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  • 1.
    Ahnesjö, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hårdemark, Björn
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The IMRT information process-mastering the degrees of freedom in external beam therapy2006In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 13, p. R381-402Article in journal (Refereed)
    Abstract [en]

    The techniques and procedures for intensity-modulated radiation therapy (IMRT) are reviewed in the context of the information process central to treatment planning and delivery of IMRT. A presentation is given of the evolution of the information based radiotherapy workflow and dose delivery techniques, as well as the volume and planning concepts for relating the dose information to image based patient representations. The formulation of the dose shaping process as an optimization problem is described. The different steps in the calculation flow for determination of machine parameters for dose delivery are described starting from the formulation of optimization objectives over dose calculation to optimization procedures. Finally, the main elements of the quality assurance procedure necessary for implementing IMRT clinically are reviewed.

  • 2.
    Bläckberg, Lisa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics. Massachusetts General Hospital & Harvard Medical School.
    El Fakhri, Georges
    Massachusetts General Hospital & Harvard Medical School.
    Sabet, Hamid
    Massachusetts General Hospital & Harvard Medical School.
    Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 21, p. 8419-8440Article in journal (Refereed)
    Abstract [en]

    A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to  >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

  • 3.
    Christensen, Jeppe Brage
    et al.
    Tech Univ Denmark, Ctr Nucl Technol, Roskilde, Denmark.
    Almhagen, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Skandion Clin, Uppsala, Sweden.
    Nystrom, Hakan
    Skandion Clin, Uppsala, Sweden.
    Andersen, Claus E.
    Tech Univ Denmark, Ctr Nucl Technol, Roskilde, Denmark.
    Quenching-free fluorescence signal from plastic-fibres in proton dosimetry: understanding the influence of Cerenkov radiation2018In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 63, no 6, article id 065001Article in journal (Refereed)
    Abstract [en]

    The origin of photons emitted in optical fibres under proton irradiation has been attributed to either entirely Cerenkov radiation or light consisting of fluorescence with a substantial amount of Cerenkov radiation. The source of the light emission is assessed in order to understand why the signal from optical fibres irradiated with protons is reportedly quenching-free. The present study uses the directional emittance of Cerenkov photons in 12 MeV and 20 MeV electron beams to validate a Monte Carlo model for simulating the emittance and transmission of Cerenkov radiation in optical fibres. We show that fewer than 0.01 Cerenkov photons are emitted and guided per 225 MeV proton penetrating the optical fibre, and that the Cerenkov signal in the optical fibre is completely negligible at the Bragg peak. Furthermore, on taking the emittance and guidance of both fluorescence and Cerenkov photons into account, it becomes evident that the reported quenching-free signal in PMMA-based optical fibres during proton irradiation is due to fluorescence.

  • 4.
    Christensen, Jeppe Brage
    et al.
    Tech Univ Denmark, Ctr Nucl Technol, Roskilde, Denmark.
    Almhagen, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Skandionkliniken, Uppsala, Sweden.
    Stolarczyk, Liliana
    Skandionkliniken, Uppsala, Sweden;Polish Acad Sci, Inst Nucl Phys, Bronowice Cyclotron Ctr, Krakow, Poland.
    Vestergaard, Anne
    Aarhus Univ Hosp, Danish Ctr Particle Therapy, Aarhus, Denmark.
    Bassler, Niels
    Stockholm Univ, Dept Phys, Med Radiat Phys, Stockholm, Sweden;Karolinska Inst, Dept Oncol & Pathol, Med Radiat Phys, Stockholm, Sweden;Aarhus Univ Hosp, Dept Expt Clin Oncol, Aarhus, Denmark.
    Andersen, Claus E.
    Tech Univ Denmark, Ctr Nucl Technol, Roskilde, Denmark.
    Ionization quenching in scintillators used for dosimetry of mixed particle fields2019In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 64, no 9, article id 095018Article in journal (Refereed)
    Abstract [en]

    Ionization quenching in ion beam dosimetry is often related to the fluence- or dose-averaged linear energy transfer (LET). Both quantities are however averaged over a wide LET range and a mixed field of primary and secondary ions. We propose a novel method to correct the quenched luminescence in scintillators exposed to ion beams. The method uses the energy spectrum of the primaries and accounts for the varying quenched luminescence in heavy, secondary ion tracks through amorphous track structure theory. The new method is assessed against more traditional approaches by correcting the quenched luminescence response from the BCF-12, BCF-60, and 81-0084 plastic scintillators exposed to a 100 MeV pristine proton beam in order to compare the effects of the averaged LET quantities and the secondary ions. Calculations and measurements show that primary protons constitute more than 92% of the energy deposition but account for more than 95% of the luminescence signal in the scintillators. The quenching corrected luminescence signal is in better agreement with the dose measurement when the secondary particles are taken into account. The Birks model provided the overall best quenching corrections, when the quenching corrected signal is adjusted for the number of free model parameters. The quenching parameter kB for the BCF-12 and BCF-60 scintillators is in agreement with literature values and was found to be kB = (10.6 +/- 0.1) x 10(-2) mu m keV(-1) for the 81-0084 scintillator. Finally, a fluence threshold for the 100 MeV proton beam was calculated to be of the order of 10(10) cm(-2), corresponding to 110 Gy, above which the quenching increases non-linearly and the Birks model no longer is applicable.

  • 5.
    Eklund, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Fast modelling of spectra and stopping-power ratios using differentiated fluence pencil kernels2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 16, p. 4231-4247Article in journal (Refereed)
    Abstract [en]

    Modern radiotherapy steadily utilizes more of the available degrees of freedom provided by radiotherapy equipment, raising the need for the dosimetric methods to deliver reliable measurements for situations where the spectral properties of the radiation field may also vary. A kernel-based superposition method is presented for which the spectra from any field modulation can be instantly calculated, thus facilitating the determination of dosimetric quantities at arbitrary locations. A database of fluence pencil kernels describing the fluence resulting from point monodirectional monoenergetic beams incident onto a water phantom has been calculated with the PENELOPE-2005 Monte Carlo package. Spectra calculated by means of the kernels are presented for various 6 MV fields. The spectra have been used to investigate depth and lateral variations of water-to-air stopping-power ratios. Results show that the stopping-power ratio decreases with depth, and that this effect is more pronounced for small fields. These variations are clearly connected to spectral variations. For a 10 x 10 cm(2) field, the difference between the stopping-power ratio at 2.5 cm depth and 30 cm depth is less than 0.3% while for a 0.3 x 0.3 cm(2) field this difference is 0.7%. Ratios outside the field were found to be sensitive to the collimator leakage spectral variations.

  • 6.
    Eklund, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Modeling silicon diode dose response factors for small photon fields2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 24, p. 7411-7423Article in journal (Refereed)
    Abstract [en]

    The dosimetry of small fields is important for the use of high resolution photon radiotherapy. Silicon diodes yield a high signal from a small detecting volume which makes them suitable for use in small fields and high dose gradients. Unshielded diodes used in large fields are known to give a varying dose response depending on the proportion of low energy scattered photons in the field. Response variations in small fields can be caused by both spectral variations, and disturbances of the local level of lateral electron equilibrium. We present a model that includes the effects from lack of charged particle equilibrium. The local spectra are calculated by use of fluence pencil kernels and divided into a low and a high energy component. The low energy part is treated with large cavity theory and the high energy part with the Spencer-Attix small cavity theory. Monte Carlo-derived correction factors are used to account for both the local level of electron equilibrium in the field, and deviations from this level in the silicon disk cavity. Results for field sizes ranging from 0.5 × 0.5 to 20 × 20 cm2 are compared to data from full Monte Carlo simulations and measurements. The achieved dose response accuracy is for the smallest fields 1-2%, and for larger fields 0.5%. Spectral variations were of little importance for the small field response, implying that volume averaging, and to some extent interface transient effects, are of importance for use of unshielded diodes in non-equilibrium conditions. The results indicate that diodes should preferably be designed to have the thin layer of active volume padded in between inactive layers of the silicon base material.

  • 7.
    Eklund, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Modeling silicon diode energy response factors for use in therapeutic photon beams2009In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 54, no 20, p. 6135-6150Article in journal (Refereed)
    Abstract [en]

    Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer–Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 × 5 cm2, 10 × 10 cm2 and 20 × 20 cm2 fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

  • 8. Enger, Shirin A.
    et al.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Verhaegen, Frank
    Beaulieu, Luc
    Dose to tissue medium or water cavities as surrogate for the dose to cell nuclei at brachytherapy photon energies2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 14, p. 4489-4500Article in journal (Refereed)
    Abstract [en]

    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,D-m, and as dose to a water cavity embedded in the medium, D-w,D-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,D-m, to D-m,D-m and D-w,D-m, for different combinations of cell nucleus compositions and tissue media for different photon energies used in brachytherapy. As D-n,D-m is very impractical to calculate directly for routine treatment planning, while D-m,D-m and D-w,D-m are much easier to obtain, the questions arise which one of these quantities is the best surrogate for D-n,D-m and which cavity theory assumptions should one use for its estimate. The Geant4.9.4 MC code was used to calculate D-m,D-m, D-w,D-m and D-n,D-m for photon energies from 20 (representing the lower energy end of brachytherapy for Pd-103 or I-125) to 300 keV (close to the mean energy of Ir-192) 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 x 10 x 10 mm(3)). The diameter of the simulated nuclei was set to 14 mu m. For each tissue medium, three different setups were simulated; (a) D-n,D-m was calculated with nuclei embedded in tissues (MC-D-n,D-m). Four different published elemental compositions of cell nuclei were used. (b) D-w,D-m was calculated with MC (MC-D-w,D-m) and compared with large cavity theory calculated D-w,D-m (LCT-D-w,D-m), and small cavity theory calculated D-w,D-m (SCT-D-w,D-m). (c) D-m,D-m was calculated with MC (MC-D-m,D-m). MC-D-w,D-m is a good substitute for MC-D-n,D-m for all photon energies and for all simulated nucleus compositions and tissue types. SCT-D-w,D-m can be used for most energies in brachytherapy, while LCT-D-w,D-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,D-m is not an appropriate substitute for MC-D-n,D-m for the lowest photon energies for adipose and breast tissues. The ratio of MC-D-m,D-m to MC-D-n,D-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,D-m is a good substitute for MC-D-n,D-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,D-m is a good substitute to MC-D-n,D-m for all simulated photon energies. Whether other studied surrogates are good approximations to MC-D-n,D-m depends on the target size, target composition, composition of the surrounding tissue and photon energy.

  • 9.
    Enger, Shirin A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Fisher, Darrell R.
    Flynn, Ryan T.
    Gadolinium-153 as a brachytherapy isotope2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 4, p. 957-964Article in journal (Refereed)
    Abstract [en]

    The purpose of this work was to present the fundamental dosimetric characteristics of a hypothetical Gd-153 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 Gd-153 as a brachytherapy source is for its potential of patient specific shielding and to enable reduced personnel shielding requirements relative to Ir-192, and as an isotope for interstitial rotating shield brachytherapy (I-RSBT). A hypothetical Gd-153 brachytherapy source with an active core of 0.84 mm diameter, 10 mm length and specific activity of 5.55 TBq of Gd-153 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 Gd-153 source. The simulated Gd-153 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 Gd-153 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 Gd-153 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 Ir-192.

  • 10.
    Enger, Shirin Abbasinejad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Hartman, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Cross-fire doses from β-emitting radionuclides in targeted radiotherapy: A theoretical study based on experimentally measured tumor characteristics2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 7, p. 1909-1920Article in journal (Refereed)
    Abstract [en]

    A mathematical model based upon histological findings of cell cluster distributions in primary breast cancers and lymph node metastases was developed. The model is unique because it accounts for tumor cell cluster formations within both primary tumors and metastases. The importance of inter-cell cluster cross-fire radiation dose for beta-emitting radionuclides of different energies was studied. The cell clusters were simulated as spheres with 15, 25 and 50 microm radii having a homogeneous radioactivity distribution. The self-dose as well as the dose distribution around the spheres was calculated for seven radionuclides, (90)Y, (188)Re, (32)P, (186)Re, (159)Gd, (131)I and (177)Lu using the GEANT4 Monte Carlo code. Generally, the self-dose was decreasing with increasing energy of the emitted beta particles. An exception was (188)Re which, compared to (32)P, had higher beta energy as well as higher self-dose. This was due to the higher emission of conversion and Auger electrons in the (188)Re-decay. When the cell clusters had a mean distance that was shorter than the maximum range of beta-particles, then the inter-cluster cross-fire radiation contributed significantly to the absorbed dose. Thus, high-energy beta-particles may, in spite of a low self-dose to single clusters, still be favorable to use due to the contribution of inter-cluster cross-fire radiation.

  • 11. Georg, Dietmar
    et al.
    Stock, Markus
    Kroupa, Bernhard
    Olofsson, Jörgen
    Nyholm, Tufve
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Karlsson, Mikael
    Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 16, p. 4981-4992Article in journal (Refereed)
    Abstract [en]

    Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm3 ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 ± 1.2% and 0.5 ± 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 ± 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach. The physical effects modelled in the dose calculation software MUV allow accurate dose calculations in individual verification points. Independent calculations may be used to replace experimental dose verification once the IMRT programme is mature.

  • 12.
    González-Muñoz, Gloria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Fernández-Varea, José M.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Monte Carlo simulation and analysis of proton energy-deposition patterns in the Bragg peak2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 11, p. 2857-75Article in journal (Refereed)
    Abstract [en]

    The spatial pattern of energy depositions is crucial for understanding the mechanisms that modify the relative biological effectiveness of different radiation qualities. In this paper, we present data on energy-deposition properties of mono-energetic protons (1-20 MeV) and their secondary electrons in liquid water. Proton-impact ionization was described by means of the Hansen-Kocbach-Stolterfoht doubly differential cross section (DDCS), thus modelling both the initial energy and angle of the emitted electron. Excitation by proton impact was included to account for the contribution of this interaction channel to the electronic stopping power of the projectile. Proton transport was implemented assuming track-segment conditions, whereas electrons were followed down to 50 eV by the Monte Carlo code PENELOPE. Electron intra-track energy-deposition properties, such as slowing-down and energy-imparted spectra of electrons, were calculated. Furthermore, the use of DDCSs enabled the scoring of electron inter-track properties. We present novel results for 1, 5 and 20 MeV single-proton-track frequencies of distances between the nearest inter- (e(-)-e(-), e(-)-H+) and intra-track (e(-)-e(-), e(-)-H+, H+-H+) energy-deposition events. By setting a threshold energy of 17.5 eV, commonly employed as a surrogate to discriminate for elementary damage in the DNA, the variation in these frequencies was studied as well. The energy deposited directly by the proton represents a large amount of the total energy deposited along the track, but when an energy threshold is adopted the relative contribution of the secondary electrons becomes larger for increasing energy of the projectile. We found that the frequencies of closest energy-deposition events per nanometre decrease with proton energy, i.e. for lower proton energies a denser ionization occurs, following the trend of the characteristic LET curves. In conclusion, considering the energy depositions due to the delta electrons and at the core of the track, 1 MeV protons have an intrinsic capability of generating about five times more dual depositions within the characteristic 2 nm of the DNA-chain structure than 20 MeV protons.

  • 13.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Comments on 'The influence of dose heterogeneity on tumor control probability in fractionated radiation therapy'2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 18, p. 6585-6589Article in journal (Other academic)
    Abstract [en]

    By analyzing the radiobiological model, and the equations derived from the model, it is shown that the main results of the article 'The influence of dose heterogeneity on tumor control probability in fractionated radiation therapy' by Wiklund et al (2011 Phys. Med. Biol. 56 7585-600) are valid only under the condition that the dose to any cell is statistically independent of the dose to any other cell in the same fraction. This condition is in practice not fulfilled for radiotherapy. Hence the main results and most of the discussion are not applicable to fractionated radiation therapy.

  • 14.
    Hollmark, M
    et al.
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Gudowska, I
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Belkić, Dz
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Brahme, A
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Sobolevsky, N
    An analytical model for light ion pencil beam dose distributions: multiple scattering of primary and secondary ions.2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 13, p. 3477-91Article in journal (Refereed)
    Abstract [en]

    An analytical algorithm based on the generalized Fermi-Eyges theory, amended for multiple Coulomb scattering and energy loss straggling, is used for calculation of the dose distribution of light ion beams in water. Pencil beam energy deposition distributions are derived for light ions by weighting a Monte Carlo (MC) calculated planar integral dose distribution with analytically calculated multiple scattering and range straggling distributions. The planar integral dose distributions are calculated using the MC code SHIELD-HIT07, in which multiple scattering and energy loss straggling processes are excluded. The contribution from nuclear reactions is included in the MC calculations. Multiple scattering processes are calculated separately for primary and secondary ions and parameters of the initial angular and radial spreads, and the covariance of these are derived by a least-square parameterization of the SHIELD-HIT07 data. The results from this analytical algorithm are compared to pencil beam dose distributions obtained from SHIELD-HIT07, where all processes are included, as well as to experimental data. The presented analytical approach allows for the accurate calculation of the spatial energy deposition distributions of ions of atomic numbers Z = 1 - 8.

  • 15.
    Hollmark, M
    et al.
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Uhrdin, J
    Dz, Belkić
    Gudowska, I
    Brahme, A
    Influence of multiple scattering and energy loss straggling on the absorbed dose distributions of therapeutic light ion beams: I. Analytical pencil beam model.2004In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 49, no 14, p. 3247-65Article in journal (Refereed)
    Abstract [en]

    The lateral and longitudinal distributions of absorbed dose of broad and narrow light ion beams in water are investigated. An analytical algorithm based on the generalized Fermi-Eyges theory is developed and used to calculate the effects of multiple scattering and range straggling on the dose distribution of light ion beams in water. A first-order Gaussian multiple scattering and energy loss straggling approach is generally sufficiently accurate for describing the lateral and longitudinal spread of the Bragg peak and the associated energy deposition distribution of therapeutic light ion beams at ranges of clinical interest. Nuclear reactions are not taken into account in this study. The analytical algorithm given in the present study allows an accurate description of the radial spread and the range straggling of light ions traversing matter. A verification of this approach by comparing with experimental data, Monte Carlo methods and other analytical techniques will be presented in a forthcoming paper.

  • 16.
    Kimstrand, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Traneus, Erik
    Experimental test of Monte Carlo proton transport at grazing incidence in GEANT4, FLUKA and MCNPX2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 4, p. 1115-1129Article in journal (Refereed)
    Abstract [en]

    The ability of the Monte Carlo (MC) particle transport codes GEANT4.8.1 and GEANT4.8.2, FLUKA2006 and MCNPX2.4.0 to model proton transport at grazing incidence onto tungsten blocks has been tested and compared to experimental measurements. The test geometry consisted of a narrow proton beam of two energies, 98 MeV and 180 MeV, impinging on a thick tungsten alloy block at grazing incidence. The distribution of forward out-scatter from the tungsten alloy block was measured with a fluorescent screen viewed with a CCD camera via a mirror. In the MC simulations, the experimental setup was modelled and the dose deposited to the fluorescent screen material was scored. Simulations and measurements were made for four different incidence angles (3.5, 5.0, 7.5 and 10°). Several different sets of calculations were performed, studying the impact of different user-defined settings in the different MC packages. The study of different parameters settings in the GEANT4.8.1 simulation showed a strong dependence of the calculated out-scatter probability on the maximum allowed step length. For the largest incidence angle an increase of 60% in the out-scatter probability was found when restricting the maximum allowed step length to 0.05 cm. We also observed that the stepping algorithm of GEANT4.8.1 and 4.8.2 introduces a small non-physical directional and positional asymmetry at the exit boundary of the tungsten alloy block. The shape of the energy spectrum of protons being out-scattered agreed between the codes. The dose-weighted forward out-scatter probability, i.e. the ratio between the total signal from the unscattered beam and the out-scattered beam, showed a qualitative agreement of simulations compared to measurements. Quantitatively, the deviation of the simulations reached as high as 37%, while the experimental uncertainty was 14%. The mean emission angle of the simulations was within 16% of the measurement for all incidence angles with a measurement uncertainty of 8%.

  • 17.
    Kimstrand, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Traneus, Erik
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    A beam source model for scanned proton beams2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 11, p. 3151-3168Article in journal (Refereed)
    Abstract [en]

    A beam source model, i.e. a model for the initial phase space of the beam, for scanned proton beams has been developed. The beam source model is based on parameterized particle sources with characteristics found by fitting towards measured data per individual beam line. A specific aim for this beam source model is to make it applicable to the majority of the various proton beam systems currently available or under development, with the overall purpose to drive dose calculations in proton beam treatment planning. The proton beam phase space is characterized by an energy spectrum, radial and angular distributions and deflections for the non-modulated elementary pencil beam. The beam propagation through the scanning magnets is modelled by applying experimentally determined focal points for each scanning dimension. The radial and angular distribution parameters are deduced from measured two-dimensional fluence distributions of the elementary beam in air. The energy spectrum is extracted from a depth dose distribution for a fixed broad beam scan pattern measured in water. The impact of a multi-slab range shifter for energy modulation is calculated with an own Monte Carlo code taking multiple scattering, energy loss and straggling, non-elastic and elastic nuclear interactions in the slab assembly into account. Measurements for characterization and verification have been performed with the scanning proton beam system at The Svedberg Laboratory in Uppsala. Both in-air fluence patterns and dose points located in a water phantom were used. For verification, dose-in-water was calculated with the Monte Carlo code GEANT 3.21 instead of using a clinical dose engine with approximations of its own. For a set of four individual pencil beams, both with the full energy and range shifted, 96.5% (99.8%) of the tested dose points satisfied the 1%/1 mm (2%/2 mm) gamma criterion.

  • 18.
    Kimstrand, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Traneus, Erik
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Parametrization and application of scatter kernels for modelling scanned proton beam collimator scatter dose2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 13, p. 3405-3429Article in journal (Refereed)
    Abstract [en]

    Collimators are routinely used in proton radiotherapy to laterally confine the field and improve the penumbra. Collimator scatter contributes up to 15% of the local dose and is therefore important to include in treatment planning dose calculation. We present a method for reconstruction of the collimator scatter phase space based on the parametrization of pre-calculated scatter kernels. Collimator scatter distributions, generated by the Monte Carlo (MC) package GEANT4.8.2, were scored differential in direction and energy. The distributions were then parametrized so as to enable a fast reconstruction by sampling. MC calculated dose distributions in water based on the parametrized phase space were compared to full MC simulations that included the collimator in the simulation geometry, as well as to experimental data. The experiments were performed at the scanned proton beam line at the The Svedberg Laboratory (TSL) in Uppsala, Sweden. Dose calculations using the parametrization of this work and the full MC for isolated typical cases of collimator scatter were compared by means of the gamma index. The result showed that in total 96.7% (99.3%) of the voxels fulfilled the gamma 2.0%/2.0 mm (3.0%/3.0 mm) criterion. The dose distribution for a collimated field was calculated based on the phase space created by the collimator scatter model incorporated into the generation of the phase space of a scanned proton beam. Comparing these dose distributions to full MC simulations, including particle transport in the MLC, yielded that in total for 18 different collimated fields, 99.1% of the voxels satisfied the gamma 1.0%/1.0 mm criterion and no voxel exceeded the gamma 2.6%/2.6 mm criterion. The dose contribution of collimator scatter along the central axis as predicted by the model showed good agreement with experimental data.

  • 19.
    Kuess, Peter
    et al.
    Med Univ Vienna, Dept Radiat Oncol, Div Med Radiat Phys, Vienna, Austria; Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria.
    Andrzejewski, Piotr
    Med Univ Vienna, Dept Radiat Oncol, Div Med Radiat Phys, Vienna, Austria; Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria.
    Nilsson, David
    Umeå Univ, Dept Chem, Computat Life Sci Cluster CliC, Umeå, Sweden.
    Georg, Petra
    Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria; EBG MedAustron GmbH, Wiener Neustadt, Austria.
    Knoth, Johannes
    Med Univ Vienna, Dept Radiat Oncol, Div Med Radiat Phys, Vienna, Austria.
    Susani, Martin
    Med Univ Vienna, Clin Inst Pathol, Vienna, Austria.
    Trygg, Johan
    Umeå Univ, Dept Chem, Computat Life Sci Cluster CliC, Umeå, Sweden.
    Helbich, Thomas H.
    Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria; Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria.
    Polanec, Stephan H.
    Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria; Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria.
    Georg, Dietmar
    Med Univ Vienna, Dept Radiat Oncol, Div Med Radiat Phys, Vienna, Austria; Christian Doppler Lab Med Radiat Res Radiat Oncol, Vienna, Austria.
    Nyholm, Tufve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Umeå Univ, Dept Radiat Sci, Radiat Phys, Umeå, Sweden.
    Association between pathology and texture features of multi parametric MRI of the prostate2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 19, p. 7833-7854Article in journal (Refereed)
    Abstract [en]

    The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific identified signature, DCE did not add complementary information to T2 and ADC maps.

  • 20. Lindblom, Emely
    et al.
    Dasu, Alexandru
    Beskow, Catharina
    Toma-Dasu, Iuliana
    High brachytherapy doses can counteract hypoxia in cervical cancer - a modelling study2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 2, p. 560-572Article in journal (Refereed)
    Abstract [en]

    Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.

  • 21.
    Lorin, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Medin, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Blom, Mikael
    Uppsala University.
    Ziemann, Volker
    Uppsala University, The Svedberg Laboratory.
    Reistad, Dag
    Uppsala University, The Svedberg Laboratory.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Development of a compact proton scanning system in Uppsala with a moveable second magnet2000In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 5, p. 1151-63Article in journal (Refereed)
    Abstract [en]

    A scanned proton beam yields dose distributions that in most cases are superior to passively scattered proton beams and to other external radiation treatment modalities. The present paper gives a description of the scanning system that has been developed at the Svedberg Laboratory (TSL) in Uppsala. The scanning technique and the technical design are described. The solution with a small pole gap of the magnets and a moveable second magnet results in a very compact scanning head, which can therefore be incorporated in a gantry of relatively limited size. A prototype was constructed that has been used to realize various dose distributions with a scanned beam of 180 MeV protons at TSL.

  • 22.
    Lorin, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Medin, Joakim
    Kimstrand, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Reference dosimetry in a scanned pulsed proton beam using ionisation chambers and a Faraday cup2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 13, p. 3519-3529Article in journal (Refereed)
    Abstract [en]

    In order to give the correct dose to a patient, the monitor chamber for a proton scanning system has to be calibrated. As recombination of ion pairs occurs in the monitor chamber, the relation between the number of particles traversing it per time unit and the ionization chamber signal is not linear. A method developed for a scanned pulsed proton beam taking the nonlinear monitor signal into account is described. A vital part of the reference dosimetry procedure is to determine the absorbed dose under reference conditions, which is recommended to be done with an ionization chamber. For a scanned pulsed proton beam, the recombination in the ionization chamber is not negligible and the signal from the ionization chamber has to be corrected. In this work, it is shown that although the pulse length is comparable to the ion transit time the beam can be considered as continuously scanned if the applied high voltage is not too small. Also shown is that the two-voltage formula for a continuous beam is under some conditions applicable for a continuous scanned beam as well.

  • 23.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Production, PET performance and dosimetric considerations of 134Ce/134La,an Auger electron and positron-emitting generator for radionuclide therapy2002In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 47, no 4, p. 615-29Article in journal (Refereed)
    Abstract [en]

    We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

  • 24.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Schneider, Harald
    Bergström, Mats
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Quantitative imaging and correction for cascade gamma radiation of 76Brwith 2D and 3D PET2002In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 47, no 19, p. 3519-34Article in journal (Refereed)
    Abstract [en]

    Several positron emitting nuclides with applications in PET, such as 76Br, 124I, 110In and 86Y, also emit gamma radiation in their decays. Measured coincidences between annihilation photons and this cascade gamma radiation are essentially true coincidences and the standard PET corrections do not account for them. We investigated the performance of 76Br in 2D and 3D PET, the effect of the gamma radiation emitted by 76Br on quantitative accuracy and the distribution of cascade gamma radiation coincidences in 2D and 3D PET sinograms. A correction method for cascade gamma radiation coincidences was implemented and evaluated. Count rate linearity was affected by the gamma radiation from the 76Br decay. Spatial resolution and sphere recovery were slightly worse for 76Br compared to 18F. Correction for cascade gamma radiation coincidences by subtraction of a linear projection tail fit improved total correction accuracy to similar values as for positron-only emitters such as 18F, and improved image contrast significantly.

  • 25. Nyholm, T.
    et al.
    Olofsson, J.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Karlsson, M.
    Modelling lateral beam quality variations in pencil kernel based photon dose calculations2006In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 16, p. 4111-4118Article in journal (Refereed)
    Abstract [en]

    Standard treatment machines for external radiotherapy are designed to yield flat dose distributions at a representative treatment depth. The common method to reach this goal is to use a flattening filter to decrease the fluence in the centre of the beam. A side effect of this filtering is that the average energy of the beam is generally lower at a distance from the central axis, a phenomenon commonly referred to as off-axis softening. The off-axis softening results in a relative change in beam quality that is almost independent of machine brand and model. Central axis dose calculations using pencil beam kernels show no drastic loss in accuracy when the off-axis beam quality variations are neglected. However, for dose calculated at off-axis positions the effect should be considered, otherwise errors of several per cent can be introduced. This work proposes a method to explicitly include the effect of off-axis softening in pencil kernel based photon dose calculations for arbitrary positions in a radiation field. Variations of pencil kernel values are modelled through a generic relation between half value layer (HVL) thickness and off-axis position for standard treatment machines. The pencil kernel integration for dose calculation is performed through sampling of energy fluence and beam quality in sectors of concentric circles around the calculation point. The method is fully based on generic data and therefore does not require any specific measurements for characterization of the off-axis softening effect, provided that the machine performance is in agreement with the assumed HVL variations. The model is verified versus profile measurements at different depths and through a model self-consistency check, using the dose calculation model to estimate HVL values at off-axis positions. A comparison between calculated and measured profiles at different depths showed a maximum relative error of 4% without explicit modelling of off-axis softening. The maximum relative error was reduced to 1% when the off-axis softening was accounted for in the calculations.

  • 26. Nyholm, Tufve
    et al.
    Olofsson, Jörgen
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Georg, Dietmar
    Karlsson, Mikael
    Pencil kernel correction and residual error estimation for quality-index-based dose calculations2006In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 23, p. 6245-6262Article in journal (Refereed)
    Abstract [en]

    Experimental data from 593 photon beams were used to quantify the errors in dose calculations using a previously published pencil kernel model. A correction of the kernel was derived in order to remove the observed systematic errors. The remaining residual error for individual beams was modelled through uncertainty associated with the kernel model. The methods were tested against an independent set of measurements. No significant systematic error was observed in the calculations using the derived correction of the kernel and the remaining random errors were found to be adequately predicted by the proposed method.

  • 27. Olofsson, Jörgen
    et al.
    Nyholm, Tufve
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Avdelningen för sjukhusfysik.
    Karlsson, Mikael
    Optimization of photon beam flatness for radiation therapy2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 6, p. 1735-1746Article in journal (Refereed)
    Abstract [en]

    In this work, we investigate the relation between lateral fluence/dose distributions and photon beam uniformity, possibly identifying ways to improve these characteristics. The calculations included treatment head scatter properties associated with three common types of linear accelerators in order to study their impact on the results. For 6 and 18 MV photon beams the lateral fluence distributions were optimized with respect to the resulting calculated flatness, as defined by the International Electrotechnical Commission (IEC), at 10 cm depth in six different field sizes. The limits proposed by IEC for maximum dose ratios ('horns') at the depth of dose maximum have also been accounted for in the optimization procedure. The conclusion was that typical head scatter variations among different types of linear accelerators have a very limited effect on the optimized results, which implies that the existing differences in measured off-axis dose distributions are related to non-equivalent optimization objectives. Finally, a comparison between the theoretically optimized lateral dose distributions and corresponding dose measurements for the three investigated accelerator types was performed. Although the measured data generally fall within the IEC requirements the optimized distributions show better results overall for the evaluated uniformity parameters, indicating that there is room for improved flatness performance in clinical photon beams.

  • 28.
    Razifar, Pasha
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blomquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ringheim, Anna
    Estrada, Sergio
    Langström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Principal component analysis with pre-normalization improves the signal-to-noise ratio and image quality in positron emission tomography studies of amyloid deposits in Alzheimer's disease2009In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 54, no 11, p. 3595-3612Article in journal (Refereed)
    Abstract [en]

    This study introduces a new approach for the application of principal component analysis (PCA) with pre-normalization on dynamic positron emission tomography (PET) images. These images are generated using the amyloid imaging agent N-methyl [C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([C-11]PIB) in patients with Alzheimer's disease (AD) and healthy volunteers (HVs). The aim was to introduce a method which, by using the whole dataset and without assuming a specific kinetic model, could generate images with improved signal-to-noise and detect, extract and illustrate changes in kinetic behavior between different regions in the brain. Eight AD patients and eight HVs from a previously published study with [C-11] PIB were used. The approach includes enhancement of brain regions where the kinetics of the radiotracer are different from what is seen in the reference region, pre-normalization for differences in noise levels and removal of negative values. This is followed by slice-wise application of PCA (SW-PCA) on the dynamic PET images. Results obtained using the new approach were compared with results obtained using reference Patlak and summed images. The new approach generated images with good quality in which cortical brain regions in AD patients showed high uptake, compared to cerebellum and white matter. Cortical structures in HVs showed low uptake as expected and in good agreement with data generated using kinetic modeling. The introduced approach generated images with enhanced contrast and improved signal-to-noise ratio (SNR) and discrimination power (DP) compared to summed images and parametric images. This method is expected to be an important clinical tool in the diagnosis and differential diagnosis of dementia.

  • 29.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Kairemo, Kalevi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Performance of coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and SPECT2004In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 49, no 24, p. 5419-32Article in journal (Refereed)
    Abstract [en]

    An important application of quantitative imaging in nuclear medicine is the estimation of absorbed doses in radionuclide therapy. Depending on the radionuclide used for therapy, quantitative imaging of the kinetics of the therapeutic radiopharmaceutical could be done using planar imaging, SPECT or PET. Since many nuclear medicine departments have a gamma camera system that is also suitable for coincidence imaging, the performance of these systems with respect to quantitative imaging of PET isotopes that could be of use in radionuclide dosimetry is of interest. We investigated the performance of a gamma camera with coincidence imaging capabilities with 99mTc, 111In, 18F and 76Br and a dedicated PET system with 18F and 76Br, using a single standard set of phantom measurements. Here, 76Br was taken as a typical example of prompt gamma-emitting PET isotopes that are applicable in radionuclide therapy dosimetry such as 86Y and 124I. Image quality measurements show comparable image contrasts for 76Br coincidence imaging and 111In SPECT. Although the spatial resolution of coincidence imaging is better than single photon imaging, the contrast obtained with 76Br is not better than that with 99mTc or 111In because of the prompt gamma involved. Additional improvements are necessary to allow for quantitative coincidence imaging of long-lived, prompt gamma producing positron emitters.

  • 30.
    Tilly, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Fast dose algorithm for generation of dose coverage probability for robustness analysis of fractionated radiotherapy2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 14, p. 5439-5454Article in journal (Refereed)
    Abstract [en]

    A fast algorithm is constructed to facilitate dose calculation for a large number of randomly sampled treatment scenarios, each representing a possible realisation of a full treatment with geometric, fraction specific displacements for an arbitrary number of fractions. The algorithm is applied to construct a dose volume coverage probability map (DVCM) based on dose calculated for several hundred treatment scenarios to enable the probabilistic evaluation of a treatment plan.For each treatment scenario, the algorithm calculates the total dose by perturbing a pre-calculated dose, separately for the primary and scatter dose components, for the nominal conditions. The ratio of the scenario specific accumulated fluence, and the average fluence for an infinite number of fractions is used to perturb the pre-calculated dose. Irregularities in the accumulated fluence may cause numerical instabilities in the ratio, which is mitigated by regularisation through convolution with a dose pencil kernel.Compared to full dose calculations the algorithm demonstrates a speedup factor of ~1000. The comparisons to full calculations show a 99% gamma index (2%/2 mm) pass rate for a single highly modulated beam in a virtual water phantom subject to setup errors during five fractions. The gamma comparison shows a 100% pass rate in a moving tumour irradiated by a single beam in a lung-like virtual phantom. DVCM iso-probability lines computed with the fast algorithm, and with full dose calculation for each of the fractions, for a hypo-fractionated prostate case treated with rotational arc therapy treatment were almost indistinguishable.

  • 31.
    Tilly, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Elekta Instruments AB, Stockholm, Sweden.
    van de Schoot, Agustinus J A J
    Academic Medical Center, Univesity of Amsterdam, Amsterdam, The Netherlands.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Bel, Arjan
    Academic Medical Center, Univesity of Amsterdam, Amsterdam, The Netherlands.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Dose coverage calculation using a statistical shape model: applied to cervical cancer radiotherapy2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 10, p. 4140-4159Article in journal (Refereed)
    Abstract [en]

    A comprehensive methodology for treatment simulation and evaluation of dose coverage probabilities is presented where a population based statistical shape model (SSM) provide samples of fraction specific patient geometry deformations.The learning data consists of vector fields from deformable image registration of repeated imaging giving intra-patient deformations which are mapped to an average patient serving as a common frame of reference. The SSM is created by extracting the most dominating eigenmodes through principal component analysis of the deformations from all patients. The sampling of a deformation is thus reduced to sampling weights for enough of the most dominating eigenmodes that describe the deformations.For the cervical cancer patient datasets in this work, we found seven eigenmodes to be sufficient to capture 90% of the variance in the deformations of the, and only three eigenmodes for stability in the simulated dose coverage probabilities. The normality assumption of the eigenmode weights was tested and found relevant for the 20 most dominating eigenmodes except for the first. Individualization of the SSM is demonstrated to be improved using two deformation samples from a new patient. The probabilistic evaluation provided additional information about the trade-offs compared to the conventional single dataset treatment planning.

  • 32.
    Tilly, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Fernandez-Varea, J. M.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Brahme, A.
    Comparison of Monte Carlo calculated electron slowing-down spectra generated by 60Co gamma-rays, electrons, protons and light ions2002In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 47, no 8, p. 1303-19Article in journal (Refereed)
    Abstract [en]

    When analysing the factors affecting the relative biological effectiveness (RBE) of different radiation qualities, it is essential to consider particularly the low-energy slowing-down electrons (around 100 eV to 1 keV) since they have the potential of inflicting severe damage to the DNA. We present a modified and extended version of the Monte Carlo code PENELOPE that enables scoring of slowing-down spectra. mean local energy imparted spectra and average intra-track nearest-neighbour energy deposition distances of the secondary electrons generated by different radiation qualities, such as electrons, photons, protons and light ions in general. The resulting spectra show that the low-linear energy transfer (LET) beams, 60Co gamma-rays and electrons with initial energies of 0.1 MeV and higher, have as expected approximately the same electron slowing-down fluence per unit dose in the biologically important low-energy interval. Consistent with the general behaviour of the RBE of low-energy electrons, protons and light ions, the low-energy electron slowing-down fluence per unit dose is larger than for low-LET beams, and it increases with decreasing initial projectile energy.

  • 33.
    Tilly, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Kimstrand, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Lorin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Gajewski, Konrad
    Uppsala University, The Svedberg Laboratory.
    Pettersson, Mikael
    Uppsala University, The Svedberg Laboratory.
    Bäcklund, Andreas
    Uppsala University, The Svedberg Laboratory.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Development and verification of the pulsed scanned proton beam at the The Swedberg Laboratory in Uppsala2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 10, p. 2741-2754Article in journal (Refereed)
    Abstract [en]

    In this paper we present the recent developments made for the scanning system for proton beams at TSL in Uppsala, showing that this system is now fully functional being able to produce conformal intensity modulated scan patterns with sufficient accuracy. A new control and supervising system handling the beam delivery including the control of the synchrocyclotron and the scanning system is developed and described in detail. A complete dosimetry system with transmission ionization chambers and a multi-wire ionization chamber for monitoring of the beam during scanning has been constructed. The details of the dose monitors and the position sensitive multi-wire ionization chamber are presented in this work. Furthermore, we have established procedures for verification measurements to ensure the quality of the beam and also methods for calibration of the beam monitors and relative and absolute dosimetry for complex scanned beams.

  • 34.
    Tilly, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Johansson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Medin, Joakim
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer2005In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 50, no 12, p. 2765-2777Article in journal (Refereed)
    Abstract [en]

    Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the alpharef/betaref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE=1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study-based on in vitro data since human tissue RBE values are scarce and have large uncertainties-can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.

  • 35.
    Villegas, Fernanda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Reply to the comment on ‘Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy 125I and 192Ir sources and 60Co cell irradiation’2016In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 61, no 13, p. 5103-5106Article in journal (Refereed)
    Abstract [en]

    A discrepancy between the Monte Carlo derived relative standard deviation sigma(rel)(z) (microdosimetric spread) and experimental data was reported by Villegas et al (2013 Phys. Med. Biol. 58 6149-62) suggesting wall effects as a plausible explanation. The comment by Lindborg et al (2015 Phys. Med. Biol. 60 8621-4) concludes that this is not a likely explanation. A thorough investigation of the Monte Carlo (MC) transport code used for track simulation revealed a critical bug. The corrected MC version yielded sigma(rel)(z) values that are now within experimental uncertainty. Other microdosimetric findings are hereby communicated.

  • 36.
    Villegas, Fernanda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy 125I and 192Ir sources and 60Co cell irradiation2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 17, p. 6149-6162Article in journal (Refereed)
    Abstract [en]

    The stochastic nature of ionizing radiation interactions causes a microdosimetric spread in energy depositions for cell or cell nucleus-sized volumes. The magnitude of the spread may be a confounding factor in dose response analysis. The aim of this work is to give values for the microdosimetric spread for a range of doses imparted by 125I and 192Ir brachytherapy radionuclides, and for a 60Co source. An upgraded version of the Monte Carlo code PENELOPE was used to obtain frequency distributions of specific energy for each of these radiation qualities and for four different cell nucleus-sized volumes. The results demonstrate that the magnitude of the microdosimetric spread increases when the target size decreases or when the energy of the radiation quality is reduced. Frequency distributions calculated according to the formalism of Kellerer and Chmelevsky using full convolution of the Monte Carlo calculated single track frequency distributions confirm that at doses exceeding 0.08 Gy for 125I, 0.1 Gy for 192Ir, and 0.2 Gy for 60Co, the resulting distribution can be accurately approximated with a normal distribution. A parameterization of the width of the distribution as a function of dose and target volume of interest is presented as a convenient form for the use in response modelling or similar contexts.

  • 37.
    Villegas, Fernanda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Bäckström, Gloria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
    Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 18, p. 5531-5543Article in journal (Refereed)
    Abstract [en]

    Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation. The results suggest that there is both a non-uniform and a uniform random component to the frequency distribution of distances to the nearest neighbour ED. The closest neighbouring EDs show high spatial correlation for all investigated radiation qualities, whilst the uniform random component dominates for neighbours with longer distances for the three higher mean photon energy sources (192Ir, 137Cs, and 60Co). The two lower energy photon emitters (103Pd and 125I) present a very small uniform random component. The ratio of frequencies of clusters with respect to 60Co differs up to 15% for the lower energy sources and less than 2% for the higher energy sources when the maximum distance between each pair of EDs is 2 nm. At distances relevant to DNA damage, cluster patterns can be differentiated between the lower and higher energy sources. This may be part of the explanation to the reported difference in RBE values with initial DSB yields as an endpoint for these brachytherapy sources.

  • 38.
    Villegas, Fernanda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Tilly, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences. Elekta Instrument AB, Box7593, SE-10393 Stockholm, Sweden.
    Bäckström, Gloria
    McGill Univ, Dept Oncol, Med Phys Unit, Montreal, PQ, Canada; McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Corrigendum to ’Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd,125I,192Ir,137Cs and 60Co’, PMB 59 (2014) 5531-432016In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 61, no 15, p. 5883-5886Article in journal (Refereed)
  • 39. Wang, Ruoxi
    et al.
    Pittet, Patrick
    Ribouton, Julien
    Lu, Guo-Neng
    Chaikh, Abdulhamid
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Implementation and validation of a fluence pencil kernels model for GaN-based dosimetry in photon beam radiotherapy2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 19, p. 6701-6712Article in journal (Refereed)
    Abstract [en]

    Gallium nitride (GaN), a direct-gap semiconductor that is radioluminescent, can be used as a transducer yielding a high signal from a small detecting volume and thus potentially suitable for use in small fields and for high dose gradients. A common drawback of semiconductor dosimeters with effective atomic numbers higher than soft tissues is that their responses depend on the presence of low energy photons for which the photoelectric cross section varies strongly with atomic number, which may affect the accuracy of dosimetric measurements. To tackle this 'over-response' issue, we propose a model for GaN-based dosimetry with readout correction. The local photon spectrum is calculated by convolving fluence pencil kernel spectra with the beam aperture fluence distribution. The response of a GaN detector is modelled by combining large cavity theory and small cavity theory for the low and high energy components of the local spectrum. Monte Carlo simulations are employed for determination of specific correction factors for different GaN transducer sizes and irradiation conditions. Some model parameters such as the cut-off energy and partitioning energy are discussed. The accuracy of the GaN dosimetric response model has been evaluated for tissue phantom ratio experiments along the central axis. These experiments have shown that calculated and measured GaN responses stay within +/- 3% at all depths beyond the build-up depth. The calculated GaN response factor is also in good agreement with measured data (+/- 2.5%). The validated model with response compensation improves significantly the accuracy of dosimetric measurements: below 2.5% deviation as compared to 13% without compensation, for a 10 x 10 cm(2) field, at depth from 1.5 to 22 cm.

  • 40. Zuluaga, Maria A.
    et al.
    Orkisz, Maciej
    Dong, Pei
    Pacureanu, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gouttenoire, Pierre-Jean
    Peyrin, Françoise
    Bone canalicular network segmentation in 3D nano-CT images through geodesic voting and image tessellation2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 9, p. 2155-2171Article in journal (Refereed)
    Abstract [en]

    Recent studies emphasized the role of the bone lacuno-canalicular network (LCN) in the understanding of bone diseases such as osteoporosis. However, suitable methods to investigate this structure are lacking. The aim of this paper is to introduce a methodology to segment the LCN from three-dimensional (3D) synchrotron radiation nano-CT images. Segmentation of such structures is challenging due to several factors such as limited contrast and signal-to-noise ratio, partial volume effects and huge number of data that needs to be processed, which restrains user interaction. We use an approach based on minimum-cost paths and geodesic voting, for which we propose a fully automatic initialization scheme based on a tessellation of the image domain. The centroids of pre-segmented lacunae are used as Voronoi-tessellation seeds and as start-points of a fast-marching front propagation, whereas the end-points are distributed in the vicinity of each Voronoi-region boundary. This initialization scheme was devised to cope with complex biological structures involving cells interconnected by multiple thread-like, branching processes, while the seminal geodesic-voting method only copes with tree-like structures. Our method has been assessed quantitatively on phantom data and qualitatively on real datasets, demonstrating its feasibility. To the best of our knowledge, presented 3D renderings of lacunae interconnected by their canaliculi were achieved for the first time.

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