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1.	Omar, A., et al. (author) A framework for organ dose estimation in x-ray angiography and interventional radiology based on dose-related data in DICOM structured reports 2016 In: Physics in Medicine and Biology. - Stockholm : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 61:8, s. 3063-3083 Journal article (peer-reviewed)abstract Although interventional x-ray angiography (XA) procedures involve relatively high radiation doses that can lead to deterministic tissue reactions in addition to stochastic effects, convenient and accurate estimation of absorbed organ doses has traditionally been out of reach. This has mainly been due to the absence of practical means to access dose-related data that describe the physical context of the numerous exposures during an XA procedure. The present work provides a comprehensive and general framework for the determination of absorbed organ dose, based on non-proprietary access to dose-related data by utilizing widely available DICOM radiation dose structured reports. The framework comprises a straightforward calculation workflow to determine the incident kerma and reconstruction of the geometrical relation between the projected x-ray beam and the patient's anatomy. The latter is difficult in practice, as the position of the patient on the table top is unknown. A novel patient-specific approach for reconstruction of the patient position on the table is presented. The proposed approach was evaluated for 150 patients by comparing the estimated position of the primary irradiated organs (the target organs) with their position in clinical DICOM images. The approach is shown to locate the target organ position with a mean (max) deviation of 1.3 (4.3), 1.8 (3.6) and 1.4 (2.9) cm for neurovascular, adult and paediatric cardiovascular procedures, respectively. To illustrate the utility of the framework for systematic and automated organ dose estimation in routine clinical practice, a prototype implementation of the framework with Monte Carlo simulations is included.
2.	Fonslet, J., et al. (author) 135La as an Auger-electron emitter for targeted internal radiotherapy 2018 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:1 Journal article (peer-reviewed)abstract 135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 19 MBq A-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the 135La with an effective molar activity of 70 20 GBq mol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.
3.	Andersson, Martin, et al. (author) A biokinetic and dosimetric model for ionic indium in humans 2017 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 62:16, s. 6397-6407 Journal article (peer-reviewed)abstract This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for 111In- and 113mIn-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for 111In and 113mIn are 0.25 mSv MBq-1 and 0.013 mSv MBq-1 respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.
4.	Andersson, Martin, et al. (author) Lifetime attributable risk as an alternative to effective dose to describe the risk of cancer for patients in diagnostic and therapeutic nuclear medicine 2017 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 62:24, s. 9177-9188 Journal article (peer-reviewed)abstract The aim of this study is to implement lifetime attributable risk (LAR) predictions of cancer for patients of various age and gender, undergoing diagnostic investigations or treatments in nuclear medicine and to compare the outcome with a population risk estimate using effective dose and the International Commission on Radiological Protection risk coefficients. The radiation induced risk of cancer occurrence (incidence) or death from four nuclear medicine procedures are estimated for both male and female between 0 and 120 years. Estimations of cancer risk are performed using recommended administered activities for two diagnostic (18F-FDG and 99mTc-phosphonate complex) and two therapeutic (131I-iodide and 223Ra-dichloride) radiopharmaceuticals to illustrate the use of cancer risk estimations in nuclear medicine. For 18F-FDG, the cancer incidence for a male of 5, 25, 50 and 75 years at exposure is 0.0021, 0.0010, 0.0008 and 0.0003, respectively. For 99mTc phosphonates complex the corresponding values are 0.000 59, 0.000 34, 0.000 27 and 0.000 13, respectively. For an 131I-iodide treatment with 3.7 GBq and 1% uptake 24 h after administration, the cancer incidence for a male of 25, 50 and 75 years at exposure is 0.041, 0.029 and 0.012, respectively. For 223Ra-dichloride with an administration of 21.9 MBq the cancer incidence for a male of 25, 50 and 75 years is 0.31, 0.21 and 0.09, respectively. The LAR estimations are more suitable in health care situations involving individual patients or specific groups of patients than the health detriment based on effective dose, which represents a population average. The detriment consideration in effective dose adjusts the cancer incidence for suffering of non-lethal cancers while LAR predicts morbidity (incidence) or mortality (cancer). The advantages of these LARs are that they are gender and age specific, allowing risk estimations for specific patients or subgroups thus better representing individuals in health care than effective dose.
5.	Arboled, C., et al. (author) Assessing lesion malignancy by scanning small-angle x-ray scattering of breast tissue with microcalcifications 2019 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 64:15 Journal article (peer-reviewed)abstract Scanning small-angle x-ray scattering (SAXS) measurements were performed on 36 formalin-fixed breast tissue biopsies obtained from two patients. All samples contained microcalcifications of type II, i.e. formed by hydroxyapatite. We demonstrate the feasibility of classifying breast lesions by scanning SAXS of tissues containing microcalcifications with a resolution of 35 mu m x 30 mu m We report a characteristic Bragg peak found around q = 1.725 nm(-1) that occurs primarily for malignant lesions. Such a clear SAXS fingerprint is potentially linked to structural changes of breast tissue and corresponds to dimensions of about 3.7 nm. This material property could be used as an early indicator of malignancy development, as it is readily assessed by SAXS. If this fingerprint is combined with other known SAXS features, which also indicate the level of malignancy, such as lipid spacing and collagen periodicity, it could complement traditional pathology-based analyses. To confirm the SAXS-based classification, a histopathological workup and a gold standard histopathological diagnosis were conducted to determine the malignancy level of the lesions. Our aim is to report this SAXS fingerprint, which is clearly related to malignant breast lesions. However, any further conclusion based on our dataset is limited by the low number of patients and samples. Running a broad study to increase the number of samples and patients is of great importance and relevance for the breast-imaging community.
6.	Edvardsson, A., et al. (author) Breathing-motion induced interplay effects for stereotactic body radiotherapy of liver tumours using flattening-filter free volumetric modulated arc therapy 2019 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 64:2 Journal article (peer-reviewed)abstract The purpose of this study was to investigate breathing-motion induced interplay effects for stereotactic body radiotherapy (SBRT) of liver tumours treated with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT). Ten patients previously treated with liver SBRT were included in this study. All patients had four-dimensional computed tomography (4DCT) scans acquired prior to treatment. The 4DCT was sorted into 8-10 phases covering an equal time interval. A FFF VMAT plan was created for one fraction in the mid-ventilation phase for each patient. To generate dose distributions including both interplay effects and dose blurring, a sub-plan was calculated for each phase. The total dose distributions were accumulated to the mid-ventilation phase using the deformed vector fields (DVF) from deformable image registration between the corresponding CT and the mid-ventilation phase CT. A blurred dose distribution, not including interplay effects, was also obtained by distributing the delivery of the whole plan uniformly on all phases, and was similarly accumulated to the mid-ventilation phase. To isolate interplay effects, this blurred dose distribution was subtracted from the total dose distribution with interplay effects. The near minimum dose (D-98%), mean dose (D-mean), heterogeneity index (HI), and the near minimum dose difference (Delta D-98%) between the accumulated dose distributions with and without interplay effects were calculated within the gross tumour volume (GTV) for each patient. Comparing the accumulated dose distributions with and without interplay effects, the D-98(%) decreased for nine of the ten patients and the HI increased for all patients. The median and minimum differences in D-98(%) were -2.1% and -5.0% (p = 0.006), respectively, and the median HI significantly increased from 6.2% to 12.2% (p = 0.002). The median Delta D-98% was -4.0% (range - 7% to - 1.5%). In conclusion, statistically significant breathing-induced interplay effects were observed for a single fraction of FFF VMAT liver SBRT, resulting in heterogeneous dose distributions within the GTV.
7.	Edvardsson, Anneli, et al. (author) Motion induced interplay effects for VMAT radiotherapy 2018 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:8 Journal article (peer-reviewed)abstract The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient-and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin(6) breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (Delta D-98% and Delta D-2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum Delta D-98% and maximum Delta D-2% being - 16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.
8.	Guillaume, Florian, et al. (author) Neutron microtomography to investigate the bone-implant interface - Comparison with histological analysis 2021 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 66:10 Journal article (peer-reviewed)abstract Bone properties and especially its microstructure around implants are crucial to evaluate the osseointegration of prostheses in orthopaedic, maxillofacial and dental surgeries. Given the intrinsic heterogeneous nature of the bone microstructure, an ideal probing tool to understand and quantify bone formation must be spatially resolved. X-ray imaging has often been employed, but is limited in the presence of metallic implants, where severe artifacts generally arise from the high attenuation of metals to x-rays. Neutron tomography has recently been proposed as a promising technique to study bone-implant interfaces, thanks to its lower interaction with metals. The aim of this study is to assess the potential of neutron tomography for the characterisation of bone tissue in the vicinity of a metallic implant. A standardised implant with a bone chamber was implanted in rabbit bone. Four specimens were imaged with neutron tomography and subsequently compared to non-decalcified histology to stain soft and mineralised bone tissues, used here as a ground-truth reference. An intensity-based image registration procedure was performed to place the 12 histological slices within the corresponding 3D neutron volume. Significant correlations (p < 0.01) were obtained between the two modalities for the bone-implant contact (BIC) ratio (R = 0.77) and the bone content inside the chamber (R = 0.89). The results indicate that mineralised bone tissue can be reliably detected by neutron tomography. However, the BIC ratio and bone content were found to be overestimated with neutron imaging, which may be explained by its sensitivity to non-mineralised soft tissues, as revealed by histological staining. This study highlights the suitability of neutron tomography for the analysis of the bone-implant interface. Future work will focus on further distinguishing soft tissues from bone tissue, which could be aided by the adoption of contrast agents.
9.	Gustafsson, C, et al. (author) Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate 2017 In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 62:8, s. 2976-2989 Journal article (peer-reviewed)abstract Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were ⩽0.02% and the radiotherapy structure mean volume deviations were <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.
10.	Gustafsson, Christian Jamtheim, et al. (author) Development and evaluation of a deep learning based artificial intelligence for automatic identification of gold fiducial markers in an MRI-only prostate radiotherapy workflow 2020 In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 65:22 Journal article (peer-reviewed)abstract Identification of prostate gold fiducial markers in magnetic resonance imaging (MRI) images is challenging when CT images are not available, due to misclassifications from intra-prostatic calcifications. It is also a time consuming task and automated identification methods have been suggested as an improvement for both objectives. Multi-echo gradient echo (MEGRE) images have been utilized for manual fiducial identification with 100% detection accuracy. The aim is therefore to develop an automatic deep learning based method for fiducial identification in MRI images intended for MRI-only prostate radiotherapy. MEGRE images from 326 prostate cancer patients with fiducials were acquired on a 3T MRI, post-processed with N4 bias correction, and the fiducial center of mass (CoM) was identified. A 9 mm radius sphere was created around the CoM as ground truth. A deep learning HighRes3DNet model for semantic segmentation was trained using image augmentation. The model was applied to 39 MRI-only patients and 3D probability maps for fiducial location and segmentation were produced and spatially smoothed. In each of the three largest probability peaks, a 9 mm radius sphere was defined. Detection sensitivity and geometric accuracy was assessed. To raise awareness of potential false findings a 'BeAware' score was developed, calculated from the total number and quality of the probability peaks. All datasets, annotations and source code used were made publicly available. The detection sensitivity for all fiducials were 97.4%. Thirty-six out of thirty-nine patients had all fiducial markers correctly identified. All three failed patients generated a user notification using the BeAware score. The mean absolute difference between the detected fiducial and ground truth CoM was 0.7 ± 0.9 [0 3.1] mm. A deep learning method for automatic fiducial identification in MRI images was developed and evaluated with state-of-the-art results. The BeAware score has the potential to notify the user regarding patients where the proposed method is uncertain.
11.	Gustafsson, Johan, et al. (author) Feasibility and limitations of quantitative SPECT for 223Ra 2020 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 65:8 Journal article (peer-reviewed)abstract The aim of this paper is to investigate the feasibility and limitations of activity-concentration estimation for 223Ra using SPECT. Phantom measurements are performed using spheres (volumes 5.5 mL to 26.4 mL, concentrations 1.6 kBq mL-1 to 4.5 kBq mL-1). Furthermore, SPECT projections are simulated using the SIMIND Monte Carlo program for two geometries, one similar to the physical phantom and the other being an anthropomorphic phantom with added lesions (volumes 34 mL to 100 mL, concentrations 0.5 kBq mL-1 to 4 kBq mL-1). Medium-energy and high-energy collimators, 60 projections with 55 s per projection and a 20% energy window at 82 keV are employed. For the Monte Carlo simulated images, Poisson-distributed noise is added in ten noise realizations. Reconstruction is performed (OS-EM, 40 iterations, 6 subsets) employing compensation for attenuation, scatter, and collimator-detector response. The estimated concentrations in the anthropomorphic phantom are also corrected using recovery coefficients. Errors for the largest sphere in the physical phantom range from -25% to -34% for the medium-energy collimator and larger deviations for smaller spheres. Corresponding results for the high-energy collimator are -15% to -31%. The corresponding Monte Carlo simulations show standard deviations of a few percentage points. For the anthropomorphic phantom, before application of recovery coefficients the bias ranges from -16% to -46% (medium-energy collimator) and -10% to -28% (high-energy collimator), with standard deviations of 2% to 14% and 1% to 16%. After the application of recovery coefficients, the biases range from -3% to -35% (medium energy collimator) and from 0% to -18%. The errors decrease with increasing concentrations. Activity-concentration estimation of 223Ra with SPECT is feasible, but problems with repeatability need to be further studied.
12.	Gustafsson, Johan, et al. (author) Monte Carlo-based SPECT reconstruction within the SIMIND framework 2018 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:24 Journal article (peer-reviewed)abstract This paper presents the development and validation of a Monte Carlo-based singe photon emission computed tomography reconstruction program for parallel-hole collimation contained within the SIMIND Monte Carlo framework. The Monte Carlo code is used as an accurate forward-projector and is combined with a simplified back-projector to perform iterative tomographic reconstruction using the Maximum Likelihood Expectation Maximization and Ordered Subsets Expectation Maximization algorithms, together forming a program called SIMREC. The Monte Carlo simulation transforms the estimated source distribution directly from activity to counts in its projections. Hence, the reconstructed image is expressed in activity without reference to an external calibration. The program is tested using phantom measurements of spheres filled with 99mTc, 177Lu and 131I placed in air and centrally and peripherally in a water-filled elliptical phantom. The feasibility of applying the reconstruction to patients is also demonstrated for a range of radiopharmaceuticals. The deviation in total activity in the spheres ranged between -4.1% and 6.2% compared with the activity determined when preparing the phantom. The SIMREC program was found to be accurate with respect to activity estimation and to reconstruct visually acceptable images within a few hours when applied to patient examples.
13.	Gustafsson, Johan, et al. (author) Theoretical aspects on the use of single-time-point dosimetry for radionuclide therapy 2022 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 67:2 Journal article (peer-reviewed)abstract Objective. This study considers the error distributions for time-integrated activity (TIA) of single-time-point (STP) methods for patient-specific dosimetry in radionuclide therapy. Approach. The general case with the same pharmaceutical labelled with different radionuclides for imaging and therapy are considered for a mono-exponential time-activity curve. Two methods for STP dosimetry, both based on the combination of one activity estimate with the population-mean effective decay constant, are investigated. The cumulative distribution functions (CDFs) and the probability density functions for the two methods are analytically derived for arbitrary distributions of the biological decay constant. The CDFs are used for determining 95% coverage intervals of the relative errors for different combinations of imaging time points, physical decay constants, and relative standard deviations of the biological decay constant. Two examples, in the form of kidney dosimetry in [177Lu]Lu-DOTA-TATE therapy and tumour dosimetry for Na[131I]I therapy for thyroid cancer with dosimetry based on imaging of Na[124I]I, are also studied in more detail with analysis of the sensitivity with respect to errors in the mean biological decay constant and to higher moments of the distribution. Main results. The distributions of the relative errors are negatively skewed, potentially leading to the situation that some TIA estimates are highly underestimated even if the majority of estimates are close to the true value. Significance. The main limitation of the studied STP dosimetry methods is the risk of large underestimations of the TIA.
14.	Medin, Joakim, et al. (author) Experimental determination of k Qfactors for two types of ionization chambers in scanned proton beams 2022 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 67:5 Journal article (peer-reviewed)abstract Objective. Experimental determination of beam quality k Q factors for two types of Farmer ionization chambers, NE2571 and IBA FC65-G, in a scanned proton beam for three nominal energies (140 MeV, 180 MeV and 220 MeV) based on water calorimetry. Approach. Beam quality correction factors were determined comparing the results obtained with water calorimetry and ionometry. Water calorimetry was performed to determine the absorbed dose at a depth of measurement in water of 5 g cm-2, limited by the extension of the calorimeter glass vessel used. For the ionometry, two chambers of each type were included in the study. The ionization chambers were calibrated in terms of absorbed dose to water in 60Co at the Swedish Secondary Standard Dosimetry Laboratory, directly traceable to the BIPM, and were used according to the IAEA TRS-398 Code of Practice. Main results. The k Q values determined in the present work have been compared with the values tabulated in TRS-398 and its forthcoming update and also with those obtained in previous water calorimetric measurements and Monte Carlo calculations. All results were found to agree within the combined uncertainties of the different data. Significance. It is expected that the present work will serve as an experimental contribution to k Q -factors for the two chamber types and three scanned proton beam qualities used.
15.	Palmans, Hugo, et al. (author) Current best estimates of beam quality correction factors for reference dosimetry of clinical proton beams 2022 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 67:19 Journal article (peer-reviewed)abstract Objective. To review the currently available data on beam quality correction factors, kQ, for ionization chambers in clinical proton beams and derive their current best estimates for the updated recommendations of the IAEA TRS-398 Code of Practice. Approach. The reviewed data come from 20 publications from which kQ values can be derived either directly from calorimeter measurements, indirectly from comparison with other chambers or from Monte Carlo calculated overall chamber factors, fQ. For cylindrical ionization chambers, a distinction is made between data obtained in the centre of a spread-out Bragg peak and those obtained in the plateau region of single-energy fields. For the latter, the effect of depth dose gradients has to be considered. To this end an empirical model for previously published displacement correction factors for single-layer scanned beams was established, while for unmodulated scattered beams experimental data were used. From all the data, chamber factors, fQ, and chamber perturbation correction factors, pQ, were then derived and analysed. Main results. The analysis showed that except for the beam quality dependence of the water-to-air mass stopping power ratio and, for cylindrical ionization chambers in unmodulated beams, of the displacement correction factor, there is no remaining beam quality dependence of the chamber perturbation correction factors pQ. Based on this approach, average values of the beam quality independent part of the perturbation factors were derived to calculate kQ values consistent with the data in the literature. Significance. The resulting data from this analysis are current best estimates of kQ values for modulated scattered beams and single-layer scanned beams used in proton therapy. Based on this, a single set of harmonized values is derived to be recommended in the update of IAEA TRS-398.
16.	Rix, Kristian R., et al. (author) Super-resolution x-ray phase-contrast and dark-field imaging with a single 2D grating and electromagnetic source stepping 2019 In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 64:16, s. 1-8 Journal article (peer-reviewed)abstract Here we report a method for increased resolution of single exposure three modality x-ray images using super-resolution. The three x-ray image modalities are absorption-, differential phase- contrast-, and dark-field-images. To create super-resolution, a non-mechanically movable micro- focus x-ray source is used. A series of almost identical x-ray projection images is obtained while the point source is translated in a two-dimensional grid pattern. The three image modalities are extracted from fourier space using spatial harmonic analysis, also known as the single-shot method. Using super-resolution on the low-resolution series of the three modalities separately results in high- resolution images for the modalities. This approach allows to compensate for the inherent loss in resolution caused by the single-shot method without increasing the need for stability or algorithms accounting for possible motion.
17.	Said, M., et al. (author) Analysis of dose heterogeneity using a subvolume-DVH 2017 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 62:21, s. 517-524 Journal article (peer-reviewed)abstract The dose-volume histogram (DVH) is universally used in radiation therapy for its highly efficient way of summarizing three-dimensional dose distributions. An apparent limitation that is inherent to standard histograms is the loss of spatial information, e.g. it is no longer possible to tell where low- and high-dose regions are, and whether they are connected or disjoint. Two methods for overcoming the spatial fragmentation of low- and high-dose regions are presented, both based on the gray-level size zone matrix, which is a two-dimensional histogram describing the frequencies of connected regions of similar intensities. The first approach is a quantitative metric which can be likened to a homogeneity index. The large cold spot metric (LCS) is here defined to emphasize large contiguous regions receiving too low a dose; emphasis is put on both size, and deviation from the prescribed dose. In contrast, the subvolume-DVH (sDVH) is an extension to the standard DVH and allows for a qualitative evaluation of the degree of dose heterogeneity. The information retained from the two-dimensional histogram is overlaid on top of the DVH and the two are presented simultaneously. Both methods gauge the underlying heterogeneity in ways that the DVH alone cannot, and both have their own merits - the sDVH being more intuitive and the LCS being quantitative.
18.	Törnquist, Elin, et al. (author) Dual modality neutron and x-ray tomography for enhanced image analysis of the bone-metal interface 2021 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 66:13 Journal article (peer-reviewed)abstract The bone tissue formed at the contact interface with metallic implants, particularly its 3D microstructure, plays a pivotal role for the structural integrity of implant fixation. X-ray tomography is the classical imaging technique used for accessing microstructural information from bone tissue. However, neutron tomography has shown promise for visualising the immediate bone-metal implant interface, something which is highly challenging with x-rays due to large differences in attenuation between metal and biological tissue causing image artefacts. To highlight and explore the complementary nature of neutron and x-ray tomography, proximal rat tibiae with titanium-based implants were imaged with both modalities. The two techniques were compared in terms of visualisation of different material phases and by comparing the properties of the individual images, such as the contrast-to-noise ratio. After superimposing the images using a dedicated image registration algorithm, the complementarity was further investigated via analysis of the dual modality histogram, joining the neutron and x-ray data. From these joint histograms, peaks with well-defined grey value intervals corresponding to the different material phases observed in the specimens were identified and compared. The results highlight differences in how neutrons and x-rays interact with biological tissues and metallic implants, as well as the benefits of combining both modalities. Future refinement of the joint histogram analysis could improve the segmentation of structures and tissues, and yield novel information about specimen-specific properties such as moisture content.
19.	Kaveckyte, Vaiva, 1991-, et al. (author) Impact of the I-value of diamond on the energy deposition in different beam qualities 2021 In: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 66:12 Journal article (peer-reviewed)abstract Diamond detectors are increasingly employed in dosimetry. Their response has been investigated by means of Monte Carlo (MC) methods, but there is no consensus on what mass density ρ, mean excitation energy I and number of conduction electrons per atom nce to use in the simulations. The ambiguity occurs due to its seeming similarity with graphite (both are carbon allotropes). Contrary to diamond, graphite has been well-characterized. Except for the difference in ρ between crystalline graphite (2.265 g cm-3) and diamond (3.515 g cm-3), their dielectric properties are assumed to be identical. This is incorrect, and the two materials should be distinguished: (ρ = 2.265 g cm-3, I = 81.0 eV, nce = 1) for graphite and (ρ = 3.515 g cm-3, I = 88.5 eV, nce = 0) for diamond. Simulations done with the MC code PENELOPE show that the energy imparted in diamond decreases by up to 1% with respect to 'pseudo-diamond' (ρ = 3.515 g cm-3, I = 81.0 eV, nce = 0) depending on the beam quality and cavity thickness. The energy imparted changed the most in cavities that are small compared with the range of electrons. The difference in the density-effect term relative to graphite was the smallest for diamond owing to an interplay effect that ρ, I and nce have on this term, in contrast to pseudo-diamond media when either ρ or I alone were adjusted. The study also presents a parameterized density-effect correction function for diamond that may be used by MC codes like EGSnrc. The ESTAR program assumes that nce = 2 for all carbon-based materials, hence it delivers an erroneous density-effect correction term for graphite and diamond. Despite the small changes of the energy imparted in diamond simulated with two different I values and expected close-to-negligible deviation from the published small-field output correction data, it is important to pay attention to material properties and model the medium faithfully.
20.	Kallioniemi, Antti, et al. (author) Contrast agent enhanced pQCT of articular cartilage. 2007 In: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 52:4, s. 1209-1219 Journal article (peer-reviewed)abstract The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n=3) and trypsin-degraded (n=3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n=16). After trypsin-induced PG loss (-70%, p<0.05) the penetration of gadopentetate and ioxaglate increased (p<0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r=-0.95, r=-0.94, p<0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.
21.	Liamsuwan, Thiansin, et al. (author) 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 water 2013 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 58:3, s. 673-702 Journal article (peer-reviewed)abstract 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.
22.	Liamsuwan, Thiansin, et al. (author) Cross sections for bare and dressed carbon ions in water and neon 2013 In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 58, s. 641-672 Journal article (peer-reviewed)abstract 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.
23.	Miettinen, Kaisa, 1965-, et al. (author) Interactive Multiobjective Optimization for Anatomy based Three-Dimensinal HDR Brachytherapy 2010 In: Physics in Medicine and Biology. - : Institute of Physics and Engineering in Medicine. - 0031-9155 .- 1361-6560. ; 55:16, s. 4703-4719 Journal article (peer-reviewed)abstract In this paper, we present an anatomy-based three-dimensional dose optimization approach for HDR brachytherapy using interactive multiobjective optimization (IMOO). In brachytherapy, the goals are to irradiate a tumor without causing damage to healthy tissue. These goals are often conflicting, i.e. when one target is optimized the other will suffer, and the solution is a compromise between them. IMOO is capable of handling multiple and strongly conflicting objectives in a convenient way. With the IMOO approach, a treatment planner’s knowledge is used to direct the optimization process. Thus, the weaknesses of widely used optimization techniques (e.g. defining weights, computational burden and trial-and-error planning) can be avoided, planning times can be shortened and the number of solutions to be calculated is small. Further, plan quality can be improved by finding advantageous trade-offs between the solutions. In addition, our approach offers an easy way to navigate among the obtained Pareto optimal solutions (i.e. different treatment plans). When considering a simulation model of clinical 3D HDR brachytherapy, the number of variables is significantly smaller compared to IMRT, for example. Thus, when solving the model, the CPU time is relatively short. This makes it possible to exploit IMOO to solve a 3D HDR brachytherapy optimization problem. To demonstrate the advantages of IMOO, two clinical examples of optimizing a gynecologic cervix cancer treatment plan are presented.
24.	Bernchou, Uffe, et al. (author) End-to-end validation of the geometric dose delivery performance of MR linac adaptive radiotherapy 2021 In: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 66:4 Journal article (peer-reviewed)abstract The clinical introduction of hybrid magnetic resonance (MR) guided radiotherapy (RT) delivery systems has led to the need to validate the end-to-end dose delivery performance on such machines. In the current study, an MR visible phantom was developed and used to test the spatial deviation between planned and delivered dose at two 1.5 T MR linear accelerator (MR linac) systems, including pre-treatment imaging, dose planning, online imaging, image registration, plan adaptation, and dose delivery. The phantom consisted of 3D printed plastic and MR visible silicone rubber. It was designed to minimise air gaps close to the radiochromic film used as a dosimeter. Furthermore, the phantom was designed to allow submillimetre, reproducible positioning of the film in the phantom. At both MR linac systems, 54 complete adaptive, MR guided RT workflow sessions were performed. To test the dose delivery performance of the MR linac systems in various adaptive RT (ART) scenarios, the sessions comprised a range of systematic positional shifts of the phantom and imaging or plan adaptation conditions. In each workflow session, the positional translation between the film and the adaptive planned dose was determined. The results showed that the accuracy of the MR linac systems was between 0.1 and 0.9 mm depending on direction. The highest mean deviance observed was in the posterior-anterior direction, and the direction of the error was consistent between centres. The precision of the systems was related to whether the workflow utilized the internal image registration algorithm of the MR linac. Workflows using the internal registration algorithm led to a worse precision (0.2-0.7 mm) compared to workflows where the algorithm was decoupled (0.2 mm). In summary, the spatial deviation between planned and delivered dose of MR-guided ART at the two MR linac systems was well below 1 mm and thus acceptable for clinical use.
25.	Speight, Richard, et al. (author) IPEM Topical Report : an international IPEM survey of MRI use for external beam radiotherapy treatment planning 2021 In: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 66:7 Journal article (peer-reviewed)abstract Introduction/Background: Despite growing interest in magnetic resonance imaging (MRI), integration in external beam radiotherapy (EBRT) treatment planning uptake varies globally. In order to understand the current international landscape of MRI in EBRT a survey has been performed in 11 countries. This work reports on differences and common themes identified.Methods: A multi-disciplinary Institute of Physics and Engineering in Medicine working party modified a survey previously used in the UK to understand current practice using MRI for EBRT treatment planning, investigate how MRI is currently used and managed as well as identify knowledge gaps. It was distributed electronically within 11 countries: Australia, Belgium, Denmark, Finland, France, Italy, the Netherlands, New Zealand, Sweden, the UK and the USA.Results: The survey response rate within the USA was <1% and hence these results omitted from the analysis. In the other 10 countries the survey had a median response rate of 77% per country. Direct MRI access, defined as either having a dedicated MRI scanner for radiotherapy (RT) or access to a radiology MRI scanner, varied between countries. France, Italy and the UK reported the lowest direct MRI access rates and all other countries reported direct access in ≥82% of centres. Whilst ≥83% of centres in Denmark and Sweden reported having dedicated MRI scanners for EBRT, all other countries reported ≤29%. Anatomical sites receiving MRI for EBRT varied between countries with brain, prostate, head and neck being most common. Commissioning and QA of image registration and MRI scanners varied greatly, as did MRI sequences performed, staffing models and training given to different staff groups. The lack of financial reimbursement for MR was a consistent barrier for MRI implementation for RT for all countries and MR access was a reported important barrier for all countries except Sweden and Denmark.Conclusion: No country has a comprehensive approach for MR in EBRT adoption and financial barriers are present worldwide. Variations between countries in practice, equipment, staffing models, training, QA and MRI sequences have been identified, and are likely to be due to differences in funding as well as a lack of consensus or guidelines in the literature. Access to dedicated MR for EBRT is limited in all but Sweden and Denmark, but in all countries there are financial challenges with ongoing per patient costs. Despite these challenges, significant interest exists in increasing MR guided EBRT planning over the next 5 years.

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