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  • 1.
    Andisheh, Bahram
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Bitaraf, Mohammad Ali
    University of Tehran.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Brahme, Anders
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 7, p. 2057-2067Article in journal (Refereed)
    Abstract [en]

    Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

  • 2.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Dose to 'water-like' media or dose to tissue in MV photons radiotherapy treatment planning: still a matter of debate2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 1, p. 309-337Article in journal (Refereed)
    Abstract [en]

    The difference between Monte Carlo Treatment Planning (MCTP) based on the assumption of 'water-like' tissues with densities obtained from CT procedures, or on tissue compositions derived from CT-determined densities, have been investigated. Stopping powers and electron fluences have been calculated for a range of media and body tissues for 6 MV photon beams, including changes in their physical data (density and stopping powers). These quantities have been used to determine absorbed doses using cavity theory. It is emphasized that tissue compositions given in ICRU or ICRP reports should not be given the standing of physical constants as they correspond to average values obtained for a limited number of human-body samples. It has been shown that mass stopping-power ratios to water are more dependent on patient-to-patient composition differences, and therefore on their mean excitation energies (I-values), than on mass density. Electron fluence in different media are also more dependent on media composition (and their I-values) than on density. However, as a consequence of the balance between fluence and stopping powers, doses calculated from their product are more constant than what the independent stopping powers and fluence variations suggest. Additionally, cancelations in dose ratios minimize the differences between the 'water-like' and 'tissue' approaches, yielding practically identical results except for bone, and to a lesser extent for adipose tissue. A priori, changing from one approach to another does not seem to be justified considering the large number of approximations and uncertainties involved throughout the treatment planning tissue segmentation and dose calculation procedures. The key issue continues to be the composition of tissues and their I-values, and as these cannot be obtained for individual patients, whatever approach is selected does not lead to significant differences from a water reference dose, the maximum of these being of the order of 5% for bone tissues. Considering, however, current developments in advanced dose calculation methods, planning in terms of dose-to-tissue should be the preferred choice, under the expectancy that progress in the field will gradually improve some of the crude approximations included in MCTP and numerical transport methods. The small differences obtained also show that a retrospective conversion from dose-to-tissue to dose-to-water, based on a widely used approach, would mostly increase the final uncertainty of the treatment planning process. It is demonstrated that, due to the difference between electron fluence distributions in water and in body tissues, the conversion requires an additional fluence correction that has so far been neglected. An improved expression for the conversion and data for the fluence correction factor are provided. These will be necessary even in a dose-to-tissue environment, for the normalization of the treatment plan to the reference dosimetry of the treatment unit, always calibrated in terms of absorbed dose to water.

  • 3.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics.
    On the clinical spatial resolution achievable with protons and heavier charged particle radiotherapy beams2009In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 54, no 11, p. n205-N215Article in journal (Refereed)
    Abstract [en]

    The 'sub-millimetre precision' often claimed to be achievable in protons and light ion beam therapy is analysed using the Monte Carlo code SHIELD-HIT for a broad range of energies. Based on the range of possible values and uncertainties of the mean excitation energy of water and human tissues, as well as of the composition of organs and tissues, it is concluded that precision statements deserve careful reconsideration for treatment planning purposes. It is found that the range of I-values of water stated in ICRU reports 37, 49 and 73 (1984, 1993 and 2005) for the collision stopping power formulae, namely 67 eV, 75 eV and 80 eV, yields a spread of the depth of the Bragg peak of protons and heavier charged particles (carbon ions) of up to 5 or 6 mm, which is also found to be energy dependent due to other energy loss competing interaction mechanisms. The spread is similar in protons and in carbon ions having analogous practical range. Although accurate depth-dose distribution measurements in water can be used at the time of developing empirical dose calculation models, the energy dependence of the spread causes a substantial constraint. In the case of in vivo human tissues, where distribution measurements are not feasible, the problem poses a major limitation. In addition to the spread due to the currently accepted uncertainties of their I-values, a spread of the depth of the Bragg peak due to the varying compositions of soft tissues is also demonstrated, even for cases which could be considered practically identical in clinical practice. For these, the spreads found were similar to those of water or even larger, providing support to international recommendations advising that body-tissue compositions should not be given the standing of physical constants. The results show that it would be necessary to increase the margins of a clinical target volume, even in the case of a water phantom, due to an 'intrinsic basic physics uncertainty', adding to those margins usually considered in normal clinical practice due to anatomical or therapeutic strategy reasons. Individualized patient determination of tissue composition along the complete beam path, rather than CT Hounsfield numbers alone, would also probably be required even to reach 'sub-centimetre precision'.

  • 4.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics.
    On the p(dis) correction factor for cylindrical chambers2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 5, p. l9-L16Article in journal (Refereed)
    Abstract [en]

    The authors of a recent paper (Wang and Rogers 2009 Phys. Med. Biol. 54 1609) have used the Monte Carlo method to simulate the 'classical' experiment made more than 30 years ago by Johansson et al (1978 National and International Standardization of Radiation Dosimetry (Atlanta 1977) vol 2 (Vienna: IAEA) pp 243-70) on the displacement (or replacement) perturbation correction factor p(dis) for cylindrical chambers in Co-60 and high-energy photon beams. They conclude that an 'unreasonable normalization at dmax' of the ionization chambers response led to incorrect results, and for the IAEA TRS-398 Code of Practice, which uses ratios of those results, 'the difference in the correction factors can lead to a beam calibration deviation of more than 0.5% for Farmer-like chambers'. The present work critically examines and questions some of the claims and generalized conclusions of the paper. It is demonstrated that for real, commercial Farmer-like chambers, the possible deviations in absorbed dose would be much smaller (typically 0.13%) than those stated by Wang and Rogers, making the impact of their proposed values negligible on practical high-energy photon dosimetry. Differences of the order of 0.4% would only appear at the upper extreme of the energies potentially available for clinical use (around 25 MV) and, because lower energies are more frequently used, the number of radiotherapy photon beams for which the deviations would be larger than say 0.2% is extremely small. This work also raises concerns on the proposed value of p(dis) for Farmer chambers at the reference quality of Co-60 in relation to their impact on electron beam dosimetry, both for direct dose determination using these chambers and for the cross-calibration of plane-parallel chambers. The proposed increase of about 1% in p(dis) (compared with TRS-398) would lower the k(Q) factors and therefore D-w in electron beams by the same amount. This would yield a severe discrepancy with the current good agreement between electron dosimetry based on an electron cross-calibrated plane-parallel chamber (against a Farmer) or on a directly Co-60 calibrated plane-parallel chamber, which is not likely to be in error by 1%. It is suggested that the influence of the Co-60 source spectrum used in the simulations may not be negligible for calculations aimed at an uncertainty level of 0.1%.

  • 5.
    Andreo, Pedro
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Burns, David T.
    Salvat, Francesc
    On the uncertainties of photon mass energy-absorption coefficients and their ratios for radiation dosimetry2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 8, p. 2117-2136Article in journal (Refereed)
    Abstract [en]

    A systematic analysis of the available data has been carried out for mass energy-absorption coefficients and their ratios for air, graphite and water for photon energies between 1 keV and 2 MeV, using representative kilovoltage x-ray spectra for mammography and diagnostic radiology below 100 kV, and for Ir-192 and Co-60 gamma-ray spectra. The aim of this work was to establish 'an envelope of uncertainty' based on the spread of the available data. Type A uncertainties were determined from the results of Monte Carlo (MC) calculations with the PENELOPE and EGSnrc systems, yielding mean values for mu(en)/rho with a given statistical standard uncertainty. Type B estimates were based on two groupings. The first grouping consisted of MC calculations based on a similar implementation but using different data and/or approximations. The second grouping was formed by various datasets, obtained by different authors or methods using the same or different basic data, and with different implementations (analytical, MC-based, or a combination of the two); these datasets were the compilations of NIST, Hubbell, Johns-Cunningham, Attix and Higgins, plus MC calculations with PENELOPE and EGSnrc. The combined standard uncertainty, u(c), for the mu(en)/rho values for the mammography x-ray spectra is 2.5%, decreasing gradually to 1.6% for kilovoltage x-ray spectra up to 100 kV. For Co-60 and Ir-192, u(c) is approximately 0.1%. The Type B uncertainty analysis for the ratios of mu(en)/rho values includes four methods of analysis and concludes that for the present data the assumption that the data interval represents 95% confidence limits is a good compromise. For the mammography x-ray spectra, the combined standard uncertainties of (mu(en)/rho)(graphite,air) and (mu(en)/rho)(graphite,water) are 1.5%, and 0.5% for (mu(en)/rho)(water,air), decreasing gradually down to u(c) = 0.1% for the three mu(en)/rho ratios for the gamma-ray spectra. The present estimates are shown to coincide well with those of Hubbell (1977 Rad. Res. 70 58-81), except for the lowest energy range (radiodiagnostic) where it is concluded that current databases and their systematic analysis represent an improvement over the older Hubbell estimations. The results for (mu(en)/rho)(graphite,air) for the gamma-ray dosimetry range are moderately higher than those of Seltzer and Bergstrom (2005 private communication).

  • 6.
    Andreo, Pedro
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Wulff, Joerg
    Burns, David T.
    Palmans, Hugo
    Consistency in reference radiotherapy dosimetry: resolution of an apparent conundrum when Co-60 is the reference quality for charged-particle and photon beams2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 19, p. 6593-6621Article in journal (Refereed)
    Abstract [en]

    Substantial changes in ion chamber perturbation correction factors in Co-60 gamma-rays, suggested by recent Monte Carlo (MC) calculations, would cause a decrease of about 1.5% in the reference dosimetry of all types of charged particles (electrons, protons and heavier ions) based on calculated k(Q) values. It has gone largely unnoticed that the ratio of calibration coefficients N-D,N-w,N-Co60 and N-K,N-air,N-Co60 yields an experimental value of F-ch,F-Co60 = (s(w-air) pch)(Co60) through N-D,N-air,N-Co60. Coefficients provided by the IAEA and traceable to the BIPM for 91 NE-2571 chambers result in an average F-ch,F-Co60 which is compared with published (and new) MC simulations and with the value in IAEA TRS-398. It is shown that TRS-398 agrees within 0.12% with the experimental F-ch,F-Co60. The 1.5% difference resulting from MC calculations (1.1% for the new simulations) cannot be justified using current fundamental data and BIPM standards if consistency in the entire dosimetry chain is sought. For photons, MC k(Q) factors are compared with TRS-398. Using the same uncertainty for W-air, the two sets of data overlap considerably. Experimental k(Q) values from standards laboratories lie between the two sets of calculated values, showing no preference for one set over the other. Observed chamber-to-chamber differences, that include the effect of waterproof sleeves (also seen for Co-60), justify the recommendation in TRS-398 for k(Q) values specifically measured for the user chamber. Current developments on I-values for the stopping powers of water and graphite are presented. A weighted average I-water = 78 +/- 2 eV is obtained from published experimental and DRF-based values; this would decrease sw-air for all types of radiotherapy beams between 0.3% and 0.6%, and would consequently decrease the MC derived F-ch,F-Co60. The implications of a recent proposal for I-graphite = 81 eV are analysed, resulting in a potential decrease of 0.7% in N-K,N-air,N-Co60 which would raise the experimental F-ch,F-Co60; this would result in an increase of about 0.8% in the current TRS-398 value when referred to the BIPM standards. MC derived F-ch,F-Co60 using new stopping powers would then agree at a level of 0.1% with the experimental value, confirming the need for consistency in the dosimetry chain data. Should world average standards be used as reference, the figures would become +0.4% for TRS-398 and -0.3% for the MC calculation. F-ch,F-Q calculated for megavoltage photons using new stopping powers would decrease by between 0.2% and 0.5%. When they enter as a ratios in k(Q), differences with MC values based on current key data would be within 0.2% but their discrepancy with k(Q) experimental photon values remains unresolved. For protons the new data would require an increase in W-air,W-Q of about 0.6%, as this is inferred from a combination of calorimetry and ionometry. This consistent scenario would leave unchanged the current TRS-398 k(Q) (NE-2571) data for protons, as well as for ions heavier than protons unless new independent W-air,W-Q values become available. Also in these advanced radiotherapy modalities, the need for maintaining data consistency in an analysis that unavoidably must include the complete dosimetry chain is demonstrated.

  • 7.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Bouchard, Hugo
    Fransson, Annette
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Backscatter factors and mass energy-absorption coefficient ratios for diagnostic radiology dosimetry2011In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 22, p. 7179-7204Article in journal (Refereed)
    Abstract [en]

    Backscatter factors, B, and mass energy-absorption coefficient ratios, (mu(en)/rho)(omega,) (air), for the determination of the surface dose in diagnostic radiology were calculated using Monte Carlo simulations. The main purpose was to extend the range of available data to qualities used in modern x-ray techniques, particularly for interventional radiology. A comprehensive database for mono-energetic photons between 4 and 150 keV and different field sizes was created for a 15 cm thick water phantom. Backscattered spectra were calculated with the PENELOPE Monte Carlo system, scoring track-length fluence differential in energy with negligible statistical uncertainty; using the Monte Carlo computed spectra, B factors and (mu(en)/rho)(omega), air were then calculated numerically for each energy. Weighted averaging procedures were subsequently used to convolve incident clinical spectra with mono-energetic data. The method was benchmarked against full Monte Carlo calculations of incident clinical spectra obtaining differences within 0.3-0.6%. The technique used enables the calculation of B and (mu(en)/rho)(w), air for any incident spectrum without further time-consuming Monte Carlo simulations. The adequacy of the extended dosimetry data to a broader range of clinical qualities than those currently available, while keeping consistency with existing data, was confirmed through detailed comparisons. Mono-energetic and spectra-averaged values were compared with published data, including those in ICRU Report 74 and IAEA TRS-457, finding average differences of 0.6%. Results are provided in comprehensive tables appropriated for clinical use. Additional qualities can easily be calculated using a designed GUI interface in conjunction with software to generate incident photon spectra.

  • 8.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Fransson, Annette
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Influence of phantom thickness and material on the backscatter factors for diagnostic x-ray beam dosimetry2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 2, p. 247-260Article in journal (Refereed)
    Abstract [en]

    Most of the existing backscatter factors for the dosimetry of clinical diagnostic x-ray beams have been calculated for 15 cm thick phantoms; these data are used for skin dose determinations which in general ignore the influence of phantom material and thickness. The former should strictly be required whenever dosimetry measurements are made on phantom materials different from those used for the backscatter factor calculations. The phantom or patient thickness is of special importance when skin dose determinations are made for infants or paediatric patients. In this work, the recently published formalism for reference dosimetry and comprehensive database of backscatter factors for clinical beams and water phantoms have been extended using two correction factors which account for phantom material and thickness. These were determined with simulations using the PENELOPE Monte Carlo system, for PMMA to analyse the influence of the phantom material relative to water, and for a broad range of thicknesses of water and PMMA to investigate the role of this parameter in patient dose estimates. The material correction factor was found to be in the range 3-10%, depending on the field size and the HVL. The thickness correction factor was in the range 2-12% for a 5 cm thick phantom and square field sizes between 5 and 35 cm, reaching a plateau of about ±1% for thicknesses beyond 13 cm. Expressions in the form of surface fits over the calculated data are provided which streamline the determination of backscatter factors for arbitrary thicknesses and phantom materials, as well as field sizes. Results demonstrate the inadequacy of using conventional backscatter factors (calculated for 15 cm thick phantoms) without correction factors that take into account the phantom material and its thickness.

  • 9.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska University Hospital, Sweden.
    Johansson, J.
    Paddick, I.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska University Hospital, Sweden.
    Monte Carlo calculated and experimentally determined output correction factors for small field detectors in Leksell Gamma Knife Perfexion beams2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 10, p. 3959-3973Article in journal (Refereed)
    Abstract [en]

    The measurement of output factors (OF) for the small photon beams generated by Leksell Gamma Knife (R) (LGK) radiotherapy units is a challenge for the physicist due to the under or over estimation of these factors by a vast majority of the detectors commercially available. Output correction factors, introduced in the international formalism published by Alfonso (2008 Med. Phys. 35 5179-86), standardize the determination of OFs for small photon beams by correcting detector-reading ratios to yield OFs in terms of absorbed-dose ratios. In this work output correction factors for a number of detectors have been determined for LGK Perfexion (TM) Co-60 gamma-ray beams by Monte Carlo (MC) calculations and measurements. The calculations were made with the MC system PENELOPE, scoring the energy deposited in the active volume of the detectors and in a small volume of water; the detectors simulated were two silicon diodes, one liquid ionization chamber (LIC), alanine and TLD. The calculated LIC output correction factors were within +/- 0.4%, and this was selected as the reference detector for experimental determinations where output correction factors for twelve detectors were measured, normalizing their readings to those of the LIC. The MC-calculated and measured output correction factors for silicon diodes yielded corrections of up to 5% for the smallest LGK collimator size of 4 mm diameter. The air ionization chamber measurements led to extremely large output correction factors, caused by the well-known effect of partial volume averaging. The corrections were up to 7% for the natural diamond detector in the 4 mm collimator, also due to partial volume averaging, and decreased to within about +/- 0.6% for the smaller synthetic diamond detector. The LIC, showing the smallest corrections, was used to investigate machine-to-machine output factor differences by performing measurements in four LGK units with different dose rates. These resulted in OFs within +/- 0.6% and +/- 0.2% for the 4 mm and 8 mm collimators, respectively, providing evidence for the use of generic OFs for these LGK beams. Using the experimentally derived output correction factors, OFs can be measured using a wide range of commercially available detectors.

  • 10.
    Böhlen, Till Tobias
    et al.
    Stockholm University, Faculty of Science, Department of Physics. CERN, Geneva, Switzerland; Karolinska Institutet, Sweden.
    Brons, S.
    Dosanjh, M.
    Ferrari, A.
    Fossati, P.
    Haberer, T.
    Patera, V.
    Mairani, A.
    Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 23, p. 7983-8004Article in journal (Refereed)
    Abstract [en]

    Uncertainties in determining clinically-used relative biological effectiveness (RBE) values for ion beam therapy carry the risk of absolute and relative misestimations of RBE-weighted doses for clinical scenarios. The present study assesses the consequences of hypothetical misestimations of input parameters to the RBE modelling for carbon ion treatment plans by a variational approach. The impact of the variations on resulting cell survival and RBE values is evaluated as a function of the remaining ion range. In addition, the sensitivity to misestimations in RBE modelling is compared for single fields and two opposed fields using differing optimization criteria. It is demonstrated for single treatment fields that moderate variations (up to ±50%) of representative nominal input parameters for four tumours result mainly in a misestimation of the RBE-weighted dose in the planning target volume (PTV) by a constant factor and only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation quality in the PTV eases the clinical importance of uncertainties in the radiobiological treatment parameters as for such a condition uncertainties tend to result only in a systematic misestimation of RBE-weighted dose in the PTV by a constant factor. Two opposed carbon ion fields with a constant RBE in the PTV are found to result in rather robust conditions. Treatments using two ion species may be used to achieve a constant RBE in the PTV irrespective of the size and depth of the spread-out Bragg peak.

  • 11.
    Böhlen, Till Tobias
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Cerutti, F.
    Dosanjh, M.
    Ferrari, A.
    Gudowska, Irena
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Mairani, A.
    Quesada, J. M.
    Benchmarking nuclear models of FLUKA and GEANT4 for carbon ion therapy2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 19, p. 5833-5847Article in journal (Refereed)
    Abstract [en]

    As carbon ions, at therapeutic energies, penetrate tissue, they undergo inelastic nuclear reactions and give rise to significant yields of secondary fragment fluences. Therefore, an accurate prediction of these fluences resulting from the primary carbon interactions is necessary in the patient's body in order to precisely simulate the spatial dose distribution and the resulting biological effect. In this paper, the performance of nuclear fragmentation models of the Monte Carlo transport codes, FLUKA and GEANT4, in tissue-like media and for an energy regime relevant for therapeutic carbon ions is investigated. The ability of these Monte Carlo codes to reproduce experimental data of charge-changing cross sections and integral and differential yields of secondary charged fragments is evaluated. For the fragment yields, the main focus is on the consideration of experimental approximations and uncertainties such as the energy measurement by time-of-flight. For GEANT4, the hadronic models G4BinaryLightIonReaction and G4QMD are benchmarked together with some recently enhanced de-excitation models. For non-differential quantities, discrepancies of some tens of percent are found for both codes. For differential quantities, even larger deviations are found. Implications of these findings for the therapeutic use of carbon ions are discussed.

  • 12.
    Böhlen, Till Tobias
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Dosanjh, M.
    Ferrari, A.
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Mairani, A.
    FLUKA simulations of the response of tissue-equivalent proportional counters to ion beams for applications in hadron therapy and space2011In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 20, p. 6545-6561Article in journal (Refereed)
    Abstract [en]

    For both cancer therapy with protons and ions (hadron therapy) and space radiation environments, the spatial energy deposition patterns of the radiation fields are of importance for quantifying the resulting radiation damage in biological structures. Tissue-equivalent proportional counters (TEPC) are the principal instruments for measuring imparted energy on a microscopic scale and for characterizing energy deposition patterns of radiation. Moreover, the distribution of imparted energy can serve as a complementary quantity to particle fluences of the primary beam and secondary fragments for characterizing a radiation field on a physical basis for radiobiological models. In this work, the Monte Carlo particle transport code FLUKA is used for simulating energy depositions in TEPC by ion beams. The capability of FLUKA in predicting imparted energy and derived quantities, such as lineal energy, for microscopic volumes is evaluated by comparing it with a large set of TEPC measurements for different ion beams with atomic numbers ranging from 1 to 26 and energies from 80 up to 1000 MeV/n. The influence of different physics configurations in the simulation is also discussed. It is demonstrated that FLUKA can simulate energy deposition patterns of ions in TEPC cavities accurately and that it provides an adequate description of the main features of the spectra.

  • 13. Christensen, Jeppe Brage
    et al.
    Almhagen, Erik
    Stolarczyk, Liliana
    Vestergaard, Anne
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden; Aarhus University Hospital, Denmark.
    Andersen, Claus E.
    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.

  • 14. Conti, Maurizio
    et al.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Physics. Siemens Healthcare Molecular Imaging, USA; Karolinska Institute, Sweden; University of Tennessee, USA.
    Rothfuss, Harold
    Sjoeholm, Therese
    Townsend, David
    Rosenqvist, Göran
    Carlier, Thomas
    Characterization of Lu-176 background in LSO-based PET scanners2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 9, p. 3700-3711Article in journal (Refereed)
    Abstract [en]

    LSO and LYSO are today the most common scintillators used in positron emission tomography. Lutetium contains traces of Lu-176, a radioactive isotope that decays beta(-) with a cascade of. photons in coincidence. Therefore, Lutetium-based scintillators are characterized by a small natural radiation background. In this paper, we investigate and characterize the Lu-176 radiation background via experiments performed on LSO-based PET scanners. LSO background was measured at different energy windows and different time coincidence windows, and by using shields to alter the original spectrum. The effect of radiation background in particularly count-starved applications, such as Y-90 imaging, is analysed and discussed. Depending on the size of the PET scanner, between 500 and 1000 total random counts per second and between 3 and 5 total true coincidences per second were measured in standard coincidence mode. The LSO background counts in a Siemens mCT in the standard PET energy and time windows are in general negligible in terms of trues, and are comparable to that measured in a BGO scanner of similar size.

  • 15. Costa Ferreira, Brigida
    et al.
    Mavroidis, Panayiotis
    Adamus-Górka, Magdalena
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Svensson, Roger
    Lind, Bengt K.
    Impact of Different Dose-Response Parameters on Biologically Optimized IMRT in Breast Cancer2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 10, p. 2733-2752Article in journal (Refereed)
    Abstract [en]

    The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I–II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose–response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

  • 16.
    Costa Ferreira, Brigida
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI). University of Aveiro, Portugal; Portuguese Institute of Oncology of Coimbra, Portugal.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI). Karolinska Institutet, Sweden; Larissa University Hospital, Greece.
    Adamus-Górka, Magdalena
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Svensson, Roger
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt K.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    The impact of different dose-response parameters on biologically optimized IMRT in breast cancer.2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 10, p. 2733-52Article in journal (Refereed)
    Abstract [en]

    The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I-II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P(+)), the biologically effective uniform dose (D), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P(+) between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P(+) are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

  • 17.
    Dasu, Alexandru
    et al.
    Umeå University.
    Toma-Dasu, Iuliana
    Umeå University.
    Fowler, Jack F.
    University of Wisconsin.
    Should single or distributed parameters be used to explain the steepness of tumour control probability curves?2003In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 48, no 3, p. 387-397Article in journal (Refereed)
    Abstract [en]

    Linear quadratic (LQ) modelling allows easy comparison of different fractionation schedules in radiotherapy. However, estimating the radiation effect of a single fractionated treatment introduces many questions with respect to the parameters to be used in the modelling process. Several studies have used tumour control probability (TCP) curves in order to derive the values for the LQ parameters that may be used further for the analysis and ranking of treatment plans. Unfortunately, little attention has been paid to the biological relevance of these derived parameters, either for the initial number of cells or their intrinsic radiosensitivity, or both. This paper investigates the relationship between single values for the TCP parameters and the resulting dose-response curve. The results of this modelling study show how clinical observations for the position and steepness of the TCP curve can be explained only by the choice of extreme values for the parameters, if they are single values. These extreme values are in contradiction with experimental observations. This contradiction suggests that single values for the parameters are not likely to explain reasonably the clinical observations and that some distributions of input parameters should be taken into consideration.

  • 18.
    Dasu, Alexandru
    et al.
    Umeå University.
    Toma-Dasu, Iuliana
    Umeå University.
    Karlsson, Mikael
    Umeå University.
    Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia2003In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 48, no 17, p. 2829-2842Article in journal (Refereed)
    Abstract [en]

    The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.

  • 19.
    Dasu, Iuliana Livia
    et al.
    Umeå University.
    Dasu, Alexandru
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Fowler, Jack F.
    University of Wisconsin.
    Comments on 'Standard effective doses for proliferative tumours'2000In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 10, p. L45-L50Article in journal (Refereed)
  • 20.
    Eriksson, Lars
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden; Siemens Healthcare Molecular Imaging, USA; University of Tennessee, USA.
    Conti, Maurizio
    Randoms and TOF gain revisited2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 4, p. 1613-1623Article in journal (Refereed)
    Abstract [en]

    Time-of-flight (TOF) positron emission tomography (PET) typically reduces the variance in the images by a factor that is proportional to the size of the object to be scanned, and inversely proportional to the time resolution of the PET scanner. Attempts to better characterize this relationship and understand its limits have been published, showing that such gain also increases with random fraction. In this paper, new experimental and simulated data are analyzed and old results are incorporated in the study. The proportionality of TOF gain with time resolution is confirmed, the proportionality constant is measured, the effect of the randoms is validated, and the limit of the model for small objects is investigated.

  • 21. Goma, C.
    et al.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet.
    Sempau, J.
    Spencer-Attix water/medium stopping-power ratios for the dosimetry of proton pencil beams2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 8, p. 2509-2522Article in journal (Refereed)
    Abstract [en]

    This paper uses Monte Carlo simulations to calculate the Spencer-Attix water/medium stopping-power ratios (s(w, med)) for the dosimetry of scanned proton pencil beams. It includes proton energies from 30 to 350 MeV and typical detection materials such as air (ionization chambers), radiochromic film, gadolinium oxysulfide (scintillating screens), silicon and lithium fluoride. Track-ends and particles heavier than protons were found to have a negligible effect on the water/air stopping-power ratios (s(w, air)), whereas the mean excitation energy values were found to carry the largest source of uncertainty. The initial energy spread of the beam was found to have a minor influence on the s(w, air) values in depth. The water/medium stopping-power ratios as a function of depth in water were found to be quite constant for air and radiochromic film-within 2.5%. Also, the s(w, med) values were found to have no clinically relevant dependence on the radial distance-except for the case of gadolinium oxysulfide and proton radiography beams. In conclusion, the most suitable detection materials for depth-dose measurements in water were found to be air and radiochromic film active layer, although a small correction is still needed to compensate for the different s(w, med) values between the plateau and the Bragg peak region. Also, all the detection materials studied in this work-except for gadolinium oxysulfide-were found to be suitable for lateral dose profiles and field-specific dose distribution measurements in water.

  • 22.
    Hollmark, Malin
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Gudowska, Irena
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Belkić, Dževad
    Brahme, Anders
    Sobolevsky, Nikolai
    Analytical model for light ion pencil beam dose distributions: multiple scattering of primary and secondary ions2008In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 53, no 13, p. 3477-3491Article 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.

  • 23.
    Hultqvist, Martha
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Fernández-Varea, José M.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI). Universitat de Barcelona, Spain.
    Izewska, Joanna
    Monte Carlo simulation of correction factors for IAEA TLD holders2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 6, p. N161-N166Article in journal (Refereed)
    Abstract [en]

    The IAEA standard thermoluminescent dosimeter (TLD) holder has been developed for the IAEA/WHO TLD postal dose program for audits of high-energy photon beams, and it is also employed by the ESTRO-QUALity assurance network (EQUAL) and several national TLD audit networks. Factors correcting for the influence of the holder on the TL signal under reference conditions have been calculated in the present work from Monte Carlo simulations with the PENELOPE code for Co-60 gamma-rays and 4, 6, 10, 15, 18 and 25 MV photon beams. The simulation results are around 0.2% smaller than measured factors reported in the literature, but well within the combined standard uncertainties. The present study supports the use of the experimentally obtained holder correction factors in the determination of the absorbed dose to water from the TL readings; the factors calculated by means of Monte Carlo simulations may be adopted for the cases where there are no measured data.

  • 24.
    Hultqvist, Martha
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Secondary absorbed doses from light ion irradiation in anthropomorphic phantoms representing an adult male and a 10 year old child2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 22, p. 6633-6653Article in journal (Refereed)
    Abstract [en]

    Secondary organ absorbed doses were calculated by Monte Carlo simulations with the SHIELD-HIT07 code coupled with the mathematical anthropomorphic phantoms CHILD-HIT and ADAM-HIT. The simulated irradiations were performed with primary 1H, 4He, 7Li, 12C and 16O ion beams in the energy range 100–400 MeV/u which were directly impinging on the phantoms, i.e. approximating scanned beams, and with a simplified beamline for 12C irradiation. The evaluated absorbed doses to the out-of-field organs were in the range 10−6 to 10−1 mGy per target Gy and with standard deviations 0.5–20%. While the contribution to the organ absorbed doses from secondary neutrons dominated in the ion beams of low atomic number Z, the produced charged fragments and their subsequent charged secondaries of higher generations became increasingly important for the secondary dose delivery as Z of the primary ions increased. As compared to the simulated scanned 12C ion beam, the implementation of a simplified beamline for prostate irradiation with 12C ions resulted in an increase of 2–50 times in the organ absorbed doses depending on the distance from the target volume. Comparison of secondary organ absorbed doses delivered by 1H and 12C beams showed smaller differences when the RBE for local tumor control of the ions was considered and normalization to the RBE-weighted dose to the target was performed.

    General scientific summary. During light ion therapy, the production of nuclear fragments results in a complex secondary radiation field which the organs and normal tissues of the patient are exposed to. In the present work, the absorbed doses to out-of-field organs and the energy distribution of secondary particle fluences in anthropomorphic phantoms have been simulated by the Monte Carlo code SHIELD-HIT07 for brain tumor and prostate irradiation with approximated scanned beams of 1H, 4He, 7Li, 12C and 16O ions in the energy range 100–400 MeV/u, as well as with a simplified beam line for 12C irradiation. The evaluated organ absorbed doses were in the range 10−6 to 10−1 mGy per target Gy. The absorbed dose contribution from secondary neutrons dominated in the ion beams of low atomic number Z, while the produced charged fragments and their subsequent charged secondaries became increasingly important for the secondary dose delivery as Z of the primary ion increased.

  • 25.
    Hultqvist, Martha
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Lazzeroni, Marta
    Botvina, Alexander
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Sobolevsky, Nikolai
    Brahme, Anders
    Evaluation of nuclear reaction cross-sections and fragment yields in carbon beams using the SHIELD-HIT Monte Carlo code. Comparison with experiments2012In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 57, no 13, p. 4369-4385Article in journal (Refereed)
    Abstract [en]

    In light ion therapy, the knowledge of the spectra of both primary and secondary particles in the target volume is needed in order to accurately describe the treatment. The transport of ions in matter is complex and comprises both atomic and nuclear processes involving primary and secondary ions produced in the cascade of events. One of the critical issues in the simulation of ion transport is the modeling of inelastic nuclear reaction processes, in which projectile nuclei interact with target nuclei and give rise to nuclear fragments. In the Monte Carlo code SHIELD-HIT, inelastic nuclear reactions are described by the Many Stage Dynamical Model (MSDM), which includes models for the different stages of the interaction process. In this work, the capability of SHIELD-HIT to simulate the nuclear fragmentation of carbon ions in tissue-like materials was studied. The value of the parameter., which determines the so-called freeze-out volume in the Fermi break-up stage of the nuclear interaction process, was adjusted in order to achieve better agreement with experimental data. In this paper, results are shown both with the default value k = 1 and the modified value k = 10 which resulted in the best overall agreement. Comparisons with published experimental data were made in terms of total and partial charge-changing cross-sections generated by the MSDM, as well as integral and differential fragment yields simulated by SHIELD-HIT in intermediate and thick water targets irradiated with a beam of 400 MeV u(-1) C-12 ions. Better agreement with the experimental data was in general obtained with the modified parameter value (k = 10), both on the level of partial charge-changing cross-sections and fragment yields.

  • 26. Høye, Ellen Marie
    et al.
    Skyt, Peter S.
    Balling, Peter
    Muren, Ludvig P.
    Taasti, Vicki T.
    Swakoń, Jan
    Mierzwińska, Gabriela
    Rydygier, Marzena
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics. Aarhus University, Denmark.
    Petersen, Jørgen B. B.
    Chemically tuned linear energy transfer dependent quenching in a deformable, radiochromic 3D dosimeter2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 4, p. N73-N89Article in journal (Refereed)
    Abstract [en]

    Most solid-state detectors, including 3D dosimeters, show lower signal in the Bragg peak than expected, a process termed quenching. The purpose of this study was to investigate how variation in chemical composition of a recently developed radiochromic, silicone-based 3D dosimeter influences the observed quenching in proton beams. The dependency of dose response on linear energy transfer, as calculated through Monte Carlo simulations of the dosimeter, was investigated in 60 MeV proton beams. We found that the amount of quenching varied with the chemical composition: peak-to-plateau ratios (1 cm into the plateau) ranged from 2.2 to 3.4, compared to 4.3 using an ionization chamber. The dose response, and thereby the quenching, was predominantly influenced by the curing agent concentration, which determined the dosimeter's deformation properties. The dose response was found to be linear at all depths. All chemical compositions of the dosimeter showed dose-rate dependency; however this was not dependent on the linear energy transfer. Track-structure theory was used to explain the observed quenching effects. In conclusion, this study shows that the silicone-based dosimeter has potential for use in measuring 3D-dose-distributions from proton beams.

  • 27.
    Janek, Sara
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI). Stockholm University, Faculty of Science, Department of Physics.
    Svensson, Roger
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Jonsson, Cathrine
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Brahme, Anders
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy2006In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 22, p. 5769-Article in journal (Refereed)
    Abstract [en]

    A method for dose delivery monitoring after high energy photon therapy has been investigated based on positron emission tomography (PET). The technique is based on the activation of body tissues by high energy bremsstrahlung beams, preferably with energies well above 20 MeV, resulting primarily in 11C and 15O but also 13N, all positron-emitting radionuclides produced by photoneutron reactions in the nuclei of 12C, 16O and 14N. A PMMA phantom and animal tissue, a frozen hind leg of a pig, were irradiated to 10 Gy and the induced positron activity distributions were measured off-line in a PET camera a couple of minutes after irradiation. The accelerator used was a Racetrack Microtron at the Karolinska University Hospital using 50 MV scanned photon beams. From photonuclear cross-section data integrated over the 50 MV photon fluence spectrum the predicted PET signal was calculated and compared with experimental measurements. Since measured PET images change with time post irradiation, as a result of the different decay times of the radionuclides, the signals from activated 12C, 16O and 14N within the irradiated volume could be separated from each other. Most information is obtained from the carbon and oxygen radionuclides which are the most abundant elements in soft tissue. The predicted and measured overall positron activities are almost equal (−3%) while the predicted activity originating from nitrogen is overestimated by almost a factor of two, possibly due to experimental noise. Based on the results obtained in this first feasibility study the great value of a combined radiotherapy–PET–CT unit is indicated in order to fully exploit the high activity signal from oxygen immediately after treatment and to avoid patient repositioning. With an RT–PET–CT unit a high signal could be collected even at a dose level of 2 Gy and the acquisition time for the PET could be reduced considerably. Real patient dose delivery verification by means of PET imaging seems to be applicable provided that biological transport processes such as capillary blood flow containing mobile 15O and 11C in the activated tissue volume can be accounted for.

  • 28.
    Janek Strååt, Sara
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Andreassen, Björn
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Jonsson, Cathrine
    Noz, Marilyn E.
    Maguire Jr, Gerald Q.
    Nafstadius, Peder
    Näslund, Ingemar
    Schoenahl, Frederic
    Brahme, Anders
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 16, p. 5541-5553Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 +/- (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard F-18-FDG treatment. When using a combination of short lived nuclides such as O-15 (half-life: 2 min) and C-11 (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to O-15 imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

  • 29.
    Liamsuwan, Thiansin
    et al.
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Nikjoo, Hooshang
    Karolinska Institutet, Institutionen för onkologi-patologi .
    A Monte Carlo track structure simulation code for the full-slowing-down carbon projectiles of energies 1 keV u-1–10 MeV u-1 in water2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 3, p. 673-702Article in journal (Refereed)
    Abstract [en]

    The paper presents a new Monte Carlo track structure code (KURBUC_carbon) for simulations of full slowing down carbon projectiles C0–C6+ of energies 1 keV/u–10 MeV/u in water vapour. The code facilitates investigation of spatial resolution effect for scoring track parameters under the Bragg peak of carbon ion beam. Interactions of carbon projectiles and secondary electrons were followed event-by-event down to 1 keV/u cutoff for primary ions, and down to 10 eV for electrons. Electronic interactions and nuclear elastic scattering were taken into account, including charge exchange reactions and double electronic interactions for the carbon projectiles. The reliability of the code was tested for radial dose, range, and W-value. The calculated results were compared with the published experimental data, and other model calculations. The results obtained showed good agreement in most cases where comparisons could be made. Depth dose profiles for 1-10 MeV/u C6+ were used to form an SOBP of 0.35 mm width in water. At all depths of the SOBP, the energy distributions of the carbon projectiles varied appreciably with the change in the scoring volume. The corresponding variation was nearly negligible for the track average LET, except at the distal end of the SOBP. By varying the scoring slab thickness from 1 to 100 µm, the maximum track average LET decreased by ~30%. The Monte Carlo track structure simulation in the full slowing down mode is a powerful tool for investigation of biophysical properties of radiation tracks under the Bragg peak and SOBP of carbon ion beam. For estimation of radiation effectiveness under the Bragg peak the new Monte Carlo track structure code provides yet another accurate and effective dosimetry tool at a single cell level. This is because radiobiology within tissue elements can only be understood with dosimetry at cellular and subcellular level.

  • 30.
    Liamsuwan, Thiansin
    et al.
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Nikjoo, Hooshang
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Cross sections for bare and dressed carbon ions in water and neon2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, p. 641-672Article in journal (Refereed)
    Abstract [en]

    The paper presents calculated cross sections for bare and dressed carbon projectiles of charge states q (0 to 6) with energies 1–104 keV/u impacting on molecular water and atomic neon targets. The cross sections of water are of interest for radiobiological studies, but there are very few experimental data for water in any phase or non-existent. The more extensive experimental database for the neon target made it possible to test the reliability of the model calculations for many-electron collision system. The current calculations cover major single and double electronic interactions of low and intermediate energy carbon projectiles. The three-body classical trajectory Monte Carlo (CTMC) method was used for the calculation of one-electron transition probabilities for target ionisation, electron capture, and projectile electron loss. The many-electron problem was taken into account using statistical methods: a modified independent event model was used for pure (direct) and simultaneous target and projectile ionisations; and the independent particle model for pure electron capture and electron capture accompanied by target ionisation. Results are presented for double differential cross sections (DDCS) for total electron emission by carbon projectile impact on neon. For the water target, we present: single differential cross sections (SDCS) and DDCS for single target ionisation; total cross sections (TCS) for electron emission; TCS for the pure single electronic interactions; equilibrium charge state fractions; and stopping cross sections. The results were found to be in satisfactory agreement with the experimental data in many cases, including DDCS and SDCS for the single target ionisation, TCS for the total electron emission, and TCS for the pure single electron capture. The stopping cross sections of this work are consistent with the other model calculations for projectile energies ≥800 keV/u, but smaller than the other calculations at lower energies. The discrepancy arises from the inclusion of all carbon charge states and coupling between electron capture and target ionisation channels, while other models use an average projectile charge. The CTMC model presented here provides a tool for cross section calculations for low and intermediate energy carbon projectiles. The calculated cross sections are required for Monte Carlo track structure simulations of full-slowing-down tracks of carbon ions. The work paves the way for biophysical studies and dosimetry at the cellular and subcellular levels in the Bragg peak area of therapeutic carbon ion beam.

  • 31.
    Lillhök, J E
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Grindborg, J E
    Lindborg, L
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Alm Carlsson, G
    Söderberg, J
    Kopeć, M
    Medin, J
    Nanodosimetry in a clinical neutron therapy beam using the variance-covariance method and Monte Carlo simulations2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 16, p. 4953-Article in journal (Refereed)
    Abstract [en]

    Nanodosimetric single-event distributions or their mean values may contribute to a better understanding of how radiation induced biological damages are produced. They may also provide means for radiation quality characterization in therapy beams. Experimental nanodosimetry is however technically challenging and Monte Carlo simulations are valuable as a complementary tool for such investigations. The dose-mean lineal energy was determined in a therapeutic p(65)+Be neutron beam and in a 60Co γ beam using low-pressure gas detectors and the variance-covariance method. The neutron beam was simulated using the condensed history Monte Carlo codes MCNPX and SHIELD-HIT. The dose-mean lineal energy was calculated using the simulated dose and fluence spectra together with published data from track-structure simulations. A comparison between simulated and measured results revealed some systematic differences and different dependencies on the simulated object size. The results show that both experimental and theoretical approaches are needed for an accurate dosimetry in the nanometer region. In line with previously reported results, the dose-mean lineal energy determined at 10 nm was shown to be related to clinical RBE values in the neutron beam and in a simulated 175 MeV proton beam as well. 

  • 32. Lillhök, J E
    et al.
    Grindborg, J-E
    Lindborg, L
    Gudowska, Irena
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Carlsson, G Alm
    Söderberg, J
    Kopeć, M
    Medin, J
    Nanodosimetry in a clinical neutron therapy beam using the variance-covariance method and Monte Carlo simulations.2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 16, p. 4953-66Article in journal (Other academic)
    Abstract [en]

    Nanodosimetric single-event distributions or their mean values may contribute to a better understanding of how radiation induced biological damages are produced. They may also provide means for radiation quality characterization in therapy beams. Experimental nanodosimetry is however technically challenging and Monte Carlo simulations are valuable as a complementary tool for such investigations. The dose-mean lineal energy was determined in a therapeutic p(65)+Be neutron beam and in a Co-60 gamma. beam using low-pressure gas detectors and the variance-covariance method. The neutron beam was simulated using the condensed history Monte Carlo codes MCNPX and SHIELD-HIT. The dose-mean lineal energy was calculated using the simulated dose and fluence spectra together with published data from track-structure simulations. A comparison between simulated and measured results revealed some systematic differences and different dependencies on the simulated object size. The results show that both experimental and theoretical approaches are needed for an accurate dosimetry in the nanometer region. In line with previously reported results, the dose-mean lineal energy determined at 10 nm was shown to be related to clinical RBE values in the neutron beam and in a simulated 175 MeV proton beam as well.

  • 33.
    Lindblom, Emely
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Dasu, Alexandru
    The Skandion Clinic, Sweden.
    Beskow, Catharina
    Karolinska University Hospital, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    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.

  • 34. Lindborg, L.
    et al.
    Hultqvist, Martha
    Stockholm University, Faculty of Science, Department of Physics.
    Tedgren, A. Carlsson
    Nikjoo, H.
    Lineal energy and radiation quality in radiation therapy: model calculations and comparison with experiment2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 10, p. 3089-3105Article in journal (Refereed)
    Abstract [en]

    Microdosimetry is a recommended method for characterizing radiation quality in situations when the biological effectiveness under test is not well known. In such situations, the radiation beams are described by their lineal energy probability distributions. Results from radiobiological investigations in the beams are then used to establish response functions that relate the lineal energy to the relative biological effectiveness (RBE). In this paper we present the influence of the size of the simulated volume on the relation to the clinical RBE values (or weighting factors). A single event probability distribution of the lineal energy is approximated by its dose average lineal energy ((y) over bar (D)) which can be measured or calculated for volumes from a few micrometres down to a few nanometres. The clinical RBE values were approximated as the ratio of the alpha-values derived from the LQ-relation. Model calculations are presented and discussed for the SOBP of a C-12 ion (290 MeV u(-1)) and the reference Co-60 gamma therapy beam. Results were compared with those for a conventional x-ray therapy beam, a 290 MeV proton beam and a neutron therapy beam. It is concluded that for a simulated volume of about 10 nm, the alpha-ratio increases approximately linearly with the (y) over bar (D)-ratio for all the investigated beams. The correlation between y and alpha provides the evidence to characterize a radiation therapy beam by the lineal energy when, for instance, weighting factors are to be estimated.

  • 35. Mairani, A.
    et al.
    Böhlen, Till Tobias
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet.
    Schiavi, A.
    Tessonnier, T.
    Molinelli, S.
    Brons, S.
    Battistoni, G.
    Parodi, K.
    Patera, V.
    A Monte Carlo-based treatment planning tool for proton therapy2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 8, p. 2471-2490Article in journal (Refereed)
    Abstract [en]

    In the field of radiotherapy, Monte Carlo (MC) particle transport calculations are recognized for their superior accuracy in predicting dose and fluence distributions in patient geometries compared to analytical algorithms which are generally used for treatment planning due to their shorter execution times. In this work, a newly developed MC-based treatment planning (MCTP) tool for proton therapy is proposed to support treatment planning studies and research applications. It allows for single-field and simultaneous multiple-field optimization in realistic treatment scenarios and is based on the MC code FLUKA. Relative biological effectiveness (RBE)-weighted dose is optimized either with the common approach using a constant RBE of 1.1 or using a variable RBE according to radiobiological input tables. A validated reimplementation of the local effect model was used in this work to generate radiobiological input tables. Examples of treatment plans in water phantoms and in patient-CT geometries together with an experimental dosimetric validation of the plans are presented for clinical treatment parameters as used at the Italian National Center for Oncological Hadron Therapy. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios against dosimetric measurements and commercial analytical TP calculations. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.

  • 36. Palmans, H.
    et al.
    Al-Sulaiti, L.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics.
    Shipley, D.
    Luehr, A.
    Bassler, N.
    Martinkovic, J.
    Dobrovodsky, J.
    Rossomme, S.
    Thomas, R. A. S.
    Kacperek, A.
    Fluence correction factors for graphite calorimetry in a low-energy clinical proton beam: I. Analytical and Monte Carlo simulations2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 10, p. 3481-3499Article in journal (Refereed)
    Abstract [en]

    The conversion of absorbed dose-to-graphite in a graphite phantom to absorbed dose-to-water in a water phantom is performed by water to graphite stopping power ratios. If, however, the charged particle fluence is not equal at equivalent depths in graphite and water, a fluence correction factor, k(fl), is required as well. This is particularly relevant to the derivation of absorbed dose-to-water, the quantity of interest in radiotherapy, from a measurement of absorbed dose-to-graphite obtained with a graphite calorimeter. In this work, fluence correction factors for the conversion from dose-to-graphite in a graphite phantom to dose-to-water in a water phantom for 60 MeV mono-energetic protons were calculated using an analytical model and five different Monte Carlo codes (Geant4, FLUKA, MCNPX, SHIELD-HIT and McPTRAN.MEDIA). In general the fluence correction factors are found to be close to unity and the analytical and Monte Carlo codes give consistent values when considering the differences in secondary particle transport. When considering only protons the fluence correction factors are unity at the surface and increase with depth by 0.5% to 1.5% depending on the code. When the fluence of all charged particles is considered, the fluence correction factor is about 0.5% lower than unity at shallow depths predominantly due to the contributions from alpha particles and increases to values above unity near the Bragg peak. Fluence correction factors directly derived from the fluence distributions differential in energy at equivalent depths in water and graphite can be described by k(fl) = 0.9964 + 0.0024 . z(w-eq) with a relative standard uncertainty of 0.2%. Fluence correction factors derived from a ratio of calculated doses at equivalent depths in water and graphite can be described by k(fl) = 0.9947 + 0.0024 . z(w-eq) with a relative standard uncertainty of 0.3%. These results are of direct relevance to graphite calorimetry in low-energy protons but given that the fluence correction factor is almost solely influenced by non-elastic nuclear interactions the results are also relevant for plastic phantoms that consist of carbon, oxygen and hydrogen atoms as well as for soft tissues.

  • 37. Ringbaek, Toke Printz
    et al.
    Weber, Uli
    Santiago, Alina
    Iancu, Gheorghe
    Wittig, Andrea
    Grzanka, Leszek
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Engenhart-Cabillic, Rita
    Zink, Klemens
    Validation of new 2D ripple filters in proton treatments of spherical geometries and non-small cell lung carcinoma cases2018In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 63, no 24, article id 245020Article in journal (Refereed)
    Abstract [en]

    A ripple filter (RiFi) is a passive energy modulator used in scanned particle therapy to broaden the Bragg peak, thus lowering the number of accelerator energies required for homogeneous target coverage, which significantly reduces the irradiation time. As we have previously shown, a new 6 mm thick RiFi with 2D groove shapes produced with 3D printing can be used in carbon ion treatments with a similar target coverage and only a marginally worse planning conformity compared to treatments with in-use 3 mm thick RiFis of an older 1D design. Where RiFis are normally not used with protons due to larger scattering and straggling effects, this new design would be beneficial in proton therapy too. Measurements of proton Bragg curves and lateral beam profiles were carried out for different RiFi designs and thicknesses as well as for no RiFi at the Heidelberg lonenstrahl-Therapiezentrum. Base data for proton treatment planning were generated with the Monte Carlo code SHIELD-HIT12A with and without the 2D 6 mm RiFi. Plans on spherical targets in water were calculated with TRiP98 for a systematic RiFi performance analysis and for comparisons with carbon ion plans for the same respective energy depth step sizes. Plans for 9 stage I static non small cell lung cancer patients were calculated with Eclipse 13.7.15. Dose-volume-histograms, spatial dose distributions and dosimetric indexes were used for plan evaluation. Measurements confirm the functionality of the new 2D RiFi design, which reduces the beam spot size compared to 1D RiFis of the same thickness. Planning studies show that a 6 mm thick 2D RiFi could be used in proton therapy to lower the irradiation time. Although slightly worse planning conformity and dose homogeneity were found for plans with the RiFi compared to plans without, satisfactory results within the planning objective were obtained for all cases.

  • 38. Roland, Teboh
    et al.
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Gutierrez, Alonso
    Goytia, Virginia
    Papanikolaou, Niko
    A radiobiological analysis of the effect of 3D versus 4D image-based planning in lung cancer radiotherapy.2009In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 54, no 18, p. 5509-23Article in journal (Refereed)
    Abstract [en]

    Dose distributions generated on a static anatomy may differ significantly from those delivered to temporally varying anatomy such as for abdominal and thoracic tumors, due largely in part to the unavoidable organ motion and deformation effects stemming from respiration. In this work, the degree of such variation for three treatment techniques, namely static conventional, gating and target tracking radiotherapy, was investigated. The actual delivered dose was approximated by planning all the phases of a 4DCT image set. Data from six (n = 6) previously treated lung cancer patients were used for this study with tumor motion ranging from 2 to 10 mm. Complete radiobiological analyses were performed to assess the clinical significance of the observed discrepancies between the 3D and 4DCT image-based dose distributions. Using the complication-free tumor control probability (P+) objective, we observed small differences in P+ between the 3D and 4DCT image-based plans (<2.0% difference on average) for the gating and static conventional regimens and higher differences in P+ (4.0% on average) for the tracking regimen. Furthermore, we observed, as a general trend, that the 3D plan underestimated the P+ values. While it is not possible to draw any general conclusions from a small patient cohort, our results suggest that there exists a patient population in which 4D planning does not provide any additional benefits beyond that afforded by 3D planning for static conventional or gated radiotherapy. This statement is consistent with previous studies based on physical dosimetric evaluations only. The higher differences observed with the tracking technique suggest that individual patient plans should be evaluated on a case-by-case basis to assess if 3D or 4D imaging is appropriate for the tracking technique.

  • 39.
    Toma-Dasu, Iuliana
    et al.
    Umeå University.
    Dasu, Alexandru
    Umeå University.
    Karlsson, Mikael
    Umeå University.
    Conversion of polarographic electrode measurements--a computer based approach2005In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 50, no 19, p. 4581-4591Article in journal (Refereed)
    Abstract [en]

    The polarographic measurement of tissue oxygenation is one of the most widely used methods in clinical practice for the quantification of tumour hypoxia. However, due to the particular features of the electrode measuring process, the results of the measurements do not accurately reflect the tumour oxygenation. This study aimed to find a correlation between the electrode measurements and the tumour oxygenation in an attempt to improve the accuracy of the predictions regarding the response to treatment based on electrode measurements. A previously developed computer model that allows the simulation of tumour tissue and electrode measurements was used. The oxygenation of a large number of tumours with biologically relevant distributions of blood vessels was theoretically calculated. Simulations of electrode measurements allowed the comparison between the real tissue oxygenation and the results obtained with the electrode. A semi-empirical relationship between the hypoxic fraction measured by the electrode and the real hypoxic fraction in the tissue has been found. The impact of the correction of the electrode measurements in terms of predictions for tumour control probability was estimated for a few clinical examples. The range of possible true values corresponding to one measurement has also proven useful for explaining the apparently unexpected response to the treatment of some patients. The corrected hypoxic fraction which is believed to be closer to the real value of tissue hypoxia predicts much smaller control probabilities than the raw electrode measurements. This could provide an explanation for the apparently unexpected failure to respond to the treatment of some of the patients with apparently favourable tumour oxygenation. This also means that the electrode measurements cannot be used directly for the quantitative modelling of tumour response to the treatment. The conversion method proposed in this paper might however strengthen the statistical power of the correlations between the electrode measurements and the treatment outcome.

  • 40.
    Toma-Dasu, Iuliana
    et al.
    Umeå University.
    Dasu, Alexandru
    Umeå University.
    Karlsson, Mikael
    Umeå University.
    The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation2004In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 49, no 19, p. 4463-4475Article in journal (Refereed)
    Abstract [en]

    The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads to a systematic deviation between the actual oxygen distribution and the measured distribution. However, as the electrode reflects the general trends of the tissue oxygenation it has the potential of being used for the general characterization of tumour hypoxia even if the actual type of hypoxia measured by the electrode cannot be determined. Indeed, the change in time of the acute hypoxic region does not compensate for the lack of oxygenation at a specific moment and therefore does not influence the polarographic oxygen measurements.

  • 41. Watson, Charles C.
    et al.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Physics.
    Kolb, Armin
    Physics and applications of positron beams in an integrated PET/MR2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 3, p. l1-L12Article in journal (Refereed)
    Abstract [en]

    In PET/MR systems having the PET component within the uniform magnetic field interior to the MR, positron beams can be injected into the PET field of view (FOV) from unshielded emission sources external to it, as a consequence of the action of the Lorentz force on the transverse components of the positron's velocity. Such beams may be as small as a few millimeters in diameter, but extend 50 cm or more axially without appreciable divergence. Larger beams form 'phantoms' of annihilations in air that can be easily imaged, and that are essentially free of gamma-ray attenuation and scatter effects, providing a unique tool for characterizing PET systems and reconstruction algorithms. Thin targets intersecting these beams can produce intense annihilation sources having the thickness of a sheet of paper, which are very useful for high resolution measurements, and difficult to achieve with conventional sources. Targeted beams can provide other point, line and surface sources for various applications, all without the need to have radioactivity within the FOV. In this paper we discuss the physical characteristics of positron beams in air and present examples of their applications.

  • 42.
    Wiklund, Kristin
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Fernández-Varea, José M.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt K.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    A Monte Carlo program for the analysis of low-energy electron tracks in liquid water2011In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 7, p. 1985-2003Article in journal (Refereed)
    Abstract [en]

    A Monte Carlo code for the event-by-event simulation of electron transport in liquid water is presented. The code, written in C++, can accommodate different interaction models. Currently it implements cross sections for ionizing collisions calculated with the model developed by Dingfelder et al (1998 Radiat. Phys. Chem. 53 1–18, 2008 Radiat. Res. 169 584–94) and cross sections for elastic scattering computed within the static-exchange approximation (Salvat et al 2005 Comput. Phys. Commun. 165 157–90). The latter cross sections coincide with those recommended in ICRU Report 77 (2007). Other included interaction mechanisms are excitation by electron impact and dissociative attachment. The main characteristics of the code are summarized. Various track penetration parameters, including the detour factor, are defined as useful tools to quantify the geometrical extent of electron tracks in liquid water. Results obtained with the present microdosimetry code are given in the form of probability density functions for initial electron kinetic energies ranging from 0.1 to 10 keV. The sensitivity of the simulated distributions to the choice of alternative physics models has been briefly explored. The discrepancies with equivalent simulations reported by Wilson et al (2004 Radiat. Res. 161 591–6) stem from the adopted cross sections for elastic scattering, which determine largely the spatial evolution of low-energy electron tracks.

  • 43. Wiklund, Kristin
    et al.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics.
    Lind, Bengt
    Reply to the comment on ‘The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy’2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 18, p. 6591-6592Article in journal (Refereed)
  • 44.
    Wiklund, Kristin
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Lind, Bengt K.
    The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy2011In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 23, p. 7585-7600Article in journal (Refereed)
    Abstract [en]

    Theoretical modelling of tumour control probability (TCP) with respect to non-uniformity in the dose to the tumour, alternate fractionation schemes and tumour kinetics is a very useful tool for assessment of the influence of changes in dosimetric or radiobiological factors on the outcome of the treatment. Various attempts have been made to also include effects from non-uniform dose to the tumour volume, but the problem has not been fully solved and many factors were totally neglected or not accurately taken into account. This paper presents derivations of analytical expressions of TCP for macroscopic inter-cell dose variations and for random inter-fractional variations in average tumour dose, based on binomial statistics for the TCP and the well-known linear quadratic model for the cell survival. Numerical calculations have been performed to validate the analytical expressions. An analysis of the influence of the deterministic and stochastic heterogeneity in dose delivery on the TCP was performed. The precision requirements in dose delivery are discussed briefly with the support of the presented results. The main finding of this paper is that it is primarily the shape of the cell survival curve that governs how the response is affected by macroscopic dose variations. The analytical expressions for TCP accounting for heterogeneity in dose can quite well describe the TCP for varying dose from cell to cell and random dose in each fraction. An increased TCP is seen when a large number of fractions are used and the variations in dose to the cells are rather high for tissues with low alpha/beta.

  • 45.
    Ödén, Jakob
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Yu, Cedric X.
    Feigenberg, Steven J.
    Regine, William F.
    Mutaf, Yildirim D.
    Dosimetric comparison between intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod(TM)2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 13, p. 4409-4421Article in journal (Refereed)
    Abstract [en]

    The GammaPod (TM) device, manufactured by Xcision Medical Systems, is a novel stereotactic breast irradiation device. It consists of a hemispherical source carrier containing 36 Cobalt-60 sources, a tungsten collimator with two built-in collimation sizes, a dynamically controlled patient support table and a breast immobilization cup also functioning as the stereotactic frame for the patient. The dosimetric output of the GammaPod (TM) was modelled using a Monte Carlo based treatment planning system. For the comparison, three-dimensional (3D) models of commonly used intra-cavitary breast brachytherapy techniques utilizing single lumen and multi-lumen balloon as well as peripheral catheter multi-lumen implant devices were created and corresponding 3D dose calculations were performed using the American Association of Physicists in Medicine Task Group-43 formalism. Dose distributions for clinically relevant target volumes were optimized using dosimetric goals set forth in the National Surgical Adjuvant Breast and Bowel Project Protocol B-39. For clinical scenarios assuming similar target sizes and proximity to critical organs, dose coverage, dose fall-off profiles beyond the target and skin doses at given distances beyond the target were calculated for GammaPod (TM) and compared with the doses achievable by the brachytherapy techniques. The dosimetric goals within the protocol guidelines were fulfilled for all target sizes and irradiation techniques. For central targets, at small distances from the target edge (up to approximately 1 cm) the brachytherapy techniques generally have a steeper dose fall-off gradient compared to GammaPod (TM) and at longer distances (more than about 1 cm) the relation is generally observed to be opposite. For targets close to the skin, the relative skin doses were considerably lower for GammaPod (TM) than for any of the brachytherapy techniques. In conclusion, GammaPod (TM) allows adequate and more uniform dose coverage to centrally and peripherally located targets with an acceptable dose fall-off and lower relative skin dose than the brachytherapy techniques considered in this study.

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