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Development of a treatment planning system for BNCT based on positron emission tomography data: preliminary results
Nuclear Instruments and Methods in Physics Research B 213 (2004) 637–640 www.elsevier.com/locate/nimb
Development of a treatment planning system for BNCT based on positron emission tomography data: preliminary results N. Cerullo
a,b,*
, G.G. Daquino
a,c
, L. Muzi a, J. Esposito
d
a
d
DIMNP, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy b DITEC, University of Genova, Genova, Italy c JRC Petten, European Commission, Petten, The Netherlands Italian National Institute of Nuclear Physics, Legnaro National Laboratory, Legnaro, Italy
Abstract Present standard treatment planning (TP) for glioblastoma multiforme (GBM – a kind of brain tumor), used in all boron neutron capture therapy (BNCT) trials, requires the construction (based on CT and/or MRI images) of a 3D model of the patient head, in which several regions, corresponding to different anatomical structures, are identified. The model is then employed by a computer code to simulate radiation transport in human tissues. The assumption is always made that considering a single value of boron concentration for each specific region will not lead to significant errors in dose computation. The concentration values are estimated ‘‘indirectly’’, on the basis of previous experience and blood sample analysis. This paper describes an original approach, with the introduction of data on the in vivo boron distribution, acquired by a positron emission tomography (PET) scan after labeling the BPA (borono-phenylalanine) with the positron emitter 18 F. The feasibility of this approach was first tested with good results using the code CARONTE. Now a complete TPS is under development. The main features of the first version of this code are described and the results of a preliminary study are presented. Significant differences in dose computation arise when the two different approaches (‘‘standard’’ and ‘‘PET-based’’) are applied to the TP of the same GBM case. 2003 Elsevier B.V. All rights reserved. PACS: 87.53.T; 87.59.V; 07.05.T; 87.53.P,Q Keywords: Boron neutron capture therapy (BNCT); Treatment planning system; Heterogeneous boron distribution; Boron dose distribution; Positron emission tomography (PET); MCNP
1. Introduction
* Corresponding author. Address: DIMNP, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy. Tel.: +39-50-836638; fax: +39-50-836665. E-mail address: [email protected] (N. Cerullo).
Immediately after the discovery of neutrons by Chadwick, in 1936 Locher proposed the general concept of neutron capture therapy (NCT). Afterwards, the interest was focused, for several reasons, on the use of boron as neutron capture
0168-583X/$ - see front matter 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-583X(03)01668-9
638
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
element; herein the name boron neutron capture therapy (BNCT). Ever since the beginning, when it was just ‘‘Curietherapy’’, great relevance was given in radiotherapy to obtaining an evaluation of the effects of radiation on both tumor and healthy tissue. In the field of BNCT this problem is of particular concern because neutrons produce many different nuclear reactions, each with a different physical and biological dose. Treatment planning systems (TPSs), by simulating the interaction of radiation with tissues, provide physicists and doctors with precious indications (e.g. optimal irradiation time and patient positioning) and are therefore essential to deliver appropriate therapeutic treatment, ensuring that the dose to healthy tissues will be within the allowed limits. Particularly, present standard TP for glioblastoma multiforme (GBM – a kind of brain tumor), used in all BNCT trials, is based on the reconstruction (by CT and/or MRI images) of a 3D model of the patient head. This model, with the introduction of data on the boron distribution is implemented in a computer code which then simulates the interaction of radiation with tissues, computing the spatial distribution of the dose delivered to each anatomical structure. Several research centers in the world have been involved in the development of TPSs and great efforts have been made in recent years to optimize them for BNCT requirements. At present, the most widely used are: • MAC-NCTPLAN (developed by MIT and based on a voxel reconstruction technique) [1]; • BNCT_rtpe (developed by INEEL, first used at BNL and based on a B-spline reconstruction technique) [2]; • SERA (still under development at INEEL; it constitutes the new version of BNCT_rtpe and is based on a pixel-by-pixel reconstruction technique) [3]. It is important to note that only two values of boron concentration (estimated by means of an ‘‘educated guess’’ based on blood sample analysis) are assumed to be uniformly distributed in tumor
Fig. 1. Central PET transaxial slice (a) and related distribution (b), calculated with CARONTE.
10
B dose
and healthy tissue, respectively. This situation was dictated by the absence of other information on the real in vivo distribution of the boron in the patient head. Five years ago, a group of Japanese researchers were able to describe through positron emission tomography (PET) the in vivo 10 B distribution (Fig. 1(a)), labeling the boron compound (BPA) with 18 F (a positron emitter) and developing a model to estimate the 10 B concentration value from the counts associated with each voxel by the PET tomography [4]. Our idea was to link the PET information, related to the in vivo boron distribution, to the 3D modeling for the Monte Carlo simulation. This idea led to the development of an original simplified TPS named CARONTE that creates automatically an input file for the MCNP radiation transport code [5]. Recently, we decided to upgrade CARONTE, creating a more user-friendly code and revisiting the transport neutron behavior due to the 10 B distribution. A new TPS is under development for this purpose.
2. Materials and methods The core of CARONTE is the Monte Carlo general-purpose code MCNP [6], which can calculate the dose released in the head model, previously created by exploiting the PET data for the boron distribution and a simplified head geometry (Snyder phantom). After the Monte Carlo calcu-
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
lations, CARONTE can display the neutronic results. The distribution of the dose released by the 10 B reaction in the head model is reported in Fig. 1(b) (grayscale). Although CARONTE proved the feasibility of this new approach to TP, it presented some shortcomings (DOS working environment, not user-friendly 3D Model creation session, huge MCNP input file with thousands of independent tally cells). Therefore we decided to develop a new TPS (provisionally named BDTPS – Boron Distribution TPS), which uses the Monte Carlo N-Particle (MCNPX) code to compute the three-dimensional dose distribution in the patient head taking the real heterogeneous distribution of boron into account. BDTPS works under Windows , with a greatly enhanced ease of use in the 3D-Model construction phase. However, MCNPX remains the core of the system, performing the dose and flux calculations. The pre-processing phase has undergone major modifications: a 3D geometric and a Monte Carlo model of the patient head are now created. The 3D geometric model is built through the CT images. The geometry and material information associated with the 3D Model is employed by BDTPS to automatically build the MCNPX Model. The heterogeneous boron distribution, in combination with neutron flux and kerma factors, leads to the dose calculation. To this purpose, BDTPS implements a third, completely original model (Boron Model), i.e. a data structure containing the boron concentration values associated to each pixel of the patientÕs PET slices. This permits a more accurate computation of the dose due to the 10 B reaction. To further improve the accuracy of dose estimation, MCNPX can be used to model the air gap between the irradiation port and the 3-D anatomical model, a fairly difficult task when SERA (or Bnct_rpte) is used, because air is not present in the default material file. However, at present new SERA-modified calculations are in progress at the JRC-IE in Petten, where the air gap could be an influential parameter. The first results show an evident variation in the recoil proton dose-depth profile.
639
Furthermore, a comparative study is being carried out using CARONTE to evaluate the extent to which this new approach influences the results of the simulation in terms of macroscopic
Fig. 2. Dose-rate distribution maps for slice 2 of the Snyder phantom as computed according to the ‘‘standard’’ approach (a) and to the innovative approach first implemented in CARONTE (b). (c) shows the map of the pixel-by-pixel difference between (a) and (b). Namely, the dose-rate value in each pixel of (b) has been subtracted from the value of the corresponding pixel in (a).
640
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
computed-dose distribution. Several simulations pertaining to the same glioblastoma multiforme (GBM) case, but based on different assumptions for the macroscopic distribution of 10 B nuclei, were run and the preliminary results are presented in the following section.
3. Results and discussion To provide an example of how the comparative study mentioned in the previous section was carried out, Fig. 2 shows the computed dose-rate maps (for the same slice) obtained employing the ‘‘standard’’ approach (a) and the ‘‘PET based’’ approach (b) as implemented by CARONTE. The computed-dose spatial distributions appear to differ markedly in the two cases. Particularly, with the ‘‘standard’’ approach the isodose regions are much more regular in shape and higher dose-rate values are more strictly confined within the tumor. In addition to these ‘‘qualitative’’ differences, Fig. 2(c) shows the distribution of the pixel-bypixel difference in computed dose between the previous two images. More specifically, the dose value in each pixel in (b) has been subtracted from the value of the corresponding pixel in (a). The results show that at the tumor margin the ‘‘standard’’ model significantly underestimates (up to 68% of the maximum computed dose value) the dose to healthy tissue with respect to the ‘‘PET based’’ model.
4. Conclusions Several years ago a research work carried out by Pisa and Genova Universities (Italy) resulted in a proposal for an original approach to BNCT treatment planning (TP) for glioblastoma multiforme (GBM), using PET results (obtained by means of an original Japanese technique). The
code CARONTE proved the feasibility of this approach. Now a Windows -based code named BDTPS has been conceived and is under development. The results of a comparative study show that the differences between this original approach and the approach currently adopted by all TPS in BNCT can in some cases lead to significant discrepancies in terms of computed dose. This suggests that the possibility to use more realistic boron-distribution maps acquired by means of PET imaging in BNCT treatment planning, deserves more consideration and further investigation, especially from the viewpoint of a future application to certain kinds of tumor (e.g. lung cancer). Acknowledgements Thanks are due to Prof. S. Ueda (Department of Neurosurgery, Kyoto University Hospital) for supplying the PET images, to Professors G. Curzio and M. Mazzini, former and present director of the Italian Project on BNCT and to Dr. D. Bufalino (SORIT Srl) for useful discussions. References [1] R.G Zamenhof, E. Redmond II, G.R. Solares, D. Katz, K.J. Riley, W.S. Kiger, O.K. Harling, Int. J. Radiat. Onc. Biol. Phys. 35 (1996) 383. [2] D.W. Nigg, F.J. Wheeler, D.E. Wessol, J. Capala, M. Chada, J. Neuro-Oncol. 33 (1997) 93. [3] D.W. Nigg, C.A. Wemple, D.E. Wessol, F.J. Wheeler, Trans. ANS 80 (1999) 66. [4] Y. Imahori, S. Ueda, Y. Ohmori, T. Kusuki, K. Ono, R. Fujii, T. Ido, J. Nucl. Med. 39 (1998) 325. [5] N. Cerullo, G. Daquino, in: Proc. 8th Int. Symp. on Neutron Capture Therapy for Cancer, La Jolla (CA) 1998, Frontiers in Neutron Capture Therapy, Vol. 1, p. 95. [6] J.F. Briesmeister, MCNP – A general Monte Carlo Nparticle transport code, LA12625-M, Version 4B, Los Alamos National Laboratory, 1997.
Development of a treatment planning system for BNCT based on positron emission tomography data: preliminary results N. Cerullo
a,b,*
, G.G. Daquino
a,c
, L. Muzi a, J. Esposito
d
a
d
DIMNP, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy b DITEC, University of Genova, Genova, Italy c JRC Petten, European Commission, Petten, The Netherlands Italian National Institute of Nuclear Physics, Legnaro National Laboratory, Legnaro, Italy
Abstract Present standard treatment planning (TP) for glioblastoma multiforme (GBM – a kind of brain tumor), used in all boron neutron capture therapy (BNCT) trials, requires the construction (based on CT and/or MRI images) of a 3D model of the patient head, in which several regions, corresponding to different anatomical structures, are identified. The model is then employed by a computer code to simulate radiation transport in human tissues. The assumption is always made that considering a single value of boron concentration for each specific region will not lead to significant errors in dose computation. The concentration values are estimated ‘‘indirectly’’, on the basis of previous experience and blood sample analysis. This paper describes an original approach, with the introduction of data on the in vivo boron distribution, acquired by a positron emission tomography (PET) scan after labeling the BPA (borono-phenylalanine) with the positron emitter 18 F. The feasibility of this approach was first tested with good results using the code CARONTE. Now a complete TPS is under development. The main features of the first version of this code are described and the results of a preliminary study are presented. Significant differences in dose computation arise when the two different approaches (‘‘standard’’ and ‘‘PET-based’’) are applied to the TP of the same GBM case. 2003 Elsevier B.V. All rights reserved. PACS: 87.53.T; 87.59.V; 07.05.T; 87.53.P,Q Keywords: Boron neutron capture therapy (BNCT); Treatment planning system; Heterogeneous boron distribution; Boron dose distribution; Positron emission tomography (PET); MCNP
1. Introduction
* Corresponding author. Address: DIMNP, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy. Tel.: +39-50-836638; fax: +39-50-836665. E-mail address: [email protected] (N. Cerullo).
Immediately after the discovery of neutrons by Chadwick, in 1936 Locher proposed the general concept of neutron capture therapy (NCT). Afterwards, the interest was focused, for several reasons, on the use of boron as neutron capture
0168-583X/$ - see front matter 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0168-583X(03)01668-9
638
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
element; herein the name boron neutron capture therapy (BNCT). Ever since the beginning, when it was just ‘‘Curietherapy’’, great relevance was given in radiotherapy to obtaining an evaluation of the effects of radiation on both tumor and healthy tissue. In the field of BNCT this problem is of particular concern because neutrons produce many different nuclear reactions, each with a different physical and biological dose. Treatment planning systems (TPSs), by simulating the interaction of radiation with tissues, provide physicists and doctors with precious indications (e.g. optimal irradiation time and patient positioning) and are therefore essential to deliver appropriate therapeutic treatment, ensuring that the dose to healthy tissues will be within the allowed limits. Particularly, present standard TP for glioblastoma multiforme (GBM – a kind of brain tumor), used in all BNCT trials, is based on the reconstruction (by CT and/or MRI images) of a 3D model of the patient head. This model, with the introduction of data on the boron distribution is implemented in a computer code which then simulates the interaction of radiation with tissues, computing the spatial distribution of the dose delivered to each anatomical structure. Several research centers in the world have been involved in the development of TPSs and great efforts have been made in recent years to optimize them for BNCT requirements. At present, the most widely used are: • MAC-NCTPLAN (developed by MIT and based on a voxel reconstruction technique) [1]; • BNCT_rtpe (developed by INEEL, first used at BNL and based on a B-spline reconstruction technique) [2]; • SERA (still under development at INEEL; it constitutes the new version of BNCT_rtpe and is based on a pixel-by-pixel reconstruction technique) [3]. It is important to note that only two values of boron concentration (estimated by means of an ‘‘educated guess’’ based on blood sample analysis) are assumed to be uniformly distributed in tumor
Fig. 1. Central PET transaxial slice (a) and related distribution (b), calculated with CARONTE.
10
B dose
and healthy tissue, respectively. This situation was dictated by the absence of other information on the real in vivo distribution of the boron in the patient head. Five years ago, a group of Japanese researchers were able to describe through positron emission tomography (PET) the in vivo 10 B distribution (Fig. 1(a)), labeling the boron compound (BPA) with 18 F (a positron emitter) and developing a model to estimate the 10 B concentration value from the counts associated with each voxel by the PET tomography [4]. Our idea was to link the PET information, related to the in vivo boron distribution, to the 3D modeling for the Monte Carlo simulation. This idea led to the development of an original simplified TPS named CARONTE that creates automatically an input file for the MCNP radiation transport code [5]. Recently, we decided to upgrade CARONTE, creating a more user-friendly code and revisiting the transport neutron behavior due to the 10 B distribution. A new TPS is under development for this purpose.
2. Materials and methods The core of CARONTE is the Monte Carlo general-purpose code MCNP [6], which can calculate the dose released in the head model, previously created by exploiting the PET data for the boron distribution and a simplified head geometry (Snyder phantom). After the Monte Carlo calcu-
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
lations, CARONTE can display the neutronic results. The distribution of the dose released by the 10 B reaction in the head model is reported in Fig. 1(b) (grayscale). Although CARONTE proved the feasibility of this new approach to TP, it presented some shortcomings (DOS working environment, not user-friendly 3D Model creation session, huge MCNP input file with thousands of independent tally cells). Therefore we decided to develop a new TPS (provisionally named BDTPS – Boron Distribution TPS), which uses the Monte Carlo N-Particle (MCNPX) code to compute the three-dimensional dose distribution in the patient head taking the real heterogeneous distribution of boron into account. BDTPS works under Windows , with a greatly enhanced ease of use in the 3D-Model construction phase. However, MCNPX remains the core of the system, performing the dose and flux calculations. The pre-processing phase has undergone major modifications: a 3D geometric and a Monte Carlo model of the patient head are now created. The 3D geometric model is built through the CT images. The geometry and material information associated with the 3D Model is employed by BDTPS to automatically build the MCNPX Model. The heterogeneous boron distribution, in combination with neutron flux and kerma factors, leads to the dose calculation. To this purpose, BDTPS implements a third, completely original model (Boron Model), i.e. a data structure containing the boron concentration values associated to each pixel of the patientÕs PET slices. This permits a more accurate computation of the dose due to the 10 B reaction. To further improve the accuracy of dose estimation, MCNPX can be used to model the air gap between the irradiation port and the 3-D anatomical model, a fairly difficult task when SERA (or Bnct_rpte) is used, because air is not present in the default material file. However, at present new SERA-modified calculations are in progress at the JRC-IE in Petten, where the air gap could be an influential parameter. The first results show an evident variation in the recoil proton dose-depth profile.
639
Furthermore, a comparative study is being carried out using CARONTE to evaluate the extent to which this new approach influences the results of the simulation in terms of macroscopic
Fig. 2. Dose-rate distribution maps for slice 2 of the Snyder phantom as computed according to the ‘‘standard’’ approach (a) and to the innovative approach first implemented in CARONTE (b). (c) shows the map of the pixel-by-pixel difference between (a) and (b). Namely, the dose-rate value in each pixel of (b) has been subtracted from the value of the corresponding pixel in (a).
640
N. Cerullo et al. / Nucl. Instr. and Meth. in Phys. Res. B 213 (2004) 637–640
computed-dose distribution. Several simulations pertaining to the same glioblastoma multiforme (GBM) case, but based on different assumptions for the macroscopic distribution of 10 B nuclei, were run and the preliminary results are presented in the following section.
3. Results and discussion To provide an example of how the comparative study mentioned in the previous section was carried out, Fig. 2 shows the computed dose-rate maps (for the same slice) obtained employing the ‘‘standard’’ approach (a) and the ‘‘PET based’’ approach (b) as implemented by CARONTE. The computed-dose spatial distributions appear to differ markedly in the two cases. Particularly, with the ‘‘standard’’ approach the isodose regions are much more regular in shape and higher dose-rate values are more strictly confined within the tumor. In addition to these ‘‘qualitative’’ differences, Fig. 2(c) shows the distribution of the pixel-bypixel difference in computed dose between the previous two images. More specifically, the dose value in each pixel in (b) has been subtracted from the value of the corresponding pixel in (a). The results show that at the tumor margin the ‘‘standard’’ model significantly underestimates (up to 68% of the maximum computed dose value) the dose to healthy tissue with respect to the ‘‘PET based’’ model.
4. Conclusions Several years ago a research work carried out by Pisa and Genova Universities (Italy) resulted in a proposal for an original approach to BNCT treatment planning (TP) for glioblastoma multiforme (GBM), using PET results (obtained by means of an original Japanese technique). The
code CARONTE proved the feasibility of this approach. Now a Windows -based code named BDTPS has been conceived and is under development. The results of a comparative study show that the differences between this original approach and the approach currently adopted by all TPS in BNCT can in some cases lead to significant discrepancies in terms of computed dose. This suggests that the possibility to use more realistic boron-distribution maps acquired by means of PET imaging in BNCT treatment planning, deserves more consideration and further investigation, especially from the viewpoint of a future application to certain kinds of tumor (e.g. lung cancer). Acknowledgements Thanks are due to Prof. S. Ueda (Department of Neurosurgery, Kyoto University Hospital) for supplying the PET images, to Professors G. Curzio and M. Mazzini, former and present director of the Italian Project on BNCT and to Dr. D. Bufalino (SORIT Srl) for useful discussions. References [1] R.G Zamenhof, E. Redmond II, G.R. Solares, D. Katz, K.J. Riley, W.S. Kiger, O.K. Harling, Int. J. Radiat. Onc. Biol. Phys. 35 (1996) 383. [2] D.W. Nigg, F.J. Wheeler, D.E. Wessol, J. Capala, M. Chada, J. Neuro-Oncol. 33 (1997) 93. [3] D.W. Nigg, C.A. Wemple, D.E. Wessol, F.J. Wheeler, Trans. ANS 80 (1999) 66. [4] Y. Imahori, S. Ueda, Y. Ohmori, T. Kusuki, K. Ono, R. Fujii, T. Ido, J. Nucl. Med. 39 (1998) 325. [5] N. Cerullo, G. Daquino, in: Proc. 8th Int. Symp. on Neutron Capture Therapy for Cancer, La Jolla (CA) 1998, Frontiers in Neutron Capture Therapy, Vol. 1, p. 95. [6] J.F. Briesmeister, MCNP – A general Monte Carlo Nparticle transport code, LA12625-M, Version 4B, Los Alamos National Laboratory, 1997.