiation immediately following the removal of a cancerous mass, where the same incision is used to direct the radiation to the tumour bed. Given its particular characteristics, IORT requires dose measurements that are different from those requested in external radiotherapy treatments. The main reason lies in the fact that in this case a single high dose must be delivered to a target volume whose extension and depths will be determined directly during the operation. Since the possibility of devising a treatment plan using a TPS (Treatment Planning System) is not available, it is necessary to know the physical and geometric characteristics of the beam. Defining the physical characteristics of the beam entails both measuring the delivered dose and defining (monitoring) procedures. In any case a much higher dose will be released than occurs with conventional external accelerators. The ionization chamber recommended by the standard protocols for radiotherapy cannot be used because of the ion recombination inside the gas. In this work we propose the use of a calorimetric phantom, the Dosiort, to measure the beam properties. We describe the main characteristics and some preliminary results of the Dosiort System, which is proposed within the framework of a research project of the INFN (Italian National Institute of Nuclear Physics). The set-up is a solid phantom of density approaching 1 g cm3 with sensitive layers of scintillating fibres at fixed a position in a calorimetric configuration for the containment of electrons of energy 4–12 MeV. The prototype will be able to define the physical and geometrical characteristics of the electron beam (energy, isotropy, homogeneity, etc) and to measure the parameters needed to select the energy, the intensity and the Monitor Units (MU) for the exposition: Percentage Depth Dose; Beam profiles; Isodose curves; Values of dose for MU. Index Terms—3D, depth-dose measurement, dosimetry, IORT, scintillating fibres. Manuscript received October 15, 2007; revised June 19, 2008. Current version published February 11, 2009. This work was supported by the Italian INFN (Istituto Nazionale di Fisica Nucleare). ICTP (Trieste) provided fellowships and grant for non-Italian citizens. E. Lamanna and A. S. Fiorillo are with the Medicine Faculty of Magna Graecia University, 88100 Catanzaro, Italy and also with Gruppo Collegato INFN, Cosenza, Italy (e-mail: [email protected]; [email protected]). C. Bruno and A. Santaniello are with the Physics Department, University of Calabria, Cosenza, Italy (e-mail: [email protected]; [email protected]. it). Y. F. T. Siaka was with the Physics Department, University of Calabria, Cosenza Italy. She is now with the Centre for Atomic Molecular Physics and Quantum Optics, University of Douala, Cameroon (e-mail: [email protected]). A. Berdondini, M. Bettuzzi, R. Brancaccio, F. Casali, and M. P. Morigi are with the Physics Department, University of Bologna, Italy and also with INFN, Bologna, Italy (e-mail: [email protected]; [email protected]; [email protected]; [email protected]; [email protected]). G. Barca and F. Castrovillari are with Medical Physics, Azienda Ospedaliera, Cosenza, Italy (e-mail: [email protected]; [email protected]). Digital Object Identifier 10.1109/TNS.2008.2004801

I. INTRODUCTION A. The Intra Operative Radiation Therapy

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HE technique of High Dose Radiation—Intra-Operative Radiation Therapy (HDR-IORT) consists of the delivery of irradiation at the time of surgery, where the same incision is used to direct a large single dose of irradiation to a surgically treated area following the removal of a tumour. Some initial experiences of this technique were described in 1905 [1] and 1909 [2] where low energy X-rays were used for patients with cervix cancer and advanced gastric and colon carcinomas. IORT treatment gained supporters between 1930s and 1950s using higher x-ray energies and high doses of radiations [3], [4]. The results were not positive because of the penetration of the radiation beyond the tumour into the normal tissues. The modern approach to IORT began in 1965 at the University of Kyoto [5] with the choice of an electronic beam, generated by a betatron, to deliver a single massive dose (25–30 Gy). Between 1965 and 1990 most clinical experiences with IORT have used electron beams generated by a linear accelerator. Some relevant problems like the transport of the patient during the surgery from the operating room to the radiotherapy departments or the cost of the remodelling of the operating room to include an accelerator and the necessary shielding prevented the increase of IORT [6]. From 1990 the number of the Medical Centers which have activated the IORT approach increased mainly because of the introduction of IORT-dedicated accelerators. The three compact LINACs (Mobetron [7], NOVAC-7 [8], LIAC [9]) are movable machines generating electron beams of variable energy in the range 3–12 MeV. The radiation is delivered through applicators and the system is capable of 3D movements. The high dose rate capability (up to 20 Gy/min) assures the delivery of the dose needed in the treatment in a few minutes. B. Dosimetry in IORT Given its particular characteristics, dedicated IORT accelerators require dose measurements that are different from those required in external radiotherapy treatments. The main reason lies in the fact that in this case a single high dose must be delivered to a target volume whose extension and depth will be determined directly during the operation. Since the possibility of devising a treatment plan using a TPS (Treatment Planning System) is not available, it is necessary to know

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LAMANNA et al.: DOSIMETRY OF HIGH INTENSITY ELECTRON BEAMS

the physical and geometric characteristics of the beam accurately. Defining the physical characteristics of the beam entails both measuring the delivered dose and defining quality control (monitoring) procedures. In any case a much higher dose per pulse (3–13 (cGy-pulse)) will be delivered than occurs with conventional external accelerators, which is typically less then 1 (cGy-pulse). Moreover it is being planned to realize a new accelerator feature for which a thick mobile beam (approximately 1 cm diameter) is delivered. In this way, the beam should be able to move inside the treatment zone in order to irradiate it with high precision, even when the area has a shape other than a circular one. This in progress feature is named incremental irradiation. The ionisation chamber recommended by the standard protocols for radiotherapy cannot be used because of ion recombination inside the gas at high dose rate [10]. Recently some appropriate corrective factors have been tested [11] although the use of ionising chambers turns out to be critical in the dosimetry of electron beams generated by IORT dedicated accelerator. To measure the absorbed dose in water the absolute dosimetric system of Fricke is used. This chemical dosimeter, managed in Italy by the Italian Primary Standard Dosimetry Laboratory (PDSL ENEA-INMRI, Rome), is based on a solution of iron sulphate. The response of the system is independent from the dose-rate [12], [13] but it cannot be used to map bidimensionally the dose because of its large size. The alanine dosimetry [12], which has shown a good degree of compatibility with the Fricke method, can be used as an alternative system The measurements of beam profiles and of isodose curves can be performed using a solid phantom and gaf-chromic films [14] or TLD [15]. However, approximately 24 hours (up to 72) are required to complete all the activated chemical reactions induced by radiation. It should be noted that the gaf-chromic films are the only proposed method able to give an extensive bidimensional image as result. Another interesting method proposed for real-time in vivo dosimetry is the technology with MOSFET or micro-MOSFET [16]. They can be used directly in relative dose measurement, without requiring correction for dose rate. The approach performs an absolute dose measurement, but the MOSFET dosimeters provide only point by point data with limited ability to show bidimensional dose distribution throughout the whole region of interest. All proposed systems can not ensure at the same time a measurement in the form of an extensive digital image, without requiring a dose rate correction in real time. Moreover, there is no instrument able to follow a moving signal as is required to monitor the incremental irradiation. To overcome these problems the authors have conceived a system able to give a response in real time, in the form of a calorimetric phantom, Dosiort, to measure the beam properties (possibility to store, manage and visualize). The system will also be able to follow a moving signal and the measure obtained will be linearly correlated to the delivered dose and not affected by high dose rate. We describe the main characteristics and some preliminary results of the Dosiort System, which was proposed within the framework of a research project of the INFN (Italian National Institute of Nuclear Physics).

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Fig. 1. System design and read-out set-up. Each double layer XY is coupled with photodiode arrays. On the bottom the zoom of the fibrefibres inside a double layer are shown.

II. SYSTEM DESIGN To overcome the problems mentioned in the previous paragraph we have selected as sensitive device the organic plastic scintillators. The first advantage of this choice is the characteristic not to saturate at high dose rate and, secondly, their response is not influenced by changes in temperature, pressure or humidity. The scintillating fibres can be produced in smaller sizes with high spatial resolution. The fast response in light can provide an immediate direct reading and the possibility to make systems for real time applications. The scintillating fibres have been successfully used in the last 10 years to describe high energy beams [17] and tested as dosimeters [18], [19] for X-rays and electron beams. The optimal selection of scintillating fibres in dosimetry applications has also been investigated in the last few years [20]. Recently a double layer of fibres XY has been used to map online the position of the electron beam generated by Novac7 [21], [22]. The good results obtained in the test convinced the authors to study the extension of the system for a dosimetric system conceived for 3D measurement. The new calorimeter is conceived as a box made from a tissue-equivalent material (polystyrene). Inside the box there are six sensitive layers spaced 4 mm apart and set perpendicularly to the Z direction of the incident beam, as shown in Fig. 1. Each layer is composed of a grid consisting of two bundles of 190 scintillating optical fibres having a square cross section of and crossing over one another so as to define a planar 0,5 . detector with an area of approximately 10 10 The light emitted following the interaction of electrons with the scintillating fibres is proportional to the energy absorbed and it is read-out by two photodiode arrays for each bundle. The read-out system is therefore composed of 24 arrays. A dedicated electronic system is able to acquire, process and display the reconstructed electron beam image in real time (within a few seconds). The set-up is thus a solid phantom having a density ap, with sensitive layers of scintillating fibres proaching 1 set at a fixed position in a calorimetric configuration for the containment of electrons of energy 4–12 MeV. The prototype will be able to define the physical and geometrical characteristics of the electron beam (energy, isotropy, homogeneity, etc) and to

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Fig. 3. Isodose regions inside the phantom for an electron beam of energy 8 Mev. An applicator of diameter 40 mm was used.

Fig. 2. Monte Carlo simulation. The electron beam is delivered to the polystyrene phantom (yellow) through the applicator. The green lines represent the photons generated by the interaction of the beam with the air and the sheets inside the applicator. The red lines are electrons generated inside the perspex of the applicator for interactions of the secondary photons.

measure the parameters needed to select the energy, intensity and Monitor Units (MU) for exposure: PDD (Percentage Depth Dose); Beam profiles; Isodose curves; Values of dose for UM (cGy/UM). III. MONTECARLO SIMULATION Geant4 code [23] was used to develop a dedicated Monte Carlo simulation for the purpose of studying and optimising the calorimeter set-up. The electromagnetic low energy processes were included in the simulation. We used the measured beam parameters of Novac7 [8] to simulate the electron beam. The beam was generated at the entrance of the cylindrical perspex applicator and it is propagated inside the cylinder crossing the sheets of material simulated as in the real system. The radiation, produced by the interaction of the beam passing through the material, air, sheets, perspex, was taken into account. At the exit of the applicator the radiation passes through a homogeneous phantom of polystyrene as shown in Fig. 2. The simulated phantom is divided into 1 voxels The voxels are assembled in XY layers, where each row represents and length of one fibre having a cross-section size of 1 20 cm. The energy loss through ionization processes has been integrated for each voxel and converted in dose and number of photons. We studied the distributions of the dose inside Dosiort in 3D form. The response of the scintillating fibres was simulated using the nominal characteristics of the BICRON square scintillating fibres BCF-60. The number of photons collected at the end of each fibre was estimated and used to analyse the dose absorbed as a function of depth.

Fig. 4. Distribution of the number of photons (arbitrary units) collected inside the Y fibres at fixed depths for a beam of energy 8 MeV.

The topology of the phantom was optimised by studying the configuration of Dosiort necessary to measure the beam parameters. In particular, we studied the response in light as a function of depth, in order to arrive at a system that would assure the containment of the delivered beam with typical energy range used in IORT, 4–12 MeV. In Fig. 3 the simulated depth dose for a beam of 8 MeV as a function of one transverse coordinate (Y) is shown. The response of Dosiort was studied considering the number of photons collected along the phantom in each fibre. This parameter corresponds to the read-out of the sensitive layers passed through in the phantom. Fig. 4 shows the distributions of the number of photons collected for electrons of energy 8 MeV. These distributions represent the map of the delivered dose along the phantom in a 3D visualisation. The processing of these data for the selected energies gives the distribution shown in Figs. 5 and 6. The number of photons collected in each sensitive layer for energies falling within the range of energies 4–12 MeV is shown in Fig. 5. The relative curves normalized to the maximum have been used to find the best configuration of Dosiort. We found that the depth intensity curves are well reconstructed using spline interpolation if the sensitive layers are separated by sheets of passive polystyrene of thickness 4 mm. In particular the last two points of each curve are needed to measure the change in slope from 0.2 to zero, with separation less than 5 mm. These requirements fix the selection of granularity for

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Fig. 5. Distribution of the relative number of photons (normalized to the maximum) collected inside the Y fibres for various energies as a function of depth in polystyrene. The markers are shown in the positions found by requiring a good representation of the curves in the energy range 4–12 MeV, The solid lines represent the curve of the spline interpolations.

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Fig. 7. Total number of photons collected in the calorimeter as a function of beam energy in the hypothesis of constant current of the accelerator (1.5 mA).

Fig. 8. Experimental set-up design. Two ribbons of scintillating fibres of different size connected optically at two photodiode arrays.

Fig. 6. Distribution of the absolute dose/pulse in the hypothesis of maximum current (1.5 mA) for the accelerator (lines). The markers show the number of photons (normalized to the maximum) collected inside the Y fibres for various energies as a function of depth in polystyrene.

Dosiort along the beam. The sensitive layers must be positioned at distances of 5 mm along the beam. In Fig. 6 the distributions of the simulated absolute depth dose are superimposed over the number of photons normalized to the maximum of the dose curves. The dose curves were evaluated at the centre of the beam line for each layer and represent the parameters to be measured. The number of photons was estimated by integrating per layer the light collected at the end of the fibres. We observe a full superposition in the energy range 4–12 MeV. The system is therefore capable to reproduce the simulated depth doses. The correlation between the total number of collected photons and the nominal energy of the beam is represented in Fig. 7. The set-up is able to measure the energy of the beam within the range 4–12 MeV using a phantom with a total thickness of 6 cm. The results of our analysis of the simulated data have enabled us to define the best configuration of the calorimeter set-up for our requirements.

IV. TESTS AND RESULTS The elements needed to make Dosiort have been checked recently in a test set-up exposed to an electron beam generated by the accelerator Varian Clinac 2100 [24] at Cosenza (Italy) Hospital. We used 32 square fibres with side of 1 mm and 64 square fibres with side of 0.5 mm. The fibres of 20 cm in length and of type BCF-60, assembled in two “ribbons” produced by Saint Gobain Crystals, were positioned as shown in Fig. 8. Each ribbon is optically coupled to one photodiode array. We selected the Hamamatsu S8865-128 with 128 photodiodes assembled with a pitch of 0.4 mm. The two arrays were read sequentially using the Hamamatsu driver C9118 as shown in Fig. 9. The dynamc range of the readout is connected directly to the array of photodiodes S8865. The maximum value of the response is 4.8 V. This value fixes the maximum number of photons at the end of each fibre which can be converted in charge inside the electronics for each acquisition. Two energies of the beam were selected for the test, 9 and 12 to irradiate MeV. The viewing field was selected 15 15 the two ribbons uniformly. The absorbed doses were determined in water at the reference depths, using the PTW Tandem dual channel Electrometer, the PTW Freiburg TM31010 ionization chamber and the PTW MP3 water phantom.

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Fig. 11. Voltage response of the 128 photodiodes of pitch 0.4 mm, coupled to the ribbon of scintillating fibre of size 0.5 mm, as a function of the photodiode channel and polystyrene depth.

Fig. 9. Experimental set-up. Two ribbons of scintillating fibres of different sizes connected optically at two photodiode arrays S8865-128 and two drivers C9118.

Fig. 12. Response of the 128 photodiodes of pitch 0.4 mm as a function of the photodiode channel and polystyrene depth. The response was normalized to the dose measured with standard ionization chamber at the build-up and corrected by geometrical effect.

Fig. 10. Comparison between the voltage response of 1 mm fibres (left side) and 0,5 mm fibres(right side) irradiated with electron beam of energy 9 MeV.

The data were taken in different acquisition steps. In each step we changed the geometry of the setup superimposing over the previous configuration a sheet of polystyrene of 4 mm in thickness. In such a way we simulate a homogeneous phantom with measurements at different depths. The final sensitivity of the multichannel scintillating fibre array, defined as the output voltage of each channel for a deposited energy in the scintillating fibre, is affected by various contributions such as the production and the transmission of the light in the fibre, the geometrical and optical coupling between the fibres and the photodiode array, and the electronic gain. Fig. 10 shows the output voltages of the 256 photodiode coupled to the 32 fibres of 1 mm (left side) and the 64 fibres of 0.5 mm (right side). The data were taken using an electron beam of energy 9 MeV, positioning the fibres at a fixed depth of 2.2 cm. The first observation is the relevant different sensitivity per channel. The measurement of the sensitivity for each channel is needed to assure a uniform response of the calorimeter. The second observation is the saturation of the channels coupled to the fibres of 1 mm. The light collected in this case produces an electronic response reaching the maximum value of

4.8 V. We stress that the saturation is connected to the electronics. The channels coupled to the fibres of 0.5 mm are able to detect the electron beam generated by the Clinac 2100 accelerator. We decided to continue the analysis of the data considering only the fibres of size 0.5 mm because the results by 1 mm fibres are saturated. The response of the set-up was studied at different depths. Each depth was tested as a sequence of 100 acquisitions. The same configuration of the setup was used to measure the system output without beam delivering in order to estimate the background signal. The voltage distribution after the subtraction of the background is shown in Fig. 11 as a function of the channel number and the depth in polystyrene. Large fluctuations between channels are visible in the plots. The optical-coupling between fibres and photodiodes produces this phenomenon because both fibres and photodiodes have a different pitch. This effect is well known as a geometrical factor and can be easily evaluated and corrected with dedicated software. Moreover, for each channel we evaluated the relative calibration factor using its distribution in depth. We assigned the same absorbed energy to all the fibres at the build-up. The energy was estimated by integrating along the fibre the dose measured through the ionization chamber and the electrometer. The calibration factor was evaluated for each photodiode as the ratio between the absorbed energy and the response in volt at the

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Fig. 13. Absolute depth dose measurements. Our results are compared to the curves obtained with standard ionization chamber and electrometer for 9 and 12 MeV. The errors are included in the marker side.

V. CONCLUSION

Fig. 14. Ouput voltage as a function of the absorbed energy in the scintillating fibres. The markers represent the average voltage between the working photodiodes as a function of the dose absorbed at different depths. The line crossing the poins is extrapolated up to the dashed lines to find the upper limit of the dynamic range of the system. The dashed line, at 4.5 V, represents the electronic saturation after the subtraction of the background (0.3 V).

Dosiort has been optimised by means of the Monte Carlo study to realize a 3D dosimetry system for IORT. The system is able to monitor an electron beam in real time and to measure beam energy, providing digital data. Dosiort is also able to map the isodose curves in depth. The read-out configuration, tested to an electron beam generated by the Varian Clinac 2100 DHX, is able to measure doses up to about 1.3 (cGy-pulse), delivered uniformly on 12 cm of scintillating fibres of size 0.5 mm. The realization of the 3D dosimeter must take into account these results. The maximum dose which can be delivered by dedicated IORT accelerator can be 10 (cGy-pulse). We are now building Dosiort, studying the possibility to increase its dynamic readout range. REFERENCES

build-up. The application of the calibration factor for each measured channel to all the data taken produced the absolute evaluation of the dose absorbed in each section of the fibre read through the photodiode. The results are shown in Fig. 12. This method is able to map the dose in depth and orthogonally to the beam line. The comparison between our results and the curves measured using standard dosimeters, for both energies 9 and 12 MeV, is represented in Fig. 13. A good agreement is shown up to 45 mm of water equivalent depth. The response is heavily affected by the background for greater depths. The linearity of our system was studied estimating the average voltage response for the photodiodes coupled with the scintillating fibres The fibres were exposed uniformly at different depths. In Fig. 14 the correlation between the output voltage and the energy absorbed in the fibre is represented. The linearity is guaranteed up to the dose of 0.8 (cGy-pulse) uniformly distributed in 12 cm of scintillating fibre of size 0.5 mm.

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