Publications

@article{decunha_patient-specific_2021,

title = {Patient-specific microdosimetry: a proof of concept},

author = {Joseph M. DeCunha and Fernanda Villegas and Martin Vallières and Jose Torres and Sophie Camilleri-Broët and Shirin A. Enger},

doi = {10.1088/1361-6560/ac1d1e},

issn = {1361-6560},

year  = {2021},

date = {2021-08-01},

journal = {Physics in Medicine and Biology},

abstract = {Microscopic energy deposition distributions from ionizing radiation are used to predict the biological effects of an irradiation and vary depending on biological target size. Ionizing radiation is thought to kill cells or inhibit cell cycling mainly by damaging DNA in the cell nucleus. The size of cells and nuclei depends on tissue type, cell cycle, and malignancy, all of which vary between patients. The aim of this study was to develop methods to perform patient-specific microdosimetry, that being, determining microdosimetric quantities in volumes that correspond to the sizes of cells and nuclei observed in a patient's tissue. A histopathological sample extracted from a stage I lung adenocarcinoma patient was analyzed. A pouring simulation was used to generate a three-dimensional tissue model from cell and nucleus size information determined from the histopathological sample. Microdosimetric distributions including f(y) and d(y) were determined for Co-60,Ir-192,Yb-169 and I-125 in a patient-specific model containing a distribution of cell and nucleus sizes. Fixed radius models and a summation method (where f(y) from many fixed radii models are summed) were compared to the full patient-specific model to evaluate their suitability for fast determination of patient-specific microdosimetric parameters. Fixed radius models do not provide a close approximation of the full patient-specific model y ̅_f or y ̅_d for the lower energy sources investigated, Yb-169 and I-125. The higher energy sources investigated, Co-60 and Ir-192 are less sensitive to target size variation than Yb-169 and I-125. A summation method yields the most accurate approximation of the full model d(y) for all radioisotopes investigated. A summation method allows for the computation of patient-specific microdosimetric distributions with the computing power of a personal computer. With appropriate biological inputs the microdosimetric distributions computed using these methods can yield a patient-specific relative biological effectiveness as part of a multiscale treatment planning approach.},

keywords = {Biological Effectiveness, Brachytherapy, Cellular Morphology, Microdosimetry, Patient-specific},

pubstate = {published},

tppubtype = {article}

}

@article{lecavalier-barsoum_utilization_2021,

title = {Utilization of brachytherapy in Quebec, Canada},

author = {Magali Lecavalier-Barsoum and Farzin Khosrow-Khavar and Krum Asiev and Marija Popovic and Te Vuong and Shirin A. Enger},

doi = {10.1016/j.brachy.2021.07.002},

issn = {1873-1449},

year  = {2021},

date = {2021-08-01},

journal = {Brachytherapy},

pages = {S1538--4721(21)00452--9},

abstract = {BACKGROUND AND PURPOSE: Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Québec, Canada, from 2011 to 2019. 

MATERIALS AND METHODS: All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministère de la Santé et des Services Sociaux du Québec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software. 

RESULTS: Between 2011 and 2019, 12 hospitals in the province of Québec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation. 

CONCLUSION: This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality.},

keywords = {High dose rate brachytherapy, Interstitial brachytherapy, Intracavitary brachytherapy, Low dose rate brachytherapy, Number of brachytherapy treatments, Trends in utilization},

pubstate = {published},

tppubtype = {article}

}

@article{morcos_impact_2021,

title = {On the impact of absorbed dose specification, tissue heterogeneities, and applicator heterogeneities on Monte Carlo-based dosimetry of Ir-192, Se-75, and Yb-169 in conventional and intensity-modulated brachytherapy for the treatment of cervical cancer},

author = {Marc Morcos and Akila N. Viswanathan and Shirin A. Enger},

doi = {10.1002/mp.14802},

issn = {2473-4209},

year  = {2021},

date = {2021-05-01},

journal = {Medical Physics},

volume = {48},

number = {5},

pages = {2604--2613},

abstract = {PURPOSE: The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192 Ir-, 75 Se-, and 169 Yb-based MRI-guided conventional and intensity-modulated brachytherapy. METHODS AND MATERIALS: Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n = 10) of cervical cancer patients treated with 192 Ir-based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4-based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (Dw,w ); (b) Dw,w taking the applicator material into consideration (Dw,wApp ); (c) dose to water in medium (Dw,m ); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (Dm,m (Nom) ) or voxel-by-voxel (Dm,m ). 

RESULTS: Ignoring the plastic Venezia applicator (Dw,wApp ) overestimates Dm,m by up to 1% (average) with high energy source (192 Ir and 75 Se) and up to 2% with 169 Yb. Scoring dose to water (Dw,wApp or Dw,m ) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than Dm,m (or Dm,m Nom ) for 169 Yb-based conventional and intensity-modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTVHR D90 and underestimation (up to 2%) of bladder D2cc due to a significant dip in the mass-energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass-density assignment per structure, rather than a CT-derived voxel-by-voxel assignment for MRI-guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered. 

CONCLUSIONS: The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity-modulated brachytherapy. In the absence of CT-derived mass densities, MRI-only-based dosimetry can adequately approximate Dm,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192 Ir and 75 Se, but do for 169 Yb; dose reporting must be explicitly defined since Dw,m and Dw,w may overstate the dosimetric benefits.},

keywords = {Brachytherapy, Computer-Assisted, dynamic shield brachytherapy, Female, Humans, IMBT, Intensity modulated brachytherapy, Iridium Radioisotopes, Monte Carlo Method, MR-guided brachytherapy, Radiotherapy Dosage, Radiotherapy Planning, rotating shield brachytherapy, RSBT, Uterine Cervical Neoplasms},

pubstate = {published},

tppubtype = {article}

}

@article{weishaupt_deep_2021,

title = {Deep learning-based tumor segmentation on digital images of histopathology slides for microdosimetry applications},

author = {Luca L. Weishaupt and Jose Torres and Sophie Camilleri-Broët and Roni F. Rayes and Jonathan D. Spicer and Sabrina Côté Maldonado and Shirin A. Enger},

url = {http://arxiv.org/abs/2105.01824},

year  = {2021},

date = {2021-05-01},

urldate = {2021-09-08},

journal = {arXiv:2105.01824 [physics]},

abstract = {$textbackslashbfPurpose:$ The goal of this study was (i) to use artificial intelligence to automate the traditionally labor-intensive process of manual segmentation of tumor regions in pathology slides performed by a pathologist and (ii) to validate the use of a well-known and readily available deep learning architecture. Automation will reduce the human error involved in manual delineation, increase efficiency, and result in accurate and reproducible segmentation. This advancement will alleviate the bottleneck in the workflow in clinical and research applications due to a lack of pathologist time. Our application is patient-specific microdosimetry and radiobiological modeling, which builds on the contoured pathology slides. $textbackslashbfMethods:$ A U-Net architecture was used to segment tumor regions in pathology core biopsies of lung tissue with adenocarcinoma stained using hematoxylin and eosin. A pathologist manually contoured the tumor regions in 56 images with binary masks for training. Overlapping patch extraction with various patch sizes and image downsampling were investigated individually. Data augmentation and 8-fold cross-validation were used. $textbackslashbfResults:$ The U-Net achieved accuracy of 0.91$textbackslashpm$0.06, specificity of 0.90$textbackslashpm$0.08, sensitivity of 0.92$textbackslashpm$0.07, and precision of 0.8$textbackslashpm$0.1. The F1/DICE score was 0.85$textbackslashpm$0.07, with a segmentation time of 3.24$textbackslashpm$0.03 seconds per image, achieving a 370$textbackslashpm$3 times increased efficiency over manual segmentation. In some cases, the U-Net correctly delineated the tumor's stroma from its epithelial component in regions that were classified as tumor by the pathologist. $textbackslashbfConclusion:$ The U-Net architecture can segment images with a level of efficiency and accuracy that makes it suitable for tumor segmentation of histopathological images in fields such as radiotherapy dosimetry, specifically in the subfields of microdosimetry.},

note = {arXiv: 2105.01824},

keywords = {Physics - Medical Physics},

pubstate = {published},

tppubtype = {article}

}

@article{morcos_novel_2021,

title = {A novel minimally invasive dynamic-shield, intensity-modulated brachytherapy system for the treatment of cervical cancer},

author = {Marc Morcos and Majd Antaki and Akila N. Viswanathan and Shirin A. Enger},

doi = {10.1002/mp.14459},

issn = {2473-4209},

year  = {2021},

date = {2021-01-01},

journal = {Medical Physics},

volume = {48},

number = {1},

pages = {71--79},

abstract = {PURPOSE: To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. 

METHODS AND MATERIALS: The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . RESULTS: Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2% ± 0.3% (P textless 0.001) and 6.7% ± 0.5% (P textless 0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7% ± 0.6% (P textless 0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D98 by 1.5% ± 0.2% (P = 0.034) and decreasing sigmoid D2cc by 1.9% ± 0.4% (P = 0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT. 

CONCLUSIONS: Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.},

keywords = {Brachytherapy, Computer-Assisted, Female, Humans, Image-guided cervix brachytherapy, Intensity modulated brachytherapy, Monte Carlo based dosimetry, Monte Carlo Method, MRI-guided GYN brachytherapy, Organs at Risk, Radiotherapy Dosage, Radiotherapy Planning, Uterine Cervical Neoplasms},

pubstate = {published},

tppubtype = {article}

}

@article{decunha_development_2021,

title = {Development of patient-specific 3D models from histopathological samples for applications in radiation therapy},

author = {Joseph M. DeCunha and Christopher M. Poole and Martin Vallières and Jose Torres and Sophie Camilleri-Broët and Roni F. Rayes and Jonathan D. Spicer and Shirin A. Enger},

doi = {10.1016/j.ejmp.2020.12.009},

issn = {1724-191X},

year  = {2021},

date = {2021-01-01},

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 = {81},

pages = {162--169},

abstract = {The biological effects of ionizing radiation depend on the tissue, tumor type, radiation quality, and patient-specific factors. Inter-patient variation in cell/nucleus size may influence patient-specific dose response. However, this variability in dose response is not well investigated due to lack of available cell/nucleus size data. The aim of this study was to develop methods to derive cell/nucleus size distributions from digital images of 2D histopathological samples and use them to build digital 3D models for use in cellular dosimetry. Nineteen of sixty hematoxylin and eosin stained lung adenocarcinoma samples investigated passed exclusion criterion to be analyzed in the study. A difference of gaussians blob detection algorithm was used to identify nucleus centers and quantify cell spacing. Hematoxylin content was measured to determine nucleus radius. Pouring simulations were conducted to generate one-hundred 3D models containing volumes of equivalent cell spacing and nuclei radius to those in histopathological samples. The nuclei radius distributions of non-tumoral and cancerous regions appearing in the same slide were significantly different (p textless 0.01) in all samples analyzed. The median nuclear-cytoplasmic ratio was 0.36 for non-tumoral cells and 0.50 for cancerous cells. The average cellular and nucleus packing densities in the 3D models generated were 65.9% (SD: 1.5%) and 13.3% (SD: 0.3%) respectively. Software to determine cell spacing and nuclei radius from histopathological samples was developed. 3D digital tissue models containing volumes with equivalent cell spacing, nucleus radius, and packing density to cancerous tissues were generated.},

keywords = {Algorithms, Cell Nucleus, Cellular dosimetry, Histopathology, Humans, Microdosimetry, Patient-specific, Radiometry},

pubstate = {published},

tppubtype = {article}

}

@article{decunha_patient-specific_2021b,

title = {Patient-specific microdosimetry: a proof of concept},

author = {Joseph M. DeCunha and Fernanda Villegas and Martin Vallières and Jose Torres and Sophie Camilleri-Broët and Shirin A. Enger},

url = {http://iopscience.iop.org/article/10.1088/1361-6560/ac1d1e},

doi = {10.1088/1361-6560/ac1d1e},

issn = {0031-9155},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Physics in Medicine & Biology},

abstract = {Microscopic energy deposition distributions from ionizing radiation are used to predict the biological effects of an irradiation and vary depending on biological target size. Ionizing radiation is thought to kill cells or inhibit cell cycling mainly by damaging DNA in the cell nucleus. The size of cells and nuclei depends on tissue type, cell cycle, and malignancy, all of which vary between patients. The aim of this study was to develop methods to perform patient-specific microdosimetry, that being, determining microdosimetric quantities in volumes that correspond to the sizes of cells and nuclei observed in a patient’s tissue. A histopathological sample extracted from a stage I lung adenocarcinoma patient was analyzed. A pouring simulation was used to generate a three-dimensional tissue model from cell and nucleus size information determined from the histopathological sample. Microdosimetric distributions including f(y) and d(y) were determined for Co-60,Ir-192,Yb-169 and I-125 in a patient-specific model containing a distribution of cell and nucleus sizes. Fixed radius models and a summation method (where f(y) from many fixed radii models are summed) were compared to the full patient-specific model to evaluate their suitability for fast determination of patient-specific microdosimetric parameters. Fixed radius models do not provide a close approximation of the full patient-specific model y ̅_f or y ̅_d for the lower energy sources investigated, Yb-169 and I-125. The higher energy sources investigated, Co-60 and Ir-192 are less sensitive to target size variation than Yb-169 and I-125. A summation method yields the most accurate approximation of the full model d(y) for all radioisotopes investigated. A summation method allows for the computation of patient-specific microdosimetric distributions with the computing power of a personal computer. With appropriate biological inputs the microdosimetric distributions computed using these methods can yield a patient-specific relative biological effectiveness as part of a multiscale treatment planning approach.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deufel_deep_2021,

title = {Deep learning for automated applicator reconstruction in high-dose-rate prostate brachytherapy},

author = {Christopher Deufel and Luca L. Weishaupt and Hisham Kamal Sayed and Chunhee Choo and Bradley Stish},

url = {https://www.estro.org/Congresses/WCB-2021/811/poster-physics/3229/deeplearningforautomatedapplicatorreconstructionin},

year  = {2021},

date = {2021-01-01},

journal = {World Congress of Brachytherapy 2021},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{weishaupt_approaching_2021-1,

title = {Approaching automated applicator digitization from a new angle: using sagittal images to improve deep learning accuracy and robustness in high-dose-rate prostate brachytherapy},

author = {Luca L. Weishaupt and Hisham Kamal Sayed and Ximeng Mao and Chunhee Choo and Bradley Stish and Shirin A. Enger and Christopher Deufel},

year  = {2021},

date = {2021-01-01},

journal = {2021 ABS Annual Meeting},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{morcos_impact_2021b,

title = {On the impact of absorbed dose specification, tissue heterogeneities, and applicator heterogeneities on Monte Carlo-based dosimetry of Ir-192, Se-75, and Yb-169 in conventional and intensity-modulated brachytherapy for the treatment of cervical cancer},

author = {Marc Morcos and Akila N. Viswanathan and Shirin A. Enger},

url = {https://aapm.onlinelibrary.wiley.com/doi/abs/10.1002/mp.14802},

doi = {10.1002/mp.14802},

issn = {2473-4209},

year  = {2021},

date = {2021-01-01},

urldate = {2021-09-08},

journal = {Medical Physics},

volume = {48},

number = {5},

pages = {2604--2613},

abstract = {Purpose The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192Ir-, 75Se-, and 169Yb-based MRI-guided conventional and intensity-modulated brachytherapy. Methods and Materials Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n = 10) of cervical cancer patients treated with 192Ir-based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4-based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (Dw,w); (b) Dw,w taking the applicator material into consideration (Dw,wApp); (c) dose to water in medium (Dw,m); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (Dm,m (Nom)) or voxel-by-voxel (Dm,m). Results Ignoring the plastic Venezia applicator (Dw,wApp) overestimates Dm,m by up to 1% (average) with high energy source (192Ir and 75Se) and up to 2% with 169Yb. Scoring dose to water (Dw,wApp or Dw,m) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than Dm,m (or Dm,m Nom) for 169Yb-based conventional and intensity-modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTVHR D90 and underestimation (up to 2%) of bladder D2cc due to a significant dip in the mass-energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass-density assignment per structure, rather than a CT-derived voxel-by-voxel assignment for MRI-guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered. Conclusions The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity-modulated brachytherapy. In the absence of CT-derived mass densities, MRI-only-based dosimetry can adequately approximate Dm,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192Ir and 75Se, but do for 169Yb; dose reporting must be explicitly defined since Dw,m and Dw,w may overstate the dosimetric benefits.},

note = {_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1002/mp.14802},

keywords = {dynamic shield brachytherapy, IMBT, Intensity modulated brachytherapy, MR-guided brachytherapy, rotating shield brachytherapy, RSBT},

pubstate = {published},

tppubtype = {article}

}

@article{antaki_fast_2020,

title = {Fast mixed integer optimization (FMIO) for high dose rate brachytherapy},

author = {Majd Antaki and Christopher L Deufel and Shirin A. Enger},

doi = {10.1088/1361-6560/aba317},

issn = {1361-6560},

year  = {2020},

date = {2020-12-01},

journal = {Physics in Medicine and Biology},

volume = {65},

number = {21},

pages = {215005},

abstract = {The purpose of this work was to develop an efficient quadratic mixed integer programming algorithm for high dose rate (HDR) brachytherapy treatment planning problems and integrate the algorithm into an open-source Monte Carlo based treatment planning software, RapidBrachyMCTPS. The mixed-integer algorithm yields a globally optimum solution to the dose volume histogram (DVH) based problem and, unlike other methods, is not susceptible to local minimum trapping. A hybrid linear-quadratic penalty model coupled to a mixed integer programming model was used to optimize treatment plans for 10 prostate cancer patients. Dose distributions for each dwell position were calculated with RapidBrachyMCTPS with type A uncertainties less than 0.2% in voxels within the planning target volume (PTV). The optimization process was divided into two parts. First, the data was preprocessed, in which the problem size was reduced by eliminating voxels that had negligible impact on the solution (e.g. far from the dwell position). Second, the best combination of dwell times to obtain a plan with the highest score was found. The dwell positions and dose volume constraints were used as input to a commercial mixed integer optimizer (Gurobi Optimization, Inc.). A penalty-based criterion was adopted for the scoring. The voxel-reduction technique successfully reduced the problem size by an average of 91%, without loss of quality. The preprocessing of the optimization process required on average 4 s and solving for the global maximum required on average 33 s. The total optimization time averaged 37 s, which is a substantial improvement over the ∼15 min optimization time reported in published literature. The plan quality was evaluated by evaluating dose volume metrics, including PTV D90, rectum and bladder D1cc and urethra D0.1cc. In conclusion, fast mixed integer optimization is an order of magnitude faster than current mixed-integer approaches for solving HDR brachytherapy treatment planning problems with DVH based metrics.},

keywords = {Algorithms, Brachytherapy, Computer-Assisted, Humans, Linear Models, Male, Monte Carlo Method, Prostatic Neoplasms, Radiation Dosage, Radiotherapy Dosage, Radiotherapy Planning, Software, Time Factors},

pubstate = {published},

tppubtype = {article}

}

@article{mao_rapidbrachydl_2020,

title = {RapidBrachyDL: Rapid Radiation Dose Calculations in Brachytherapy Via Deep Learning},

author = {Ximeng Mao and Joelle Pineau and Roy Keyes and Shirin A. Enger},

doi = {10.1016/j.ijrobp.2020.04.045},

issn = {1879-355X},

year  = {2020},

date = {2020-11-01},

journal = {International Journal of Radiation Oncology, Biology, Physics},

volume = {108},

number = {3},

pages = {802--812},

abstract = {PURPOSE: Detailed and accurate absorbed dose calculations from radiation interactions with the human body can be obtained with the Monte Carlo (MC) method. However, the MC method can be slow for use in the time-sensitive clinical workflow. The aim of this study was to provide a solution to the accuracy-time trade-off for 192Ir-based high-dose-rate brachytherapy by using deep learning. 

METHODS AND MATERIALS: RapidBrachyDL, a 3-dimensional deep convolutional neural network (CNN) model, is proposed to predict dose distributions calculated with the MC method given a patient's computed tomography images, contours of clinical target volume (CTV) and organs at risk, and treatment plan. Sixty-one patients with prostate cancer and 10 patients with cervical cancer were included in this study, with data from 47 patients with prostate cancer being used to train the model. 

RESULTS: Compared with ground truth MC simulations, the predicted dose distributions by RapidBrachyDL showed a consistent shape in the dose-volume histograms (DVHs); comparable DVH dosimetric indices including 0.73% difference for prostate CTV D90, 1.1% for rectum D2cc, 1.45% for urethra D0.1cc, and 1.05% for bladder D2cc; and substantially smaller prediction time, acceleration by a factor of 300. RapidBrachyDL also demonstrated good generalization to cervical data with 1.73%, 2.46%, 1.68%, and 1.74% difference for CTV D90, rectum D2cc, sigmoid D2cc, and bladder D2cc, respectively, which was unseen during the training. 

CONCLUSION: Deep CNN-based dose estimation is a promising method for patient-specific brachytherapy dosimetry. Desired radiation quantities can be obtained with accuracies arbitrarily close to those of the source MC algorithm, but with much faster computation times. The idea behind deep CNN-based dose estimation can be safely extended to other radiation sources and tumor sites by following a similar training process.},

keywords = {Brachytherapy, Colon, Computer, Computer-Assisted, Deep Learning, Female, Humans, Iridium Radioisotopes, Male, Monte Carlo Method, Neural Networks, Organs at Risk, Prostate, Prostatic Neoplasms, Radiotherapy Dosage, Radiotherapy Planning, Rectum, Retrospective Studies, Sigmoid, Urinary Bladder, Uterine Cervical Neoplasms},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_monte_2020,

title = {Monte Carlo dosimetric characterization of a new high dose rate 169 Yb brachytherapy source and independent verification using a multipoint plastic scintillator detector},

author = {Gabriel Famulari and Haydee M. Linares Rosales and Justine Dupere and David C. Medich and Luc Beaulieu and Shirin A. Enger},

doi = {10.1002/mp.14336},

issn = {2473-4209},

year  = {2020},

date = {2020-09-01},

journal = {Medical Physics},

volume = {47},

number = {9},

pages = {4563--4573},

abstract = {PURPOSE: A prototype 169 Yb source was developed in combination with a dynamic rotating platinum shield system (AIM-Brachy) to deliver intensity modulated brachytherapy (IMBT). The purpose of this study was to evaluate the dosimetric characteristics of the bare/shielded 169 Yb source using Monte Carlo (MC) simulations and perform an independent dose verification using a dosimetry platform based on a multipoint plastic scintillator detector (mPSD). 

METHODS: The TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles ( 0 ∘ , 9 0 ∘ , 18 0 ∘ , and 27 0 ∘ ). 

RESULTS: The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5-10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6-6.2%) for BCF-10, 1.7% (0.9-2.9%) for BCF-12, and 2.2% (0.3-4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8 ± 1.2%, compared to 83.5 ± 0.5% as calculated by MC. 

CONCLUSIONS: The dose distribution for the bare/shielded 169 Yb source was independently verified using mPSD with good agreement in regions close to the source. The 169 Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.},

keywords = {Brachytherapy, Geant4, IMBT, Monte Carlo Method, mPSD, Plastics, Radiometry, Radiotherapy Dosage, shielded applicator, TG-186, TG-43, Yb-169},

pubstate = {published},

tppubtype = {article}

}

@article{carroll_cross-validation_2020,

title = {Cross-validation of a non-invasive positron detector to measure the arterial input function for pharmacokinetic modelling in dynamic positron emission tomography},

author = {Liam Carroll and Etienne Croteau and Gustavo Kertzscher and Otman Sarrhini and Vincent Turgeon and Roger Lecomte and Shirin A. Enger},

doi = {10.1016/j.ejmp.2020.06.009},

issn = {1724-191X},

year  = {2020},

date = {2020-08-01},

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 = {76},

pages = {92--99},

abstract = {Kinetic modeling of positron emission tomography (PET) data can assess index rate of uptake, metabolism and predict disease progression more accurately than conventional static PET. However, it requires knowledge of the time-course of the arterial blood radioactivity concentration, called the arterial input function (AIF). The gold standard to acquire the AIF is by invasive means. The purpose of this study was to validate a previously developed dual readout scintillating fiber-based non-invasive positron detector, hereinafter called non-invasive detector (NID), developed to determine the AIF for dynamic PET measured from the human radial artery. The NID consisted of a 3 m long plastic scintillating fiber with each end coupled to a 5 m long transmission fiber followed by a silicon photomultiplier. The scintillating fiber was enclosed inside the grooves of a plastic cylindrical shell. Two sets of experiments were performed to test the NID against a previously validated microfluidic positron detector. A closed-loop microfluidic system combined with a wrist phantom was used. During the first experiment, the three PET radioisotopes 18F, 11C and 68Ga were tested. After optimizing the detector, a second series of tests were performed using only 18F and 11C. The maximum pulse amplitude to electronic noise ratio was 52 obtained with 11C. Linear regressions showed a linear relation between the two detectors. These preliminary results show that the NID can accurately detect positrons from a patient's wrist and has the potential to non-invasively measure the AIF during a dynamic PET scan. The accuracy of these measurements needs to be determined.},

keywords = {Algorithms, Arterial input function, Arteries, Dynamic PET, Electrons, Humans, Imaging, Non-invasive detector development, Phantoms, Positron-Emission Tomography, Scintillation},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_can_2020,

title = {Can intermediate-energy sources lead to elevated bone doses for prostate and head & neck high-dose-rate brachytherapy?},

author = {Gabriel Famulari and Joanne Alfieri and Marie Duclos and Té Vuong and Shirin A. Enger},

doi = {10.1016/j.brachy.2019.12.004},

issn = {1873-1449},

year  = {2020},

date = {2020-04-01},

journal = {Brachytherapy},

volume = {19},

number = {2},

pages = {255--263},

abstract = {PURPOSE: Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. METHODS AND MATERIALS: Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). 

RESULTS: Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%-2% for prostate and 4%-7% for oral tongue). Dose differences were not clinically relevant (textless5%) for soft tissues in general. Going from Dw,w to Dm,m, bone doses were increased two- to three-fold for 169Yb and four- to five-fold for 153Gd, whereas the ratio was close to ∼1 for high-energy sources. 

CONCLUSIONS: Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.},

keywords = {Bone and Bones, Brachytherapy, Cobalt Radioisotopes, Computer Simulation, Computer-Assisted, Dose calculation, Gadolinium, Humans, Intermediate-energy source, Iridium Radioisotopes, Male, Monte Carlo, Prostatic Neoplasms, Radiation Dosage, Radioisotopes, Radiotherapy Dosage, Radiotherapy Planning, Selenium Radioisotopes, Tissue composition, Tongue Neoplasms, Ytterbium},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_novel_2020,

title = {A novel 169 Yb-based dynamic-shield intensity modulated brachytherapy delivery system for prostate cancer},

author = {Gabriel Famulari and Marie Duclos and Shirin A. Enger},

doi = {10.1002/mp.13959},

issn = {2473-4209},

year  = {2020},

date = {2020-03-01},

journal = {Medical Physics},

volume = {47},

number = {3},

pages = {859--868},

abstract = {PURPOSE: Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer. 

METHODS: The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from an 169 Yb source. Conventional HDR BT (10 Ci 192 Ir) and IMBT (18 Ci 169 Yb) plans were generated for 12 patients using an in-house column generation-based optimizer, coupled to a Geant4-based dose calculation engine, RapidBrachyMC. Treatment plans were normalized to match the same PTV D90 coverage as the clinical plan. Intershield attenuation effects were taken into account. A sensitivity analysis was performed to evaluate the dosimetric impact of systematic longitudinal source positioning errors ( ± 1 mm, ± 2 mm, and ± 3 mm) and rotational errors ( ± 5 ∘ , ± 10 ∘ , and ± 15 ∘ ) on clinically relevant parameters (PTV D90 and urethra D10 ). 

RESULTS: The platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV D90 coverage, the urethral D10 was reduced by 13.3% ± 4.7%, without change to other plan quality indices (PTV V100 , V150, V200 , bladder V75 , rectum V75 , HI, COIN). Delivery times for HDR BT and IMBT were 9.2 ± 1.6 min and 18.6 ± 4.0 min, respectively. In general, the PTV D90 was more sensitive to source positioning errors than rotational errors, while the urethral D10 was more sensitive to rotational errors than source positioning errors. For a typical range of positioning errors ( ± 1 mm, ± 5 ∘ ), the overall tolerance was textless2%. 

CONCLUSIONS: The AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.},

keywords = {Brachytherapy, Cohort Studies, Computer-Assisted, Humans, IMBT, Intensity-Modulated, Male, Monte Carlo, Monte Carlo Method, prostate cancer, Prostatic Neoplasms, Radioisotopes, Radiotherapy, Radiotherapy Planning, Uncertainty, Yb-169, Ytterbium},

pubstate = {published},

tppubtype = {article}

}

@article{morcos_monte_2020,

title = {Monte Carlo dosimetry study of novel rotating MRI-compatible shielded tandems for intensity modulated cervix brachytherapy},

author = {Marc Morcos and Shirin A. Enger},

doi = {10.1016/j.ejmp.2020.02.014},

issn = {1724-191X},

year  = {2020},

date = {2020-03-01},

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 = {71},

pages = {178--184},

abstract = {PURPOSE: Intensity modulated brachytherapy (IMBT) with rotating metal shields enables dose modulation that can better conform to the tumor while reducing OAR doses. In this work, we investigate novel rotating shields, compatible with MRI-compatible tandems used for cervix brachytherapy. Three unique shields were evaluated using the traditional 192Ir source. Additionally, 75Se and 169Yb isotopes were investigated as alternative sources. 

METHODS: Three different IMBT shields were modeled and simulated in RapidBrachyMCTPS. Each tungsten shield was designed to fit inside a 6 mm-wide MRI-compatible tandem. The active core of the source was replaced with 192Ir, 75Se and 169Yb. Transmission factors (TFs) were calculated and defined as the dose ratio at 1 cm on opposite sides of the shielded tandem on the transverse plane. Polar and azimuthal anisotropy plots were extracted from simulations. Dose homogeneities V200%V100% were calculated for all radionuclide-shield combinations. 

RESULTS: TFs are favorable for IMBT and ranged between 12.9% and 32.2% for 192Ir, 4.0%-16.1% for 75Se and 1.2-6.4% for 169Yb for all shield designs. Average beam-widths in the polar and azimuthal directions were reduced to the range of 42°-112° and 27°-107°, respectively, for all shield-radionuclide combinations. Dose homogeneities for all the radionuclide-shield combinations were within 12% of the non-IMBT tandem. 

CONCLUSIONS: This study has quantitatively assessed the influence of various rotating cervical cancer-specific IMBT tandem shields on dosimetry. The dynamic single-channel shields and narrow beam-widths in the polar and azimuthal direction give rise to highly anisotropic distributions. Intermediate-to-high energy radionuclides, 75Se and 169Yb substantially improve the modulation capacity of IMBT and pave the way for treating large and complex cervical cancer without interstitial needle implantation.},

keywords = {Anisotropy, Brachytherapy, Female, Humans, Image-guided cervix brachytherapy, Intensity modulated brachytherapy, Intensity-Modulated, Iridium Radioisotopes, Magnetic Resonance Imaging, Monte Carlo based dosimetry, Monte Carlo Method, MRI-guided GYN brachytherapy, Radiometry, Radiotherapy, Selenium Radioisotopes, Uterine Cervical Neoplasms, Ytterbium},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_can_2020b,

title = {Can intermediate-energy sources lead to elevated bone doses for prostate and head & neck high-dose-rate brachytherapy?},

author = {Gabriel Famulari and Joanne Alfieri and Marie Duclos and Té Vuong and Shirin A. Enger},

url = {https://www.sciencedirect.com/science/article/pii/S1538472119306531},

doi = {10.1016/j.brachy.2019.12.004},

issn = {1538-4721},

year  = {2020},

date = {2020-03-01},

urldate = {2021-09-08},

journal = {Brachytherapy},

volume = {19},

number = {2},

pages = {255--263},

abstract = {Purpose 

Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. 

Methods and Materials Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). 

Results 

Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%–2% for prostate and 4%–7% for oral tongue). Dose differences were not clinically relevant (textless5%) for soft tissues in general. Going from Dw,w to Dm,m, bone doses were increased two- to three-fold for 169Yb and four- to five-fold for 153Gd, whereas the ratio was close to ∼1 for high-energy sources. 

Conclusions 

Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.},

keywords = {Brachytherapy, Dose calculation, Intermediate-energy source, Monte Carlo, Tissue composition},

pubstate = {published},

tppubtype = {article}

}

@article{RN218,

title = {RapidBrachyDL: Rapid Radiation Dose Calculations in Brachytherapy Via Deep Learning},

author = {Ximeng Mao and Joelle Pineau and Roy Keyes and Shirin A. Enger},

doi = {10.1016/j.ijrobp.2020.04.045},

issn = {0360-3016},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Int J Radiat Oncol Biol Phys},

volume = {108},

number = {3},

pages = {802-812},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{enger_model-based_2020,

title = {Model-Based Dose Calculation Algorithms for Brachytherapy Dosimetry},

author = {Shirin A. Enger and Javier Vijande and Mark J. Rivard},

doi = {10.1016/j.semradonc.2019.08.006},

issn = {1532-9461},

year  = {2020},

date = {2020-01-01},

journal = {Seminars in Radiation Oncology},

volume = {30},

number = {1},

pages = {77--86},

abstract = {The purpose of this study was to review the limitations of dose calculation formalisms for photon-emitting brachytherapy sources based on the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) report and to provide recommendations to transition to model-based dose calculation algorithms. Additionally, an overview of these algorithms and approaches is presented. The influence of tissue and seed/applicator heterogeneities on brachytherapy dose distributions for breast, gynecologic, head and neck, rectum, and prostate cancers as well as eye plaques and electronic brachytherapy treatments were investigated by comparing dose calculations based on the TG-43 formalism and model-based dose calculation algorithms.},

keywords = {Algorithms, Brachytherapy, Computer-Assisted, Female, Humans, Male, Medical, Models, Neoplasms, Photons, Practice Guidelines as Topic, Radiometry, Radiotherapy Dosage, Radiotherapy Planning, Societies, Theoretical},

pubstate = {published},

tppubtype = {article}

}

@article{weishaupt_classification_2020,

title = {Classification and Segmentation of Tumor Cells and Nuclei On Biopsy Slides Using Deep Learning for Microdosimetry Applications},

author = {Luca L. Weishaupt and Jose Torres and Sophie Camilleri-Broët and Sabrina Côté Maldonado and Shirin A. Enger},

url = {https://w3.aapm.org/meetings/2020AM/programInfo/programAbs.php?sid=8797&aid=51830},

year  = {2020},

date = {2020-01-01},

journal = {2020 Joint AAPM textbar COMP Virtual Meeting},

abstract = {Purpose: 

To automate the classification and segmentation of tumor cells in images of biopsy slides using deep learning to minimize manual labor, the time required, and human error. The segmented tumor cells and nuclei will be used for patient-specific microdosimetry studies. 

 

Methods: 

A pathologist manually contoured images of 57 pathology core biopsies in TIFF format, each containing 3750x3750 pixels with a 248 nm per pixel resolution on a pixel by pixel basis. The contoured pixels were used as the ground truth for a three-dimensional deep convolutional neural network model based on a UNet architecture using Keras and Tensorflow. Forty-eight of the core images were used to train the model with data augmentation using binary cross-entropy as the loss function on a 120 GB GPU cluster for 12 hours. The remaining nine core images were used for testing. Testing was done by applying a 50% confidence threshold on the model’s prediction and comparing the results with the manual contours. 

 

Results: 

The average time for the pathologist to contour a core image was 20 minutes. The model was able to segment three images per minute with an accuracy of 90.9%, specificity of 91.2%, sensitivity of 90.0%, precision of 73.0%, and a dice coefficient of 80.6%. The model’s predictions were visually similar to the manual segmentation. The model’s predictions were more confident about the center of the tumor regions than the edges. 

 

Conclusion: 

The proposed model can closely and consistently replicate tumor cell contours made by a pathologist 60 times faster than manual contouring. It can autonomously and efficiently generate large amounts of contoured pathology data that can be used for further research, such as microdosimetry performed on patient-specific tumor nuclei and cells. Future studies will investigate the accuracy and consistency of the manually contoured data, which was used as the ground truth.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_monte_2020b,

title = {Monte Carlo dosimetric characterization of a new high dose rate Yb brachytherapy source and independent verification using a multipoint plastic scintillator detector},

author = {Gabriel Famulari and Haydee M. Linares Rosales and Justine Dupere and David C. Medich and Luc Beaulieu and Shirin A. Enger},

url = {https://aapm.onlinelibrary.wiley.com/doi/abs/10.1002/mp.14336},

doi = {10.1002/mp.14336},

issn = {2473-4209},

year  = {2020},

date = {2020-01-01},

urldate = {2021-09-08},

journal = {Medical Physics},

volume = {47},

number = {9},

pages = {4563--4573},

abstract = {Purpose A prototype Yb source was developed in combination with a dynamic rotating platinum shield system (AIM-Brachy) to deliver intensity modulated brachytherapy (IMBT). The purpose of this study was to evaluate the dosimetric characteristics of the bare/shielded Yb source using Monte Carlo (MC) simulations and perform an independent dose verification using a dosimetry platform based on a multipoint plastic scintillator detector (mPSD). Methods The TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles ( , 9 , 18 , and 27 ). Results The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5–10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6–6.2%) for BCF-10, 1.7% (0.9–2.9%) for BCF-12, and 2.2% (0.3–4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8 ± 1.2%, compared to 83.5 ± 0.5% as calculated by MC. Conclusions The dose distribution for the bare/shielded Yb source was independently verified using mPSD with good agreement in regions close to the source. The Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.},

note = {_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1002/mp.14336},

keywords = {Geant4, IMBT, mPSD, shielded applicator, TG-186, TG-43, Yb-169},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_novel_2020b,

title = {A novel 169Yb-based dynamic-shield intensity modulated brachytherapy delivery system for prostate cancer},

author = {Gabriel Famulari and Marie Duclos and Shirin A. Enger},

url = {https://aapm.onlinelibrary.wiley.com/doi/abs/10.1002/mp.13959},

doi = {10.1002/mp.13959},

issn = {2473-4209},

year  = {2020},

date = {2020-01-01},

urldate = {2021-09-08},

journal = {Medical Physics},

volume = {47},

number = {3},

pages = {859--868},

abstract = {Purpose Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer. Methods The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from an 169Yb source. Conventional HDR BT (10 Ci 192Ir) and IMBT (18 Ci 169Yb) plans were generated for 12 patients using an in-house column generation-based optimizer, coupled to a Geant4-based dose calculation engine, RapidBrachyMC. Treatment plans were normalized to match the same PTV D90 coverage as the clinical plan. Intershield attenuation effects were taken into account. A sensitivity analysis was performed to evaluate the dosimetric impact of systematic longitudinal source positioning errors (1 mm, 2 mm, and 3 mm) and rotational errors (5, 10 and 15) on clinically relevant parameters (PTV D90 and urethra D10). Results The platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV D90 coverage, the urethral D10 was reduced by 13.3% 4.7%, without change to other plan quality indices (PTV V100, V150, V200, bladder V75, rectum V75, HI, COIN). Delivery times for HDR BT and IMBT were 9.2 ± 1.6 min and 18.6 ± 4.0 min, respectively. In general, the PTV D90 was more sensitive to source positioning errors than rotational errors, while the urethral D10 was more sensitive to rotational errors than source positioning errors. For a typical range of positioning errors (1 mm, 5), the overall tolerance was textless2%. Conclusions The AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.},

note = {_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1002/mp.13959},

keywords = {Brachytherapy, IMBT, Monte Carlo, prostate cancer, Yb-169},

pubstate = {published},

tppubtype = {article}

}

@article{enger_model-based_2020b,

title = {Model-Based Dose Calculation Algorithms for Brachytherapy Dosimetry},

author = {Shirin A. Enger and Javier Vijande and Mark J. Rivard},

url = {https://www.sciencedirect.com/science/article/pii/S1053429619300608},

doi = {10.1016/j.semradonc.2019.08.006},

issn = {1053-4296},

year  = {2020},

date = {2020-01-01},

urldate = {2021-09-08},

journal = {Seminars in Radiation Oncology},

volume = {30},

number = {1},

pages = {77--86},

series = {Advances in Brachytherapy},

abstract = {The purpose of this study was to review the limitations of dose calculation formalisms for photon-emitting brachytherapy sources based on the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) report and to provide recommendations to transition to model-based dose calculation algorithms. Additionally, an overview of these algorithms and approaches is presented. The influence of tissue and seed/applicator heterogeneities on brachytherapy dose distributions for breast, gynecologic, head and neck, rectum, and prostate cancers as well as eye plaques and electronic brachytherapy treatments were investigated by comparing dose calculations based on the TG-43 formalism and model-based dose calculation algorithms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{song_commentary_2019,

title = {Commentary on Systematic Review of Intensity Modulated Brachytherapy (IMBT): Static and Dynamic Techniques},

author = {William Y. Song and Shirin A. Enger},

doi = {10.1016/j.ijrobp.2019.07.050},

issn = {1879-355X},

year  = {2019},

date = {2019-11-01},

journal = {International Journal of Radiation Oncology, Biology, Physics},

volume = {105},

number = {3},

pages = {493--494},

keywords = {Brachytherapy, Computer-Assisted, Radiotherapy Dosage, Radiotherapy Planning},

pubstate = {published},

tppubtype = {article}

}

@article{shoemaker_dosimetric_2019,

title = {Dosimetric Considerations for Ytterbium-169, Selenium-75, and Iridium-192 Radioisotopes in High-Dose-Rate Endorectal Brachytherapy},

author = {Tristan Shoemaker and Té Vuong and Harry Glickman and Samar Kaifi and Gabriel Famulari and Shirin A. Enger},

doi = {10.1016/j.ijrobp.2019.07.003},

issn = {1879-355X},

year  = {2019},

date = {2019-11-01},

journal = {International Journal of Radiation Oncology, Biology, Physics},

volume = {105},

number = {4},

pages = {875--883},

abstract = {PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. 

METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. 

CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.},

keywords = {Brachytherapy, Femur, Humans, Iridium Radioisotopes, Monte Carlo Method, Organs at Risk, Pelvic Bones, Radioisotopes, Radiotherapy Dosage, Rectal Neoplasms, Rectum, Selenium Radioisotopes, Tomography, Urinary Bladder, X-Ray Computed, Ytterbium},

pubstate = {published},

tppubtype = {article}

}

@article{turgeon_characterization_2019,

title = {Characterization of scintillating fibers for use as positron detector in positron emission tomography},

author = {Vincent Turgeon and Gustavo Kertzscher and Liam Carroll and Robert Hopewell and Gassan Massarweh and Shirin A. Enger},

doi = {10.1016/j.ejmp.2019.08.009},

issn = {1724-191X},

year  = {2019},

date = {2019-09-01},

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 = {65},

pages = {114--120},

abstract = {PURPOSE: Manual and automatic blood sampling at different time intervals is considered the gold standard to determine the arterial input function (AIF) in dynamic positron emission tomography (PET). However, blood sampling is characterized by poor time resolution and is an invasive procedure. The aim of this study was to characterize the scintillating fibers used to develop a non-invasive positron detector. 

METHODS: The detector consists of a scintillating fiber coupled at each end to transmission fiber-optic cables that are connected to photo multiplier tubes in a dual readout setup. The detector is designed to be wrapped around the wrist of the patient undergoing dynamic PET. The attenuation length and bending losses were measured with excitation from gamma radiation (137Cs) and ultraviolet (UV) light. The response to positron-emitting radio-tracers was evaluated with 18F and 11C. 

RESULTS: The attenuation length for a 3.0 m and 1.5 m long scintillating fiber both coincides with the attenuation length given by the manufacturer when excited with the 137Cs source, but not with the UV source due to the differences in scintillation mechanisms. The bending losses are smaller than the measurement uncertainty for the 137Cs source irradiation, and increase when the bending radius decrease for the UV source irradiation. The signal-to-noise ratio for 18F and 11C solutions are 1.98 and 22.54 respectively. The measured decay constant of 11C agrees with its characteristic value. 

CONCLUSION: The performed measurements in the dual readout configuration suggest that scintillating fibers may be suitable to determine the AIF non-invasively.},

keywords = {Arterial input function, Dynamic PET, Electrons, Positron-Emission Tomography, Radiation detector, Scintillating fibers, Scintillation Counting},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_rapidbrachymctps_2018,

title = {RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications},

author = {Gabriel Famulari and Marc-André Renaud and Christopher M. Poole and Michael D. C. Evans and Jan Seuntjens and Shirin A. Enger},

doi = {10.1088/1361-6560/aad97a},

issn = {1361-6560},

year  = {2018},

date = {2018-08-01},

journal = {Physics in Medicine and Biology},

volume = {63},

number = {17},

pages = {175007},

abstract = {Despite being considered the gold standard for brachytherapy dosimetry, Monte Carlo (MC) has yet to be implemented into a software for brachytherapy treatment planning. The purpose of this work is to present RapidBrachyMCTPS, a novel treatment planning system (TPS) for brachytherapy applications equipped with a graphical user interface (GUI), optimization tools and a Geant4-based MC dose calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were implemented in RapidBrachyMC and made available to the user via a source and applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models and were compared against previously validated MC brachytherapy codes. The performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions with a cylindrical shielded/unshielded applicator were validated against film measurements in a Solid WaterTM phantom. TG-43 parameters calculated using RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously published work. For the prostate case, clinical dosimetric indices showed general agreement with Oncentra TPS within 1%. Simulation times were on the order of minutes on a single core to achieve uncertainties below 2% in voxels within the prostate. The calculation time was decreased further using the multithreading features of Geant4. In the comparison between MC-calculated and film-measured dose distributions, at least 95% of points passed the 3%/3 mm gamma index criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This software is especially well suited for the development of new source and applicator models.},

keywords = {Brachytherapy, Computer-Assisted, Humans, Imaging, Monte Carlo Method, Phantoms, Radiotherapy Dosage, Radiotherapy Planning, Software},

pubstate = {published},

tppubtype = {article}

}

@article{decunha_new_2018,

title = {A new delivery system to resolve dosimetric issues in intravascular brachytherapy},

author = {Joseph M. DeCunha and Shirin A. Enger},

doi = {10.1016/j.brachy.2018.01.012},

issn = {1873-1449},

year  = {2018},

date = {2018-06-01},

journal = {Brachytherapy},

volume = {17},

number = {3},

pages = {634--643},

abstract = {PURPOSE: Renewed interest is being expressed in intravascular brachytherapy (IVBT). A number of unresolved issues exist in the discipline. Providing a homogeneous and adequate dose to the target remains difficult in IVBT. The guidewire that delivers the device to the target, arterial plaques, and stent struts are all known to reduce the dose delivered to target. The viability and efficacy of a proposed IVBT delivery system designed to resolve the issue of guidewire attenuation is evaluated and compared to that of a popular and commercially available IVBT device. 

METHODS AND MATERIALS: Monte Carlo simulations are conducted to determine distributions of absorbed dose around an existing and proposed IVBT delivery system. 

RESULTS: For the Novoste Beta-Cath 3.5F (TeamBest®), dose in water varies by 10% as a function of angle in the plane perpendicular to the delivery catheter due to off-centering of seeds in the catheter. Dose is reduced by 52% behind a stainless steel guidewire and 64% behind a guidewire, arterial plaque, and stent strut for the Novoste Beta-Cath 3.5F. Dose is not perturbed by the presence of a guidewire for the proposed device and is reduced by 46% by an arterial plaque and stent strut. 

CONCLUSIONS: Dose attenuation by guidewire is likely the single greatest source of dose attenuation in IVBT in terms of absolute dose reduction and is greater than previously reported for the Novoste Beta-Cath 3.5F. The Novoste Beta-Cath 3.5F delivers an inhomogeneous dose to target. A delivery system is proposed, which resolves the issue of guidewire attenuation in IVBT and should reduce treatment times.},

keywords = {Brachytherapy, Catheterization, Catheters, Computer Simulation, Coronary Vessels, Humans, Intravascular, Monte Carlo Method, Physics, Radiation Dosage, Radiometry, Restenosis, Stents, Strontium Radioisotopes},

pubstate = {published},

tppubtype = {article}

}

@article{mann-krzisnik_influence_2018,

title = {The influence of tissue composition uncertainty on dose distributions in brachytherapy},

author = {Dylan Mann-Krzisnik and Frank Verhaegen and Shirin A. Enger},

doi = {10.1016/j.radonc.2018.01.007},

issn = {1879-0887},

year  = {2018},

date = {2018-03-01},

journal = {Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology},

volume = {126},

number = {3},

pages = {394--410},

abstract = {BACKGROUND AND PURPOSE: Model-based dose calculation algorithms (MBDCAs) have evolved from serving as a research tool into clinical practice in brachytherapy. This study investigates primary sources of tissue elemental compositions used as input to MBDCAs and the impact of their variability on MBDCA-based dosimetry. 

MATERIALS AND METHODS: Relevant studies were retrieved through PubMed. Minimum dose delivered to 90% of the target (D90), minimum dose delivered to the hottest specified volume for organs at risk (OAR) and mass energy-absorption coefficients (μen/ρ) generated by using EGSnrc "g" user-code were compared to assess the impact of compositional variability. 

RESULTS: Elemental composition for hydrogen, carbon, oxygen and nitrogen are derived from the gross contents of fats, proteins and carbohydrates for any given tissue, the compositions of which are taken from literature dating back to 1940-1950. Heavier elements are derived from studies performed in the 1950-1960. Variability in elemental composition impacts greatly D90 for target tissues and doses to OAR for brachytherapy with low energy sources and less for 192Ir-based brachytherapy. Discrepancies in μen/ρ are also indicative of dose differences. 

CONCLUSIONS: Updated elemental compositions are needed to optimize MBDCA-based dosimetry. Until then, tissue compositions based on gross simplifications in early studies will dominate the uncertainties in tissue heterogeneity.},

keywords = {Algorithms, Body Composition, Brachytherapy, Elemental composition, Humans, Mass energy-absorption coefficient, MBDCA, Organs at Risk, Radiotherapy Dosage, Review, Tissue heterogeneity, Uncertainty},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_microdosimetric_2018,

title = {Microdosimetric Evaluation of Current and Alternative Brachytherapy Sources-A Geant4-DNA Simulation Study},

author = {Gabriel Famulari and Piotr Pater and Shirin A. Enger},

doi = {10.1016/j.ijrobp.2017.09.040},

issn = {1879-355X},

year  = {2018},

date = {2018-01-01},

journal = {International Journal of Radiation Oncology, Biology, Physics},

volume = {100},

number = {1},

pages = {270--277},

abstract = {PURPOSE: Radioisotopes such as 75Se, 169Yb, and 153Gd have photon energy spectra and half-lives that make them excellent candidates as alternatives to 192Ir for high-dose-rate brachytherapy. The aim of the present study was to evaluate the relative biological effectiveness (RBE) of current (192Ir, 125I, 103Pd) and alternative (75Se, 169Yb, 153Gd) brachytherapy radionuclides using Monte Carlo simulations of lineal energy distributions. 

METHODS AND MATERIALS: Brachytherapy sources (microSelectron v2 [192Ir, 75Se, 169Yb, 153Gd], SelectSeed [125I], and TheraSeed [103Pd]) were placed in the center of a spherical water phantom with a radius of 40 cm using the Geant4 Monte Carlo simulation toolkit. The kinetic energy of all primary, scattered, and fluorescence photons interacting in a scoring volume were tallied at various depths from the source. Electron tracks were generated by sampling the photon interaction spectrum and tracking all the interactions down to 10 eV using the event-by-event capabilities of the Geant4-DNA models. The dose mean lineal energy (y¯D) values were obtained through random sampling of transfer points and overlaying spherical scoring volumes within the associated volume of the tracks. The scoring volume diameter was determined by fitting the y¯D ratio for 125I to its observed RBE. 

RESULTS: y¯D increased with the increasing distance from the source for 192Ir, 75Se, and 169Yb, remained constant for 153Gd and 125I, and decreased for 103Pd. The diameter at which the y¯D ratio coincided with the RBE of 1.15 to 1.20 for 125I was ∼25 to 40 nm. The RBE (reference 1 MeV photons) at high doses and dose rates for 192Ir, 75Se, 169Yb, 153Gd, 125I, and 103Pd was 1.028 to 1.034, 1.05 to 1.07, 1.12 to 1.15, 1.16 to 1.21, 1.15 to 1.20, and 1.17 to 1.22, respectively. 

CONCLUSIONS: The radiation quality of the radionuclides under investigation was greater than that of high-energy photons. The present study has provided a set of values to modify the prescription doses for brachytherapy to account for the variation in radiation quality among radionuclides.},

keywords = {Brachytherapy, Gadolinium, Imaging, Iodine Radioisotopes, Iridium Radioisotopes, Linear Energy Transfer, Monte Carlo Method, Phantoms, Radioisotopes, Radiometry, Radiotherapy Dosage, Relative Biological Effectiveness, Selenium Radioisotopes, Ytterbium},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_practical_2017,

title = {Practical aspects of 153Gd as a radioactive source for use in brachytherapy},

author = {Gabriel Famulari and Tomas Urlich and Andrea Armstrong and Shirin A. Enger},

doi = {10.1016/j.apradiso.2017.09.028},

issn = {1872-9800},

year  = {2017},

date = {2017-12-01},

journal = {Applied Radiation and Isotopes: Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine},

volume = {130},

pages = {131--139},

abstract = {The goal of this study was to investigate the production, purification and immobilization techniques for a 153Gd brachytherapy source. We have investigated the maximum attainable specific activity of 153Gd through the irradiation of Gd2O3 enriched to 30.6% 152Gd at McMaster Nuclear Reactor. The advantage of producing 153Gd through this production pathway is the possibility to irradiate pre-sealed pellets of 152Gd enriched Gd2O3, thereby removing the need to perform chemical separation with large quantities of radio-impurities. However, small amounts of long-lived impurities are produced from the irradiation of enriched 152Gd targets due to traces of Eu in the sample. If the amount of impurities produced is deemed unacceptable, 153Gd can be isolated as an aqueous solution, chemically separated from impurities and loaded onto a sorbent with a high affinity for Gd before encapsulation.},

keywords = {(153)Gd, Brachytherapy, Gadolinium, Humans, Neutron Capture Therapy, Nuclear Reactors, Radiochemical separation, Radioisotopes, Radionuclide production, Radiotherapy Dosage, Specific activity, Thermal neutron capture cross section},

pubstate = {published},

tppubtype = {article}

}

@article{famulari_microdosimetry_2017,

title = {Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm},

author = {Gabriel Famulari and Piotr Pater and Shirin A. Enger},

doi = {10.1088/1361-6560/aa71f6},

issn = {1361-6560},

year  = {2017},

date = {2017-07-01},

journal = {Physics in Medicine and Biology},

volume = {62},

number = {13},

pages = {5495--5508},

abstract = {The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(textgreaterE)/f(textgreater0) and dose mean lineal energy ([Formula: see text]) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The [Formula: see text] values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length ([Formula: see text]), the [Formula: see text] calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of [Formula: see text] values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.},

keywords = {Algorithms, DNA, DNA Damage, Electrons, Imaging, Monte Carlo Method, Phantoms, Photons, Radiometry},

pubstate = {published},

tppubtype = {article}

}

@article{decunha_investigation_2017,

title = {Investigation of a New Device to Improve Dosimetric Outcomes in Intravascular Brachytherapy},

author = {Joseph M. DeCunha and Shirin A. Enger},

url = {https://www.brachyjournal.com/article/S1538-4721(17)30207-6/abstract},

doi = {10.1016/j.brachy.2017.04.146},

issn = {1538-4721, 1873-1449},

year  = {2017},

date = {2017-05-01},

urldate = {2017-05-01},

journal = {Brachytherapy},

volume = {16},

number = {3},

pages = {S80},

abstract = {Coronary artery disease is amongst the main causes of death in developed countries. 

Percutaneous Transluminal Coronary Angioplasty (PTCA or angioplasty) is a procedure 

used to open stenoted (narrowed) arteries. Restenosis (renarrowing) of the treated 

vessel is a major complication of PTCA. A metal mesh tube (stent) is expanded inside 

the vessel to prevent restenosis. Tissue stress incurred during angioplasty and stenting 

can provoke rapid proliferation of neointimal cells leading to in stent restenosis 

(ISR).},

note = {Publisher: Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{quast_brachytherapy_2016,

title = {A brachytherapy photon radiation quality index Q(BT) for probe-type dosimetry},

author = {Ulrich Quast and Theodor W. Kaulich and José T. Álvarez-Romero and Sa Carlsson Tedgren and Shirin A. Enger and David C. Medich and Firas Mourtada and Jose Perez-Calatayud and Mark J. Rivard and G. Abu Zakaria},

doi = {10.1016/j.ejmp.2016.03.008},

issn = {1724-191X},

year  = {2016},

date = {2016-06-01},

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 = {32},

number = {6},

pages = {741--748},

abstract = {INTRODUCTION: In photon brachytherapy (BT), experimental dosimetry is needed to verify treatment plans if planning algorithms neglect varying attenuation, absorption or scattering conditions. The detector's response is energy dependent, including the detector material to water dose ratio and the intrinsic mechanisms. The local mean photon energy E¯(r) must be known or another equivalent energy quality parameter used. We propose the brachytherapy photon radiation quality indexQ(BT)(E¯), to characterize the photon radiation quality in view of measurements of distributions of the absorbed dose to water, Dw, around BT sources. MATERIALS AND METHODS: While the external photon beam radiotherapy (EBRT) radiation quality index Q(EBRT)(E¯)=TPR10(20)(E¯) is not applicable to BT, the authors have applied a novel energy dependent parameter, called brachytherapy photon radiation quality index, defined as Q(BT)(E¯)=Dprim(r=2cm,θ0=90°)/Dprim(r0=1cm,θ0=90°), utilizing precise primary absorbed dose data, Dprim, from source reference databases, without additional MC-calculations. RESULTS AND DISCUSSION: For BT photon sources used clinically, Q(BT)(E¯) enables to determine the effective mean linear attenuation coefficient μ¯(E) and thus the effective energy of the primary photons Eprim(eff)(r0,θ0) at the TG-43 reference position Pref(r0=1cm,θ0=90°), being close to the mean total photon energy E¯tot(r0,θ0). If one has calibrated detectors, published E¯tot(r) and the BT radiation quality correction factor [Formula: see text] for different BT radiation qualities Q and Q0, the detector's response can be determined and Dw(r,θ) measured in the vicinity of BT photon sources. 

CONCLUSIONS: This novel brachytherapy photon radiation quality indexQ(BT) characterizes sufficiently accurate and precise the primary photon's penetration probability and scattering potential.},

keywords = {Absorbed dose to water, Brachytherapy, Detector response, Effective energy, Photon brachytherapy radiation quality index, Photons, Radiation, Radiometry, Scattering, Uncertainty},

pubstate = {published},

tppubtype = {article}

}

@article{tran_geant4_2016,

title = {Geant4 Monte Carlo simulation of absorbed dose and radiolysis yields enhancement from a gold nanoparticle under MeV proton irradiation},

author = {H. N. Tran and M. Karamitros and V. N. Ivanchenko and S. Guatelli and S. McKinnon and K. Murakami and T. Sasaki and S. Okada and M. C. Bordage and Z. Francis and Z. El Bitar and M. A. Bernal and J. I. Shin and S. B. Lee and Ph. Barberet and T. T. Tran and J. M. C. Brown and T. V. Nhan Hao and S. Incerti},

url = {https://www.sciencedirect.com/science/article/pii/S0168583X16000653},

doi = {10.1016/j.nimb.2016.01.017},

issn = {0168-583X},

year  = {2016},

date = {2016-04-01},

urldate = {2021-09-07},

journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms},

volume = {373},

pages = {126--139},

abstract = {Gold nanoparticles have been reported as a possible radio-sensitizer agent in radiation therapy due to their ability to increase energy deposition and subsequent direct damage to cells and DNA within their local vicinity. Moreover, this increase in energy deposition also results in an increase of the radiochemical yields. In this work we present, for the first time, an in silico investigation, based on the general purpose Monte Carlo simulation toolkit Geant4, into energy deposition and radical species production around a spherical gold nanoparticle 50nm in diameter via proton irradiation. Simulations were preformed for incident proton energies ranging from 2 to 170MeV, which are of interest for clinical proton therapy.},

keywords = {Geant4-DNA, Nanoparticle, Proton beam, Radiation therapy, Radiolysis},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{poole_determination_2015,

title = {Determination of subcellular compartment sizes for estimating dose variations in radiotherapy},

author = {Christopher M. Poole and Anders Ahnesjö and Shirin A. Enger},

doi = {10.1093/rpd/ncv305},

issn = {1742-3406},

year  = {2015},

date = {2015-09-01},

journal = {Radiation Protection Dosimetry},

volume = {166},

number = {1-4},

pages = {361--364},

abstract = {The variation in specific energy absorbed to different cell compartments caused by variations in size and chemical composition is poorly investigated in radiotherapy. The aim of this study was to develop an algorithm to derive cell and cell nuclei size distributions from 2D histology samples, and build 3D cellular geometries to provide Monte Carlo (MC)-based dose calculation engines with a morphologically relevant input geometry. Stained and unstained regions of the histology samples are segmented using a Gaussian mixture model, and individual cell nuclei are identified via thresholding. Delaunay triangulation is applied to determine the distribution of distances between the centroids of nearest neighbour cells. A pouring simulation is used to build a 3D virtual tissue sample, with cell radii randomised according to the cell size distribution determined from the histology samples. A slice with the same thickness as the histology sample is cut through the 3D data and characterised in the same way as the measured histology. The comparison between this virtual slice and the measured histology is used to adjust the initial cell size distribution into the pouring simulation. This iterative approach of a pouring simulation with adjustments guided by comparison is continued until an input cell size distribution is found that yields a distribution in the sliced geometry that agrees with the measured histology samples. The thus obtained morphologically realistic 3D cellular geometry can be used as input to MC-based dose calculation programs for studies of dose response due to variations in morphology and size of tumour/healthy tissue cells/nuclei, and extracellular material.},

keywords = {Algorithms, Breast Neoplasms, Cell Nucleus, Computer Simulation, Computer-Assisted, ErbB-2, Female, Humans, Image Processing, Imaging, Immunoenzyme Techniques, Male, Monte Carlo Method, Prostatic Neoplasms, Radiotherapy Dosage, Radiotherapy Planning, Receptor, Signal Processing, Subcellular Fractions, Three-Dimensional},

pubstate = {published},

tppubtype = {article}

}

@article{adams_interstitial_2014,

title = {Interstitial rotating shield brachytherapy for prostate cancer},

author = {Quentin E. Adams and Jinghzu Xu and Elizabeth K. Breitbach and Xing Li and Shirin A. Enger and William R. Rockey and Yusung Kim and Xiaodong Wu and Ryan T. Flynn},

doi = {10.1118/1.4870441},

issn = {2473-4209},

year  = {2014},

date = {2014-05-01},

journal = {Medical Physics},

volume = {41},

number = {5},

pages = {051703},

abstract = {PURPOSE: To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). 

METHODS: A wire-mounted 62 GBq(153)Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 μm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0-5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. 

RESULTS: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D(98%)), I-RSBT reduced urethral D(0.1cc) below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D(1cc) was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D(1cc) was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq (153)Gd sources. 

CONCLUSIONS: For the case considered, the proposed(153)Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%-44% if the clinician allows a urethral dose gradient volume of 0-5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed (153)Gd-based I-RSBT technique in reasonable treatment times.},

keywords = {Brachytherapy, Catheters, Computer-Assisted, Equipment Design, Gadolinium, Humans, Iridium Radioisotopes, Male, Monte Carlo Method, Needles, Nickel, Platinum Compounds, Prostatic Neoplasms, Radiation Protection, Radioisotopes, Radiotherapy Dosage, Radiotherapy Planning, Rectum, Time Factors, Titanium, Urethra, Urinary Bladder},

pubstate = {published},

tppubtype = {article}

}

@article{enger_gadolinium-153_2013,

title = {Gadolinium-153 as a brachytherapy isotope},

author = {Shirin A. Enger and Darrell R. Fisher and Ryan T. Flynn},

doi = {10.1088/0031-9155/58/4/957},

issn = {1361-6560},

year  = {2013},

date = {2013-02-01},

journal = {Physics in Medicine and Biology},

volume = {58},

number = {4},

pages = {957--964},

abstract = {The purpose of this work was to present the fundamental dosimetric characteristics of a hypothetical (153)Gd brachytherapy source using the AAPM TG-43U1 dose-calculation formalism. Gadolinium-153 is an intermediate-energy isotope that emits 40-100 keV photons with a half-life of 242 days. The rationale for considering (153)Gd as a brachytherapy source is for its potential of patient specific shielding and to enable reduced personnel shielding requirements relative to (192)Ir, and as an isotope for interstitial rotating shield brachytherapy (I-RSBT). A hypothetical (153)Gd brachytherapy source with an active core of 0.84 mm diameter, 10 mm length and specific activity of 5.55 TBq of (153)Gd per gram of Gd was simulated with Geant4. The encapsulation material was stainless steel with a thickness of 0.08 mm. The radial dose function, anisotropy function and photon spectrum in water were calculated for the (153)Gd source. The simulated (153)Gd source had an activity of 242 GBq and a dose rate in water 1 cm off axis of 13.12 Gy h(-1), indicating that it would be suitable as a low-dose-rate or pulsed-dose-rate brachytherapy source. The beta particles emitted have low enough energies to be absorbed in the source encapsulation. Gadolinium-153 has an increasing radial dose function due to multiple scatter of low-energy photons. Scattered photon dose takes over with distance from the source and contributes to the majority of the absorbed dose. The anisotropy function of the (153)Gd source decreases at low polar angles, as a result of the long active core. The source is less anisotropic at polar angles away from the longitudinal axes. The anisotropy function increases with increasing distance. The (153)Gd source considered would be suitable as an intermediate-energy low-dose-rate or pulsed-dose-rate brachytherapy source. The source could provide a means for I-RSBT delivery and enable brachytherapy treatments with patient specific shielding and reduced personnel shielding requirements relative to (192)Ir.},

keywords = {Anisotropy, Brachytherapy, Equipment Design, Gadolinium, Humans, Iridium Radioisotopes, Male, Monte Carlo Method, Photons, Prostatic Neoplasms, Radiation, Radiation Protection, Radioisotopes, Radiotherapy Dosage, Scattering},

pubstate = {published},

tppubtype = {article}

}

@article{enger_layered_2012,

title = {Layered mass geometry: a novel technique to overlay seeds and applicators onto patient geometry in Geant4 brachytherapy simulations},

author = {Shirin A. Enger and Guillaume Landry and Michel D'Amours and Frank Verhaegen and Luc Beaulieu and Makoto Asai and Joseph Perl},

doi = {10.1088/0031-9155/57/19/6269},

issn = {1361-6560},

year  = {2012},

date = {2012-10-01},

journal = {Physics in Medicine and Biology},

volume = {57},

number = {19},

pages = {6269--6277},

abstract = {A problem faced by all Monte Carlo (MC) particle transport codes is how to handle overlapping geometries. The Geant4 MC toolkit allows the user to create parallel geometries within a single application. In Geant4 the standard mass-containing geometry is defined in a simulation volume called the World Volume. Separate parallel geometries can be defined in parallel worlds, that is, alternate three dimensional simulation volumes that share the same coordinate system with the World Volume for geometrical event biasing, scoring of radiation interactions, and/or the creation of hits in detailed readout structures. Until recently, only one of those worlds could contain mass so these parallel worlds provided no solution to simplify a complex geometric overlay issue in brachytherapy, namely the overlap of radiation sources and applicators with a CT based patient geometry. The standard method to handle seed and applicator overlay in MC requires removing CT voxels whose boundaries would intersect sources, placing the sources into the resulting void and then backfilling the remaining space of the void with a relevant material. The backfilling process may degrade the accuracy of patient representation, and the geometrical complexity of the technique precludes using fast and memory-efficient coding techniques that have been developed for regular voxel geometries. The patient must be represented by the less memory and CPU-efficient Geant4 voxel placement technique, G4PVPlacement, rather than the more efficient G4NestedParameterization (G4NestedParam). We introduce for the first time a Geant4 feature developed to solve this issue: Layered Mass Geometry (LMG) whereby both the standard (CT based patient geometry) and the parallel world (seeds and applicators) may now have mass. For any area where mass is present in the parallel world, the parallel mass is used. Elsewhere, the mass of the standard world is used. With LMG the user no longer needs to remove patient CT voxels that would include for example seeds. The patient representation can be a regular voxel grid, conducive to G4NestedParam, and the patient CT derived materials remain exact, avoiding the inaccuracy of the backfilling technique. Post-implant dosimetry for one patient with (125)I permanent seed implant was performed using Geant4 version 9.5.p01 using three different geometrical techniques. The first technique was the standard described above (G4PVPlacement). The second technique placed patient voxels as before, but placed seeds with LMG (G4PVPlacement+LMG). The third technique placed patient voxels through G4NestedParam and seeds through LMG (G4NestedParam+LMG). All the scenarios were calculated with 3 different image compression factors to manipulate the number of voxels. Additionally, the dosimetric impact of the backfilling technique was investigated for the case of calcifications in close proximity of sources. LMG eliminated the need for backfilling and simplified geometry description. Of the two LMG techniques, G4PVPlacement+LMG had no benefit to calculation time or memory use, actually increasing calculation time, but G4NestedParam+LMG reduced both calculation time and memory. The benefits of G4NestedParam+LMG over standard G4PVPlacement increased with increasing voxel numbers. For the case of calcifications in close proximity to sources, LMG not only increased efficiency but also yielded more accurate dose calculation than G4PVPlacement. G4NestedParam in combination with LMG present a new, efficient approach to simulate radiation sources that overlap patient geometry. Cases with brachytherapy applicators would constitute a direct extension of the method.},

keywords = {Brachytherapy, Computer-Assisted, Humans, Monte Carlo Method, Radiotherapy Dosage, Radiotherapy Planning},

pubstate = {published},

tppubtype = {article}

}

@article{enger_dose_2012,

title = {Dose to tissue medium or water cavities as surrogate for the dose to cell nuclei at brachytherapy photon energies},

author = {Shirin A. Enger and Anders Ahnesjö and Frank Verhaegen and Luc Beaulieu},

doi = {10.1088/0031-9155/57/14/4489},

issn = {1361-6560},

year  = {2012},

date = {2012-07-01},

journal = {Physics in Medicine and Biology},

volume = {57},

number = {14},

pages = {4489--4500},

abstract = {It has been suggested that modern dose calculation algorithms should be able to report absorbed dose both as dose to the local medium, D(m,m,) and as dose to a water cavity embedded in the medium, D(w,m), using conversion factors from cavity theory. Assuming that the cell nucleus with its DNA content is the most important target for biological response, the aim of this study is to investigate, by means of Monte Carlo (MC) simulations, the relationship of the dose to a cell nucleus in a medium, D(n,m,) to D(m,m) and D(w,m), for different combinations of cell nucleus compositions and tissue media for different photon energies used in brachytherapy. As D(n,m) is very impractical to calculate directly for routine treatment planning, while D(m,m) and D(w,m) are much easier to obtain, the questions arise which one of these quantities is the best surrogate for D(n,m) and which cavity theory assumptions should one use for its estimate. The Geant4.9.4 MC code was used to calculate D(m,m,) D(w,m) and D(n,m) for photon energies from 20 (representing the lower energy end of brachytherapy for ¹⁰³Pd or ¹²⁵I) to 300 keV (close to the mean energy of (¹⁹²Ir) and for the tissue media adipose, breast, prostate and muscle. To simulate the cell and its nucleus, concentric spherical cavities were placed inside a cubic phantom (10 × 10 × 10 mm³). The diameter of the simulated nuclei was set to 14 µm. For each tissue medium, three different setups were simulated; (a) D(n,m) was calculated with nuclei embedded in tissues (MC-D(n,m)). Four different published elemental compositions of cell nuclei were used. (b) D(w,m) was calculated with MC (MC-D(w,m)) and compared with large cavity theory calculated D(w,m) (LCT-D(w,m)), and small cavity theory calculated D(w,m) (SCT-D(w,m)). (c) D(m,m) was calculated with MC (MC-D(m,m)). MC-D(w,m) is a good substitute for MC-D(n,m) for all photon energies and for all simulated nucleus compositions and tissue types. SCT-D(w,m) can be used for most energies in brachytherapy, while LCT-D(w,m) should only be considered for source spectra well below 50 keV, since contributions to the absorbed dose inside the nucleus to a large degree stem from electrons released in the surrounding medium. MC-D(m,m) is not an appropriate substitute for MC-D(n,m) for the lowest photon energies for adipose and breast tissues. The ratio of MC-D(m,m) to MC-D(n,m) for adipose and breast tissue deviates from unity by 34% and 15% respectively for the lowest photon energy (20 keV), whereas the ratio is close to unity for higher energies. For prostate and muscle tissue MC-D(m,m) is a good substitute for MC-D(n,m). However, for all photon energies and tissue types the nucleus composition with the highest hydrogen content behaves differently than other compositions. Elemental compositions of the tissue and nuclei affect considerably the absorbed dose to the cell nuclei for brachytherapy sources, in particular those at the low-energy end of the spectrum. Thus, there is a need for more accurate data for the elemental compositions of tumours and healthy cells. For the nucleus compositions and tissue types investigated, MC-D(w,m) is a good substitute to MC-D(n,m) for all simulated photon energies. Whether other studied surrogates are good approximations to MC-D(n,m) depends on the target size, target composition, composition of the surrounding tissue and photon energy.},

keywords = {Brachytherapy, Cell Line, Cell Nucleus, Humans, Monte Carlo Method, Photons, Radiation Dosage, Radiotherapy Dosage, Water},

pubstate = {published},

tppubtype = {article}

}

@article{enger_exploring_2012,

title = {Exploring (57)Co as a new isotope for brachytherapy applications},

author = {Shirin A. Enger and Hans Lundqvist and Michel D'Amours and Luc Beaulieu},

doi = {10.1118/1.3700171},

issn = {0094-2405},

year  = {2012},

date = {2012-05-01},

journal = {Medical Physics},

volume = {39},

number = {5},

pages = {2342--2345},

abstract = {PURPOSE: The characteristics of the radionuclide (57)Co make it interesting for use as a brachytherapy source. (57)Co combines a possible high specific activity with the emission of relatively low-energy photons and a half-life (272 days) suitable for regular source exchanges in an afterloader. (57)Co decays by electron capture to the stable (57)Fe with emission of 136 and 122 keV photons. 

METHODS: A hypothetical (57)Co source based on the Flexisource brachytherapy encapsulation with the active core set as a pure cobalt cylinder (length 3.5 mm and diameter 0.6 mm) covered with a cylindrical stainless-steel capsule (length 5 mm and thickness 0.125 mm) was simulated using Geant4 Monte Carlo (MC) code version 9.4. The radial dose function, g(r), and anisotropy function F(r,θ), for the line source approximation were calculated following the TG-43U1 formalism. The results were compared to well-known (192)Ir and (125)I radionuclides, representing the higher and the lower energy end of brachytherapy, respectively. 

RESULTS: The mean energy of photons in water, after passing through the core and the encapsulation material was 123 keV. This hypothetical (57)Co source has an increasing g(r) due to multiple scatter of low-energy photons, which results in a more uniform dose distribution than (192)Ir. 

CONCLUSIONS: (57)Co has many advantages compared to (192)Ir due to its low-energy gamma emissions without any electron contamination. (57)Co has an increasing g(r) that results in a more uniform dose distribution than (192)Ir due to its multiple scattered photons. The anisotropy of the (57)Co source is comparable to that of (192)Ir. Furthermore, (57)Co has lower shielding requirements than (192)Ir.},

keywords = {Anisotropy, Brachytherapy, Cobalt Radioisotopes, Monte Carlo Method, Radiation, Radiometry, Scattering},

pubstate = {published},

tppubtype = {article}

}

@article{enger_modeling_2011,

title = {Modeling a hypothetical 170Tm source for brachytherapy applications},

author = {Shirin A. Enger and Michel D'Amours and Luc Beaulieu},

doi = {10.1118/1.3626482},

issn = {0094-2405},

year  = {2011},

date = {2011-10-01},

journal = {Medical Physics},

volume = {38},

number = {10},

pages = {5307--5310},

abstract = {PURPOSE: To perform absorbed dose calculations based on Monte Carlo simulations for a hypothetical (170)Tm source and to investigate the influence of encapsulating material on the energy spectrum of the emitted electrons and photons. 

METHODS: GEANT4 Monte Carlo code version 9.2 patch 2 was used to simulate the decay process of (170)Tm and to calculate the absorbed dose distribution using the GEANT4 Penelope physics models. A hypothetical (170)Tm source based on the Flexisource brachytherapy design with the active core set as a pure thulium cylinder (length 3.5 mm and diameter 0.6 mm) and different cylindrical source encapsulations (length 5 mm and thickness 0.125 mm) constructed of titanium, stainless-steel, gold, or platinum were simulated. The radial dose function for the line source approximation was calculated following the TG-43U1 formalism for the stainless-steel encapsulation. 

RESULTS: For the titanium and stainless-steel encapsulation, 94% of the total bremsstrahlung is produced inside the core, 4.8 and 5.5% in titanium and stainless-steel capsules, respectively, and less than 1% in water. For the gold capsule, 85% is produced inside the core, 14.2% inside the gold capsule, and a negligible amount (textless1%) in water. Platinum encapsulation resulted in bremsstrahlung effects similar to those with the gold encapsulation. The range of the beta particles decreases by 1.1 mm with the stainless-steel encapsulation compared to the bare source but the tissue will still receive dose from the beta particles several millimeters from the source capsule. The gold and platinum capsules not only absorb most of the electrons but also attenuate low energy photons. The mean energy of the photons escaping the core and the stainless-steel capsule is 113 keV while for the gold and platinum the mean energy is 160 keV and 165 keV, respectively. 

CONCLUSIONS: A (170)Tm source is primarily a bremsstrahlung source, with the majority of bremsstrahlung photons being generated in the source core and experiencing little attenuation in the source encapsulation. Electrons are efficiently absorbed by the gold and platinum encapsulations. However, for the stainless-steel capsule (or other lower Z encapsulations) electrons will escape. The dose from these electrons is dominant over the photon dose in the first few millimeter but is not taken into account by current standard treatment planning systems. The total energy spectrum of photons emerging from the source depends on the encapsulation composition and results in mean photon energies well above 100 keV. This is higher than the main gamma-ray energy peak at 84 keV. Based on our results, the use of (170)Tm as a brachytherapy source presents notable challenges.},

keywords = {Algorithms, Brachytherapy, Computer Simulation, Computer-Assisted, Electrons, Equipment Design, Gold, Humans, Models, Monte Carlo Method, Photons, Platinum, Radioisotopes, Radiotherapy Planning, Stainless Steel, Theoretical, Thulium, Titanium},

pubstate = {published},

tppubtype = {article}

}

@article{xu_algorithm_2011,

title = {An algorithm for efficient metal artifact reductions in permanent seed},

author = {Chen Xu and Frank Verhaegen and Denis Laurendeau and Shirin A. Enger and Luc Beaulieu},

doi = {10.1118/1.3519988},

issn = {0094-2405},

year  = {2011},

date = {2011-01-01},

journal = {Medical Physics},

volume = {38},

number = {1},

pages = {47--56},

abstract = {PURPOSE: In permanent seed implants, 60 to more than 100 small metal capsules are inserted in the prostate, creating artifacts in x-ray computed tomography (CT) imaging. The goal of this work is to develop an automatic method for metal artifact reduction (MAR) from small objects such as brachytherapy seeds for clinical applications. 

METHODS: The approach for MAR is based on the interpolation of missing projections by directly using raw helical CT data (sinogram). First, an initial image is reconstructed from the raw CT data. Then, the metal objects segmented from the reconstructed image are reprojected back into the sinogram space to produce a metal-only sinogram. The Steger method is used to determine precisely the position and edges of the seed traces in the raw CT data. By combining the use of Steger detection and reprojections, the missing projections are detected and replaced by interpolation of non-missing neighboring projections. 

RESULTS: In both phantom experiments and patient studies, the missing projections have been detected successfully and the artifacts caused by metallic objects have been substantially reduced. The performance of the algorithm has been quantified by comparing the uniformity between the uncorrected and the corrected phantom images. The results of the artifact reduction algorithm are indistinguishable from the true background value. 

CONCLUSIONS: An efficient algorithm for MAR in seed brachytherapy was developed. The test results obtained using raw helical CT data for both phantom and clinical cases have demonstrated that the proposed MAR method is capable of accurately detecting and correcting artifacts caused by a large number of very small metal objects (seeds) in sinogram space. This should enable a more accurate use of advanced brachytherapy dose calculations, such as Monte Carlo simulations.},

keywords = {Algorithms, Artifacts, Brachytherapy, Humans, Imaging, Metals, Monte Carlo Method, Phantoms, Tomography, X-Ray Computed},

pubstate = {published},

tppubtype = {article}

}

@article{enger_monte_2006,

title = {Monte Carlo calculations of thermal neutron capture in gadolinium: a comparison of GEANT4 and MCNP with measurements},

author = {Shirin A. Enger and Per Munck af Rosenschöld and Arash Rezaei and Hans Lundqvist},

doi = {10.1118/1.2150787},

issn = {0094-2405},

year  = {2006},

date = {2006-02-01},

journal = {Medical Physics},

volume = {33},

number = {2},

pages = {337--341},

abstract = {GEANT4 is a Monte Carlo code originally implemented for high-energy physics applications and is well known for particle transport at high energies. The capacity of GEANT4 to simulate neutron transport in the thermal energy region is not equally well known. The aim of this article is to compare MCNP, a code commonly used in low energy neutron transport calculations and GEANT4 with experimental results and select the suitable code for gadolinium neutron capture applications. To account for the thermal neutron scattering from chemically bound atoms [S(alpha,beta)] in biological materials a comparison of thermal neutron fluence in tissue-like poly(methylmethacrylate) phantom is made with MCNP4B, GEANT4 6.0 patch1, and measurements from the neutron capture therapy (NCT) facility at the Studsvik, Sweden. The fluence measurements agreed with MCNP calculated results considering S(alpha,beta). The location of the thermal neutron peak calculated with MCNP without S(alpha,beta) and GEANT4 is shifted by about 0.5 cm towards a shallower depth and is 25%-30% lower in amplitude. Dose distribution from the gadolinium neutron capture reaction is then simulated by MCNP and compared with measured data. The simulations made by MCNP agree well with experimental results. As long as thermal neutron scattering from chemically bound atoms are not included in GEANT4 it is not suitable for NCT applications.},

keywords = {Computer-Assisted, Fast Neutrons, Gadolinium, Humans, Imaging, Monte Carlo Method, Neutron Capture Therapy, Phantoms, Radiologic, Radiometry, Radiotherapy Planning, Reproducibility of Results, Technology},

pubstate = {published},

tppubtype = {article}

}

@article{enger_gadolinium_2006,

title = {Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy},

author = {Shirin A. Enger and Arash Rezaei and Per Munck af Rosenschöld and Hans Lundqvist},

doi = {10.1118/1.2146050},

issn = {0094-2405},

year  = {2006},

date = {2006-01-01},

journal = {Medical Physics},

volume = {33},

number = {1},

pages = {46--51},

abstract = {Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.},

keywords = {Biological, Blood Vessel Prosthesis, Brachytherapy, Computer Simulation, Computer-Assisted, Gadolinium, Graft Occlusion, Humans, Models, Monte Carlo Method, Neutron Capture Therapy, Radiometry, Radiotherapy Dosage, Radiotherapy Planning, Relative Biological Effectiveness, Statistical, Stents, Vascular},

pubstate = {published},

tppubtype = {article}

}

@article{noauthor_novel_nodate,

title = {A novel minimally invasive dynamic‐shield, intensity‐modulated brachytherapy system for the treatment of cervical cancer},

url = {https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.14459},

doi = {10.1002/mp.14459},

urldate = {2021-09-08},

keywords = {},

pubstate = {published},

tppubtype = {article}

}