Publications by authors named "Anna Subiel"

10 Publications

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Eigencolor radiochromic film dosimetry.

Med Phys 2021 Feb 1. Epub 2021 Feb 1.

National Physical Laboratory, Chemical, Medical and Environmental Science Department, Hampton Rd, Teddington, TW11 0LW, United Kingdom.

Purpose: The goal of this work is to propose a new multichannel method correcting for systematic thickness disturbances and to evaluate its precision in relevant radiation dosimetry applications.

Methods: The eigencolor ratio technique is introduced and theoretically developed to provide a method correcting for thickness disturbances. The method is applied to EBT3 GafchromicTM film irradiated with cobalt-60 and 6 MV photon beams and digitized with an Epson 10000XL photo scanner. Dose profiles and output factors of different field sizes are measured and analyzed. Variance analysis of the previous method of Bouchard et al. ["On the characterization and uncertainty analysis of radiochromic film dosimetry" Med.Phys. 36(6), 1931-1946 (2009)] is adapted to the new approach. Uncertainties are predicted for relevant applications.

Results: Results show that systematic disturbances attributed to thickness variations are efficiently corrected. The method is shown efficient to identify and correct for dark spots which cause systematic errors in single-channel distributions. Applications of the method in the context of relative dosimetry yields standard uncertainties ranging between 0.8% and 1.9%, depending on the ROI size and the film irradiation. Variance analysis predicts that uncertainty levels between 0.3% and 0.6% are achievable with repeated measurements. Uncertainties are found to vary with absorbed dose and ROI size.

Conclusions: The proposed multichannel method is efficient for accurate dosimetry, reaching uncertainty levels comparable to previous publications with EBT film. The method is also promising for applications beyond clinical QA, such as machine characterization and other advanced dosimetry applications.
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http://dx.doi.org/10.1002/mp.14742DOI Listing
February 2021

The European Joint Research Project UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates.

Phys Med 2020 Dec 9;80:134-150. Epub 2020 Nov 9.

Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.
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http://dx.doi.org/10.1016/j.ejmp.2020.09.020DOI Listing
December 2020

Corrigendum to "Challenges of dosimetry of ultra-short pulsed very high energy electron beams" [Phys. Med. 42 (2017) 327-331].

Phys Med 2020 08 2;76:345. Epub 2020 Jul 2.

Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, Glasgow G4 0NG, UK. Electronic address:

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http://dx.doi.org/10.1016/j.ejmp.2020.06.022DOI Listing
August 2020

An open source heterogeneous 3D printed mouse phantom utilising a novel bone representative thermoplastic.

Phys Med Biol 2020 06 3;65(10):10NT02. Epub 2020 Jun 3.

University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. Authors contributed equally. Author to whom any correspondence should be addressed.

The lack of rigorous quality standards in pre-clinical radiation dosimetry has renewed interest in the development of anthropomorphic phantoms. Using 3D printing customisable phantoms can be created to assess all parts of pre-clinical radiation research: planning, image guidance and treatment delivery. We present the full methodology, including material development and printing designs, for the production of a high spatial resolution, anatomically realistic heterogeneous small animal phantom. A methodology for creating and validating tissue equivalent materials is presented. The technique is demonstrated through the development of a bone-equivalent material. This material is used together with a soft-tissue mimicking ABS plastic filament to reproduce the corresponding structure geometries captured from a CT scan of a nude mouse. Air gaps are used to represent the lungs. Phantom validation was performed through comparison of the geometry and x-ray attenuation of CT images of the phantom and animal images. A 6.6% difference in the attenuation of the bone-equivalent material compared to the reference standard in softer beams (0.5 mm Cu HVL) rapidly decreases as the beam is hardened. CT imaging shows accurate (sub-millimetre) reproduction of the skeleton (Distance-To-Agreement 0.5 mm ± 0.4 mm) and body surface (0.7 mm ± 0.5 mm). Histograms of the voxel intensity profile of the phantom demonstrate suitable similarity to those of both the original mouse image and that of a different animal. We present an approach for the efficient production of an anthropomorphic phantom suitable for the quality assurance of pre-clinical radiotherapy. Our design and full methodology are provided as open source to encourage the pre-clinical radiobiology community to adopt a common QA standard.
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http://dx.doi.org/10.1088/1361-6560/ab8078DOI Listing
June 2020

Development and Implementation of an End-To-End Test for Absolute Dose Verification of Small Animal Preclinical Irradiation Research Platforms.

Int J Radiat Oncol Biol Phys 2020 07 10;107(3):587-596. Epub 2020 Mar 10.

Medical Physics Department, National Physical Laboratory, Teddington, United Kingdom; Department of Physics, Faculty of Engineering and Physical Sciences. University of Surrey, Guildford, United Kingdom.

Purpose: Lack of standardization and inaccurate dosimetry assessment in preclinical research is hampering translational opportunities for new radiation therapy interventions. The aim of this work was to develop and implement an end-to-end dosimetry test for small animal radiation research platforms to monitor and help improve accuracy of dose delivery and standardization across institutions.

Methods And Materials: The test is based on a bespoke zoomorphic heterogeneous mouse and WT1 Petri dish phantoms with alanine as a reference detector. Alanine measurements within the mouse phantom were validated with Monte Carlo simulations at 0.5 mm Cu x-ray reference beam. Energy dependence of alanine in medium x-ray beam qualities was taken into consideration. For the end-to-end test, treatment plans considering tissue heterogeneities were created in Muriplan treatment planning systems (TPS) and delivered to the phantoms at 5 institutions using Xstrahl's small animal irradiation platforms. Mean calculated dose to the pellets were compared with alanine measured dose.

Results: Monte Carlo simulations and in phantom alanine measurements in NPL's reference beam were in excellent agreement, validating the experimental approach. At 1 institute, initial measurements showed a larger than 12% difference between calculated and measured dose caused by incorrect input data. The physics data used by the calculation engine were corrected, and the TPS was recommissioned. Subsequent end-to-end test measurements showed differences <5%. With an anterior field, 4 of the participating institutes delivered dose within 5% to both phantoms.

Conclusions: An end-to-end dosimetry test was developed and implemented for dose evaluation in preclinical irradiation with small animal irradiation research platforms. The test was capable of detecting treatment planning commissioning errors and highlighted critical elements in dose calculation. Absolute dosimetry with alanine in relevant preclinical irradiation conditions showed reasonable levels of accuracy compared with TPS calculations. This work provides an independent and traceable dosimetric validation in preclinical research involving small animal irradiation.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.001DOI Listing
July 2020

The influence of lack of reference conditions on dosimetry in pre-clinical radiotherapy with medium energy x-ray beams.

Phys Med Biol 2020 04 23;65(8):085016. Epub 2020 Apr 23.

National Physical Laboratory, Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom. Author to whom any correspondence should be addressed.

Despite well-established dosimetry in clinical radiotherapy, dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of published findings. The lack of suitable dosimetry protocols, coupled with the increasing complexity of pre-clinical irradiation platforms, undermines confidence in preclinical studies and represents a serious obstacle in the translation to clinical practice. To accurately measure output of a pre-clinical radiotherapy unit, appropriate Codes of Practice (CoP) for medium energy x-rays needs to be employed. However, determination of absorbed dose to water (D) relies on application of backscatter factor (B) employing in-air method or carrying out in-phantom measurement at the reference depth of 2 cm in a full backscatter (i.e. 30 × 30 × 30 cm) condition. Both of these methods require thickness of at least 30 cm of underlying material, which are never fulfilled in typical pre-clinical irradiations. This work is focused on evaluation the effects of the lack of recommended reference conditions in dosimetry measurements for pre-clinical settings and is aimed at extending the recommendations of the current CoP to practical experimental conditions and highlighting the potential impact of the lack of correct backscatter considerations on radiobiological studies.
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http://dx.doi.org/10.1088/1361-6560/ab7b30DOI Listing
April 2020

Evaluation of a pixelated large format CMOS sensor for x-ray microbeam radiotherapy.

Med Phys 2020 Mar 6;47(3):1305-1316. Epub 2020 Jan 6.

Rutherford Appleton Laboratory, Didcot, OX11 0QX, UK.

Purpose: Current techniques and procedures for dosimetry in microbeams typically rely on radiochromic film or small volume ionization chambers for validation and quality assurance in 2D and 1D, respectively. Whilst well characterized for clinical and preclinical radiotherapy, these methods are noninstantaneous and do not provide real time profile information. The objective of this work is to determine the suitability of the newly developed vM1212 detector, a pixelated CMOS (complementary metal-oxide-semiconductor) imaging sensor, for in situ and in vivo verification of x-ray microbeams.

Methods: Experiments were carried out on the vM1212 detector using a 220 kVp small animal radiation research platform (SARRP) at the Helmholtz Centre Munich. A 3 x 3 cm square piece of EBT3 film was placed on top of a marked nonfibrous card overlaying the sensitive silicon of the sensor. One centimeter of water equivalent bolus material was placed on top of the film for build-up. The response of the detector was compared to an Epson Expression 10000XL flatbed scanner using FilmQA Pro with triple channel dosimetry. This was also compared to a separate exposure using 450 µm of silicon as a surrogate for the detector and a Zeiss Axio Imager 2 microscope using an optical microscopy method of dosimetry. Microbeam collimator slits with range of nominal widths of 25, 50, 75, and 100 µm were used to compare beam profiles and determine sensitivity of the detector and both film measurements to different microbeams.

Results: The detector was able to measure peak and valley profiles in real-time, a significant reduction from the 24 hr self-development required by the EBT3 film. Observed full width at half maximum (FWHM) values were larger than the nominal slit widths, ranging from 130 to 190 µm due to divergence. Agreement between the methods was found for peak-to-valley dose ratio (PVDR), peak to peak separation and FWHM, but a difference in relative intensity of the microbeams was observed between the detectors.

Conclusions: The investigation demonstrated that pixelated CMOS sensors could be applied to microbeam radiotherapy for real-time dosimetry in the future, however the relatively large pixel pitch of the vM1212 detector limit the immediate application of the results.
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http://dx.doi.org/10.1002/mp.13971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078942PMC
March 2020

Development of an anatomically correct mouse phantom for dosimetry measurement in small animal radiotherapy research.

Phys Med Biol 2019 06 21;64(12):12NT02. Epub 2019 Jun 21.

Department of Biomedical Sciences, University of Hull, Hull, United Kingdom. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.

Significant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be carried out in orthotopic models. Dose assessment in such systems is complex however, and a lack of established tools and methodologies for traceable and accurate dosimetry is currently limiting the capabilities of such platforms and slowing the clinical uptake of new approaches. Here we report the creation of an anatomically correct phantom, fabricated from materials with tissue-equivalent electron density, into which dosimetry detectors can be incorporated for measurement as part of quality control (QC). The phantom also allows training in preclinical radiotherapy planning and cross-institution validation of dose delivery protocols for small animal radiotherapy platforms without the need to sacrifice animals, with high reproducibility. Mouse CT data was acquired and segmented into soft tissue, bone and lung. The skeleton was fabricated using 3D printing, whilst lung was created using computer numerical control (CNC) milling. Skeleton and lung were then set into a surface-rendered mould and soft tissue material added to create a whole-body phantom. Materials for fabrication were characterized for atomic composition and attenuation for x-ray energies typically found in small animal irradiators. Finally cores were CNC milled to allow intracranial incorporation of bespoke detectors (alanine pellets) for dosimetry measurement.
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http://dx.doi.org/10.1088/1361-6560/ab215bDOI Listing
June 2019

Challenges of dosimetry of ultra-short pulsed very high energy electron beams.

Phys Med 2017 Oct 11;42:327-331. Epub 2017 May 11.

Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, Glasgow G4 0NG, UK. Electronic address:

Very high energy electrons (VHEE) in the range from 100 to 250MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetric properties compared with 6-20MV photons generated by clinical linear accelerators (LINACs). VHEE beams have characteristics unlike any other beams currently used for radiotherapy: femtosecond to picosecond duration electron bunches, which leads to very high dose per pulse, and energies that exceed that currently used in clinical applications. Dosimetry with conventional online detectors, such as ionization chambers or diodes, is a challenge due to non-negligible ion recombination effects taking place in the sensitive volumes of these detectors. FLUKA and Geant4 Monte Carlo (MC) codes have been employed to study the temporal and spectral evolution of ultrashort VHEE beams in a water phantom. These results are complemented by ion recombination measurements employing an IBA CC04 ionization chamber for a 165MeV VHEE beam. For comparison, ion recombination has also been measured using the same chamber with a conventional 20MeV electron beam. This work demonstrates that the IBA CC04 ionization chamber exhibits significant ion recombination and is therefore not suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional correction factors. Further study is required to investigate the applicability of ion chambers in VHEE dosimetry.
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http://dx.doi.org/10.1016/j.ejmp.2017.04.029DOI Listing
October 2017

Standards and Methodologies for Characterizing Radiobiological Impact of High-Z Nanoparticles.

Theranostics 2016 20;6(10):1651-71. Epub 2016 Jun 20.

Radiation Dosimetry, National Physical Laboratory, Hampton Road, Teddington, Middlesex, TW11 0LW, UK.

Research on the application of high-Z nanoparticles (NPs) in cancer treatment and diagnosis has recently been the subject of growing interest, with much promise being shown with regards to a potential transition into clinical practice. In spite of numerous publications related to the development and application of nanoparticles for use with ionizing radiation, the literature is lacking coherent and systematic experimental approaches to fully evaluate the radiobiological effectiveness of NPs, validate mechanistic models and allow direct comparison of the studies undertaken by various research groups. The lack of standards and established methodology is commonly recognised as a major obstacle for the transition of innovative research ideas into clinical practice. This review provides a comprehensive overview of radiobiological techniques and quantification methods used in in vitro studies on high-Z nanoparticles and aims to provide recommendations for future standardization for NP-mediated radiation research.
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http://dx.doi.org/10.7150/thno.15019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955064PMC
October 2017