Journal Articles
2019
Kim, S. Peter; Cohalan, Claire; Kopek, Neil; Enger, Shirin A.
A guide to 90Y radioembolization and its dosimetry Journal Article
In: Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB), vol. 68, pp. 132–145, 2019, ISSN: 1724-191X.
Abstract | Links | BibTeX | Tags: (90)Y, Clinical Background, Computer-Assisted, Dosimetry, Embolization, Humans, Radioembolization, Radiometry, Radiotherapy Planning, Therapeutic, Yttrium Radioisotopes
@article{kim_guide_2019,
title = {A guide to 90Y radioembolization and its dosimetry},
author = {S. Peter Kim and Claire Cohalan and Neil Kopek and Shirin A. Enger},
doi = {10.1016/j.ejmp.2019.09.236},
issn = {1724-191X},
year = {2019},
date = {2019-12-01},
journal = {Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB)},
volume = {68},
pages = {132--145},
abstract = {Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization's treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization's dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization's intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.},
keywords = {(90)Y, Clinical Background, Computer-Assisted, Dosimetry, Embolization, Humans, Radioembolization, Radiometry, Radiotherapy Planning, Therapeutic, Yttrium Radioisotopes},
pubstate = {published},
tppubtype = {article}
}
Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization’s treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization’s dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization’s intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.2017
DeCunha, Joseph M.; Janicki, Christian; Enger, Shirin A.
A retrospective analysis of catheter-based sources in intravascular brachytherapy Journal Article
In: Brachytherapy, vol. 16, no. 3, pp. 586–596, 2017, ISSN: 1538-4721.
Abstract | Links | BibTeX | Tags: Attenuation, Brachytherapy, Dose, Dosimetry, Intracoronary, Intravascular, Physics, Planning, Restenosis, Treatment
@article{decunha_retrospective_2017,
title = {A retrospective analysis of catheter-based sources in intravascular brachytherapy},
author = {Joseph M. DeCunha and Christian Janicki and Shirin A. Enger},
url = {https://www.sciencedirect.com/science/article/pii/S1538472117300077},
doi = {10.1016/j.brachy.2017.01.004},
issn = {1538-4721},
year = {2017},
date = {2017-05-01},
urldate = {2017-05-01},
journal = {Brachytherapy},
volume = {16},
number = {3},
pages = {586--596},
abstract = {Purpose
Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.
Methods and Materials
A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.
Results
Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.
Conclusions
Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.},
keywords = {Attenuation, Brachytherapy, Dose, Dosimetry, Intracoronary, Intravascular, Physics, Planning, Restenosis, Treatment},
pubstate = {published},
tppubtype = {article}
}
Purpose
Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.
Methods and Materials
A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.
Results
Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.
Conclusions
Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.2016
Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan; Naqa, Issam El
Proton and light ion RBE for the induction of direct DNA double strand breaks Journal Article
In: Medical Physics, vol. 43, no. 5, pp. 2131–2140, 2016, ISSN: 2473-4209, (_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1118/1.4944870).
Abstract | Links | BibTeX | Tags: biological effects of ionising particles, biomolecular effects of radiation, Cell Nucleus, cell nucleus model, cellular effects of radiation, DNA, DNA double-strand breaks, Dosimetry, Dosimetry/exposure assessment, Energy transfer, Genomics, Ion beams, Ion radiation effects, Monte Carlo calculations, Monte Carlo methods, Monte Carlo simulations, Monte Carlo track structure, Protons, RBE, Schottky barriers, Scintigraphy
@article{pater_proton_2016b,
title = {Proton and light ion RBE for the induction of direct DNA double strand breaks},
author = {Piotr Pater and Gloria Bäckstöm and Fernanda Villegas and Anders Ahnesjö and Shirin A. Enger and Jan Seuntjens and Issam El Naqa},
url = {https://aapm.onlinelibrary.wiley.com/doi/abs/10.1118/1.4944870},
doi = {10.1118/1.4944870},
issn = {2473-4209},
year = {2016},
date = {2016-01-01},
urldate = {2021-09-07},
journal = {Medical Physics},
volume = {43},
number = {5},
pages = {2131--2140},
abstract = {Purpose: To present and characterize a Monte Carlo (MC) tool for the simulation of the relative biological effectiveness for the induction of direct DNA double strand breaks () for protons and light ions. Methods: The MC tool uses a pregenerated event-by-event tracks library of protons and light ions that are overlaid on a cell nucleus model. The cell nucleus model is a cylindrical arrangement of nucleosome structures consisting of 198 DNA base pairs. An algorithm relying on k-dimensional trees and cylindrical symmetries is used to search coincidences of energy deposition sites with volumes corresponding to the sugar–phosphate backbone of the DNA molecule. Strand breaks (SBs) are scored when energy higher than a threshold is reached in these volumes. Based on the number of affected strands, they are categorized into either single strand break (SSB) or double strand break (DSB) lesions. The number of SBs composing each lesion (i.e., its size) is also recorded. is obtained by taking the ratio of DSB yields of a given radiation field to a 60Co field. The MC tool was used to obtain SSB yields, DSB yields, and as a function of linear energy transfer (LET) for protons (1H+), 4He2+, 7Li3+, and 12C6+ ions. Results: For protons, the SSB yields decreased and the DSB yields increased with LET. At ≈24.5 keV μm−1, protons generated 15% more DSBs than 12C6+ ions. The varied between 1.24 and 1.77 for proton fields between 8.5 and 30.2 keV μm−1, and it was higher for iso-LET ions with lowest atomic number. The SSB and DSB lesion sizes showed significant differences for all radiation fields. Generally, the yields of SSB lesions of sizes ≥2 and the yields of DSB lesions of sizes ≥3 increased with LET and increased for iso-LET ions of lower atomic number. On the other hand, the ratios of SSB to DSB lesions of sizes 2–4 did not show variability with LET nor projectile atomic number, suggesting that these metrics are independent of the radiation quality. Finally, a variance of up to 8% in the DSB yields was observed as a function of the particle incidence angle on the cell nucleus. This simulation effect is due to the preferential alignment of ion tracks with the DNA nucleosomes at specific angles. Conclusions: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate . In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.},
note = {_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1118/1.4944870},
keywords = {biological effects of ionising particles, biomolecular effects of radiation, Cell Nucleus, cell nucleus model, cellular effects of radiation, DNA, DNA double-strand breaks, Dosimetry, Dosimetry/exposure assessment, Energy transfer, Genomics, Ion beams, Ion radiation effects, Monte Carlo calculations, Monte Carlo methods, Monte Carlo simulations, Monte Carlo track structure, Protons, RBE, Schottky barriers, Scintigraphy},
pubstate = {published},
tppubtype = {article}
}
Purpose: To present and characterize a Monte Carlo (MC) tool for the simulation of the relative biological effectiveness for the induction of direct DNA double strand breaks () for protons and light ions. Methods: The MC tool uses a pregenerated event-by-event tracks library of protons and light ions that are overlaid on a cell nucleus model. The cell nucleus model is a cylindrical arrangement of nucleosome structures consisting of 198 DNA base pairs. An algorithm relying on k-dimensional trees and cylindrical symmetries is used to search coincidences of energy deposition sites with volumes corresponding to the sugar–phosphate backbone of the DNA molecule. Strand breaks (SBs) are scored when energy higher than a threshold is reached in these volumes. Based on the number of affected strands, they are categorized into either single strand break (SSB) or double strand break (DSB) lesions. The number of SBs composing each lesion (i.e., its size) is also recorded. is obtained by taking the ratio of DSB yields of a given radiation field to a 60Co field. The MC tool was used to obtain SSB yields, DSB yields, and as a function of linear energy transfer (LET) for protons (1H+), 4He2+, 7Li3+, and 12C6+ ions. Results: For protons, the SSB yields decreased and the DSB yields increased with LET. At ≈24.5 keV μm−1, protons generated 15% more DSBs than 12C6+ ions. The varied between 1.24 and 1.77 for proton fields between 8.5 and 30.2 keV μm−1, and it was higher for iso-LET ions with lowest atomic number. The SSB and DSB lesion sizes showed significant differences for all radiation fields. Generally, the yields of SSB lesions of sizes ≥2 and the yields of DSB lesions of sizes ≥3 increased with LET and increased for iso-LET ions of lower atomic number. On the other hand, the ratios of SSB to DSB lesions of sizes 2–4 did not show variability with LET nor projectile atomic number, suggesting that these metrics are independent of the radiation quality. Finally, a variance of up to 8% in the DSB yields was observed as a function of the particle incidence angle on the cell nucleus. This simulation effect is due to the preferential alignment of ion tracks with the DNA nucleosomes at specific angles. Conclusions: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate . In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.
Journal Articles
2019
Kim, S. Peter; Cohalan, Claire; Kopek, Neil; Enger, Shirin A.
A guide to 90Y radioembolization and its dosimetry Journal Article
In: Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB), vol. 68, pp. 132–145, 2019, ISSN: 1724-191X.
Abstract | Links | BibTeX | Tags: (90)Y, Clinical Background, Computer-Assisted, Dosimetry, Embolization, Humans, Radioembolization, Radiometry, Radiotherapy Planning, Therapeutic, Yttrium Radioisotopes
@article{kim_guide_2019,
title = {A guide to 90Y radioembolization and its dosimetry},
author = {S. Peter Kim and Claire Cohalan and Neil Kopek and Shirin A. Enger},
doi = {10.1016/j.ejmp.2019.09.236},
issn = {1724-191X},
year = {2019},
date = {2019-12-01},
journal = {Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB)},
volume = {68},
pages = {132--145},
abstract = {Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization's treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization's dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization's intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.},
keywords = {(90)Y, Clinical Background, Computer-Assisted, Dosimetry, Embolization, Humans, Radioembolization, Radiometry, Radiotherapy Planning, Therapeutic, Yttrium Radioisotopes},
pubstate = {published},
tppubtype = {article}
}
Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization’s treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization’s dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization’s intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.
2017
DeCunha, Joseph M.; Janicki, Christian; Enger, Shirin A.
A retrospective analysis of catheter-based sources in intravascular brachytherapy Journal Article
In: Brachytherapy, vol. 16, no. 3, pp. 586–596, 2017, ISSN: 1538-4721.
Abstract | Links | BibTeX | Tags: Attenuation, Brachytherapy, Dose, Dosimetry, Intracoronary, Intravascular, Physics, Planning, Restenosis, Treatment
@article{decunha_retrospective_2017,
title = {A retrospective analysis of catheter-based sources in intravascular brachytherapy},
author = {Joseph M. DeCunha and Christian Janicki and Shirin A. Enger},
url = {https://www.sciencedirect.com/science/article/pii/S1538472117300077},
doi = {10.1016/j.brachy.2017.01.004},
issn = {1538-4721},
year = {2017},
date = {2017-05-01},
urldate = {2017-05-01},
journal = {Brachytherapy},
volume = {16},
number = {3},
pages = {586--596},
abstract = {Purpose
Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.
Methods and Materials
A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.
Results
Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.
Conclusions
Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.},
keywords = {Attenuation, Brachytherapy, Dose, Dosimetry, Intracoronary, Intravascular, Physics, Planning, Restenosis, Treatment},
pubstate = {published},
tppubtype = {article}
}
Purpose
Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.
Methods and Materials
A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.
Results
Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.
Conclusions
Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.
Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.
Methods and Materials
A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.
Results
Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.
Conclusions
Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.
2016
Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan; Naqa, Issam El
Proton and light ion RBE for the induction of direct DNA double strand breaks Journal Article
In: Medical Physics, vol. 43, no. 5, pp. 2131–2140, 2016, ISSN: 2473-4209, (_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1118/1.4944870).
Abstract | Links | BibTeX | Tags: biological effects of ionising particles, biomolecular effects of radiation, Cell Nucleus, cell nucleus model, cellular effects of radiation, DNA, DNA double-strand breaks, Dosimetry, Dosimetry/exposure assessment, Energy transfer, Genomics, Ion beams, Ion radiation effects, Monte Carlo calculations, Monte Carlo methods, Monte Carlo simulations, Monte Carlo track structure, Protons, RBE, Schottky barriers, Scintigraphy
@article{pater_proton_2016b,
title = {Proton and light ion RBE for the induction of direct DNA double strand breaks},
author = {Piotr Pater and Gloria Bäckstöm and Fernanda Villegas and Anders Ahnesjö and Shirin A. Enger and Jan Seuntjens and Issam El Naqa},
url = {https://aapm.onlinelibrary.wiley.com/doi/abs/10.1118/1.4944870},
doi = {10.1118/1.4944870},
issn = {2473-4209},
year = {2016},
date = {2016-01-01},
urldate = {2021-09-07},
journal = {Medical Physics},
volume = {43},
number = {5},
pages = {2131--2140},
abstract = {Purpose: To present and characterize a Monte Carlo (MC) tool for the simulation of the relative biological effectiveness for the induction of direct DNA double strand breaks () for protons and light ions. Methods: The MC tool uses a pregenerated event-by-event tracks library of protons and light ions that are overlaid on a cell nucleus model. The cell nucleus model is a cylindrical arrangement of nucleosome structures consisting of 198 DNA base pairs. An algorithm relying on k-dimensional trees and cylindrical symmetries is used to search coincidences of energy deposition sites with volumes corresponding to the sugar–phosphate backbone of the DNA molecule. Strand breaks (SBs) are scored when energy higher than a threshold is reached in these volumes. Based on the number of affected strands, they are categorized into either single strand break (SSB) or double strand break (DSB) lesions. The number of SBs composing each lesion (i.e., its size) is also recorded. is obtained by taking the ratio of DSB yields of a given radiation field to a 60Co field. The MC tool was used to obtain SSB yields, DSB yields, and as a function of linear energy transfer (LET) for protons (1H+), 4He2+, 7Li3+, and 12C6+ ions. Results: For protons, the SSB yields decreased and the DSB yields increased with LET. At ≈24.5 keV μm−1, protons generated 15% more DSBs than 12C6+ ions. The varied between 1.24 and 1.77 for proton fields between 8.5 and 30.2 keV μm−1, and it was higher for iso-LET ions with lowest atomic number. The SSB and DSB lesion sizes showed significant differences for all radiation fields. Generally, the yields of SSB lesions of sizes ≥2 and the yields of DSB lesions of sizes ≥3 increased with LET and increased for iso-LET ions of lower atomic number. On the other hand, the ratios of SSB to DSB lesions of sizes 2–4 did not show variability with LET nor projectile atomic number, suggesting that these metrics are independent of the radiation quality. Finally, a variance of up to 8% in the DSB yields was observed as a function of the particle incidence angle on the cell nucleus. This simulation effect is due to the preferential alignment of ion tracks with the DNA nucleosomes at specific angles. Conclusions: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate . In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.},
note = {_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1118/1.4944870},
keywords = {biological effects of ionising particles, biomolecular effects of radiation, Cell Nucleus, cell nucleus model, cellular effects of radiation, DNA, DNA double-strand breaks, Dosimetry, Dosimetry/exposure assessment, Energy transfer, Genomics, Ion beams, Ion radiation effects, Monte Carlo calculations, Monte Carlo methods, Monte Carlo simulations, Monte Carlo track structure, Protons, RBE, Schottky barriers, Scintigraphy},
pubstate = {published},
tppubtype = {article}
}
Purpose: To present and characterize a Monte Carlo (MC) tool for the simulation of the relative biological effectiveness for the induction of direct DNA double strand breaks () for protons and light ions. Methods: The MC tool uses a pregenerated event-by-event tracks library of protons and light ions that are overlaid on a cell nucleus model. The cell nucleus model is a cylindrical arrangement of nucleosome structures consisting of 198 DNA base pairs. An algorithm relying on k-dimensional trees and cylindrical symmetries is used to search coincidences of energy deposition sites with volumes corresponding to the sugar–phosphate backbone of the DNA molecule. Strand breaks (SBs) are scored when energy higher than a threshold is reached in these volumes. Based on the number of affected strands, they are categorized into either single strand break (SSB) or double strand break (DSB) lesions. The number of SBs composing each lesion (i.e., its size) is also recorded. is obtained by taking the ratio of DSB yields of a given radiation field to a 60Co field. The MC tool was used to obtain SSB yields, DSB yields, and as a function of linear energy transfer (LET) for protons (1H+), 4He2+, 7Li3+, and 12C6+ ions. Results: For protons, the SSB yields decreased and the DSB yields increased with LET. At ≈24.5 keV μm−1, protons generated 15% more DSBs than 12C6+ ions. The varied between 1.24 and 1.77 for proton fields between 8.5 and 30.2 keV μm−1, and it was higher for iso-LET ions with lowest atomic number. The SSB and DSB lesion sizes showed significant differences for all radiation fields. Generally, the yields of SSB lesions of sizes ≥2 and the yields of DSB lesions of sizes ≥3 increased with LET and increased for iso-LET ions of lower atomic number. On the other hand, the ratios of SSB to DSB lesions of sizes 2–4 did not show variability with LET nor projectile atomic number, suggesting that these metrics are independent of the radiation quality. Finally, a variance of up to 8% in the DSB yields was observed as a function of the particle incidence angle on the cell nucleus. This simulation effect is due to the preferential alignment of ion tracks with the DNA nucleosomes at specific angles. Conclusions: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate . In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.